CZ20002006A3 - Léčivo pro kontrolu obezity - Google Patents
Léčivo pro kontrolu obezity Download PDFInfo
- Publication number
- CZ20002006A3 CZ20002006A3 CZ20002006A CZ20002006A CZ20002006A3 CZ 20002006 A3 CZ20002006 A3 CZ 20002006A3 CZ 20002006 A CZ20002006 A CZ 20002006A CZ 20002006 A CZ20002006 A CZ 20002006A CZ 20002006 A3 CZ20002006 A3 CZ 20002006A3
- Authority
- CZ
- Czechia
- Prior art keywords
- obesity
- endothelin
- receptor antagonists
- medicament
- med
- Prior art date
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- 208000008589 Obesity Diseases 0.000 title claims abstract description 15
- 235000020824 obesity Nutrition 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title claims abstract description 11
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims abstract description 7
- 239000002308 endothelin receptor antagonist Substances 0.000 claims abstract description 7
- 201000010099 disease Diseases 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 4
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- 102000002045 Endothelin Human genes 0.000 description 6
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 6
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- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 3
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- 238000013258 ApoE Receptor knockout mouse model Methods 0.000 description 1
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- 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 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038372 Renal arteriosclerosis Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108010047918 TAK 044 Proteins 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 1
- LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
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- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
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- UWHBIISPHYTOGL-PFSAEEMXSA-L disodium;2-[(2r,5s,8s,11s,14s,17r)-8-(carboxylatomethyl)-17-(1h-indol-3-ylmethyl)-14-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-5-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-11-thiophen-2-yl-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetate Chemical compound [Na+].[Na+].C([C@H]1C(=O)N[C@@H](CC([O-])=O)C(=O)N[C@@H](C(=O)N[C@H](C(N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](CC([O-])=O)C(=O)N1)=O)CC(C)C)C=1SC=CC=1)C(=O)N(CC1)CCN1C1=CC=CC=C1 UWHBIISPHYTOGL-PFSAEEMXSA-L 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
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- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
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- -1 invert sugar Substances 0.000 description 1
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- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- LJGUZUROJOJEMI-UHFFFAOYSA-N n-(3,4-dimethyl-1,2-oxazol-5-yl)-2-[4-(1,3-oxazol-2-yl)phenyl]benzenesulfonamide Chemical compound CC1=NOC(NS(=O)(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C=2OC=CN=2)=C1C LJGUZUROJOJEMI-UHFFFAOYSA-N 0.000 description 1
- ORJRYNKVKJAJPY-UHFFFAOYSA-N n-[[2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n,3,3-trimethylbutanamide Chemical compound CC(C)(C)CC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C ORJRYNKVKJAJPY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
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- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960002578 sitaxentan Drugs 0.000 description 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
- COKFAUSKNMGISZ-BMGIYVBOSA-M sodium;(z)-2-(2,1,3-benzothiadiazol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate Chemical compound [Na+].C1=CC(OC)=CC=C1C(=O)C(\CC=1C=C(OC)C(OC)=C(OC)C=1)=C(/C([O-])=O)C1=CC2=NSN=C2C=C1 COKFAUSKNMGISZ-BMGIYVBOSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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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
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Předložený vynález se týká způsobu kontrol^ obezity a nemocí způsobených obezitou.
Dosavadní stav techniky
Peptidový hormon endotelin je znám pro své silné vasokonstrikční vlastnosti. Antagonisté receptorů endotelinu jsou proto hlavně testovány při kardiovaskulárních patologiích.
Předložený vynález se týká použití antagonistů receptorů endotelinu pro přípravu léčiv pro kontrolu obezity a nemocí způsobených obezitou.
Antagonisté receptorů endotelinu, kteří mohou být použiti jsou jak antagonisté receptorů endotelinuA a tak i smíšení antagonisté receptorů endotelinuA/B.
Obzvláště vhodné příklady antagonistů receptorů endotelinu j sou
1. TBC-11251 (J. Med. Chem., 40, No. 11, 1690-97, 1997),
2. BMS-193884 (EP 558,258)
3. BMS-207940 (Pharmaprojects (13,06,97)),
4. BQ-123 (Exp. Opin. Invest. Drugs, 1997, 6, No. 5, 475487) , • · • fc
99 9
9
| • | • · · | ·♦·· · fcfc » | ||||
| - 2 - | • • * | fcfcfc fc fcfc fcfc | • ♦ fcfcfc · • fcfc fcfc fcfc | |||
| 5. SB-209670 | (Exp. Opin, | . Invest. Drugs, | 1997 | , 6, | No. 5, | 475- |
| 487) , | ||||||
| 6. SB-217242 | (Exp. Opin. | . Invest. Drugs, | 1997 | , β, | No. 5, | 4 75- |
| 487) , | ||||||
| 7. SB-209598 | (Trends in | Pharmacol. Sci. | , 17, | 177- | -81, 1996), | |
| 8. TAK-044 (Exp. Opin. | Invest. Drugs, | 1997, | 6, | No. 5, | 475- |
487) ,
9. Bosentan (Trends in Pharmacol. Sci., 18, 408-12, 1997),
10. PD-156707 (J. Med. Chem., 40, No. 7, 1063-74, 1997),
11. L-749329 (Bioorg. Med. Chem. Lett., 7, No. 3, 275-280,
1997) ,
12. L-754142 (Exp. Opin. Invest. Drugs, 1997, 6, No. 5, 475487) ,
13. ABT-627 (J. Med. Chem., 40, No. 20, 3217-27, 1997),
14. A-127772 (J. Med. Chem., 39, No. 5, 1039-1048, 1996),
15. A-206377 (213th American Chemical Society National
Meeting, San Francisco, California, USA, 13 - 17 Apríl,
1997, Poster, MÉDI 193),
16. A-182086 (J. Med. Chem., 40, No. 20, 3217-27, 1997),
17. EMD-93246 (211th American Chemical Society National
Meeting, New Orleans, USA, 1996, Poster, MÉDI 143),
18. EMD-122801 (Bioorg. Med. Chem. Lett., 8, No. 1, 17-22,
1998) ,
19. ZD-1611 (Trends in Pharmacol. Sci., 18, 408-12, 1997),
20. AC-610612 (R&D Focus Drug News (18,05,98)),
21. T-0201 (70th Annual Meeting of the Japanese Pharmacological Society, Chiba, Japan, 22-25 March 1997, Lecture, 0-133),
22. J-104132 (R&D Focus Drug News (15,12,97)) a obzvláště • ·
23:
24:
H3C —
H3C-
26:
Obezita je výraz používaný pro označení případu, kdy tělesná hmotnost je o alespoň 20% vyšší než normální tělesná hmotnost. Příčinami obezity jsou přejídání nebo nesprávné využívání potravy, například familiální hypercholesterolemie. Nemoci způsobované obezitou nebo často doprovázející obezitu, které mohou být specificky uvedeny ···· · » · · · · · · · · ·· • · 9 · · · · · · · « « « · · · · · « · · » • « ··· · · » · · « · jsou hypertenze, diabetes typu 2, hyperlipidemie, chronické selhání ledvin a arterioskleróza a popřípadě také dna.
Do současné doby bylo pouze s velkými obtížemi možné simulovat patologický stav obezity v experimentech se zvířaty (podávání extremně vysokých dávek cholesterolu). V nedávné době však byly vyšlechtěny „knockout myši, postrádající gen pro apolipoprotein E, které mohou být používány pro testování látek pro boj s obezitou.
Účinek antagonisty receptorů endotelinu představovaného látkou 23 byl zkoumán ve zvířecím modelu apoE knockout myši. U kontrolních krys, jak bylo očekáváno, vzrostla tělesná hmotnost zvířat silně s dietou s vysokým obsahem tuků. Tento vzrůst byl spojen s růstem velikosti jater se současnou mastnou degenerací jater. V paralelní skupině byla zvířata ošetřena látkou 23 (50 mg/kg/den) . V této skupině se zcela předešlo vzrůstu tělesné hmotnosti i hmotnosti jater. Játra byla také histologicky nepoznamenaná.
Antogonisté receptorů endotelinuA a endotelinuA/B musí být podávání po celý život. Jejich dávkování je od 50 do 500 mg na pacienta a den.
Antogonisté receptorů endotelinuA a endotelinuA/B jsou obecně podáváni orálně, například ve formě nepotahovaných, potahovaných, lakových a cukrem potahovaných tablet, tvrdých a měkkých želatinových kapslí, roztoků, emulzí nebo suspenzí. Podávání však také může být prováděno rektálně, například ve formě čípků, nebo parenterálně, například ve formě injekčních roztoků.
• · • · · ·
4 « · · 4 4 4 4
4 4 · · · · · ·
4 4 4 4 4 4 4 4 4
9 4 4 9 4 44 9 9 4 4 4
Pro přípravu nepotahovaných, lakových a cukrem potahovaných tablet a tvrdých želatinových kapslí může být kombinace podle předloženého vynálezu zpracována s farmaceuticky inertními anorganickými nebo organickými excipienty. Excipienty těchto typů, které mohou být použity pro nepotahované a cukrem potahované tablety a tvrdé želatinové kapsle jsou laktóza, kukuřičný škrob nebo jejich deriváty, talek, kyselina stearová nebo její soli. Excipienty vhodné pro měkké želatinové kapsle jsou rostlinné oleje, vosky, tuky, polotuhé a tekuté polyoly.
Excipienty vhodné pro přípravu roztoků a sirupů jsou například voda, polyoly, sacharóza, invertovaný cukr, glukóze a podobně. Excipienty vhodné pro injekční roztoky jsou voda, alkoholy, polyoly, glycerol, rostlinné oleje. Excipienty vhodné pro čípky jsou přírodní nebo ztužené oleje, vosky, tuky, polotuhé nebo tekuté polyoly a podobně.
Farmaceutické přípravky mohou dále obsahovat konzervační činidla, činidla usnadňující rozpouštění,, stabilizátory, smáčedla, emulgační činidla, sladidla, barviva, aromatická činidla, soli pro změnu osmotického tlaku, pufry, povlaky a/nebo antioxidanty.
• 44
4
4 β
• · ·
4 4 · * 4 4 « 4
4 4 · ·· 4 4444 • 4 · · 44 4 · 4 44 44
Příklady provedení vynálezu
Následující příklady ilustrují předložený vynález.
Příklad 1
Byly připraveny potahované tablety následujícího složení:
| Sloučenina 23 | 300,0 | mg |
| Bezvodá laktóza | 30,0 | mg |
| Mikrokrystalická celulóza | 30,0 | mg |
| Polyvinylpyrrolidon | 20,0 | mg |
| Stearan hořečnatý | 5,0 | mg |
| Polyethylenglykol 6000 | 0,8 | mg |
| Žlutý oxid železnatý | 1,2 | mg |
| Oxid titaničitý | 0,3 | mg |
| Talek | 0,7 | mg |
Sloučenina 23, laktóza, celulóza a polyvinylpyrrolidon se granulují za mokra a suší. Prosáté granule se smíchají se stearanem horečnatým a směs se lisuje na oválná tabletová jádra, vážící každé 390,0 mg. Jádra se potom potahují na potahované tablety s konečnou hmotností 400 mg.
Příklad 2
Potahované tablety byly vytvořeny analogicky s Příkladem 1, ale s obsahem 300 mg Sloučeniny 26 namísto 300 mg Sloučeniny
23.
·· *· » « · » · · « » · · 4 » · · a • · · • · · 4 ·
Příklad 3
Příprava tvrdých želatinových kapslí následujícího složení:
Sloučenina 23
Krystalická laktóza
Polyvinylpyrrolidon
Mikrokrystalická celulóza Sodný karboxymethylový škrob Talek
Stearan hořečnatý
| 250,0 | mg |
| 18,0 | mg |
| 15,0 | mg |
| 17,5 | mg |
| 10,0 | mg |
| 0,7 | mg |
| 3,0 | mg |
| mokra | a |
se smíchají se sodným karboxymethylovým škrobem, talkem a stearanem hořečnatým a směs se plní do tvrdých želatinových kapslí velikosti 0.
Claims (1)
- Použití antagonistů receptorů endotelinu pro přípravu léčiv pro kontrolu obezity a nemocí způsobených obezitou.Zastupuj e:
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19754082A DE19754082A1 (de) | 1997-12-05 | 1997-12-05 | Methode zur Bekämpfung der Fettleibigkeit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ20002006A3 true CZ20002006A3 (cs) | 2000-11-15 |
| CZ300442B6 CZ300442B6 (cs) | 2009-05-20 |
Family
ID=7850913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20002006A CZ300442B6 (cs) | 1997-12-05 | 1998-11-21 | Zpusob kontroly hyperlipidemie |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6197780B1 (cs) |
| EP (1) | EP1035851B1 (cs) |
| JP (1) | JP2002512173A (cs) |
| KR (1) | KR20010032779A (cs) |
| CN (1) | CN1152685C (cs) |
| AT (1) | ATE204172T1 (cs) |
| AU (1) | AU751053B2 (cs) |
| BR (1) | BR9815335A (cs) |
| CA (1) | CA2311423C (cs) |
| CZ (1) | CZ300442B6 (cs) |
| DE (2) | DE19754082A1 (cs) |
| ES (1) | ES2162493T3 (cs) |
| HU (1) | HUP0100171A3 (cs) |
| NO (2) | NO324694B1 (cs) |
| RU (1) | RU2292891C2 (cs) |
| WO (1) | WO1999029308A2 (cs) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19533023B4 (de) * | 1994-10-14 | 2007-05-16 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung |
| EP1130027A1 (de) * | 2000-02-29 | 2001-09-05 | Aventis Pharma Deutschland GmbH | Memno-Peptide, Verfahren zu ihrer Herstellung und Verwendung derselben |
| US20050175667A1 (en) * | 2004-02-10 | 2005-08-11 | Wenda Carlyle | Use of endothelin antagonists to prevent restenosis |
| EP2190433A2 (en) | 2007-08-22 | 2010-06-02 | Gilead Colorado, Inc. | Therapy for complications of diabetes |
| EP3628320B1 (en) * | 2011-11-11 | 2022-03-16 | Gilead Apollo, LLC | Acc inhibitors and uses thereof |
| WO2016099233A2 (ru) * | 2014-10-20 | 2016-06-23 | Товарищество С Ограниченной Ответственностью "Фармацевтическая Компания "Ромат" | Фармацевтическая композиция для лечения туберкулеза |
| AR106472A1 (es) | 2015-10-26 | 2018-01-17 | Gilead Apollo Llc | Inhibidores de acc y usos de los mismos |
| JP2019503338A (ja) | 2015-11-25 | 2019-02-07 | ギリアド アポロ， エルエルシー | ２，４−ジオキソ−１，４−ジヒドロチエノ［２，３−ｄ］ピリミジンの誘導体を含む殺真菌組成物 |
| MX2018006286A (es) | 2015-11-25 | 2018-09-07 | Gilead Apollo Llc | Inhibidores de acc pirazolicos y usos de los mismos. |
| CA3005900C (en) | 2015-11-25 | 2023-10-31 | Gilead Apollo, Llc | Triazole acc inhibitors and uses thereof |
| EP3380478B1 (en) | 2015-11-25 | 2020-12-23 | Gilead Apollo, LLC | Ester acc inhibitors and uses thereof |
| CN108699078A (zh) | 2016-03-02 | 2018-10-23 | 吉利德阿波罗公司 | 噻吩并嘧啶二酮acc抑制剂的固体形式及其制备方法 |
| EP4424364B1 (en) | 2017-03-28 | 2026-01-21 | Gilead Sciences, Inc. | Combinations for use in the treatment of cirrhosis and liver fibrosis |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0670320A4 (en) * | 1992-12-01 | 1997-05-02 | Green Cross Corp | 1,8-NAPHTHYRIDIN-2-ON DERIVATIVE AND ITS USE. |
| AU6603996A (en) * | 1995-08-24 | 1997-03-19 | Warner-Lambert Company | Furanone endothelin antagonists |
| JP3116347B2 (ja) * | 1996-11-13 | 2000-12-11 | 田辺製薬株式会社 | 医薬組成物 |
-
1997
- 1997-12-05 DE DE19754082A patent/DE19754082A1/de not_active Withdrawn
-
1998
- 1998-11-21 CZ CZ20002006A patent/CZ300442B6/cs not_active IP Right Cessation
- 1998-11-21 KR KR1020007006075A patent/KR20010032779A/ko not_active Ceased
- 1998-11-21 US US09/530,131 patent/US6197780B1/en not_active Expired - Lifetime
- 1998-11-21 AT AT98965685T patent/ATE204172T1/de active
- 1998-11-21 HU HU0100171A patent/HUP0100171A3/hu unknown
- 1998-11-21 EP EP98965685A patent/EP1035851B1/de not_active Expired - Lifetime
- 1998-11-21 JP JP2000523980A patent/JP2002512173A/ja active Pending
- 1998-11-21 WO PCT/EP1998/007501 patent/WO1999029308A2/de not_active Ceased
- 1998-11-21 DE DE59801230T patent/DE59801230D1/de not_active Expired - Lifetime
- 1998-11-21 AU AU21535/99A patent/AU751053B2/en not_active Ceased
- 1998-11-21 CA CA002311423A patent/CA2311423C/en not_active Expired - Fee Related
- 1998-11-21 ES ES98965685T patent/ES2162493T3/es not_active Expired - Lifetime
- 1998-11-21 BR BR9815335-8A patent/BR9815335A/pt not_active Application Discontinuation
- 1998-11-21 CN CNB988118327A patent/CN1152685C/zh not_active Expired - Fee Related
-
2000
- 2000-05-30 NO NO20002777A patent/NO324694B1/no not_active IP Right Cessation
-
2003
- 2003-12-29 RU RU2003138080/15A patent/RU2292891C2/ru not_active IP Right Cessation
-
2007
- 2007-08-30 NO NO20074419A patent/NO20074419L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE19754082A1 (de) | 1999-06-10 |
| DE59801230D1 (de) | 2001-09-20 |
| HK1037141A1 (en) | 2002-02-01 |
| HUP0100171A2 (hu) | 2003-02-28 |
| BR9815335A (pt) | 2000-10-17 |
| CN1152685C (zh) | 2004-06-09 |
| JP2002512173A (ja) | 2002-04-23 |
| ATE204172T1 (de) | 2001-09-15 |
| ES2162493T3 (es) | 2001-12-16 |
| AU751053B2 (en) | 2002-08-08 |
| NO20002777L (no) | 2000-06-02 |
| AU2153599A (en) | 1999-06-28 |
| NO20074419L (no) | 2000-06-02 |
| NO20002777D0 (no) | 2000-05-30 |
| CZ300442B6 (cs) | 2009-05-20 |
| WO1999029308A2 (de) | 1999-06-17 |
| CN1301162A (zh) | 2001-06-27 |
| EP1035851A2 (de) | 2000-09-20 |
| CA2311423A1 (en) | 1999-06-17 |
| KR20010032779A (ko) | 2001-04-25 |
| RU2003138080A (ru) | 2005-06-10 |
| WO1999029308A3 (de) | 1999-09-30 |
| CA2311423C (en) | 2008-01-29 |
| NO324694B1 (no) | 2007-12-03 |
| RU2292891C2 (ru) | 2007-02-10 |
| EP1035851B1 (de) | 2001-08-16 |
| US6197780B1 (en) | 2001-03-06 |
| HUP0100171A3 (en) | 2003-10-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 19981121 |