CN111494323B - 包含递送剂的组合物及其制备 - Google Patents
包含递送剂的组合物及其制备 Download PDFInfo
- Publication number
- CN111494323B CN111494323B CN202010243609.7A CN202010243609A CN111494323B CN 111494323 B CN111494323 B CN 111494323B CN 202010243609 A CN202010243609 A CN 202010243609A CN 111494323 B CN111494323 B CN 111494323B
- Authority
- CN
- China
- Prior art keywords
- ethoxy
- glp
- composition
- amino
- lubricant
- Prior art date
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 224
- 229940124447 delivery agent Drugs 0.000 title abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 19
- 239000008187 granular material Substances 0.000 claims abstract description 151
- 238000000034 method Methods 0.000 claims abstract description 110
- 238000002156 mixing Methods 0.000 claims abstract description 91
- 239000000314 lubricant Substances 0.000 claims abstract description 89
- 230000008569 process Effects 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 claims abstract description 18
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims description 80
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 78
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 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(=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 description 72
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 68
- 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 61
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims description 55
- 235000019359 magnesium stearate Nutrition 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 37
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 27
- UOENJXXSKABLJL-UHFFFAOYSA-M sodium;8-[(2-hydroxybenzoyl)amino]octanoate Chemical group [Na+].OC1=CC=CC=C1C(=O)NCCCCCCCC([O-])=O UOENJXXSKABLJL-UHFFFAOYSA-M 0.000 claims description 24
- -1 2- {2- [2- (2- {2- [ (S) -4-carboxy-4- (17-carboxyheptadecanoylamino) butyrylamino ] ethoxy } ethoxy) acetylamino ] ethoxy } ethoxy Chemical group 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 12
- 239000007909 solid dosage form Substances 0.000 claims description 11
- 238000005096 rolling process Methods 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 5
- 102000009027 Albumins Human genes 0.000 claims description 3
- 108010088751 Albumins Proteins 0.000 claims description 3
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 238000005469 granulation Methods 0.000 abstract description 35
- 230000003179 granulation Effects 0.000 abstract description 35
- 239000003814 drug Substances 0.000 abstract description 10
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 69
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 66
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 61
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 55
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 47
- 238000002474 experimental method Methods 0.000 description 34
- 239000000945 filler Substances 0.000 description 33
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 32
- 238000007908 dry granulation Methods 0.000 description 32
- 229960002446 octanoic acid Drugs 0.000 description 32
- 150000001408 amides Chemical class 0.000 description 27
- 238000007906 compression Methods 0.000 description 26
- 230000006835 compression Effects 0.000 description 26
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 21
- 239000011230 binding agent Substances 0.000 description 21
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 21
- 239000008108 microcrystalline cellulose Substances 0.000 description 21
- 229940016286 microcrystalline cellulose Drugs 0.000 description 21
- 239000002245 particle Substances 0.000 description 17
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 16
- 101100395023 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-7 gene Proteins 0.000 description 16
- 238000007429 general method Methods 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 15
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 15
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 15
- 229940069328 povidone Drugs 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- 239000000463 material Substances 0.000 description 14
- 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 description 11
- 238000012512 characterization method Methods 0.000 description 11
- 238000012217 deletion Methods 0.000 description 11
- 230000037430 deletion Effects 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 229920003091 Methocel™ Polymers 0.000 description 10
- 208000008589 Obesity Diseases 0.000 description 10
- 238000007792 addition Methods 0.000 description 10
- 206010012601 diabetes mellitus Diseases 0.000 description 10
- 238000003780 insertion Methods 0.000 description 10
- 230000037431 insertion Effects 0.000 description 10
- 235000020824 obesity Nutrition 0.000 description 10
- 230000002265 prevention Effects 0.000 description 10
- 238000009490 roller compaction Methods 0.000 description 10
- 238000003801 milling Methods 0.000 description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 7
- 238000005461 lubrication Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 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 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 239000013543 active substance Substances 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 description 5
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 5
- 238000010647 peptide synthesis reaction Methods 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000007916 tablet composition Substances 0.000 description 5
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 108010063245 glucagon-like peptide 1 (7-36)amide Proteins 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 208000028399 Critical Illness Diseases 0.000 description 3
- 208000002705 Glucose Intolerance Diseases 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 230000002473 insulinotropic effect Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 201000009104 prediabetes syndrome Diseases 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 2
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 208000030814 Eating disease Diseases 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 208000035180 MODY Diseases 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000004368 Modified starch Substances 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- 235000019887 Solka-Floc® Nutrition 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 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
- 239000003086 colorant Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 235000014632 disordered eating Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 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 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 201000006950 maturity-onset diabetes of the young Diseases 0.000 description 2
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229940100486 rice starch Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229930195727 α-lactose Natural products 0.000 description 2
- 229930195724 β-lactose Natural products 0.000 description 2
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- RUVRGYVESPRHSZ-UHFFFAOYSA-N 2-[2-(2-azaniumylethoxy)ethoxy]acetate Chemical compound NCCOCCOCC(O)=O RUVRGYVESPRHSZ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 208000000575 Arteriosclerosis Obliterans Diseases 0.000 description 1
- UMHUHHJMEXNSIV-CIUDSAMLSA-N Asp-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UMHUHHJMEXNSIV-CIUDSAMLSA-N 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 101100335894 Caenorhabditis elegans gly-8 gene Proteins 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920002307 Dextran Polymers 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
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- YJIUYQKQBBQYHZ-ACZMJKKPSA-N Gln-Ala-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YJIUYQKQBBQYHZ-ACZMJKKPSA-N 0.000 description 1
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 1
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- AFPFGFUGETYOSY-HGNGGELXSA-N His-Ala-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AFPFGFUGETYOSY-HGNGGELXSA-N 0.000 description 1
- HAPWZEVRQYGLSG-IUCAKERBSA-N His-Gly-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O HAPWZEVRQYGLSG-IUCAKERBSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101500028774 Homo sapiens Glucagon-like peptide 1 Proteins 0.000 description 1
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010058179 Hypertensive emergency Diseases 0.000 description 1
- WZPIKDWQVRTATP-SYWGBEHUSA-N Ile-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 WZPIKDWQVRTATP-SYWGBEHUSA-N 0.000 description 1
- WCNWGAUZWWSYDG-SVSWQMSJSA-N Ile-Thr-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)O)N WCNWGAUZWWSYDG-SVSWQMSJSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 108010033266 Lipoprotein(a) Proteins 0.000 description 1
- 102000057248 Lipoprotein(a) Human genes 0.000 description 1
- CKSBRMUOQDNPKZ-SRVKXCTJSA-N Lys-Gln-Met Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O CKSBRMUOQDNPKZ-SRVKXCTJSA-N 0.000 description 1
- DUTMKEAPLLUGNO-JYJNAYRXSA-N Lys-Glu-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O DUTMKEAPLLUGNO-JYJNAYRXSA-N 0.000 description 1
- 229920003107 Methocel™ A15C Polymers 0.000 description 1
- 229920003106 Methocel™ A4C Polymers 0.000 description 1
- 229920003108 Methocel™ A4M Polymers 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- KRYSMKKRRRWOCZ-QEWYBTABSA-N Phe-Ile-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KRYSMKKRRRWOCZ-QEWYBTABSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920003082 Povidone K 90 Polymers 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical group CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 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
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 1
- RRVUOLRWIZXBRQ-IHPCNDPISA-N Trp-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RRVUOLRWIZXBRQ-IHPCNDPISA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 1
- JYVKKBDANPZIAW-AVGNSLFASA-N Val-Arg-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N JYVKKBDANPZIAW-AVGNSLFASA-N 0.000 description 1
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical group 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 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- CGMRCMMOCQYHAD-UHFFFAOYSA-K dicalcium;phosphate;hydrate Chemical compound O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-K 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
- 239000008202 granule composition Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 108010045383 histidyl-glycyl-glutamic acid Proteins 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000009491 slugging Methods 0.000 description 1
- 108091008012 small dense LDL Proteins 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 239000002888 zwitterionic surfactant Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/609—Amides, e.g. salicylamide
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12160742 | 2012-03-22 | ||
| EP12160742.8 | 2012-03-22 | ||
| US201361748844P | 2013-01-04 | 2013-01-04 | |
| US61/748844 | 2013-01-04 | ||
| EP13153422 | 2013-01-31 | ||
| EP13153422.4 | 2013-01-31 | ||
| CN201380015235.1A CN104203221A (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
| PCT/EP2013/055363 WO2013139695A1 (en) | 2012-03-22 | 2013-03-15 | Compositions comprising a delivery agent and preparation thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380015235.1A Division CN104203221A (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111494323A CN111494323A (zh) | 2020-08-07 |
| CN111494323B true CN111494323B (zh) | 2023-03-28 |
Family
ID=49221869
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010243609.7A Active CN111494323B (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
| CN201380015235.1A Pending CN104203221A (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
| CN202010243610.XA Active CN111494324B (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380015235.1A Pending CN104203221A (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
| CN202010243610.XA Active CN111494324B (zh) | 2012-03-22 | 2013-03-15 | 包含递送剂的组合物及其制备 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US10335369B2 (enExample) |
| EP (3) | EP3542790B1 (enExample) |
| JP (1) | JP6356660B2 (enExample) |
| CN (3) | CN111494323B (enExample) |
| ES (1) | ES2965469T3 (enExample) |
| HR (1) | HRP20231613T1 (enExample) |
| HU (1) | HUE064694T2 (enExample) |
| PL (2) | PL3542790T3 (enExample) |
| RS (2) | RS58636B1 (enExample) |
| SI (1) | SI2827845T1 (enExample) |
| WO (1) | WO2013139695A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3326620T3 (pl) | 2010-12-16 | 2020-08-24 | Novo Nordisk A/S | Kompozycje stałe zawierające agonistę glp-1 i sól kwasu n-(8-(2- hydroksybenzoilo)amino)kaprylowego |
| BR112013026195A2 (pt) | 2011-04-12 | 2016-11-29 | Novo Nordisk As | derivados de glp-1 duplamente acilados |
| HUE062740T2 (hu) | 2012-03-22 | 2023-12-28 | Novo Nordisk As | GLP-1 peptidek készítményei és elõállításuk |
| DK2827845T3 (en) * | 2012-03-22 | 2019-04-01 | Novo Nordisk As | COMPOSITIONS INCLUDING A PROCEDURE AND PREPARING THEREOF |
| CN111494323B (zh) | 2012-03-22 | 2023-03-28 | 诺和诺德股份有限公司 | 包含递送剂的组合物及其制备 |
| US9993430B2 (en) | 2012-06-20 | 2018-06-12 | Novo Nordisk A/S | Tablet formulation comprising semaglutide and a delivery agent |
| PT2991671T (pt) | 2013-05-02 | 2018-11-05 | Novo Nordisk As | Dosagem oral de compostos de glp-1 |
| CN104173313B (zh) * | 2014-08-25 | 2017-05-17 | 杭州朱养心药业有限公司 | 利伐沙班片剂药物组合物 |
| AU2016206950B2 (en) | 2015-01-12 | 2021-05-06 | Enteris Biopharma, Inc. | Solid oral dosage forms |
| WO2018121702A1 (zh) * | 2016-12-30 | 2018-07-05 | 江苏恒瑞医药股份有限公司 | 一种glp-1类似物的药物组合物及其制备方法 |
| TWI797133B (zh) | 2017-06-09 | 2023-04-01 | 丹麥商諾佛 儂迪克股份有限公司 | 用於經口投予的固體組成物 |
| SG11202006595RA (en) * | 2018-02-02 | 2020-08-28 | Novo Nordisk As | Solid compositions comprising a glp-1 agonist, a salt of n-(8-(2-hydroxybenzoyl)amino)caprylic acid and a lubricant |
| TWI829687B (zh) * | 2018-05-07 | 2024-01-21 | 丹麥商諾佛 儂迪克股份有限公司 | 包含glp-1促效劑與n-(8-(2-羥基苯甲醯基)胺基)辛酸之鹽的固體組成物 |
| WO2020152304A1 (en) * | 2019-01-24 | 2020-07-30 | Novo Nordisk A/S | Roller compactor and method of dry granulation using a roller compactor |
| CN114222581A (zh) * | 2019-08-07 | 2022-03-22 | 诺和诺德股份有限公司 | 包含egf(a)衍生物和n-(8-(2-羟基苯甲酰基)氨基)辛酸的盐的固体组合物 |
| WO2021043803A1 (en) | 2019-09-02 | 2021-03-11 | Novo Nordisk A/S | Process for producing a tablet comprising glp-1 peptides |
| US12364663B2 (en) | 2019-09-06 | 2025-07-22 | Novo Nordisk A/S | Method and equipment for fractionation of granules for use in pharmaceutical compositions |
| EP4054536A1 (en) | 2019-11-07 | 2022-09-14 | Novo Nordisk A/S | Solid compositions comprising a glp-1 agonist, an sglt2 inhibitor and a salt of n-(8-(2-hydroxybenzoyl)amino)caprylic acid |
| US20230165939A1 (en) * | 2020-04-29 | 2023-06-01 | Novo Nordisk A/S | Solid compositions comprising a glp-1 agonist and histidine |
| CN111517980B (zh) * | 2020-05-14 | 2021-02-09 | 台州浦凯医药科技有限公司 | N-[8-(2-羟基苯甲酰基)氨基]辛酸一钾晶型化合物、制备方法及用途 |
| EP4185606A1 (en) * | 2020-07-22 | 2023-05-31 | Novo Nordisk A/S | Glp-1 and gip receptor co-agonists |
| PE20231841A1 (es) * | 2020-07-22 | 2023-11-21 | Novo Nordisk As | Coagonistas de los receptores glp-1 y gip adecuados para el suministro oral |
| CN113117050B (zh) * | 2021-05-06 | 2022-04-26 | 合肥天汇孵化科技有限公司 | 多肽组合物及其用途 |
| CA3218339A1 (en) | 2021-05-07 | 2022-11-10 | Aktham Aburub | Erodible tablet |
| AU2022312702A1 (en) | 2021-07-15 | 2024-01-18 | Novo Nordisk A/S | Tablet comprising a salt of n-(8-(2-hydroxybenzoyl)amino)caprylic acid |
| KR20240118786A (ko) * | 2021-12-01 | 2024-08-05 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | Glp-1 및 gip 수용체 이중 작용제의 약학적 조성물 및 이의 용도 |
| TW202330584A (zh) | 2022-01-20 | 2023-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 前藥及其用途 |
| CN114984191B (zh) * | 2022-07-04 | 2022-10-25 | 北京惠之衡生物科技有限公司 | 一种多肽类药物口服递送组合物 |
| TW202421645A (zh) | 2022-11-25 | 2024-06-01 | 丹麥商諾佛 儂迪克股份有限公司 | 如ｇｌｐ—１之肽治療劑的口服投與 |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4609675A (en) | 1984-08-17 | 1986-09-02 | The Upjohn Company | Stable, high dose, high bulk density ibuprofen granulations for tablet and capsule manufacturing |
| ES2059366T3 (es) | 1986-03-12 | 1994-11-16 | American Cyanamid Co | Compuestos macrolidos. |
| DK39892D0 (da) | 1992-03-25 | 1992-03-25 | Bernard Thorens | Peptid |
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| US5866536A (en) | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| SE9600070D0 (sv) | 1996-01-08 | 1996-01-08 | Astra Ab | New oral pharmaceutical dosage forms |
| JP3149958B2 (ja) | 1996-08-30 | 2001-03-26 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ―１誘導体 |
| US5773647A (en) | 1997-02-07 | 1998-06-30 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| JP2003522099A (ja) | 1998-02-27 | 2003-07-22 | ノボ ノルディスク アクティーゼルスカブ | 遅延作用プロファイルを有するｇｌｐ−１のｇｌｐ−１誘導体及びエキセンジン |
| WO1999043341A1 (en) | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | Glp-1 derivatives with helix-content exceeding 25 %, forming partially structured micellar-like aggregates |
| AU2610899A (en) | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | N-terminally modified glp-1 derivatives |
| AU2610699A (en) | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | Derivatives of glp-1 analogs |
| SE9802080D0 (sv) | 1998-06-11 | 1998-06-11 | Hellstroem | Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein |
| CA2361716C (en) | 1999-02-05 | 2009-04-28 | Emisphere Technologies, Inc. | Method of preparing alkylated salicylamides |
| ES2301477T3 (es) | 1999-02-22 | 2008-07-01 | Merrion Research I Limited | Forma de dosificacion oral solida que contiene un potenciador. |
| US7658938B2 (en) | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
| WO2000048589A1 (en) | 1999-02-22 | 2000-08-24 | Emisphere Holdings, Inc. | Solid oral dosage form containing heparin or a heparinoid in combination with a carrier |
| GB9923436D0 (en) | 1999-10-04 | 1999-12-08 | American Home Prod | Pharmaceutical compositions |
| US6793934B1 (en) | 1999-12-08 | 2004-09-21 | Shire Laboratories, Inc. | Solid oral dosage form |
| US7262325B2 (en) | 2000-06-02 | 2007-08-28 | Emisphere Technologies, Inc. | Method of preparing salicylamides |
| US7049283B2 (en) | 2000-12-06 | 2006-05-23 | Novartis Ag | Pharmaceutical compositions for the oral delivery of pharmacologically active agents |
| CZ20032828A3 (en) | 2001-03-27 | 2004-07-14 | Ranbaxy Laboratories Limited | A stable pharmaceutical composition of pravastatin |
| IL158518A0 (en) | 2001-05-15 | 2004-05-12 | Warner Lambert Co | Compaction process for manufacture of sodium phenytoin dosage form |
| US20030068356A1 (en) | 2001-07-10 | 2003-04-10 | Pather S. Indiran | Sequential drug delivery systems |
| US20040259952A1 (en) | 2001-11-29 | 2004-12-23 | Richat Abbas | Formulations for oral administration of cromolyn sodium |
| NZ534234A (en) | 2002-02-01 | 2007-05-31 | Pfizer Prod Inc | Dry granulated formulations of non-dihydrate form of azithromycin |
| CA2473340C (en) | 2002-02-20 | 2014-12-09 | Eli Lilly And Company | Formulations comprising a glp-1 compound and a delivery agent, and uses thereof |
| JP2004131398A (ja) | 2002-10-08 | 2004-04-30 | Taihei Chemical Industrial Co Ltd | 錠剤用滑沢剤 |
| JP2006528982A (ja) | 2003-05-14 | 2006-12-28 | エミスフェアー・テクノロジーズ・インク | ペプチドｙｙおよびｐｙｙ作用薬の送達用組成物 |
| PT1651248E (pt) | 2003-07-11 | 2009-11-10 | Novartis Ag | Composições farmacêuticas para dose oral compreendendo um agente de administração na forma micronizada |
| KR101241862B1 (ko) | 2003-09-19 | 2013-03-13 | 노보 노르디스크 에이/에스 | 신규 ｇｌｐ-1 유도체 |
| AU2004298424A1 (en) | 2003-12-18 | 2005-06-30 | Novo Nordisk A/S | Novel GLP-1 compounds |
| MXPA06006746A (es) | 2003-12-18 | 2006-08-18 | Novo Nordisk As | Analogos de glp-1 novedosos ligados a agentes similares a albumina. |
| US20060286129A1 (en) | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| WO2005099672A1 (en) | 2004-04-13 | 2005-10-27 | Ranbaxy Laboratories Limited | A modified release pharmaceutical formulation comprising amoxicillin and clavulanate |
| NZ550894A (en) * | 2004-05-06 | 2011-02-25 | Emisphere Tech Inc | Solid dosage form of wetted heparin |
| JP4903690B2 (ja) | 2004-05-06 | 2012-03-28 | エミスフェアー・テクノロジーズ・インク | Ｎ−［８−（２−ヒドリキシベンゾイル）アミノ］カプリル酸一ナトリウムの結晶多形体 |
| US8273794B2 (en) | 2004-05-14 | 2012-09-25 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO2005115347A1 (en) | 2004-05-31 | 2005-12-08 | Sam-A Pharmaceuticals Co., Ltd. | Dispersible tablet comprising beta lactam antibiotics and process for preparing the same |
| CN101010339B (zh) | 2004-07-02 | 2011-11-09 | 布里斯托尔-迈尔斯斯奎布公司 | 人类胰高血糖素样肽-1调节剂及它们在治疗糖尿病及相关病况中的用途 |
| EP2289560B1 (en) | 2004-07-08 | 2015-04-22 | Novo Nordisk A/S | Polypeptide protracting tags comprising a tetrazole moiety |
| JP2008509933A (ja) * | 2004-08-13 | 2008-04-03 | エミスフェアー・テクノロジーズ・インク | 送達剤のマイクロ粒子またはナノ粒子を含む医薬製剤 |
| US7893017B2 (en) | 2004-10-07 | 2011-02-22 | Novo Nordisk A/S | Protracted GLP-1 compounds |
| EP1799711B1 (en) | 2004-10-07 | 2012-06-20 | Novo Nordisk A/S | Protracted exendin-4 compounds |
| US8852632B2 (en) | 2004-12-03 | 2014-10-07 | Merck Sharp & Dohme Corp. | Pharmaceutical formulation containing a release rate controlling composition |
| EP1843755B1 (en) | 2005-02-01 | 2015-04-01 | Emisphere Technologies, Inc. | Gastric retention and controlled release delivery system |
| TWI372629B (en) | 2005-03-18 | 2012-09-21 | Novo Nordisk As | Acylated glp-1 compounds |
| WO2006097538A1 (en) | 2005-03-18 | 2006-09-21 | Novo Nordisk A/S | Extended glp-1 compounds |
| EP1863449A2 (en) | 2005-03-28 | 2007-12-12 | Dexcel Pharma Technologies Ltd. | Controlled absorption of statins in the intestine |
| US20070049557A1 (en) | 2005-08-24 | 2007-03-01 | Hashim Ahmed | Solid pharmaceutical dosage forms comprising bisphosphonates and modified amino acid carriers |
| BRPI0618723A2 (pt) | 2005-11-17 | 2011-09-06 | Novartis Ag | composição farmacêutica oral na forma de um comprimido prensado |
| US7704977B2 (en) | 2006-04-07 | 2010-04-27 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
| WO2007121318A2 (en) | 2006-04-12 | 2007-10-25 | Emisphere Technologies, Inc. | Formulations for delivering insulin |
| US20070292512A1 (en) | 2006-06-09 | 2007-12-20 | Merrion Research Ii Limited | Solid Oral Dosage Form Containing an Enhancer |
| US9364502B2 (en) * | 2006-06-28 | 2016-06-14 | Emisphere Technologies, Inc. | Gallium nitrate formulations |
| ES2296529B1 (es) | 2006-08-07 | 2009-04-01 | Laboratorios Farmaceuticos Rovi, S.A. | Composicion farmaceutica con promotores de absorcion. |
| EP2057189B1 (en) | 2006-08-25 | 2013-03-06 | Novo Nordisk A/S | Acylated exendin-4 compounds |
| CN101506147B (zh) | 2006-09-07 | 2012-03-21 | 霍夫曼-拉罗奇有限公司 | 用于制备snac（n-（8-[2-羟基苯甲酰基]-氨基）辛酸钠）的方法 |
| AR062925A1 (es) | 2006-09-22 | 2008-12-17 | Novartis Ag | Metodo para fabricar tabletas que contienen agentes farmacologicamente activos |
| WO2008070547A1 (en) * | 2006-12-01 | 2008-06-12 | Emisphere Technologies Inc. | Improved acyclovir formulations |
| ATE507818T1 (de) | 2007-03-02 | 2011-05-15 | Novartis Ag | Orale verabreichung eines calcitonins |
| US20110183889A1 (en) | 2007-08-29 | 2011-07-28 | The Regents Of The University Of California | Salicylanilide modified peptides for use as oral therapeutics |
| EP2190873B1 (en) | 2007-09-05 | 2015-07-22 | Novo Nordisk A/S | Truncated glp-1 derivatives and their therapeutical use |
| EP2190460B1 (en) | 2007-09-05 | 2014-12-17 | Novo Nordisk A/S | Peptides derivatized with a-b-c-d- and their therapeutical use |
| EP2190872B1 (en) | 2007-09-05 | 2018-03-14 | Novo Nordisk A/S | Glucagon-like peptide-1 derivatives and their pharmaceutical use |
| PL2203181T3 (pl) | 2007-10-16 | 2018-07-31 | Biocon Limited | Podawana doustnie stała kompozycja farmaceutyczna i jej sposób |
| PL2215047T3 (pl) | 2007-11-02 | 2014-05-30 | Emisphere Tech Inc | Sposób leczenia niedoborów witaminy b12 |
| US20090124639A1 (en) | 2007-11-06 | 2009-05-14 | Emisphere Technologies Inc. | valacyclovir formulations |
| US20100317057A1 (en) * | 2007-12-28 | 2010-12-16 | Novo Nordisk A/S | Semi-recombinant preparation of glp-1 analogues |
| CA2734442C (en) | 2008-08-18 | 2016-08-16 | Oramed Ltd | Methods and compositions for oral administration of proteins |
| NZ594044A (en) | 2009-02-13 | 2014-08-29 | Boehringer Ingelheim Int | Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics |
| CA2784120A1 (en) | 2009-12-16 | 2011-07-14 | Nod Pharmaceuticals, Inc. | Compositions and methods for oral drug delivery |
| US20110182985A1 (en) | 2010-01-28 | 2011-07-28 | Coughlan David C | Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof |
| WO2011109787A1 (en) | 2010-03-05 | 2011-09-09 | Conjuchem, Llc | Methods of administering insulinotropic peptides |
| GB2478849A (en) | 2010-03-16 | 2011-09-21 | Chiasma Inc | Improved pharmecutical compositions and methods of delivery |
| ES3017582T3 (en) | 2010-04-07 | 2025-05-13 | Vertex Pharma | Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof |
| KR101819609B1 (ko) | 2010-05-05 | 2018-01-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법 |
| DE202010015867U1 (de) | 2010-11-25 | 2011-05-05 | Buchhalter, Thomas | Elektromechanische Halterung zur Aufnahme von Navigations- und Kommunikationsgeräte im KFZ |
| PL3326620T3 (pl) * | 2010-12-16 | 2020-08-24 | Novo Nordisk A/S | Kompozycje stałe zawierające agonistę glp-1 i sól kwasu n-(8-(2- hydroksybenzoilo)amino)kaprylowego |
| HUE062740T2 (hu) | 2012-03-22 | 2023-12-28 | Novo Nordisk As | GLP-1 peptidek készítményei és elõállításuk |
| CN111494323B (zh) | 2012-03-22 | 2023-03-28 | 诺和诺德股份有限公司 | 包含递送剂的组合物及其制备 |
| US9993430B2 (en) | 2012-06-20 | 2018-06-12 | Novo Nordisk A/S | Tablet formulation comprising semaglutide and a delivery agent |
| PT2991671T (pt) | 2013-05-02 | 2018-11-05 | Novo Nordisk As | Dosagem oral de compostos de glp-1 |
-
2013
- 2013-03-15 CN CN202010243609.7A patent/CN111494323B/zh active Active
- 2013-03-15 EP EP18212576.5A patent/EP3542790B1/en active Active
- 2013-03-15 ES ES18212576T patent/ES2965469T3/es active Active
- 2013-03-15 CN CN201380015235.1A patent/CN104203221A/zh active Pending
- 2013-03-15 CN CN202010243610.XA patent/CN111494324B/zh active Active
- 2013-03-15 WO PCT/EP2013/055363 patent/WO2013139695A1/en not_active Ceased
- 2013-03-15 JP JP2015500854A patent/JP6356660B2/ja active Active
- 2013-03-15 SI SI201331386T patent/SI2827845T1/sl unknown
- 2013-03-15 EP EP23195317.5A patent/EP4331667A3/en active Pending
- 2013-03-15 PL PL18212576.5T patent/PL3542790T3/pl unknown
- 2013-03-15 RS RS20190386A patent/RS58636B1/sr unknown
- 2013-03-15 US US14/386,218 patent/US10335369B2/en active Active
- 2013-03-15 EP EP13709232.6A patent/EP2827845B1/en not_active Revoked
- 2013-03-15 PL PL13709232T patent/PL2827845T3/pl unknown
- 2013-03-15 HR HRP20231613TT patent/HRP20231613T1/hr unknown
- 2013-03-15 HU HUE18212576A patent/HUE064694T2/hu unknown
- 2013-03-15 RS RS20231190A patent/RS64942B1/sr unknown
Non-Patent Citations (1)
| Title |
|---|
| Orally Administered Glucagon-Like Peptide-1 Affects Glucose Homeostasis Following an Oral Glucose Tolerance Test in Healthy Male Subjects;RE Steinert等;《Clinical Pharmacology & Therapeutics》;20091231;644-650 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013139695A1 (en) | 2013-09-26 |
| CN111494324A (zh) | 2020-08-07 |
| EP3542790A1 (en) | 2019-09-25 |
| US10335369B2 (en) | 2019-07-02 |
| PL2827845T3 (pl) | 2019-06-28 |
| EP3542790B1 (en) | 2023-09-13 |
| US20150031606A1 (en) | 2015-01-29 |
| EP4331667A3 (en) | 2024-05-08 |
| JP2015515459A (ja) | 2015-05-28 |
| EP2827845A1 (en) | 2015-01-28 |
| HRP20231613T1 (hr) | 2024-03-15 |
| HUE064694T2 (hu) | 2024-04-28 |
| RS58636B1 (sr) | 2019-05-31 |
| CN104203221A (zh) | 2014-12-10 |
| PL3542790T3 (pl) | 2024-02-26 |
| CN111494324B (zh) | 2023-05-16 |
| RS64942B1 (sr) | 2024-01-31 |
| ES2965469T3 (es) | 2024-04-15 |
| CN111494323A (zh) | 2020-08-07 |
| EP4331667A2 (en) | 2024-03-06 |
| SI2827845T1 (sl) | 2019-04-30 |
| EP3542790C0 (en) | 2023-09-13 |
| EP2827845B1 (en) | 2018-12-26 |
| JP6356660B2 (ja) | 2018-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111494323B (zh) | 包含递送剂的组合物及其制备 | |
| US11759502B2 (en) | Compositions of GLP-1 peptides and preparation thereof | |
| US11123296B2 (en) | Compositions comprising a delivery agent and preparation thereof | |
| JP5902194B2 (ja) | Ｇｌｐ−１アゴニストとｎ−（８−（２−ヒドロキシベンゾイル）アミノ）カプリル酸の塩とを含む固形組成物 | |
| KR102266299B1 (ko) | Ｇｌｐ-1 펩티드의 조성물 및 그것의 제조 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |