JP2006506386A - 糖尿病の処置 - Google Patents

Info

Publication number

JP2006506386A

JP2006506386A JP2004547077A JP2004547077A JP2006506386A JP 2006506386 A JP2006506386 A JP 2006506386A JP 2004547077 A JP2004547077 A JP 2004547077A JP 2004547077 A JP2004547077 A JP 2004547077A JP 2006506386 A JP2006506386 A JP 2006506386A

Authority

JP

Japan

Prior art keywords

receptor ligand

composition

gastrin

cells

facgint

Prior art date

2002-10-22

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 141
• 238000011282 treatment Methods 0.000 title claims description 45
• 239000003446 ligand Substances 0.000 claims abstract description 432
• 239000000203 mixture Substances 0.000 claims abstract description 296
• 238000000034 method Methods 0.000 claims abstract description 199
• AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims abstract description 168
• 108010089448 Cholecystokinin B Receptor Proteins 0.000 claims abstract description 108
• 102000004859 Cholecystokinin Receptors Human genes 0.000 claims abstract description 104
• 108090001085 Cholecystokinin Receptors Proteins 0.000 claims abstract description 104
• 238000013268 sustained release Methods 0.000 claims abstract description 91
• 239000012730 sustained-release form Substances 0.000 claims abstract description 90
• 238000009472 formulation Methods 0.000 claims abstract description 77
• 102000001301 EGF receptor Human genes 0.000 claims abstract description 75
• 108060006698 EGF receptor Proteins 0.000 claims abstract description 75
• 241000124008 Mammalia Species 0.000 claims abstract description 54
• 230000009707 neogenesis Effects 0.000 claims abstract description 45
• 238000012384 transportation and delivery Methods 0.000 claims abstract description 42
• 210000000056 organ Anatomy 0.000 claims abstract description 21
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 14
• 230000001939 inductive effect Effects 0.000 claims abstract description 10
• 102000052874 Gastrin receptors Human genes 0.000 claims abstract description 9
• 102000005962 receptors Human genes 0.000 claims description 199
• 108020003175 receptors Proteins 0.000 claims description 199
• 102400000921 Gastrin Human genes 0.000 claims description 171
• 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 description 116
• 210000004027 cell Anatomy 0.000 claims description 71
• 108010052343 Gastrins Proteins 0.000 claims description 67
• 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 claims description 64
• 239000008103 glucose Substances 0.000 claims description 62
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 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(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 description 58
• 102000004877 Insulin Human genes 0.000 claims description 58
• 108090001061 Insulin Proteins 0.000 claims description 58
• 102100040918 Pro-glucagon Human genes 0.000 claims description 58
• 229940125396 insulin Drugs 0.000 claims description 58
• 108010057464 Prolactin Proteins 0.000 claims description 57
• 102100024819 Prolactin Human genes 0.000 claims description 57
• 239000003814 drug Substances 0.000 claims description 57
• 229940097325 prolactin Drugs 0.000 claims description 57
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 claims description 52
• 238000002347 injection Methods 0.000 claims description 49
• 239000007924 injection Substances 0.000 claims description 49
• 108090000623 proteins and genes Proteins 0.000 claims description 47
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims description 46
• 210000004369 blood Anatomy 0.000 claims description 46
• 239000008280 blood Substances 0.000 claims description 46
• 229940079593 drug Drugs 0.000 claims description 45
• 239000000122 growth hormone Substances 0.000 claims description 42
• 102000004169 proteins and genes Human genes 0.000 claims description 41
• 210000000130 stem cell Anatomy 0.000 claims description 40
• 108010051696 Growth Hormone Proteins 0.000 claims description 37
• 102000018997 Growth Hormone Human genes 0.000 claims description 37
• 239000003795 chemical substances by application Substances 0.000 claims description 36
• 102000009024 Epidermal Growth Factor Human genes 0.000 claims description 33
• 210000002660 insulin-secreting cell Anatomy 0.000 claims description 29
• 101710098940 Pro-epidermal growth factor Proteins 0.000 claims description 28
• 102000003951 Erythropoietin Human genes 0.000 claims description 23
• 108090000394 Erythropoietin Proteins 0.000 claims description 23
• 229940105423 erythropoietin Drugs 0.000 claims description 23
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 23
• 239000003018 immunosuppressive agent Substances 0.000 claims description 22
• 102000002808 Pituitary adenylate cyclase-activating polypeptide Human genes 0.000 claims description 21
• 108010004684 Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 claims description 21
• UFTCZKMBJOPXDM-XXFCQBPRSA-N pituitary adenylate cyclase-activating polypeptide Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 UFTCZKMBJOPXDM-XXFCQBPRSA-N 0.000 claims description 21
• 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 claims description 19
• 102100039994 Gastric inhibitory polypeptide Human genes 0.000 claims description 19
• 229940112869 bone morphogenetic protein Drugs 0.000 claims description 19
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 claims description 18
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 claims description 18
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 18
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 18
• 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims description 18
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims description 18
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 18
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 18
• 150000001413 amino acids Chemical group 0.000 claims description 18
• 238000007459 endoscopic retrograde cholangiopancreatography Methods 0.000 claims description 18
• 230000028993 immune response Effects 0.000 claims description 18
• 210000000496 pancreas Anatomy 0.000 claims description 18
• 210000003240 portal vein Anatomy 0.000 claims description 18
• 208000024891 symptom Diseases 0.000 claims description 18
• 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 17
• 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 17
• 108010025020 Nerve Growth Factor Proteins 0.000 claims description 17
• 102000015336 Nerve Growth Factor Human genes 0.000 claims description 17
• 229940126864 fibroblast growth factor Drugs 0.000 claims description 17
• 229940053128 nerve growth factor Drugs 0.000 claims description 17
• 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 16
• 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 16
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 16
• 238000001990 intravenous administration Methods 0.000 claims description 16
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 15
• 102000003972 Fibroblast growth factor 7 Human genes 0.000 claims description 14
• 108090000385 Fibroblast growth factor 7 Proteins 0.000 claims description 14
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims description 14
• 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 claims description 14
• 102000013275 Somatomedins Human genes 0.000 claims description 14
• 239000007943 implant Substances 0.000 claims description 14
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 14
• 108010011459 Exenatide Proteins 0.000 claims description 13
• 229960001519 exenatide Drugs 0.000 claims description 13
• 238000001802 infusion Methods 0.000 claims description 13
• 238000007920 subcutaneous administration Methods 0.000 claims description 13
• JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 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(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=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 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 12
• 239000002502 liposome Substances 0.000 claims description 12
• -1 mitoki Santron Chemical compound 0.000 claims description 12
• 238000002054 transplantation Methods 0.000 claims description 12
• 102000006747 Transforming Growth Factor alpha Human genes 0.000 claims description 11
• 101800004564 Transforming growth factor alpha Proteins 0.000 claims description 11
• 108010023082 activin A Proteins 0.000 claims description 11
• 210000001367 artery Anatomy 0.000 claims description 11
• 239000004615 ingredient Substances 0.000 claims description 11
• 238000007912 intraperitoneal administration Methods 0.000 claims description 11
• 210000004153 islets of langerhan Anatomy 0.000 claims description 11
• 206010062016 Immunosuppression Diseases 0.000 claims description 10
• 230000001506 immunosuppresive effect Effects 0.000 claims description 10
• 150000002632 lipids Chemical class 0.000 claims description 10
• 230000002829 reductive effect Effects 0.000 claims description 10
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
• 102100020948 Growth hormone receptor Human genes 0.000 claims description 9
• 108091058544 REG family proteins Proteins 0.000 claims description 9
• 108010068542 Somatotropin Receptors Proteins 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• 229960003444 immunosuppressant agent Drugs 0.000 claims description 9
• 230000035755 proliferation Effects 0.000 claims description 9
• 230000003248 secreting effect Effects 0.000 claims description 9
• 210000002966 serum Anatomy 0.000 claims description 9
• 238000002604 ultrasonography Methods 0.000 claims description 9
• 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 claims description 8
• 101800003838 Epidermal growth factor Proteins 0.000 claims description 8
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 claims description 8
• 102100028927 Secretin receptor Human genes 0.000 claims description 8
• 230000004069 differentiation Effects 0.000 claims description 8
• 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 claims description 8
• 229940116977 epidermal growth factor Drugs 0.000 claims description 8
• 210000002767 hepatic artery Anatomy 0.000 claims description 8
• 108010029560 keratinocyte growth factor receptor Proteins 0.000 claims description 8
• 108700027603 secretin receptor Proteins 0.000 claims description 8
• 230000001225 therapeutic effect Effects 0.000 claims description 8
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 8
• 108010000521 Human Growth Hormone Proteins 0.000 claims description 7
• 102000002265 Human Growth Hormone Human genes 0.000 claims description 7
• 239000000854 Human Growth Hormone Substances 0.000 claims description 7
• 102000002297 Laminin Receptors Human genes 0.000 claims description 7
• 108010000851 Laminin Receptors Proteins 0.000 claims description 7
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 7
• 238000007918 intramuscular administration Methods 0.000 claims description 7
• 230000003204 osmotic effect Effects 0.000 claims description 7
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 7
• 229960002930 sirolimus Drugs 0.000 claims description 7
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 7
• 230000009885 systemic effect Effects 0.000 claims description 7
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 7
• 108010024044 Glucagon-Like Peptide-2 Receptor Proteins 0.000 claims description 6
• 102100032879 Glucagon-like peptide 2 receptor Human genes 0.000 claims description 6
• 101001002317 Homo sapiens Gastrin Proteins 0.000 claims description 6
• 108010002519 Prolactin Receptors Proteins 0.000 claims description 6
• 102100029000 Prolactin receptor Human genes 0.000 claims description 6
• GKDWRERMBNGKCZ-RNXBIMIWSA-N gastrin-17 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 GKDWRERMBNGKCZ-RNXBIMIWSA-N 0.000 claims description 6
• 210000004923 pancreatic tissue Anatomy 0.000 claims description 6
• 230000004936 stimulating effect Effects 0.000 claims description 6
• 231100000419 toxicity Toxicity 0.000 claims description 6
• 230000001988 toxicity Effects 0.000 claims description 6
• 102000017011 Glycated Hemoglobin A Human genes 0.000 claims description 5
• 108010014663 Glycated Hemoglobin A Proteins 0.000 claims description 5
• 229960002806 daclizumab Drugs 0.000 claims description 5
• NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims description 5
• 230000001861 immunosuppressant effect Effects 0.000 claims description 5
• 230000000968 intestinal effect Effects 0.000 claims description 5
• 210000000277 pancreatic duct Anatomy 0.000 claims description 5
• 238000007910 systemic administration Methods 0.000 claims description 5
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 4
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 4
• 108010036949 Cyclosporine Proteins 0.000 claims description 4
• 210000004204 blood vessel Anatomy 0.000 claims description 4
• 229960001265 ciclosporin Drugs 0.000 claims description 4
• 229930182912 cyclosporin Natural products 0.000 claims description 4
• SWZTYAVBMYWFGS-UHFFFAOYSA-N fingolimod hydrochloride Chemical compound Cl.CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 SWZTYAVBMYWFGS-UHFFFAOYSA-N 0.000 claims description 4
• 108010066264 gastrin 17 Proteins 0.000 claims description 4
• 210000003734 kidney Anatomy 0.000 claims description 4
• 210000004185 liver Anatomy 0.000 claims description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
• 230000037317 transdermal delivery Effects 0.000 claims description 4
• 230000002227 vasoactive effect Effects 0.000 claims description 4
• IDINUJSAMVOPCM-UHFFFAOYSA-N 15-Deoxyspergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 claims description 3
• 238000009826 distribution Methods 0.000 claims description 3
• 239000007928 intraperitoneal injection Substances 0.000 claims description 3
• 238000013425 morphometry Methods 0.000 claims description 3
• BLUYEPLOXLPVCJ-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxyethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC[C@H](O)NC(=O)CCCCCCNC(N)=N BLUYEPLOXLPVCJ-INIZCTEOSA-N 0.000 claims description 3
• 238000002360 preparation method Methods 0.000 claims description 3
• 239000007921 spray Substances 0.000 claims description 3
• 210000003954 umbilical cord Anatomy 0.000 claims description 3
• KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
• 101001134456 Homo sapiens Pancreatic triacylglycerol lipase Proteins 0.000 claims description 2
• 102000014150 Interferons Human genes 0.000 claims description 2
• 108010050904 Interferons Proteins 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• 229960002459 alefacept Drugs 0.000 claims description 2
• 229940092117 atgam Drugs 0.000 claims description 2
• 229960002170 azathioprine Drugs 0.000 claims description 2
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 2
• 229960004669 basiliximab Drugs 0.000 claims description 2
• 239000003246 corticosteroid Substances 0.000 claims description 2
• 238000012258 culturing Methods 0.000 claims description 2
• 229960004397 cyclophosphamide Drugs 0.000 claims description 2
• 229960000284 efalizumab Drugs 0.000 claims description 2
• 210000002257 embryonic structure Anatomy 0.000 claims description 2
• 229950002798 enlimomab Drugs 0.000 claims description 2
• 229960000556 fingolimod Drugs 0.000 claims description 2
• 239000013022 formulation composition Substances 0.000 claims description 2
• 108010043649 gastrin I Proteins 0.000 claims description 2
• 229960000598 infliximab Drugs 0.000 claims description 2
• 229940079322 interferon Drugs 0.000 claims description 2
• 238000010255 intramuscular injection Methods 0.000 claims description 2
• 239000007927 intramuscular injection Substances 0.000 claims description 2
• 238000010253 intravenous injection Methods 0.000 claims description 2
• 229960001428 mercaptopurine Drugs 0.000 claims description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• 230000003232 mucoadhesive effect Effects 0.000 claims description 2
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 2
• 229960004866 mycophenolate mofetil Drugs 0.000 claims description 2
• 238000007911 parenteral administration Methods 0.000 claims description 2
• 230000004043 responsiveness Effects 0.000 claims description 2
• 238000010254 subcutaneous injection Methods 0.000 claims description 2
• 239000007929 subcutaneous injection Substances 0.000 claims description 2
• 229940107955 thymoglobulin Drugs 0.000 claims description 2
• 102400001368 Epidermal growth factor Human genes 0.000 claims 3
• OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 claims 2
• 230000000699 topical effect Effects 0.000 claims 2
• SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 claims 1
• 102000051325 Glucagon Human genes 0.000 claims 1
• 108060003199 Glucagon Proteins 0.000 claims 1
• 101000655540 Homo sapiens Protransforming growth factor alpha Proteins 0.000 claims 1
• 102100032350 Protransforming growth factor alpha Human genes 0.000 claims 1
• 210000000601 blood cell Anatomy 0.000 claims 1
• OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 claims 1
• 230000002708 enhancing effect Effects 0.000 claims 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon 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@@H](C)O)C(O)=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 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims 1
• 229960004666 glucagon Drugs 0.000 claims 1
• 102000014187 peptide receptors Human genes 0.000 claims 1
• 108010011903 peptide receptors Proteins 0.000 claims 1
• 230000000295 complement effect Effects 0.000 abstract description 4
• 241000699670 Mus sp. Species 0.000 description 32
• 235000018102 proteins Nutrition 0.000 description 32
• 108090000765 processed proteins & peptides Proteins 0.000 description 26
• 230000000694 effects Effects 0.000 description 25
• 235000001014 amino acid Nutrition 0.000 description 18
• 102000004196 processed proteins & peptides Human genes 0.000 description 18
• 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 description 16
• 239000000381 Placental Lactogen Substances 0.000 description 16
• 108010003044 Placental Lactogen Proteins 0.000 description 16
• 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 16
• 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 16
• 229940024606 amino acid Drugs 0.000 description 16
• 230000001965 increasing effect Effects 0.000 description 16
• VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 15
• 150000001875 compounds Chemical class 0.000 description 13
• 229940125721 immunosuppressive agent Drugs 0.000 description 13
• 239000003102 growth factor Substances 0.000 description 12
• 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 11
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 11
• 229920000642 polymer Polymers 0.000 description 11
• 230000004044 response Effects 0.000 description 11
• 229940124597 therapeutic agent Drugs 0.000 description 11
• 210000001519 tissue Anatomy 0.000 description 11
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 10
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 10
• 239000000556 agonist Substances 0.000 description 10
• 230000001976 improved effect Effects 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 9
• 125000003275 alpha amino acid group Chemical group 0.000 description 9
• 230000004071 biological effect Effects 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 239000012634 fragment Substances 0.000 description 9
• 229920001184 polypeptide Polymers 0.000 description 9
• SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 8
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 8
• 101000610097 Mesocricetus auratus Pancreatic beta cell growth factor Proteins 0.000 description 8
• 241000699666 Mus <mouse, genus> Species 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 8
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 230000001737 promoting effect Effects 0.000 description 8
• 230000002792 vascular Effects 0.000 description 8
• 101800000221 Glucagon-like peptide 2 Proteins 0.000 description 7
• 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 7
• 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 7
• 201000001421 hyperglycemia Diseases 0.000 description 7
• GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 7
• 229920008347 Cellulose acetate propionate Polymers 0.000 description 6
• 102000018386 EGF Family of Proteins Human genes 0.000 description 6
• 108010066486 EGF Family of Proteins Proteins 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
• 239000002202 Polyethylene glycol Substances 0.000 description 6
• 238000012377 drug delivery Methods 0.000 description 6
• TWSALRJGPBVBQU-PKQQPRCHSA-N glucagon-like peptide 2 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(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]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=CC=C1 TWSALRJGPBVBQU-PKQQPRCHSA-N 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 239000004005 microsphere Substances 0.000 description 6
• 210000000865 mononuclear phagocyte system Anatomy 0.000 description 6
• 230000008929 regeneration Effects 0.000 description 6
• 238000011069 regeneration method Methods 0.000 description 6
• VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 5
• 206010018429 Glucose tolerance impaired Diseases 0.000 description 5
• 241000282412 Homo Species 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 125000000539 amino acid group Chemical group 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 230000015556 catabolic process Effects 0.000 description 5
• 238000006731 degradation reaction Methods 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 239000000194 fatty acid Chemical class 0.000 description 5
• 229930195729 fatty acid Chemical class 0.000 description 5
• 230000003914 insulin secretion Effects 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 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 description 5
• 239000002904 solvent Substances 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 230000000638 stimulation Effects 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• ZDQNWDNMNKSMHI-UHFFFAOYSA-N 1-[2-(2-prop-2-enoyloxypropoxy)propoxy]propan-2-yl prop-2-enoate Chemical compound C=CC(=O)OC(C)COC(C)COCC(C)OC(=O)C=C ZDQNWDNMNKSMHI-UHFFFAOYSA-N 0.000 description 4
• DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 4
• 108010075254 C-Peptide Proteins 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• 241000283984 Rodentia Species 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• HKQOBOMRSSHSTC-UHFFFAOYSA-N cellulose acetate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 HKQOBOMRSSHSTC-UHFFFAOYSA-N 0.000 description 4
• 238000012217 deletion Methods 0.000 description 4
• 230000037430 deletion Effects 0.000 description 4
• STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 230000004927 fusion Effects 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• UACSZOWTRIJIFU-UHFFFAOYSA-N hydroxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCO UACSZOWTRIJIFU-UHFFFAOYSA-N 0.000 description 4
• 238000003384 imaging method Methods 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• 238000007913 intrathecal administration Methods 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• HMZGPNHSPWNGEP-UHFFFAOYSA-N octadecyl 2-methylprop-2-enoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)C(C)=C HMZGPNHSPWNGEP-UHFFFAOYSA-N 0.000 description 4
• 230000006320 pegylation Effects 0.000 description 4
• FSDNTQSJGHSJBG-UHFFFAOYSA-N piperidine-4-carbonitrile Chemical compound N#CC1CCNCC1 FSDNTQSJGHSJBG-UHFFFAOYSA-N 0.000 description 4
• 239000000018 receptor agonist Substances 0.000 description 4
• 229940044601 receptor agonist Drugs 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 241000894007 species Species 0.000 description 4
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 230000002459 sustained effect Effects 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 102000009027 Albumins Human genes 0.000 description 3
• 108010088751 Albumins Proteins 0.000 description 3
• 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 3
• 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 3
• DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 description 3
• 101800001982 Cholecystokinin Proteins 0.000 description 3
• 102000004127 Cytokines Human genes 0.000 description 3
• 108090000695 Cytokines Proteins 0.000 description 3
• 102100037642 Elongation factor G, mitochondrial Human genes 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 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 description 3
• 101000687438 Homo sapiens Prolactin Proteins 0.000 description 3
• 108010019598 Liraglutide Proteins 0.000 description 3
• 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 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 229920000954 Polyglycolide Polymers 0.000 description 3
• ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 238000010171 animal model Methods 0.000 description 3
• 230000008827 biological function Effects 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 229920006218 cellulose propionate Polymers 0.000 description 3
• 210000000981 epithelium Anatomy 0.000 description 3
• 230000037406 food intake Effects 0.000 description 3
• 235000012631 food intake Nutrition 0.000 description 3
• 208000004104 gestational diabetes Diseases 0.000 description 3
• 229940088597 hormone Drugs 0.000 description 3
• 239000005556 hormone Substances 0.000 description 3
• 239000000017 hydrogel Substances 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 229960002701 liraglutide Drugs 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 239000011859 microparticle Substances 0.000 description 3
• 238000002703 mutagenesis Methods 0.000 description 3
• 231100000350 mutagenesis Toxicity 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 230000002572 peristaltic effect Effects 0.000 description 3
• 229920000747 poly(lactic acid) Polymers 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 210000000664 rectum Anatomy 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 230000001172 regenerating effect Effects 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 3
• 229960001052 streptozocin Drugs 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 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 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 102400001242 Betacellulin Human genes 0.000 description 2
• 101800001382 Betacellulin Proteins 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• 229920002101 Chitin Polymers 0.000 description 2
• 102100025841 Cholecystokinin Human genes 0.000 description 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 description 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 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• 102100021022 Gastrin Human genes 0.000 description 2
• 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 2
• 101000976075 Homo sapiens Insulin Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 2
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 2
• 108010018112 LY 315902 Proteins 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
• 101800001442 Peptide pr Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• 108010086019 Secretin Proteins 0.000 description 2
• 102100037505 Secretin Human genes 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 241000209140 Triticum Species 0.000 description 2
• 235000021307 Triticum Nutrition 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 239000003708 ampul Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
• 239000012867 bioactive agent Substances 0.000 description 2
• 230000000975 bioactive effect Effects 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002301 cellulose acetate Polymers 0.000 description 2
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 2
• 229940106189 ceramide Drugs 0.000 description 2
• 229940107137 cholecystokinin Drugs 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 230000010405 clearance mechanism Effects 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 229960004544 cortisone Drugs 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 238000009792 diffusion process Methods 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 150000002191 fatty alcohols Chemical class 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 230000030136 gastric emptying Effects 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 2
• 150000002334 glycols Chemical class 0.000 description 2
• 230000013595 glycosylation Effects 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 230000036039 immunity Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 2
• 210000004347 intestinal mucosa Anatomy 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 108010057670 laminin 1 Proteins 0.000 description 2
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 230000005923 long-lasting effect Effects 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 239000008176 lyophilized powder Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 210000001161 mammalian embryo Anatomy 0.000 description 2
• 238000000691 measurement method Methods 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 210000004379 membrane Anatomy 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 238000012544 monitoring process Methods 0.000 description 2
• 210000002200 mouth mucosa Anatomy 0.000 description 2
• 229920005615 natural polymer Polymers 0.000 description 2
• 210000001331 nose Anatomy 0.000 description 2
• 108020004707 nucleic acids Proteins 0.000 description 2
• 102000039446 nucleic acids Human genes 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 210000003577 pancreatic endocrine progenitor Anatomy 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 239000001814 pectin Substances 0.000 description 2
• 235000010987 pectin Nutrition 0.000 description 2
• 229920001277 pectin Polymers 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000004962 physiological condition Effects 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 108010012766 preprogastrin Proteins 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• 108060006613 prolamin Proteins 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• 238000005070 sampling Methods 0.000 description 2
• 229960002101 secretin Drugs 0.000 description 2
• OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 2
• 229920000260 silastic Polymers 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 229960001967 tacrolimus Drugs 0.000 description 2
• 231100001274 therapeutic index Toxicity 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 description 1
• HCXLBYNBTBNDQZ-KFHPIRAKSA-N (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(1aS,3S,4aS,6S,7aS,9S,10aS,12S,15S,16aS,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51S,54S,57S,60S,63S,66S,69S,72S,75S,78S,81S,84S,87R,92R,95S,98S)-87-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(4R,7S,10S,13S,16R)-16-amino-13-(carboxymethyl)-7-[(1R)-1-hydroxyethyl]-10-methyl-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carbonyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-carboxypropanoyl]amino]-81,98-bis(4-aminobutyl)-10a,63-bis(2-amino-2-oxoethyl)-6,42,54,78,84-pentakis(3-amino-3-oxopropyl)-1a,27-dibenzyl-95-(2-carboxyethyl)-15-(carboxymethyl)-12,24,30,36,39,51-hexakis[(1R)-1-hydroxyethyl]-7a,9,21,48,66-pentakis(hydroxymethyl)-69,72-bis(1H-imidazol-5-ylmethyl)-33,75-dimethyl-3,57-bis(2-methylpropyl)-18-(2-methylsulfanylethyl)-a,2,3a,5,6a,8,9a,11,12a,14,15a,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80,83,86,94,97-heptatriacontaoxo-4a,45,60-tri(propan-2-yl)-89,90-dithia-1,2a,4,5a,7,8a,10,11a,13,14a,16,19,22,25,28,31,34,37,40,43,46,49,52,55,58,61,64,67,70,73,76,79,82,85,93,96,99-heptatriacontazabicyclo[114.3.0]nonadecahectane-92-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-[[(2S)-1-[[(2S)-6-amino-1-[[(1S)-1-carboxyethyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC1=O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O HCXLBYNBTBNDQZ-KFHPIRAKSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 102000007299 Amphiregulin Human genes 0.000 description 1
• 108010033760 Amphiregulin Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 108700001281 BIM 51077 Proteins 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 102400000948 Big gastrin Human genes 0.000 description 1
• 101800000285 Big gastrin Proteins 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• CUBGUDOSDBKVII-FHAQVOQBSA-O CC[C@H](C)[C@@H](C(O)=O)[NH3+].[C-]1=NC=CS1 Chemical compound CC[C@H](C)[C@@H](C(O)=O)[NH3+].[C-]1=NC=CS1 CUBGUDOSDBKVII-FHAQVOQBSA-O 0.000 description 1
• 108010055448 CJC 1131 Proteins 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
• 241000283707 Capra Species 0.000 description 1
• 229920001661 Chitosan Polymers 0.000 description 1
• 101800004067 Cholecystokinin-58 Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 description 1
• 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100033183 Epithelial membrane protein 1 Human genes 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 102100035976 Exostosin-like 3 Human genes 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• 108010061711 Gliadin Proteins 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• 241000282575 Gorilla Species 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 101000850989 Homo sapiens Epithelial membrane protein 1 Proteins 0.000 description 1
• 101000875556 Homo sapiens Exostosin-like 3 Proteins 0.000 description 1
• 101000788682 Homo sapiens GATA-type zinc finger protein 1 Proteins 0.000 description 1
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 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 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 206010022491 Insulin resistant diabetes Diseases 0.000 description 1
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
• 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
• 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
• 206010023379 Ketoacidosis Diseases 0.000 description 1
• 208000007976 Ketosis Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 108010085895 Laminin Proteins 0.000 description 1
• 102000007547 Laminin Human genes 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 101710144475 Maxadilan Proteins 0.000 description 1
• 101000788683 Mus musculus GATA-type zinc finger protein 1 Proteins 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 208000006809 Pancreatic Fistula Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000015731 Peptide Hormones Human genes 0.000 description 1
• 108010038988 Peptide Hormones Proteins 0.000 description 1
• 102000014743 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Human genes 0.000 description 1
• 108010064032 Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Proteins 0.000 description 1
• 206010035148 Plague Diseases 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 102000009087 Prolactin-Releasing Hormone Human genes 0.000 description 1
• 108010087786 Prolactin-Releasing Hormone Proteins 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 206010057430 Retinal injury Diseases 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• 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 1
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
• 102000009618 Transforming Growth Factors Human genes 0.000 description 1
• 108010009583 Transforming Growth Factors Proteins 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 241000607479 Yersinia pestis Species 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 229920002494 Zein Polymers 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 235000011054 acetic acid Nutrition 0.000 description 1
• AVMNFQHJOOYCAP-UHFFFAOYSA-N acetic acid;propanoic acid Chemical compound CC(O)=O.CCC(O)=O AVMNFQHJOOYCAP-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 239000002253 acid Substances 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 230000002730 additional effect Effects 0.000 description 1
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
• 210000004198 anterior pituitary gland Anatomy 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 239000012062 aqueous buffer Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 238000000889 atomisation Methods 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• VJBCNMFKFZIXHC-UHFFFAOYSA-N azanium;2-(4-methyl-5-oxo-4-propan-2-yl-1h-imidazol-2-yl)quinoline-3-carboxylate Chemical compound N.N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O VJBCNMFKFZIXHC-UHFFFAOYSA-N 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000000227 bioadhesive Substances 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000001364 causal effect Effects 0.000 description 1
• IWZOWZRQLJAOGS-KLTSADKFSA-N cck-22 Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O)C1=CN=CN1 IWZOWZRQLJAOGS-KLTSADKFSA-N 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 150000001783 ceramides Chemical class 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000013043 chemical agent Substances 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 108010018351 cholecystokinin 12 C-terminal fragment Proteins 0.000 description 1
• 108010033954 cholecystokinin 22 C-terminal fragment Proteins 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• RSOZZQTUMVBTMR-XGUNBQNXSA-N colforsin daropate Chemical compound O[C@H]([C@@]12C)CCC(C)(C)[C@@H]1[C@H](OC(=O)CCN(C)C)[C@H](OC(C)=O)[C@]1(C)[C@]2(O)C(=O)C[C@](C)(C=C)O1 RSOZZQTUMVBTMR-XGUNBQNXSA-N 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 239000002872 contrast media Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000000599 controlled substance Substances 0.000 description 1
• 239000012050 conventional carrier Substances 0.000 description 1
• 230000002079 cooperative effect Effects 0.000 description 1
• 150000004696 coordination complex Chemical class 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 238000012937 correction Methods 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
• 230000006240 deamidation Effects 0.000 description 1
• 238000002716 delivery method Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 210000003890 endocrine cell Anatomy 0.000 description 1
• 238000009558 endoscopic ultrasound Methods 0.000 description 1
• 210000003158 enteroendocrine cell Anatomy 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Substances OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 210000001508 eye Anatomy 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 229960004887 ferric hydroxide Drugs 0.000 description 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 description 1
• 230000027119 gastric acid secretion Effects 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000003588 gastrin derivative Substances 0.000 description 1
• SSBRJDBGIVUNDK-QOGDCIHTSA-N gastrin-14 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=C(O)C=C1 SSBRJDBGIVUNDK-QOGDCIHTSA-N 0.000 description 1
• FMIHGWZLPSIAFY-WGFKALLTSA-N gastrin-34 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCC(N)=O)C(C)C)C1=CC=C(O)C=C1 FMIHGWZLPSIAFY-WGFKALLTSA-N 0.000 description 1
• OKGNKPYIPKMGLR-ZPCKCTIPSA-N gastrins Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CN=CN1 OKGNKPYIPKMGLR-ZPCKCTIPSA-N 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 229920001519 homopolymer Polymers 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• 235000011167 hydrochloric acid Nutrition 0.000 description 1
• 229920001600 hydrophobic polymer Polymers 0.000 description 1
• 230000002218 hypoglycaemic effect Effects 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 230000003832 immune regulation Effects 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000002649 immunization Methods 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 230000006651 lactation Effects 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 108010076432 minigastrin Proteins 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 230000023187 negative regulation of glucagon secretion Effects 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 229940127264 non-peptide agonist Drugs 0.000 description 1
• 235000015816 nutrient absorption Nutrition 0.000 description 1
• 235000006286 nutrient intake Nutrition 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 1
• 229960000381 omeprazole Drugs 0.000 description 1
• 230000008816 organ damage Effects 0.000 description 1
• 230000011164 ossification Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000003961 penetration enhancing agent Substances 0.000 description 1
• 239000000813 peptide hormone Substances 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• 108010021753 peptide-Gly-Leu-amide Proteins 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 230000001766 physiological effect Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 210000003635 pituitary gland Anatomy 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• XXRYFVCIMARHRS-UHFFFAOYSA-N propan-2-yl n-dimethoxyphosphorylcarbamate Chemical compound COP(=O)(OC)NC(=O)OC(C)C XXRYFVCIMARHRS-UHFFFAOYSA-N 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 230000033458 reproduction Effects 0.000 description 1
• 230000029054 response to nutrient Effects 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
• 229920002379 silicone rubber Polymers 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 229940126586 small molecule drug Drugs 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 239000000243 solution Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008227 sterile water for injection Substances 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 239000000021 stimulant Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 230000019635 sulfation Effects 0.000 description 1
• 238000005670 sulfation reaction Methods 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000012385 systemic delivery Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide 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)NC(C)(C)C(=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(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 description 1
• 229950007151 taspoglutide Drugs 0.000 description 1
• 239000010936 titanium Substances 0.000 description 1
• 229910052719 titanium Inorganic materials 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 231100000397 ulcer Toxicity 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 239000002435 venom Substances 0.000 description 1
• 210000001048 venom Anatomy 0.000 description 1
• 231100000611 venom Toxicity 0.000 description 1
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000005019 zein Substances 0.000 description 1
• 229940093612 zein Drugs 0.000 description 1