HRP20120678T1 - Farmaceutski pripravci zasnovani na antagonistima kininskog b2 receptora i kortikosteroidima te njihova upotreba - Google Patents
Farmaceutski pripravci zasnovani na antagonistima kininskog b2 receptora i kortikosteroidima te njihova upotreba Download PDFInfo
- Publication number
- HRP20120678T1 HRP20120678T1 HRP20120678AT HRP20120678T HRP20120678T1 HR P20120678 T1 HRP20120678 T1 HR P20120678T1 HR P20120678A T HRP20120678A T HR P20120678AT HR P20120678 T HRP20120678 T HR P20120678T HR P20120678 T1 HRP20120678 T1 HR P20120678T1
- Authority
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- Croatia
- Prior art keywords
- methyl
- arg
- kinin
- dichloro
- receptor
- Prior art date
Links
- 108010093008 Kinins Proteins 0.000 title claims abstract 13
- 102000002397 Kinins Human genes 0.000 title claims abstract 13
- 239000003246 corticosteroid Substances 0.000 title claims abstract 8
- 239000002464 receptor antagonist Substances 0.000 title claims abstract 8
- 229940044551 receptor antagonist Drugs 0.000 title claims abstract 8
- 229960001334 corticosteroids Drugs 0.000 title claims 2
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 6
- 239000001257 hydrogen Substances 0.000 claims abstract 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims abstract 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract 4
- -1 parametazone Chemical compound 0.000 claims abstract 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract 3
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims abstract 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 claims abstract 2
- XUHBBTKJWIBQMY-MHZLTWQESA-N Anatibant Chemical compound O=C([C@@H]1CCCN1S(=O)(=O)C=1C=CC(Cl)=C(C=1Cl)COC1=CC=CC2=C(C)C=C(N=C21)C)NCCCNC(=O)C1=CC=C(C(N)=N)C=C1 XUHBBTKJWIBQMY-MHZLTWQESA-N 0.000 claims abstract 2
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims abstract 2
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 claims abstract 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 claims abstract 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 claims abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 claims abstract 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims abstract 2
- 125000003277 amino group Chemical group 0.000 claims abstract 2
- 229950004248 anatibant Drugs 0.000 claims abstract 2
- 150000001450 anions Chemical class 0.000 claims abstract 2
- 229940092705 beclomethasone Drugs 0.000 claims abstract 2
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 claims abstract 2
- 229960002537 betamethasone Drugs 0.000 claims abstract 2
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims abstract 2
- 229960004436 budesonide Drugs 0.000 claims abstract 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract 2
- 229960004544 cortisone Drugs 0.000 claims abstract 2
- 239000003937 drug carrier Substances 0.000 claims abstract 2
- 150000002148 esters Chemical class 0.000 claims abstract 2
- 229960002714 fluticasone Drugs 0.000 claims abstract 2
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 claims abstract 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims abstract 2
- 229960000890 hydrocortisone Drugs 0.000 claims abstract 2
- QURWXBZNHXJZBE-SKXRKSCCSA-N icatibant Chemical compound NC(N)=NCCC[C@@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2SC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@H](CC3=CC=CC=C3C2)C(=O)N2[C@@H](C[C@@H]3CCCC[C@@H]32)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C[C@@H](O)C1 QURWXBZNHXJZBE-SKXRKSCCSA-N 0.000 claims abstract 2
- 108700023918 icatibant Proteins 0.000 claims abstract 2
- 229960001062 icatibant Drugs 0.000 claims abstract 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract 2
- 229960001810 meprednisone Drugs 0.000 claims abstract 2
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 claims abstract 2
- 229960004584 methylprednisolone Drugs 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims abstract 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract 2
- 229960005205 prednisolone Drugs 0.000 claims abstract 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims abstract 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract 2
- 229960005294 triamcinolone Drugs 0.000 claims abstract 2
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 claims abstract 2
- 229940005605 valeric acid Drugs 0.000 claims abstract 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 8
- 239000005557 antagonist Substances 0.000 claims 6
- 239000000243 solution Substances 0.000 claims 5
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- 229960003950 combination of corticosteroids Drugs 0.000 claims 3
- 206010061218 Inflammation Diseases 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 230000000172 allergic effect Effects 0.000 claims 2
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
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- 239000007924 injection Substances 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
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- 206010006811 Bursitis Diseases 0.000 claims 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims 1
- 206010010741 Conjunctivitis Diseases 0.000 claims 1
- 208000034656 Contusions Diseases 0.000 claims 1
- 206010012438 Dermatitis atopic Diseases 0.000 claims 1
- 206010058314 Dysplasia Diseases 0.000 claims 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims 1
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 claims 1
- 206010051841 Exposure to allergen Diseases 0.000 claims 1
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- 201000009859 Osteochondrosis Diseases 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- MKPDWECBUAZOHP-AFYJWTTESA-N Paramethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O MKPDWECBUAZOHP-AFYJWTTESA-N 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
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- 244000028419 Styrax benzoin Species 0.000 claims 1
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- QIAWOUUTKDMGTE-UJXPALLWSA-M [(4s)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium;chloride;hydrochloride Chemical group Cl.[Cl-].C12=NC(C)=CC(C)=C2C=CC=C1OCC(C=1Cl)=C(Cl)C=CC=1S(=O)(=O)NC1(C(=O)N2CCN(CC2)C(=O)[C@@H](N)CCC[N+](C)(C)C)CCOCC1 QIAWOUUTKDMGTE-UJXPALLWSA-M 0.000 claims 1
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- WXURHACBFYSXBI-GQKYHHCASA-N flumethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-GQKYHHCASA-N 0.000 claims 1
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- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 claims 1
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- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 abstract 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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Abstract
Farmaceutski pripravci koji sadr·i kortikosteroid i antagonist kininskog B2 receptora skupa s farmaceutski prihvatljivim nosačima i ekscipijensima, naznačen time da jea) kortikosteroid, prirodni ili sintetski, odabran od sljedećih: kortizon, hidrokortizon, beklometazon, betametazon, budezonid, deksametazon, flumetazon, flunisolid, fluokorton, flutikazon, metilprednisolon, metilprednison, parametazon, prednisolon, triamcinolon, koji mogu tvoriti ester s octenom, benzojevom, kapronskom, jantarnom, fosfornom ili valerijsnskom kiselinom ili tvoriti acetonid, b) antagonist kininskog B2 receptora odabran od sljedećih: - H-D=Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-FSF-Igl-Arg-OH, - H-Arg-Arg-Pro-Hyp-Gly-Igl=Ser-D-Igl-Oic-Arg-OH, - H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (ikatibant), - 4-[2-[([[3-(3-brom-2-metil-imidazo[1.2-a]piridin-8-il oksimetil)-2,4-diklor-fenil]-metil-karbamoil]-metil)-karbamoil]-vinil]-N,N-dimetil-benzamid, - 3-(6-acetilamino-piridin-3-il)-N-([[2,4-diklor-3-(2-metil-kinolin-8-il oksimetil)-fenil]-metil-karbamoil]-metil)-akrilamid, - 1-[2,4-diklor-3-(2,4-dimetil-kinolin-8-il oksimetil)-benzen sulfonil]-pirolidin-2-karboksilna kiselina, [3-(4-karbamidoil-benzoilamino)-propil]-amid (anatibant), - bradizid, - 4-(4-[1-[2,4-diklor-3-(2,4-dimetil-kinolin-8-iloksimetil)-benzensulfonil]-pirolidin-2-karbonil]-piperazin-1-karbonil)-benzamidin, - 2-[5-(4-cijano-benzoil)-1-metil-1H-pirol-2-il]-N-[2,4-diklor-3-(2-metil-kinoline-8-il-1-oksimetil)-fenil]-N-metil-acetamid, - spoj opće formule (I): (I) u kojojR jest vodik ili metil; W predstavlja jednostruku vezu ili kisikov atom, n = 3, 4, X je vodik ili amino-skupina -NR1R2 u kojoj R1 i R2 neovisno jedan od drugog jesu vodik ili skupina odabrana od sljedećih: metil, etil, n-propil, izopropil, Y je kvaterna amonijeva sol -NR3R4R5 u kojoj R3, R4, R5, neovisno jedan od drugog jesu metil, etil, n-propil, izopropil, butil, izobutil, n-pentil, A- je anion koji se formalno izvodi od farmaceutski prihvatljive kiseline, njene farmaceutski prihvatljive soli, enantiomera i enantiomerne smjese. Patent sadr·i jo® 10 patentnih zahtjeva.
Claims (11)
1. Farmaceutski pripravci koji sadrži kortikosteroid i antagonist kininskog B2 receptora skupa s farmaceutski prihvatljivim nosačima i ekscipijensima, naznačen time da je
a) kortikosteroid, prirodni ili sintetski, odabran od sljedećih: kortizon, hidrokortizon, beklometazon, betametazon, budezonid, deksametazon, flumetazon, flunisolid, fluokorton, flutikazon, metilprednisolon, metilprednison, parametazon, prednisolon, triamcinolon, koji mogu tvoriti ester s octenom, benzojevom, kapronskom, jantarnom, fosfornom ili valerijsnskom kiselinom ili tvoriti acetonid,
b) antagonist kininskog B2 receptora odabran od sljedećih:
- H-D=Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-FSF-Igl-Arg-OH,
- H-Arg-Arg-Pro-Hyp-Gly-Igl=Ser-D-Igl-Oic-Arg-OH,
- H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (ikatibant),
- 4-[2-[([[3-(3-brom-2-metil-imidazo[1.2-a]piridin-8-il oksimetil)-2,4-diklor-fenil]-metil-karbamoil]-metil)-karbamoil]-vinil]-N,N-dimetil-benzamid,
- 3-(6-acetilamino-piridin-3-il)-N-([[2,4-diklor-3-(2-metil-kinolin-8-il oksimetil)-fenil]-metil-karbamoil]-metil)-akrilamid,
- 1-[2,4-diklor-3-(2,4-dimetil-kinolin-8-il oksimetil)-benzen sulfonil]-pirolidin-2-karboksilna kiselina, [3-(4-karbamidoil-benzoilamino)-propil]-amid (anatibant),
- bradizid,
- 4-(4-[1-[2,4-diklor-3-(2,4-dimetil-kinolin-8-iloksimetil)-benzensulfonil]-pirolidin-2-karbonil]-piperazin-1-karbonil)-benzamidin,
- 2-[5-(4-cijano-benzoil)-1-metil-1H-pirol-2-il]-N-[2,4-diklor-3-(2-metil-kinoline-8-il-1-oksimetil)-fenil]-N-metil-acetamid,
- spoj opće formule (I):
[image]
(I)
u kojoj
R jest vodik ili metil;
W predstavlja jednostruku vezu ili kisikov atom,
n = 3, 4,
X je vodik ili amino-skupina -NR1R2 u kojoj R1 i R2 neovisno jedan od drugog jesu vodik ili skupina odabrana od sljedećih: metil, etil, n-propil, izopropil,
Y je kvaterna amonijeva sol -NR3R4R5 u kojoj R3, R4, R5, neovisno jedan od drugog jesu metil, etil, n-propil, izopropil, butil, izobutil, n-pentil,
A– je anion koji se formalno izvodi od farmaceutski prihvatljive kiseline, njene farmaceutski prihvatljive soli, enantiomera i enantiomerne smjese.
2. Farmaceutski pripravak prema patentnom zahtjevu 1, naznačen time da antagonist kininskog B2 receptora jest ikatiban ili spoj opće formule (I).
3. Farmaceutski pripravak prema patentnom zahtjevu 2, naznačen time da rečeni antagonist kininskog B2 receptora u skladu s općom formulom (1) jest spoj (4-(S)-amino-5-(4-{4-[2,4-diklor-3-(2,4-dimetil-kinolin-8-iloksimetil)-benzensulfonilamino]-tetrahidro-piran-4-karbonil}-piperazin-1-il)-5-oksi-pentil]-trimetil-amonijeva sol klorovodične, octene, sumporne, trifluoroctene, metansulfonske, jantarne ili etilendiaminotetraoctene kiseline, preferirano u obliku bis-hidrokidnog klorida (MEN16132).
4. Farmaceutski pripravak prema patentnim zahtjevima 1-3, naznačen time da količina kortikosteroida po jediničnoj dozi iznosi 0.01–100 mg, preferirano 0.1–10 mg.
5. Farmaceutski pripravak prema patentnim zahtjevima 1-4, naznačen time da je količina antagonista kininskog B2 receptora po jediničnoj dozi u rasponu od 6×10–5 do 2×10–2, preferirano od 1×10–4 do 1×10–2, preferiranije od 3×10–4 4 do 6×10–3 mmol, što odgovara količini MEN16132 u rasponu od 0.05 do 17, od 0.09 do 9, odnosno od 0.26 do 5 mg po jediničnoj dozi.
6. Farmaceutski pripravak prema patentnim zahtjevima 1-5, naznačen time da je u obliku intra-artikularne ili intrabuklne otopine za injekcije ili u transdermalnom obliku odabranom od sljedećih: krema, gel, transdermalni zavoj, očne kapi, sprej ili aerosolne otopine, te nazalni sprej.
7. Farmaceutski pripravak prema patnenom zahtjevu 6, naznačen time da je rečeni antagonist kininskog B2 receptora kristalinična, amorfna ili liofilizirana krutina koju valja otopini prije upotrebe otopine koja sadrži kortikosteroid, čime nastaje intrabruskalna otopina za injekciju.
8. Farmaceutski pripravak prema patentnim zahtjevima 1-7, naznačen time da dalje sadrži, neovisno jedne od drugih, fosfatnu ili citratnu sol kao pufer, natrijev klorid kao sredstvo za toničnost, natrijev edetat kao konzervans i sredstvo za keliranje.
9. Upotreba kombinacije kortikosteroida i antagonista kininskog B2 receptora prema patentnom zahtjevu 1, naznačena time da su kortikosteroid antagonista kininskog B2 receptora, u skladu s patentnim zahtjevom 1, za pripravu lijeka za prevenciju ili terapiju sljedećih: artikularna upala, lezija i degeneracija, a posebice osteoartritis i posttraumatski osteoartritis, osteoartroza (gonartroza, spondilartroza), spondiloza, sinovitis, tenosinovitis, bursitis, kontuzija, distrozija, dislokacija i subdislokacija te artropatija uzrokovana alteracijom rasta kao što je osteokondroza i displazija.
10. Upotreba kombinacije kortikosteroida i antagonista kininskog B2 receptora prema patentnom zahtjevu 1, naznačena time da je za pripravu lijeka za prevenciju i terapiju upala respiratornog trakta dermatoloških i oftalmoloških bolesti, alergijskih ili nealergijskih, kroničnih ili akutnih, posebice sljedećih: astma, rinitis, opstruktuvna kronična bronhopatija, dermatitis od opeklina (sunca ili topline), dermatitis ili ekcem zbog izlaganja alargenima ili tvarima koje zrače, atopični dermatitis, autoimuni dermatitis (psorijaza), blefaritis, konjunktivitis i befarokonjuktivitis.
11. Upotreba kombinacije kortikosteroida i antagonista kininskog B2 receptora prema patentnim zahtjevima 9 ili 10, naznačena time da rečeni antagonist kininskog B2 receptora jest MEN 16132.
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ITMI2008A001264A IT1391236B1 (it) | 2008-07-11 | 2008-07-11 | Composizioni farmaceutiche a base di antagonisti del recettore b2 delle chinine e corticosteroidi e loro uso |
PCT/EP2009/004847 WO2010003601A1 (en) | 2008-07-11 | 2009-07-03 | Pharmaceutical compositions based on kinin b2 receptor antagonists and corticosteroids, and their use |
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