KR102531540B1 - Composition for prevention or treatment of rheumatoid arthritis - Google Patents
Composition for prevention or treatment of rheumatoid arthritis Download PDFInfo
- Publication number
- KR102531540B1 KR102531540B1 KR1020200120924A KR20200120924A KR102531540B1 KR 102531540 B1 KR102531540 B1 KR 102531540B1 KR 1020200120924 A KR1020200120924 A KR 1020200120924A KR 20200120924 A KR20200120924 A KR 20200120924A KR 102531540 B1 KR102531540 B1 KR 102531540B1
- Authority
- KR
- South Korea
- Prior art keywords
- rheumatoid arthritis
- present
- composition
- administration
- acid
- Prior art date
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 55
- 239000000203 mixture Substances 0.000 title claims description 48
- 238000011282 treatment Methods 0.000 title abstract description 23
- 230000002265 prevention Effects 0.000 title abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 239000004480 active ingredient Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims description 36
- 235000013305 food Nutrition 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 206010061218 Inflammation Diseases 0.000 claims description 15
- 230000004054 inflammatory process Effects 0.000 claims description 15
- 210000001258 synovial membrane Anatomy 0.000 claims description 14
- 210000001519 tissue Anatomy 0.000 claims description 13
- 206010051728 Bone erosion Diseases 0.000 claims description 12
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 230000008961 swelling Effects 0.000 claims description 10
- 241001111421 Pannus Species 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 201000004595 synovitis Diseases 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 230000007850 degeneration Effects 0.000 claims description 5
- 230000009545 invasion Effects 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 abstract description 7
- XCUXYNYVUMLDKH-NSHDSACASA-N (2S)-2-[[4-[4-(trifluoromethyl)phenyl]phenyl]methylamino]propanamide Chemical compound C[C@H](NCC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(N)=O XCUXYNYVUMLDKH-NSHDSACASA-N 0.000 abstract description 5
- 230000006872 improvement Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 201000010099 disease Diseases 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 229940079593 drug Drugs 0.000 description 19
- 238000000034 method Methods 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- -1 alkali metal salt Chemical class 0.000 description 16
- 239000000796 flavoring agent Substances 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 241000283984 Rodentia Species 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 208000009386 Experimental Arthritis Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 239000003995 emulsifying agent Substances 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 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 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 235000013376 functional food Nutrition 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000018937 joint inflammation Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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 3
- 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 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 3
- 239000004386 Erythritol Substances 0.000 description 3
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 244000299461 Theobroma cacao Species 0.000 description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 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 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 235000019414 erythritol Nutrition 0.000 description 3
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 3
- 229940009714 erythritol Drugs 0.000 description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 3
- 229940093471 ethyl oleate Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 208000008822 Ankylosis Diseases 0.000 description 2
- 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 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010023198 Joint ankylosis Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 2
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000001046 cacaotero Nutrition 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000000378 calcium silicate Substances 0.000 description 2
- 229910052918 calcium silicate Inorganic materials 0.000 description 2
- 235000012241 calcium silicate Nutrition 0.000 description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001934 delay Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 210000005067 joint tissue Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229960003511 macrogol Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000845 maltitol Substances 0.000 description 2
- 235000010449 maltitol Nutrition 0.000 description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 2
- 229940035436 maltitol Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- AXIUZWFYRNNIFL-MERQFXBCSA-N methanesulfonic acid (2S)-2-[[4-[4-(trifluoromethyl)phenyl]phenyl]methylamino]propanamide Chemical compound CS(=O)(=O)O.FC(C1=CC=C(C=C1)C1=CC=C(C=C1)CN[C@H](C(=O)N)C)(F)F AXIUZWFYRNNIFL-MERQFXBCSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000003516 pericardium Anatomy 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 210000004224 pleura Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 210000003786 sclera Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 210000001179 synovial fluid Anatomy 0.000 description 2
- 210000002437 synoviocyte Anatomy 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 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 2
- 235000013311 vegetables Nutrition 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- 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
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 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
- 241000287828 Gallus gallus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 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
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 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
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 235000021405 artificial diet Nutrition 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
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 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
- 230000001164 bioregulatory effect Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229940013361 cresol Drugs 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte 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
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 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
- 239000012676 herbal extract Substances 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- CBATUQSECWXTQY-UHFFFAOYSA-N methanesulfonic acid propanamide Chemical compound CCC(N)=O.CS(O)(=O)=O CBATUQSECWXTQY-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 238000011457 non-pharmacological treatment Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000011903 nutritional therapy Methods 0.000 description 1
- 238000001584 occupational therapy Methods 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid 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
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 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 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000011764 rheumatoid arthritis animal model Methods 0.000 description 1
- 238000011808 rodent model Methods 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
- 150000004760 silicates Chemical class 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 108010027322 single cell proteins Proteins 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 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
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/111—Aromatic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Rheumatology (AREA)
- Food Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염(rheumatoid arthritis)의 예방, 개선 또는 치료용도에 관한 것이다.The present invention relates to the treatment of rheumatoid arthritis (rheumatoid) containing (S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide or a pharmaceutically acceptable salt thereof as an active ingredient. It relates to prevention, improvement or treatment of arthritis).
Description
본 발명은 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염의 예방, 개선 또는 치료용도에 관한 것이다.The present invention relates to prevention of rheumatoid arthritis comprising (S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide or a pharmaceutically acceptable salt thereof as an active ingredient. , improvement or therapeutic use.
류마티스 관절염(rheumatoid arthritis)은 자가면역성 갑상선염과 함께 대표적인 자가면역질환의 하나이다. 주로 30 내지 50대에서 가장 흔하게 나타나며, 남성보다는 여성에서 발병률이 높은 편이다. 관절의 변이 및 합병증으로 인해서 적절한 치료가 수반되지 않는다면 일상생활에 큰 장애를 갖고 살아가야 하므로, 환자의 삶의 질이 크게 저하되고 수명까지 단축될 수 있다. 정확한 원인은 밝혀지지 않았지만 유전적, 바이러스성, 환경적 요인이 관련이 높다고 받아들여지고 있다.Rheumatoid arthritis is one of the representative autoimmune diseases along with autoimmune thyroiditis. It is most common in people in their 30s to 50s, and the incidence is higher in women than in men. If appropriate treatment is not accompanied due to joint mutations and complications, patients have to live with great disabilities in their daily lives, which can greatly reduce the quality of life and shorten the lifespan of patients. The exact cause is unknown, but it is accepted that genetic, viral, and environmental factors are highly involved.
병리학적으로, 병의 진행은 주로 관절 연골의 파괴 및 관절의 강직(ankylosis)을 수반한다. 또한, 폐, 심막(pericardium), 늑막(pleura) 및/또는 눈의 공막(sclera)으로 염증이 확산되기도 한다. 병의 진행은 활막 주변의 염증과 관련이 있고, 다량의 활막액으로 인해 활막세포가 붓게되며, 활막 안의 섬유조직이 발달한다. 나아가 활막의 염증은 관절의 연골을 손상시키기 골미란을 발생시키며 관절을 파괴하기도 하며, 이는 일상 속 장애를 초래할 수 있다. 심지어 만성적 염증이 타기관에도 영향을 미칠 수 있으므로 합병증에도 주의해야 한다.Pathologically, the progression of the disease is primarily accompanied by destruction of articular cartilage and ankylosis of the joint. Inflammation may also spread to the lungs, pericardium, pleura and/or sclera of the eye. Progression of the disease is related to inflammation around the synovial membrane, synovial cells swell due to a large amount of synovial fluid, and fibrous tissue develops in the synovial membrane. Furthermore, inflammation of the synovial membrane damages the cartilage of the joint, causes bone erosion and destroys the joint, which can lead to disability in daily life. Even chronic inflammation can affect other organs, so you need to be careful about complications.
이와 관련하여, 시중에 많은 약물이 선보이고 있지만, 모든 류마티스 관절염 환자의 완치가 어려움, 단일치료법의 부재, 재발 및 부작용 등으로 인해서 효과적인 약물 및 치료법이 지속적인 관심을 받아오고 있다. 또한, 류마티스 관절염과 종종 동반되는 우울증 및 인지 장애에 대한 부분은 원인의 파악이 어려워 적절히 다뤄지지 못하고 있어서 더욱 폭이 넓은 치료법이 필요하다.In this regard, although many drugs are being introduced on the market, effective drugs and treatments have been receiving continuous attention due to the difficulty of curing all patients with rheumatoid arthritis, the absence of a single treatment method, recurrence and side effects, and the like. In addition, depression and cognitive impairment, which often accompany rheumatoid arthritis, are not properly treated because the cause is difficult to identify, so a wider range of treatments are needed.
이러한 배경하에서, 본 발명자들은 본 발명의 KDS2010 화합물이 류마티스 관절염 동물 모델인 CIA 마우스의 염증 발생을 억제하여 관절 염증 및/또는 변성으로 인한 붓기를 억제하는, 구체적으로, 활막 안의 섬유조직(pannus) 형성, 염증물질의 침범(synovitis inflammatory infiltrate), 또는 골미란(bone erosion)을 억제하는 효능을 통해 류마티스 관절염의 치료에 유용하게 활용될 수 있음을 확인함으로써 본 발명을 완성하였다.Under this background, the present inventors found that the KDS2010 compound of the present invention suppresses the inflammation of the CIA mouse, which is an animal model for rheumatoid arthritis, to suppress swelling caused by joint inflammation and/or degeneration, specifically, the formation of fibrous tissue (pannus) in the synovial membrane. , synovitis inflammatory infiltrate, or bone erosion, the present invention was completed by confirming that it can be usefully used for the treatment of rheumatoid arthritis.
본 발명의 하나의 목적은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염(rheumatoid arthritis)의 예방 또는 치료용 약학적 조성물을 제공하는 것이다:One object of the present invention is to provide a pharmaceutical composition for preventing or treating rheumatoid arthritis, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
본 발명의 다른 하나의 목적은 상기 약학적 조성물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 류마티스 관절염의 예방 또는 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating rheumatoid arthritis comprising administering the pharmaceutical composition to a subject in need thereof.
본 발명의 또 다른 하나의 목적은 상기 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for preventing or improving rheumatoid arthritis, comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 상기 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염의 예방 또는 개선용 사료 조성물을 제공하는 것이다.Another object of the present invention is to provide a feed composition for preventing or improving rheumatoid arthritis, comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.A detailed description of this is as follows. Meanwhile, each description and embodiment disclosed in the present invention may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 하기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염(rheumatoid arthritis)의 예방 또는 치료용 약학적 조성물을 제공한다:As one aspect for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating rheumatoid arthritis, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient. to provide:
[화학식 1][Formula 1]
. .
본 발명의 상기 화학식 1로 표시되는 화합물은 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드((S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide)의 IUPAC 명을 갖는 화합물이다.The compound represented by Formula 1 of the present invention is (S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide ((S)-2-((4 It is a compound with the IUPAC name of '-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide).
상기 화합물의 구체적인 약리활성에 대해서는 아직 연구가 진행 중이나, 직접적으로 류마티스 관절염의 예방 및 치료 효과를 갖는지 여부에 대해서는 밝혀진 바가 없다.Although studies are still in progress on the specific pharmacological activity of the compound, it has not been clarified whether it has direct preventive and therapeutic effects on rheumatoid arthritis.
또 하나의 양태로서, 본 발명은 상기 약학적 조성물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 류마티스 관절염의 예방 또는 치료방법을 제공한다.As another aspect, the present invention provides a method for preventing or treating rheumatoid arthritis comprising administering the pharmaceutical composition to a subject in need thereof.
본 발명의 류마티스 관절염의 예방 또는 치료방법은 재활훈련과 병행할 수 있다.The method for preventing or treating rheumatoid arthritis of the present invention may be combined with rehabilitation training.
본 발명의 약학적 조성물에 유효성분으로 함유되는 상기 화학식 1의 화합물은 약학적으로 허용 가능한 염의 형태로 존재할 수 있다. 상기 염으로는 약학적으로 허용가능한 유리산(free acid)에 의해 형성된 산가염이 유용하다. 본 발명의 용어 "약학적으로 허용가능한 염"이란 환자에게 비교적 비독성이고 무해한 유효작용을 갖는 농도로서 이 염에 기인한 부작용이 상기 화합물의 이로운 효능을 저하시키지 않는 상기 화합물의 임의의 모든 유기 또는 무기 부가염을 의미한다.The compound of Formula 1 contained as an active ingredient in the pharmaceutical composition of the present invention may exist in the form of a pharmaceutically acceptable salt. As the salt, an acid salt formed by a pharmaceutically acceptable free acid is useful. As used herein, the term "pharmaceutically acceptable salt" refers to a concentration that has an effective effect that is relatively non-toxic and harmless to patients, and any organic or It means inorganic addition salt.
산부가염은 통상의 방법, 예를 들어 화합물을 과량의 산 수용액에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들어 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조한다. 동 몰량의 화합물 및 물 중의 산 또는 알코올(예, 글리콜 모노메틸에테르)을 가열하고, 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다.Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and an acid or alcohol (eg, glycol monomethyl ether) in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered.
이때, 유리산으로는 유기산과 무기산을 사용할 수 있으며, 무기산으로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있고 유기산으로는 메탄술폰산, p-톨루엔술폰산, 아세트산, 트리플루오로아세트산, 말레인산(maleic acid), 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산(fumaric acid), 만데르산, 프로피온산(propionic acid), 구연산(citric acid), 젖산(lactic acid), 글리콜산(glycollic acid), 글루콘산(gluconic acid), 갈락투론산, 글루탐산, 글루타르산(glutaric acid), 글루쿠론산(glucuronic acid), 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 요오드화수소산(hydroiodic acid) 등을 사용할 수 있으며, 이들에 제한되지 않는다.At this time, organic acids and inorganic acids can be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid can be used as the organic acid. (maleic acid), succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc. can be used. , but not limited to these.
또한, 염기를 사용하여 약학적으로 허용가능한 금속염을 만들 수 있다. 알칼리 금속염 또는 알칼리 토금속염은, 예를 들어 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해시키고, 비용해 화합물 염을 여과한 후 여액을 증발, 건조시켜 얻는다. 이때, 금속염으로는 특히 나트륨, 칼륨, 또는 칼슘염을 제조하는 것이 제약상 적합하나 이들에 제한되는 것은 아니다. 또한 이에 대응하는 은염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 은염(예, 질산은)과 반응시켜 얻을 수 있다.In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for preparing a sodium, potassium, or calcium salt, but is not limited thereto. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
본 발명의 화합물의 약학적으로 허용가능한 염은, 달리 지시되지 않는 한, 상기 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 포함한다. 예를 들어, 약학적으로 허용가능한 염으로는 히드록시기의 나트륨, 칼슘 및 칼륨염 등이 포함될 수 있고, 아미노기의 기타 약학적으로 허용가능한 염으로는 히드로브롬화물, 황산염, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄술포네이트(메실레이트) 및 p-톨루엔술포네이트(토실레이트) 염 등이 있으며, 당업계에 알려진 염의 제조방법을 통하여 제조될 수 있다.Pharmaceutically acceptable salts of the compounds of the present invention, unless otherwise indicated, include salts of acidic or basic groups that may be present in the compounds. For example, pharmaceutically acceptable salts may include sodium, calcium, and potassium salts of a hydroxy group, and other pharmaceutically acceptable salts of an amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, and hydrogen phosphate. , dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, etc., preparation of salts known in the art It can be produced through the method.
또한, 상기 화합물은, 이의 약학적으로 허용 가능한 염뿐만 아니라 이로부터 제조될 수 있는 가능한 수화물 등의 용매화물을 제한없이 포함한다. 상기 화합물의 용매화물은 당업계에 공지된 방법을 사용하여 제조할 수 있다.In addition, the compound includes not only pharmaceutically acceptable salts thereof, but also solvates such as possible hydrates that can be prepared therefrom without limitation. Solvates of these compounds can be prepared using methods known in the art.
나아가, 상기 화합물은 결정 형태 또는 비결정 형태로 제조될 수 있으며, 결정 형태로 제조될 경우 임의로 수화되거나 용매화될 수 있다. 본 발명에서는 상기 화합물의 화학양론적 수화물뿐만 아니라 다양한 양의 물을 함유하는 화합물이 포함될 수 있다. 본 발명에 따른 상기 화합물의 용매화물은 화학양론적 용매화물 및 비화학양론적 용매화물 모두를 포함한다.Furthermore, the compound may be prepared in crystalline or amorphous form, and when prepared in crystalline form, it may optionally be hydrated or solvated. In the present invention, compounds containing various amounts of water may be included as well as stoichiometric hydrates of the above compounds. Solvates of the compounds according to the present invention include both stoichiometric and non-stoichiometric solvates.
구체적으로, 본 발명의 약학적 조성물에 사용되는 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드는 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 메탄술폰산염일 수 있으나, 이에 제한되지 않는다.Specifically, (S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide used in the pharmaceutical composition of the present invention is (S)-2-(( 4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide methanesulfonate, but is not limited thereto.
한편, 본 발명의 약학적 조성물에 사용되는 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 또는 이의 약학적으로 허용 가능한 염의 획득 방법에 특별히 한정되지 않으며, 당업계에 공지된 방법으로 화학적으로 합성하거나, 시판되는 물질을 사용할 수 있다.Meanwhile, a method for obtaining (S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide or a pharmaceutically acceptable salt thereof used in the pharmaceutical composition of the present invention It is not particularly limited to, and may be chemically synthesized by a method known in the art, or a commercially available material may be used.
본 발명의 용어, "류마티스 관절염(rheumatoid arthritis)"은 많은 조직과 장기에서 전신적 염증을 일으키지만 주로 유연한 활막에서 발생한다. 대표적인 증상은 발열감, 붓기, 및 관절의 통증이다. 류마티스 관절염은 통증을 수반하며, 운동에 장애를 주며, 적절히 치료되지 못하면 기능과 운동성을 상실할 수 있다. 병의 진행은 활막 주변의 염증과 관련이 있고, 다량의 활막액으로 인해 활막세포가 붓게되며, 활막 안의 섬유조직이 발달한다. 나아가 활막의 염증은 관절의 연골을 손상시키기 골미란을 발생시키며 관절을 파괴하기도 한다. 병리학적으로, 병의 진행은 주로 관절 연골의 파괴 및 관절의 강직(ankylosis)을 수반한다. 또한, 폐, 심막(pericardium), 늑막(pleura) 및/또는 눈의 공막(sclera)으로 염증이 확산되기도 한다. 이의 원인은 알려져 있지 않으나, 유전적 및 환경적 요인이 복합적으로 관여하는 것으로 여겨지며, 자가면역이 원인인 것으로 추정되는 전신성 자가면역질환으로 알려져 있다. 증상, 물리적 검사 및 X선 촬영 등을 통해 임상적 진단을 내릴 수 있다. 치료 방법으로는 약리적 방법과 비약리적 방법이 있다. 비약리적 치료는 물리치료, 정형술(orthoses), 작업치료(occupational therapy) 및 영양치료 등이 있으나, 이러한 치료방법으로는 관절의 손상 진행을 멈추게 할 수는 없다. 약리적 치료에 사용되는 진통제(analgesia) 및 항염증제(스테로이드 등)는 증상을 억제하지만, 이 역시 관절의 손상 진행을 멈출수는 없다. 이와 같이, 근본적으로 류마티스 관절염의 발생 자체를 억제하거나 지연시키면서 증상을 완화할 수 있는 치료 방법은 알려진 바 없다.As used herein, "rheumatoid arthritis" causes systemic inflammation in many tissues and organs, but mainly occurs in the flexible synovial membrane. Typical symptoms are fever, swelling, and joint pain. Rheumatoid arthritis is painful, impairs movement, and can lead to loss of function and mobility if not properly treated. Progression of the disease is related to inflammation around the synovial membrane, synovial cells swell due to a large amount of synovial fluid, and fibrous tissue develops in the synovial membrane. Furthermore, inflammation of the synovial membrane damages the cartilage of the joint, causes bone erosion, and destroys the joint. Pathologically, the progression of the disease is primarily accompanied by destruction of articular cartilage and ankylosis of the joint. Inflammation may also spread to the lungs, pericardium, pleura and/or sclera of the eye. Its cause is unknown, but it is believed to be complexly involved in genetic and environmental factors, and it is known as a systemic autoimmune disease presumed to be caused by autoimmunity. A clinical diagnosis can be made based on symptoms, physical examination, and X-rays. Treatment methods include pharmacological and non-pharmacological methods. Non-pharmacological treatments include physical therapy, orthoses, occupational therapy, and nutritional therapy, but these treatments cannot stop the progression of joint damage. Although analgesia and anti-inflammatory drugs (such as steroids) used in pharmacological treatment suppress symptoms, they cannot stop the progression of joint damage. As such, there is no known treatment method capable of alleviating symptoms while fundamentally suppressing or delaying the occurrence of rheumatoid arthritis itself.
예컨대, 본 발명의 약학적 조성물은 염증 발생을 억제할 수 있다.For example, the pharmaceutical composition of the present invention can inhibit inflammation.
또한, 본 발명의 약학적 조성물은 관절의 염증 또는 변성으로 인한 붓기를 억제할 수 있다.In addition, the pharmaceutical composition of the present invention can suppress swelling due to inflammation or degeneration of the joint.
나아가, 본 발명의 약학적 조성물은 활막 안의 섬유조직(pannus) 형성, 염증물질의 침범(synovitis inflammatory infiltrate), 또는 골미란(bone erosion)을 억제할 수 있다.Furthermore, the pharmaceutical composition of the present invention can inhibit the formation of fibrous tissue (pannus) in the synovial membrane, the invasion of inflammatory substances (synovitis inflammatory infiltrate), or bone erosion (bone erosion).
이상의 현상은 류마티스 관절염의 진행에 관여하는 주요 인자이며, 본 발명의 약학적 조성물은 이들 현상을 효과적으로 억제할 수 있으므로, 류마티스 관절염을 예방하거나, 발병을 지연시키고 이로 인한 증상을 완화하는 효과를 발휘할 수 있다.The above phenomena are major factors involved in the progression of rheumatoid arthritis, and the pharmaceutical composition of the present invention can effectively inhibit these phenomena, thereby preventing rheumatoid arthritis, delaying the onset, and relieving symptoms caused by it. there is.
본 발명의 구체적인 일 실시예에서는, 본 발명의 화학식 1의 화합물의 메탄술폰산염을 류마티스 관절염 동물 모델에 처리하였을 때, 약물 비투여 대조군에 비해 관절염의 척도인 붓기를 기준으로 하는 임상 스코어를 현저히 감소시키고 발의 두께 증가도 눈에 띄게 감소시키며, 활막 안의 섬유조직(pannus) 형성, 염증물질의 침범(synovitis inflammatory infiltrate), 또는 골미란(bone erosion)을 억제함을 확인하였다(도 2 및 도 3).In a specific embodiment of the present invention, when a rheumatoid arthritis animal model was treated with the methanesulfonate salt of the compound of Formula 1 of the present invention, the clinical score based on swelling, which is a measure of arthritis, was significantly reduced compared to the drug-free control group. It was also confirmed that the increase in the thickness of the foot was noticeably reduced, and the formation of fibrous tissue (pannus) in the synovial membrane, the invasion of inflammatory substances (synovitis inflammatory infiltrate), or bone erosion were inhibited (FIGS. 2 and 3).
이는 본 발명의 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 포함하는 조성물이 류마티스 관절염의 예방 또는 치료 용도로 우수한 효과를 발휘할 수 있음을 나타내는 것이다.This indicates that the composition containing the compound of Formula 1 or a pharmaceutically acceptable salt thereof of the present invention can exert excellent effects for use in preventing or treating rheumatoid arthritis.
본 발명의 용어 "예방"이란 본 발명의 약학적 조성물의 투여로 류마티스 관절염의 발생, 확산 및 재발을 억제시키거나 지연시키는 모든 행위를 의미하고, "치료"란 본 발명의 약학적 조성물의 투여로 상기 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term "prevention" of the present invention refers to any action that inhibits or delays the occurrence, spread, and recurrence of rheumatoid arthritis by administration of the pharmaceutical composition of the present invention, and "treatment" is the administration of the pharmaceutical composition of the present invention It means any action that improves or beneficially changes the symptoms of the disease.
본 발명의 구체적인 일 구현예에서, 상기 치료는 류마티스 관절염의 징후의 감소 또는 완화, 상기 질병의 정도의 축소, 질병의 지연 또는 완행(slowing), 질병 상태의 일시적 완화(palliation) 또는 안정화, 및 그 외 이로운 결과를 의미할 수 있으나, 이에 제한되지 않는다.In a specific embodiment of the present invention, the treatment reduces or alleviates the symptoms of rheumatoid arthritis, reduces the severity of the disease, delays or slows the disease, palliates or stabilizes the disease state, and It may mean other beneficial results, but is not limited thereto.
본 발명의 용어 "개체"란, 류마티스 관절염이 발명하였거나 발병할 수 있는, 류마티스 관절염이 의심되는 개체로서, 인간을 포함한 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 쥐, 토끼 또는 기니아 피그를 포함한 모든 동물을 의미하고, 본 발명의 약학적 조성물을 이들 개체에게 투여함으로써 상기 질환을 효과적으로 예방 또는 치료할 수 있다. 또한, 본 발명의 약학적 조성물은 기존의 치료제와 병행하여 투여함으로써 시너지적인 효과를 나타낼 수 있다.The term "individual" of the present invention refers to an individual suspected of having rheumatoid arthritis, who may have or develop rheumatoid arthritis, including humans, monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, It means any animal including mouse, rat, rabbit or guinea pig, and the disease can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to these subjects. In addition, the pharmaceutical composition of the present invention can exhibit a synergistic effect by being administered in parallel with existing therapeutic agents.
본 발명의 용어 "투여"란, 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강내 투여, 정맥내 투여, 근육내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비내 투여, 폐내투여, 직장내 투여될 수 있으나, 이에 제한되지는 않는다. 또한, 본 발명의 약학적 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수도 있다. 바람직한 투여방식 및 제제는 정맥 주사제, 피하 주사제, 피내 주사제, 근육 주사제, 점적 주사제 등이다. 주사제는 생리식염액, 링겔액 등의 수성 용제, 식물유, 고급 지방산 에스테르(예, 올레인산에칠 등), 알코올 류(예, 에탄올, 벤질알코올, 프로필렌글리콜, 글리세린 등) 등의 비수성 용제 등을 이용하여 제조할 수 있고, 변질 방지를 위한 안정화제(예, 아스코르빈산, 아황산수소나트륨, 피로아황산나트륨, BHA, 토코페롤, EDTA 등), 유화제, pH 조절을 위한 완충제, 미생물 발육을 저지하기 위한 보존제(예, 질산페닐수은, 치메로살, 염화벤잘코늄, 페놀, 크레솔, 벤질알코올 등) 등의 약학적 담체를 포함할 수 있다.The term "administration" of the present invention means providing a predetermined substance to a patient by any suitable method, and the administration route of the composition of the present invention may be administered through any general route as long as it can reach the target tissue. there is. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, or intrarectal administration may be administered, but is not limited thereto. In addition, the pharmaceutical composition of the present invention may be administered by any device capable of transporting an active substance to a target cell. Preferred administration modes and preparations are intravenous injections, subcutaneous injections, intradermal injections, intramuscular injections, drip injections, and the like. Injections are formulated with aqueous solvents such as physiological saline and IV, non-aqueous solvents such as vegetable oil, higher fatty acid esters (e.g., ethyl oleate, etc.), alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Stabilizers (e.g., ascorbic acid, sodium hydrogensulfite, sodium pyrosulfite, BHA, tocopherol, EDTA, etc.) to prevent deterioration, emulsifiers, buffers to control pH, A pharmaceutical carrier such as a preservative (eg, phenylmercuric nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) may be included.
예컨대, 본 발명의 조성물은 약학적으로 허용가능한 담체, 희석제 또는 부형제를 추가로 포함할 수 있으며, 각각의 사용 목적에 맞게 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁제, 에멀젼, 시럽, 에어로졸 등의 경구 제형, 멸균 주사 용액의 주사제 등 다양한 형태로 제형화하여 사용할 수 있으며, 경구 투여하거나 정맥내, 복강내, 피하, 직장, 국소 투여 등을 포함한 다양한 경로를 통해 투여될 수 있다. 이러한 조성물에 포함될 수 있는 적합한 담체, 부형제 또는 희석제의 예로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸셀룰로즈, 미정질셀룰로스, 폴리비닐피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 들 수 있다. 또한, 본 발명의 조성물은 충전제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.For example, the composition of the present invention may further include a pharmaceutically acceptable carrier, diluent or excipient, and powders, granules, tablets, capsules, suspensions, emulsions, It can be formulated and used in various forms, such as oral formulations such as syrups and aerosols and injections of sterile injection solutions, and can be administered orally or through various routes including intravenous, intraperitoneal, subcutaneous, rectal, and topical administration. . Examples of suitable carriers, excipients or diluents that may be included in such compositions include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil; and the like. In addition, the composition of the present invention may further include fillers, anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like.
경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면 전분, 탄산칼슘, 수크로스, 락토즈, 젤라틴 등을 혼합하여 제형화한다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크와 같은 윤활제가 사용될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the composition, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. Formulated by mixing. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients.
경구용 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 예시될 수 있으며, 흔히 사용되는 단순 희석제인 물, 액체 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Oral liquid preparations may include suspensions, solutions for internal use, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. can
비경구 투여를 위한 제제에는 멸균된 수용액제, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈61. 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 한편, 주사제에는 용해제, 등장화제, 현탁화제, 유화제, 안정화제, 방부제 등과 같은 종래의 첨가제가 포함될 수 있다.Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions. The suppositories are Witepsol, Macrogol, and Tween 61. Cacao fat, laurin fat, glycerogeratin and the like can be used. Meanwhile, conventional additives such as solubilizers, tonicity agents, suspending agents, emulsifiers, stabilizers, and preservatives may be included in the injection.
상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있으며 활성 성분을 약 0.1 내지 75 중량%, 바람직하게는 약 1 내지 50 중량%의 범위에서 함유할 수 있다. 약 50 내지 70 kg의 포유동물에 대한 단위 제형은 약 10 내지 200 mg의 활성성분을 함유한다.The formulation may be prepared by conventional mixing, granulation or coating methods and may contain the active ingredient in an amount of about 0.1 to 75% by weight, preferably about 1 to 50% by weight. A unit dosage for a mammal of about 50 to 70 kg contains about 10 to 200 mg of active ingredient.
이때, 본 발명의 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명의 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.At this time, the composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" of the present invention means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, and the effective dose level is the patient's health condition, Depending on the type of disease, severity, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field can The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.
예컨대, 투여 경로, 질병의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.For example, the dosage may increase or decrease depending on the route of administration, severity of disease, sex, weight, age, etc., so the dosage is not limited to the scope of the present invention in any way.
본 발명의 화합물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물의 형태, 투여 경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 화합물을 1일 0.0001 내지 100 mg/kg(체중), 바람직하게는 0.001 내지 100 mg/kg(체중)으로 투여하는 것이 좋다. 투여는 1일 1회 또는 분할하여 경구 또는 비경구적 경로를 통해 투여될 수 있다.A preferred dose of the compound of the present invention varies depending on the condition and weight of the patient, the severity of the disease, the type of drug, the route and duration of administration, but can be appropriately selected by those skilled in the art. However, for desirable effects, it is recommended to administer the compound of the present invention at 0.0001 to 100 mg/kg (body weight) per day, preferably 0.001 to 100 mg/kg (body weight). Administration can be administered via an oral or parenteral route once a day or in divided doses.
본 발명의 류마티스 관절염의 예방 또는 치료용 조성물은, 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 약학적 제형으로 제조될 수 있다. 제형의 제조에 있어서, 활성 성분을 담체와 함께 혼합 또는 희석하거나, 용기 형태의 담체 내에 봉입시킬 수 있다.The composition for preventing or treating rheumatoid arthritis of the present invention can be prepared into a pharmaceutical formulation using a method well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. . In preparation of the formulation, the active ingredient may be mixed or diluted with a carrier, or encapsulated in a carrier in the form of a container.
이에 따라, 본 발명의 약학적 조성물은 약학적으로 허용가능한 담체, 희석제 또는 부형제를 추가로 포함할 수 있으며, 각각의 사용 목적에 맞게 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁제, 에멀젼, 시럽, 에어로졸 등의 경구 제형, 멸균 주사 용액의 주사제 등 다양한 형태로 제형화하여 사용할 수 있으며, 경구 투여하거나 정맥내, 복강내, 피하, 직장, 국소 투여 등을 포함한 다양한 경로를 통해 투여될 수 있다. 이러한 조성물에 포함될 수 있는 적합한 담체, 부형제 또는 희석제의 예로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸셀룰로즈, 미정질셀룰로스, 폴리비닐피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 들 수 있다. 또한, 본 발명의 조성물은 충전제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.Accordingly, the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, diluent, or excipient, and may be prepared in powders, granules, tablets, capsules, or suspensions according to conventional methods according to each purpose of use. It can be formulated and used in various forms, such as oral formulations such as emulsions, syrups, and aerosols, and injections of sterile injection solutions. It can be. Examples of suitable carriers, excipients or diluents that may be included in such compositions include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil; and the like. In addition, the composition of the present invention may further include fillers, anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like.
경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면 전분, 탄산칼슘, 수크로스, 락토즈, 젤라틴 등을 혼합하여 제형화한다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크와 같은 윤활제가 사용될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the composition, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. Formulated by mixing. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients.
경구용 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 예시될 수 있으며, 흔히 사용되는 단순 희석제인 물, 액체 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Oral liquid preparations may include suspensions, solutions for internal use, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. can
비경구 투여를 위한 제제에는 멸균된 수용액제, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈61. 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 한편, 주사제에는 용해제, 등장화제, 현탁화제, 유화제, 안정화제, 방부제 등과 같은 종래의 첨가제가 포함될 수 있다.Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions. The suppositories are Witepsol, Macrogol, and Tween 61. Cacao fat, laurin fat, glycerogeratin and the like can be used. Meanwhile, conventional additives such as solubilizers, tonicity agents, suspending agents, emulsifiers, stabilizers, and preservatives may be included in the injection.
상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있으며 활성 성분을 약 0.1 내지 75 중량%, 바람직하게는 약 1 내지 50 중량%의 범위에서 함유할 수 있다. 약 50 내지 70 kg의 포유동물에 대한 단위 제형은 약 10 내지 200 mg의 활성성분을 함유한다.The formulation may be prepared by conventional mixing, granulation or coating methods and may contain the active ingredient in an amount of about 0.1 to 75% by weight, preferably about 1 to 50% by weight. A unit dosage for a mammal of about 50 to 70 kg contains about 10 to 200 mg of active ingredient.
이때, 본 발명의 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명의 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.At this time, the composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" of the present invention means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, and the effective dose level is the patient's health condition, Depending on the type of disease, severity, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field can
본 발명의 화합물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물의 형태, 투여 경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 화합물을 1일 0.0001 내지 100 mg/kg(체중), 바람직하게는 0.001 내지 100 mg/kg(체중)으로 투여하는 것이 좋다. 투여는 1일 1회 또는 분할하여 경구 또는 비경구적 경로를 통해 투여될 수 있다.A preferred dose of the compound of the present invention varies depending on the condition and weight of the patient, the severity of the disease, the type of drug, the route and duration of administration, but can be appropriately selected by those skilled in the art. However, for desirable effects, it is recommended to administer the compound of the present invention at 0.0001 to 100 mg/kg (body weight) per day, preferably 0.001 to 100 mg/kg (body weight). Administration can be administered via an oral or parenteral route once a day or in divided doses.
예컨대, 투여 경로, 질병의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.For example, the dosage may increase or decrease depending on the route of administration, severity of disease, sex, weight, age, etc., so the dosage is not limited to the scope of the present invention in any way.
또한 본 발명의 약학적 조성물은 류마티스 관절염의 예방 및 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 약물 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다. 본 발명의 목적상, 본 발명에 따른 약학적 조성물은 류마티스 관절염의 치료에 통상적으로 사용되는 하나 이상의 추가적인 약물과 병용 투여될 수 있다.In addition, the pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy, and biological response modifiers for the prevention and treatment of rheumatoid arthritis. For the purposes of the present invention, the pharmaceutical composition according to the present invention may be administered in combination with one or more additional drugs commonly used in the treatment of rheumatoid arthritis.
본 발명에 따른 약학적 조성물을 류마티스 관절염의 치료를 위해 투여하는 경우, 류마티스 관절염의 치료 또는 예방에 효과가 있는 성분 및/또는 약제 1종 이상과 병용 및/또는 조합하여 투여할 수 있다. 이때 전술한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다When the pharmaceutical composition according to the present invention is administered for the treatment of rheumatoid arthritis, it may be administered in combination and/or combination with one or more ingredients and/or drugs effective in treating or preventing rheumatoid arthritis. At this time, it is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, which can be easily determined by those skilled in the art.
구체적으로 상기 병용 및/또는 조합 투여는 본 발명의 화합물 또는 이의 약학적으로 허용가능한 염과 상기 하나 이상의 추가적인 약물을 각각 동시, 순차적, 또는 역순으로 투여할 수 있으며, 적절한 유효량의 조합으로 동시에 투여하거나, 각각 별도의 용기에 보관한 후 동시, 순차적 또는 역순으로 병용 투여할 수 있다.Specifically, the concomitant and / or combined administration may be the simultaneous, sequential, or reverse order administration of the compound of the present invention or a pharmaceutically acceptable salt thereof and the one or more additional drugs, respectively, and simultaneously administered in a combination of appropriate effective amounts, or , Can be administered simultaneously, sequentially or in reverse order after each is stored in a separate container.
또 다른 양태로서, 본 발명은 상기 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염의 예방 또는 개선용 식품 조성물을 제공한다.In another aspect, the present invention provides a food composition for preventing or improving rheumatoid arthritis, comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
상기 "류마티스 관절염", 및 "예방"은 상기에서 설명한 바와 같다.The "rheumatoid arthritis" and "prevention" are as described above.
또한, 본 발명의 용어, "식품학적으로 허용 가능한 염"은 전술한 약학적으로 허용 가능한 염과 동일하게 정의될 수 있다.In addition, the term of the present invention, "food acceptable salt" may be defined the same as the pharmaceutically acceptable salt described above.
본 발명의 "개선"은 상기 화학식 1의 화합물 또는 이의 식품학적으로 허용가능한 염을 포함하는 조성물을 이용하여 대상 질환의 의심 및 발명 개체의 증상이 호전되거나 이롭게 되는 모든 행위를 말한다."Improvement" of the present invention refers to all activities that improve or benefit the symptoms of suspected disease and inventive subject by using a composition containing the compound of Formula 1 or a food-acceptable salt thereof.
본 발명에 따른 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐 또는 액제 등의 형태를 포함하며, 본 발명의 조성물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있다.The food composition according to the present invention includes forms such as pills, powders, granules, precipitates, tablets, capsules or liquids, and as foods to which the composition of the present invention can be added, for example, various foods, such as , beverages, gum, tea, vitamin complexes, and health supplements.
본 발명의 식품 조성물에서 포함할 수 있는 필수 성분으로 상기 화학식 1의 화합물 또는 이의 식품학적으로 허용가능한 염의 함유 외에는 다른 성분에는 제한이 없으며 통상의 식품과 같이 여러 생약추출물, 식품 보조 첨가제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.As an essential ingredient that can be included in the food composition of the present invention, there are no restrictions on other ingredients except for the compound of Formula 1 or a food-acceptable salt thereof, and, like conventional foods, various herbal extracts, food supplement additives, or natural carbohydrates, etc. may be included as an additional component.
또한, 상기 식품 보조 첨가제는 당업계에 통상적인 식품 보조 첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함한다.In addition, the food auxiliary additives include food auxiliary additives common in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like.
상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 상술한 것 이외에 향미제로서 천연 향미제(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.Examples of the natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the above, natural flavors (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can advantageously be used as flavoring agents.
상기 외에 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.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, colorants and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained. In addition, it may contain fruit flesh for the manufacture of natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination.
본 발명에서 상기 식품 조성물은 건강기능식품 및 건강보조식품 등을 포함한다.In the present invention, the food composition includes health functional food and health supplement food.
상기 건강 기능(성) 식품(functional food)이란, 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및/또는 가공한 식품으로서, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 "기능(성)"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 이상과 같이 인체에 유용한 성분을 포함하는 식품으로서 식약처가 그 기능과 안정성을 인정한 식품을 건강기능식품이라 하며, 이외 식약처의 허가를 받지는 않았으나, 인체에 유리한 효과를 갖는 식품으로 여겨지는 것을 건강(보조)식품이라 구분한다. 본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나다.The health functional food (functional food) is the same term as food for special health use (FoSHU), and is a food manufactured and/or processed using raw materials or ingredients having useful functionality for the human body. As, in addition to nutritional supply, it means food with high medical and medical effects processed so that the bioregulatory function appears efficiently. Here, "function (sex)" means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. As described above, food containing useful ingredients for the human body and recognized for its function and safety by the Ministry of Food and Drug Safety is called health functional food. It is classified as (supplementary) food. The food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the preparation. In addition, the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food. The food composition of the present invention can be prepared in various types of dosage forms, and unlike general medicines, it has the advantage of not having side effects that may occur when taking medicines for a long time by using food as a raw material, and has excellent portability.
또 다른 양태로서, 본 발명은 상기 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 류마티스 관절염의 예방 또는 개선용 사료 조성물을 제공한다.In another aspect, the present invention provides a feed composition for preventing or improving rheumatoid arthritis, comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
상기 "류마티스 관절염", "예방", 및 "개선"은 상기에서 설명한 바와 같다.The "rheumatoid arthritis", "prevention", and "improvement" are as described above.
또한, 본 발명의 용어, "사료학적으로 허용 가능한 염"은 전술한 약학적으로 허용 가능한 염과 동일하게 정의될 수 있다.In addition, the term of the present invention, "feed-safe salt" may be defined the same as the above-mentioned pharmaceutically acceptable salt.
본 발명의 용어, "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미한다.As used herein, the term "feed" refers to any natural or artificial diet, meal, etc., or component of said meal, intended for or suitable for consumption by animals.
상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.The type of feed is not particularly limited, and feeds commonly used in the art may be used. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.
본 발명의 사료는 분말 사료, 고형 사료, 모이스트 펠릿 사료, 드라이 펠릿 사료, EP(Extruder Pellet) 사료, 날먹이 등일 수 있으나, 이에 제한되지 않는다.The feed of the present invention may be powder feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, raw feed, etc., but is not limited thereto.
본 발명의 사료용 조성물은 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 있을 수 있으며, 상기 사료용 조성물은 사료 첨가제를 포함할 수 있다. 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 향미제, 비단백질태질소화합물, 규산염제, 완충제, 추출제, 올리고당 등이 있을 수 있다. 그 외에도 사료 혼합제 등을 추가로 포함할 수 있으며, 이에 제한되는 것은 아니다.The feed composition of the present invention may include a binder, an emulsifier, and a preservative added to prevent quality deterioration, and the feed composition may include a feed additive. There may be amino acids, vitamins, enzymes, flavors, non-protein nitrogen compounds, silicates, buffers, extractants, oligosaccharides, etc. added to the feed to increase efficacy. In addition, it may further include a feed mixture and the like, but is not limited thereto.
본 발명의 화학식 1의 화합물 또는 이의 약학적으로 허용 가능한 염을 포함하는 조성물은 류마티스 관절염의 발병으로 수반되는 증상인 붓기를 현저히 저해하고, 병리학적으로 병의 진행을 나타내는 활막 안의 섬유조직(pannus) 형성, 염증물질의 침범(synovitis inflammatory infiltrate), 또는 골미란(bone erosion)을 억제하는 효과를 나타내므로 류마티스 관절염의 예방 또는 치료에 유용하게 사용될 수 있다.The composition comprising the compound of Formula 1 or a pharmaceutically acceptable salt thereof of the present invention significantly inhibits swelling, which is a symptom accompanying the onset of rheumatoid arthritis, and reduces the pathologically progressing fibrous tissue (pannus) in the synovium. Formation, invasion of inflammatory substances (synovitis inflammatory infiltrate), or exhibits the effect of suppressing bone erosion (bone erosion), so it can be usefully used for the prevention or treatment of rheumatoid arthritis.
도 1은 설치류 류마티스 관절염 모델의 제작 및 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 메탄술폰산염(이하, KDS2010) 투여에 대한 개요를 나타낸 도이다.
도 2는 설치류 류마티스 관절염 모델에서 KDS2010 투여로 인한 관절 염증의 회복 정도를 나타낸 도이다. 도 2의 A 및 B는 각각 류마티스 관절염 정도 및 붓기를 수치화한 임상 스코어 및 발 두께(paw thickness)를 나타낸다. 도 2의 C 내지 F는 Figure 1 shows the preparation of a rodent rheumatoid arthritis model and the administration of (S) -2 - ((4'-(trifluoromethyl) biphenyl-4-yl) methylamino) propanamide methanesulfonate (hereinafter referred to as KDS2010). This is an overview diagram.
2 is a diagram showing the degree of recovery of joint inflammation due to administration of KDS2010 in a rodent rheumatoid arthritis model. A and B of FIG. 2 show clinical scores and paw thickness quantifying the degree of rheumatoid arthritis and swelling, respectively. C to F in FIG. 2 are
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. However, these examples are intended to illustrate the present invention by way of example, and the scope of the present invention is not limited to these examples.
제조예 1: 투여 약물 준비Preparation Example 1: Administration drug preparation
투여 대상 약물인 (S)-2-((4'-(트리플루오로메틸)바이페닐-4-일)메틸아미노)프로판아미드 메탄술폰산염(이하, KDS2010)를 한국등록특허공보 제10-1746060호에 기재된 방법, 구체적으로, 실시예 9에 기재된 방법으로 합성하여 준비하였다.(S)-2-((4'-(trifluoromethyl)biphenyl-4-yl)methylamino)propanamide methanesulfonate (hereinafter KDS2010), which is a drug to be administered, It was synthesized and prepared by the method described in No., specifically, the method described in Example 9.
제조예 2: 설치류 류마티스 관절염 모델 제작Preparation Example 2: Production of rodent rheumatoid arthritis model
8주령의 DBA/1 마우스를 이용하여, 류마티스 관절염 연구를 위해 가장 많이 사용되는 콜라겐 유도성 관절염(collagen induced arthritis, CIA) 설치류 모델을 제작하였다.Using 8-week-old DBA/1 mice, a collagen induced arthritis (CIA) rodent model, which is most commonly used for research on rheumatoid arthritis, was constructed.
구체적으로, 비변성 제2형 콜라겐(type II collagen)과 완전프로인트항원보강제(complete Freund's adjuvant; CFA)를 1:1의 비율로 저온에서 충분히 혼합하여 준비한 혼합물을 8주령의 DBA/1 마우스의 꼬리의 복부쪽과 옆쪽 혈관 사이 진피 피부조직에 100 μL 주사하였다. 대조군은 100 μL의 생리식염수를 동일한 위치에 주사하였다. 3주 경과 후에는 비변성 제2형 콜라겐과 불완전프로인트항원보강제(incomplete Freund's adjuvant; IFA)를 1:1의 비율로 저온에서 충분히 혼합하여 준비한 혼합물을 앞선 주사와 동일한 방법으로 혈관 사이 진피 피부조직에 주사하였다. 상기 류마티스 관절염(콜라겐 유도성 관절염, CIA) 동물모델 제작 타임라인 및 약물 투여 개요를 도 1에 나타내었다.Specifically, a mixture prepared by sufficiently mixing undenatured type II collagen and complete Freund's adjuvant (CFA) at a ratio of 1:1 at low temperature was mixed with 8-week-old DBA/1 mice. 100 μL was injected into the dermal skin tissue between the ventral and lateral blood vessels of the tail. As a control group, 100 μL of physiological saline was injected at the same location. After 3 weeks, a mixture prepared by sufficiently mixing
실시예 1: 약물 투여Example 1: Drug Administration
제조예 1에 따라 준비한 KDS2010을 물에 녹여 마우스들이 마시는 음수통에 첨가하여 상기 제조예 2에 따라 준비한 설치류 류마티스 관절염 모델에 10 또는 30 mg/kg 용량으로 투여하였다. 음수통의 약물은 매 이틀 간격으로 새롭게 갈아주었다.KDS2010 prepared according to Preparation Example 1 was dissolved in water, added to a drinking water bottle for mice, and administered to the rodent rheumatoid arthritis model prepared according to Preparation Example 2 at a dose of 10 or 30 mg/kg. The drug in the water bottle was changed every two days.
실시예 2: 관절 평가Example 2: Joint evaluation
설치류 류마티스 관절염 모델에 KDS2010의 효과를 확인하기 위하여, KDS2010 투여 후 관절의 염증 정도를 측정하였다. 류마티스 관절염의 정도를 수치화하기 위해, 공통적으로 사용하는 관절염증 스코어를 적용하여 임상 스코어를 산출하였다. 이때, 정상적 수준의 관절은 0점, 염증의 정도가 심해져서 붓기가 높아질수록 보다 높은 점수를 부여하고, 가장 염증이 심한 정도에는 최고점인 16점을 부여하였다. 나아가, 관절의 두께, 예컨대, 발의 두께를 측정하여 관절의 붓기를 측정하였다. 산출된 임상 스코어와 측정된 발의 두께를 각각 도 2의 A 및 B에 나타내었다.In order to confirm the effect of KDS2010 on the rodent rheumatoid arthritis model, the degree of joint inflammation was measured after administration of KDS2010. In order to quantify the degree of rheumatoid arthritis, a commonly used arthritis score was applied to calculate a clinical score. At this time, a normal level of joint was given 0 points, the degree of inflammation was severe and the higher the swelling, the higher score was given, and the highest score, 16 points, was given to the most severe degree of inflammation. Further, joint swelling was measured by measuring the thickness of the joint, for example, the thickness of the foot. The calculated clinical score and the measured paw thickness are shown in A and B of FIG. 2 , respectively.
도 2의 A 및 B에 나타난 바와 같이, KDS2010를 투여한 설치류 류마티스 관절염 모델에서 대조군(염수 투여 정상 마우스)과 달리 IFA 투여 이후로부터 시간의 경과에 따라 급격히 증가하던 임상 스코어는 KDS2010 투여군에서 그 증가폭이 감소하였으며, 상기 감소율은 KDS2010 투여량에 따라 증가하였다. 이는 발 두께 측정에서도 동일한 경향을 나타내었다. 이는 KDS2010이 류마티스 관절염 임상 스코어를 낫추고 붓기를 억제하는 효과를 나타내며, 이러한 효과는 농도 의존적임을 나타내는 것이다.As shown in A and B of FIG. 2, unlike the control group (saline-administered normal mice) in the rodent rheumatoid arthritis model administered with KDS2010, the clinical score, which increased rapidly over time from IFA administration, was increased in the KDS2010-administered group. decreased, and the rate of decrease increased according to the KDS2010 dose. This showed the same tendency in the paw thickness measurement. This indicates that KDS2010 has an effect of reducing the clinical score of rheumatoid arthritis and suppressing swelling, and that this effect is concentration dependent.
실시예 3: 관절 조직 염색Example 3: Joint tissue staining
상기 제조예 2에 따라 준비한 설치류 류마티스 관절염 모델에서 KDS2010 투여에 의한 효과를 관절 염색을 통해 추가로 확인하였다. 구체적으로, 적출한 관절조직에 H&E(hematoxylin & eosin) 염색법을 수행하고, 이로부터 활막 안의 섬유조직(pannus), 염증물질 침범정도(synovitis inflammatory infiltrate)와 골미란(bone erosion) 정도를 산출하여 각각 도 2의 C 내지 F에 나타내었다. 또한 면역조직화학염색법(immunohistochemistry; IHC)을 수행하였다.In the rodent rheumatoid arthritis model prepared according to Preparation Example 2, the effect of KDS2010 administration was further confirmed through joint staining. Specifically, H&E (hematoxylin & eosin) staining was performed on the extracted joint tissue, and the degree of fibrous tissue (pannus) in the synovial membrane, synovitis inflammatory infiltrate, and bone erosion were calculated, respectively. It is shown in C to F of 2. In addition, immunohistochemistry (IHC) was performed.
도 2의 C 내지 F에 나타난 바와 같이, 정상 마우스(CTR)에 비해 제조예 2의 CIA 모델 마우스의 관절에서 활막 안의 섬유조직, 염증물질 침범정도 및 골미란 정도가 모두 현저히 증가하였으나, KDS2010 투여군에서는 이러한 증상이 눈에 띄게 회복되었다. 특히 KDS2010을 10 mg/kg 용량으로 투여하여도 상당한 증상의 호전을 달성할 수 있었다. 이는, KDS2010이 류마티스 관절염 몸델에서 관절의 염증 및/또는 변성을 억제함으로써 이의 치료에 사용될 수 있음을 나타내는 것이다.As shown in C to F of FIG. 2, the fibrous tissue in the synovial membrane, the degree of invasion of inflammatory substances, and the degree of bone erosion in the joint of the CIA model mouse of Preparation Example 2 were all significantly increased compared to the normal mouse (CTR), but in the KDS2010 administration group, these Symptoms markedly improved. In particular, even when KDS2010 was administered at a dose of 10 mg/kg, significant symptomatic improvement was achieved. This indicates that KDS2010 can be used for the treatment of rheumatoid arthritis by inhibiting joint inflammation and/or degeneration in the body.
이상의 결과는 KDS2010이 류마티스 관절염 모델에서 질병의 신경학적인 임상증상 척도를 개선하고, 발병을 지연시킬 뿐만 아니라, 관절의 염증 및/또는 변성을 완화하여 이로 인한 붓기를 억제할 수 있으므로, 류마티스 관절염의 예방 또는 치료에 유용하게 사용될 수 있음을 나타내는 것이다.The above results show that KDS2010 can improve the neurological clinical symptom scale of the disease in the rheumatoid arthritis model, delay the onset, and alleviate inflammation and/or degeneration of the joint to suppress the resulting swelling, thus preventing rheumatoid arthritis. Or it indicates that it can be usefully used for treatment.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not limiting. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described later and equivalent concepts rather than the detailed description above are included in the scope of the present invention.
Claims (7)
[화학식 1]
.
A pharmaceutical composition for preventing or treating rheumatoid arthritis comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]
.
상기 화합물은 메탄술폰산염의 형태인 것인, 약학적 조성물.
According to claim 1,
The pharmaceutical composition, wherein the compound is in the form of methanesulfonic acid salt.
상기 조성물은 염증 발생을 억제하는 것인, 약학적 조성물.
According to claim 1,
Wherein the composition inhibits the occurrence of inflammation, the pharmaceutical composition.
상기 조성물은 관절의 염증 또는 변성으로 인한 붓기를 억제하는 것인, 약학적 조성물.
According to claim 1,
The composition is to inhibit swelling due to inflammation or degeneration of the joint, a pharmaceutical composition.
상기 조성물은 활막 안의 섬유조직(pannus) 형성, 염증물질의 침범(synovitis inflammatory infiltrate), 또는 골미란(bone erosion)을 억제하는 것인, 약학적 조성물.
According to claim 1,
The composition is a pharmaceutical composition that inhibits the formation of fibrous tissue (pannus) in the synovial membrane, invasion of inflammatory substances (synovitis inflammatory infiltrate), or bone erosion (bone erosion).
[화학식 1]
.
A food composition for preventing or improving rheumatoid arthritis comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]
.
[화학식 1]
.
A feed composition for preventing or improving rheumatoid arthritis comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]
.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020200120924A KR102531540B1 (en) | 2020-09-18 | 2020-09-18 | Composition for prevention or treatment of rheumatoid arthritis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020200120924A KR102531540B1 (en) | 2020-09-18 | 2020-09-18 | Composition for prevention or treatment of rheumatoid arthritis |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20220038232A KR20220038232A (en) | 2022-03-28 |
KR102531540B1 true KR102531540B1 (en) | 2023-05-16 |
Family
ID=80997102
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020200120924A KR102531540B1 (en) | 2020-09-18 | 2020-09-18 | Composition for prevention or treatment of rheumatoid arthritis |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR102531540B1 (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016052928A1 (en) | 2014-10-02 | 2016-04-07 | 한국과학기술연구원 | Alpha-aminoamide derivative compound and pharmaceutical composition comprising same |
JP2019031495A (en) * | 2013-08-30 | 2019-02-28 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | Selective MAO-B inhibitor compound, pharmaceutical composition thereof and use thereof |
KR102005019B1 (en) | 2018-04-04 | 2019-07-31 | 한국과학기술연구원 | A composition for preventing and treating stroke |
WO2019244014A2 (en) | 2018-06-19 | 2019-12-26 | Istituto Di Ricerca Pediatrica Città Della Speranza | New use of inhibitors of monoamine oxidase type b |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015504054A (en) | 2011-12-27 | 2015-02-05 | バイオ−ファーム ソリューションズ カンパニー リミテッド | Phenyl carbamate compounds used for the treatment or prevention of multiple sclerosis |
KR101679568B1 (en) * | 2014-10-02 | 2016-11-28 | 한국과학기술연구원 | Alpha-aminoamide derivatives and pharmaceutical composition comprising the same |
KR101781060B1 (en) | 2016-02-23 | 2017-09-25 | 주식회사 레스코퍼레이션 | Pharmaceutical Composition for Treatment and Prophylaxis for Ischemic Stroke |
-
2020
- 2020-09-18 KR KR1020200120924A patent/KR102531540B1/en active IP Right Grant
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019031495A (en) * | 2013-08-30 | 2019-02-28 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | Selective MAO-B inhibitor compound, pharmaceutical composition thereof and use thereof |
WO2016052928A1 (en) | 2014-10-02 | 2016-04-07 | 한국과학기술연구원 | Alpha-aminoamide derivative compound and pharmaceutical composition comprising same |
KR102005019B1 (en) | 2018-04-04 | 2019-07-31 | 한국과학기술연구원 | A composition for preventing and treating stroke |
WO2019244014A2 (en) | 2018-06-19 | 2019-12-26 | Istituto Di Ricerca Pediatrica Città Della Speranza | New use of inhibitors of monoamine oxidase type b |
Non-Patent Citations (2)
Title |
---|
International Journal of Immunopharmacology 22:1007-1008(2000)* |
논문1: REGUL. TOXICOL. PHARMACOL. |
Also Published As
Publication number | Publication date |
---|---|
KR20220038232A (en) | 2022-03-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6930037B2 (en) | Stroke preventive or therapeutic composition | |
KR102275782B1 (en) | Composition for the prevention or treatment of metabolic liver disease | |
AU2023255014A1 (en) | Composition for preventing and treating muscular disease | |
KR102531540B1 (en) | Composition for prevention or treatment of rheumatoid arthritis | |
KR20200140749A (en) | Composition for improvement, treatment or prevention of muscular disorders, or improvement of muscular functions comprising Cudrania tricuspidata | |
EP4331601A1 (en) | Food composition and pharmaceutical composition for preventing or alleviating sarcopenia, containing low-molecular-weight collagen as active ingredient | |
KR102539121B1 (en) | Pharmaceutical compositions for preventing or treating allodynia induced by anticancer agents | |
KR20200063772A (en) | Composition for anti-inflammation comprising extract of mealworm containing ginsenoside Re | |
CN112402428B (en) | Application of remazolin in preparation of medicine for treating postoperative hyperalgesia induced by opioid | |
KR102229760B1 (en) | Fraction of Melissa Leaf Extract and Novel Pharmaceutical Composition Comprising the Same | |
KR101406231B1 (en) | Therapeutic agent for meniere's disease | |
KR102427769B1 (en) | Composition for prevention or treatment of multiple sclerosis | |
KR100732614B1 (en) | A pharmaceutical composition for the prevention and treatment of obesity or diabetes mellitus comprising an extract of a puffer | |
KR20220055887A (en) | Pharmaceutical composition for the prevention or treatment of sarcopenic obesity containing Ecklonia cava extract | |
WO2021151122A1 (en) | Therapeutic compositions comprising sodium diacetate for cancer pain and metabolic abnormalities | |
WO2020222166A1 (en) | Composition for the prevention and treatment of urinary stones | |
JP6345783B2 (en) | Composition for preventing or treating growth disorders containing malt extract | |
KR102543789B1 (en) | Composition for preventing or treating metabolic disease comprising torsemide and cromolyn | |
KR102467123B1 (en) | Composition for improving endurance comprising limonium tetragonum extract | |
KR102588612B1 (en) | Composition for prevention or improvement of cognitive impairment | |
KR102376806B1 (en) | Compositions for reducing weight comprising Oenothein B analogs as effective component | |
KR20220010708A (en) | Composition for prevention or treatment of metabolic liver disease | |
KR20230165499A (en) | Use of 6-diazo-5-oxo-L-norleucine for treating non-alcoholic fatty liver diseases | |
KR20240029547A (en) | Composition for improvement, prevention or treatment of muscular disorders, or improvement of muscular functions comprising quinic acid | |
KR20230016994A (en) | Pharmaceutical composition comprising the extract from larva of zophobas atratus as an effective component for prevention or treatment of diabetes and health functional food comprising the same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |