RU2012135686A - Фармацевтическая композиция для лечения метаболического синдрома - Google Patents
Фармацевтическая композиция для лечения метаболического синдрома Download PDFInfo
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- RU2012135686A RU2012135686A RU2012135686/15A RU2012135686A RU2012135686A RU 2012135686 A RU2012135686 A RU 2012135686A RU 2012135686/15 A RU2012135686/15 A RU 2012135686/15A RU 2012135686 A RU2012135686 A RU 2012135686A RU 2012135686 A RU2012135686 A RU 2012135686A
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 24
- 208000001145 Metabolic Syndrome Diseases 0.000 title claims 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 title claims 5
- 238000011282 treatment Methods 0.000 title claims 5
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 claims abstract 24
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 claims abstract 24
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 claims abstract 12
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 claims abstract 9
- 150000001875 compounds Chemical class 0.000 claims abstract 8
- 229940127003 anti-diabetic drug Drugs 0.000 claims abstract 7
- 239000003472 antidiabetic agent Substances 0.000 claims abstract 7
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims abstract 7
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims abstract 6
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims abstract 6
- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 claims abstract 6
- 239000000203 mixture Substances 0.000 claims abstract 6
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims abstract 5
- 108020001507 fusion proteins Proteins 0.000 claims abstract 5
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- 150000001413 amino acids Chemical group 0.000 claims abstract 4
- 238000009472 formulation Methods 0.000 claims abstract 4
- GNZCSGYHILBXLL-UHFFFAOYSA-N n-tert-butyl-6,7-dichloro-3-methylsulfonylquinoxalin-2-amine Chemical compound ClC1=C(Cl)C=C2N=C(S(C)(=O)=O)C(NC(C)(C)C)=NC2=C1 GNZCSGYHILBXLL-UHFFFAOYSA-N 0.000 claims abstract 4
- 101001116436 Mus musculus Xaa-Pro dipeptidase Proteins 0.000 claims abstract 2
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- 102000004169 proteins and genes Human genes 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims abstract 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 7
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 4
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- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 claims 2
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- OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 claims 2
- 230000037396 body weight Effects 0.000 claims 2
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- -1 exenatide-LAR Chemical compound 0.000 claims 2
- 229940125396 insulin Drugs 0.000 claims 2
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- 229960001093 lixisenatide Drugs 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
- 108010055448 CJC 1131 Proteins 0.000 claims 1
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- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims 1
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims 1
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- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims 1
- 101800001388 Oxyntomodulin Proteins 0.000 claims 1
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- 229940123464 Thiazolidinedione Drugs 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims 1
- 229940093265 berberine Drugs 0.000 claims 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims 1
- 235000005911 diet Nutrition 0.000 claims 1
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- 229960001519 exenatide Drugs 0.000 claims 1
- AIWAEWBZDJARBJ-PXUUZXDZSA-N fz7co35x2s Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCNC(=O)COCCOCCNC(=O)CCN1C(C=CC1=O)=O)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 AIWAEWBZDJARBJ-PXUUZXDZSA-N 0.000 claims 1
- 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 claims 1
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- 238000011866 long-term treatment Methods 0.000 claims 1
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- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 1
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- PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 claims 1
- 150000002894 organic compounds Chemical class 0.000 claims 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical group C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
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- 229960004937 saxagliptin Drugs 0.000 claims 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 claims 1
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- 229960004034 sitagliptin Drugs 0.000 claims 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims 1
- 229960001254 vildagliptin Drugs 0.000 claims 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims 1
- 102100040918 Pro-glucagon Human genes 0.000 abstract 2
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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Abstract
1. Фармацевтическая композиция, содержащая, по меньшей мере, одно соединение FGF-21 (фактор роста фибробластов 21) и, по меньшей мере, один агонист GLP-1R (рецептора глюкагон-подобного пептида-1).2. Фармацевтическая композиция по п.1, где композиция дополнительно содержит, по меньшей мере, одно противодиабетическое лекарственное средство и/или, по меньшей мере, один ингибитор DPP-4 (дипептил-пептидазы-4).3. Фармацевтическая композиция по п.1, где соединение (соединения) FGF-21, агонист(ы) GLP-1R, необязательно, противодиабетическое лекарственное средство (средства) и, необязательно, ингибитор DPP-4 комбинируются одной препаративной форме или содержатся в нескольких препаративных формах.4. Фармацевтическая композиция по п.3, где препаративные формы соединения (соединений) FGF-21, агониста (агонистов) GLP-1R, необязательно, противодиабетического лекарственного средства (средств) и, необязательно, ингибитора DPP-4 подходят для одновременного или последовательного введения (введений).5. Фармацевтическая композиция, по п.1, где соединение FGF-21 выбрано из FGF-21 или миметика FGF-21.6. Фармацевтическая композиция по п.5, где миметик FGF-21 выбран из белка, имеющего, идентичность аминокислотной последовательности, по меньшей мере, 96% относительно аминокислотной последовательности, показанной в SEQ ID NO: 1, и имеющего активность FGF-21, слитого белка FGF-21 и/или конъюгата FGF-21.7. Фармацевтическая композиция по п.6, где миметик FGF-21 выбран из мутеина FGF-21, слитого белка FGF-21-Fc, слитого белка FGF-21-HSA и/или ПЭГилированного FGF-21.8. Фармацевтическая композиция по п.1, где агонист GLP-1R выбран из биологически активного GLP-1, аналога GLP-1 или заменителя GLP-1.9. Фармацевтическая композиция по п.8, гд
Claims (16)
1. Фармацевтическая композиция, содержащая, по меньшей мере, одно соединение FGF-21 (фактор роста фибробластов 21) и, по меньшей мере, один агонист GLP-1R (рецептора глюкагон-подобного пептида-1).
2. Фармацевтическая композиция по п.1, где композиция дополнительно содержит, по меньшей мере, одно противодиабетическое лекарственное средство и/или, по меньшей мере, один ингибитор DPP-4 (дипептил-пептидазы-4).
3. Фармацевтическая композиция по п.1, где соединение (соединения) FGF-21, агонист(ы) GLP-1R, необязательно, противодиабетическое лекарственное средство (средства) и, необязательно, ингибитор DPP-4 комбинируются одной препаративной форме или содержатся в нескольких препаративных формах.
4. Фармацевтическая композиция по п.3, где препаративные формы соединения (соединений) FGF-21, агониста (агонистов) GLP-1R, необязательно, противодиабетического лекарственного средства (средств) и, необязательно, ингибитора DPP-4 подходят для одновременного или последовательного введения (введений).
5. Фармацевтическая композиция, по п.1, где соединение FGF-21 выбрано из FGF-21 или миметика FGF-21.
6. Фармацевтическая композиция по п.5, где миметик FGF-21 выбран из белка, имеющего, идентичность аминокислотной последовательности, по меньшей мере, 96% относительно аминокислотной последовательности, показанной в SEQ ID NO: 1, и имеющего активность FGF-21, слитого белка FGF-21 и/или конъюгата FGF-21.
7. Фармацевтическая композиция по п.6, где миметик FGF-21 выбран из мутеина FGF-21, слитого белка FGF-21-Fc, слитого белка FGF-21-HSA и/или ПЭГилированного FGF-21.
8. Фармацевтическая композиция по п.1, где агонист GLP-1R выбран из биологически активного GLP-1, аналога GLP-1 или заменителя GLP-1.
9. Фармацевтическая композиция по п.8, где агонист GLP-1 выбран из GLP-1(7-37), GLP-1(7-36)амида, экстендина-4, лираглутида, CJC-1131, албугона, албиглутида, эксенатида, эксенатид-LAR, оксинтомодулина, ликсисенатида, генипрозида, AVE-0010 (SEQ ID NO: 9), короткого пептида с агонистической активностью в отношении GLP-1R и/или низкомолекулярного органического соединения с агонистической активностью в отношении GLP-1R.
10. Фармацевтическая композиция по п.2, где противодиабетическое лекарственное средство выбрано из метформина, тиазолидиндиона, сульфонилмочевины и/или инсулина.
11. Фармацевтическая композиция по п.2, где ингибитор DPP-4 выбран из ситаглиптина, вилдаглиптина, саксаглиптина, линаглиптина, адоглиптина и/или берберина.
12. Фармацевтическая композиция, по меньшей мере, по одному из п.п.1-10, для применения при лечении, по меньшей мере, одного метаболического синдрома и/или атеросклероза.
13. Фармацевтическая композиция по п.12, где метаболический синдром выбран из диабета, дислипидемии, ожирения и/или избыточной массы тела, в частности, диабета 2-го типа.
14. Применение фармацевтической композиции, по меньшей мере, по одному из п.п.1-11, для получения лекарственного препарата для лечения, по меньшей мере, одного метаболического синдрома и/или атеросклероза у пациента.
15. Применение по п.14, где метаболический синдром выбран из диабета, дислипидемии, ожирения и/или избыточной массы тела, в частности, диабета 2-го типа.
16. Применение по п.14 или 15, где пациент выбран из пациента с диабетом 1-го типа, пациента с диабетом 2-го типа, в частности, пациента с диабетом 2-го типа, получающего диетологическое лечение; пациента с диабетом 2-го типа, получающего лечение сульфонилмочевиной; пациента с диабетом 2-го типа в далеко запущенной стадии и/или пациента с диабетом 2-го типа, получающего длительное лечение инсулином.
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| US20200376080A1 (en) | 2017-12-22 | 2020-12-03 | Novartis Ag | Methods of treating metabolic disorders with fgf21 variants |
| MA52994A (fr) * | 2018-01-31 | 2021-05-05 | Sanofi Sa | Peptides à chaîne b de relaxine lipidés modifiés et leur utilisation thérapeutique |
| AU2019218147B2 (en) | 2018-02-08 | 2023-06-08 | Sunshine Lake Pharma Co., Ltd. | FGF21 variant, fusion protein and application thereof |
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| CN115322794B (zh) | 2020-01-11 | 2025-09-19 | 北京质肽生物医药科技有限公司 | Glp-1和fgf21的融合蛋白的缀合物 |
| KR20210149366A (ko) * | 2020-06-02 | 2021-12-09 | 주식회사 고바이오랩 | Icam-2에 결합하는 물질을 유효성분으로 포함하는 대사질환 예방 또는 치료용 약학 조성물 |
| WO2022002408A1 (en) * | 2020-07-02 | 2022-01-06 | Sanofi | Glp-1r agonist / fgf21 fusion proteins |
| US12054551B2 (en) | 2020-07-02 | 2024-08-06 | Sanofi | FGFR1/KLB targeting agonistic antigen-binding proteins and conjugates thereof with GLP-1R agonistic peptides |
| WO2022144021A1 (zh) * | 2021-01-04 | 2022-07-07 | 华领医药技术（上海）有限公司 | Dorzagliatin和胰高血糖素样肽-1类似物的药物组合物 |
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