JP2013512226A5 - - Google Patents

Info

Publication number

JP2013512226A5

JP2013512226A5 JP2012540439A JP2012540439A JP2013512226A5 JP 2013512226 A5 JP2013512226 A5 JP 2013512226A5 JP 2012540439 A JP2012540439 A JP 2012540439A JP 2012540439 A JP2012540439 A JP 2012540439A JP 2013512226 A5 JP2013512226 A5 JP 2013512226A5

Authority

JP

Japan

Prior art keywords

mucosal delivery

peptide

delivery composition

active agent

composition according

Prior art date

2010-11-25

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.)

Granted

Links

• Espacenet
• Global Dossier
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• 239000000203 mixture Substances 0.000 claims 35
• 239000003795 chemical substances by application Substances 0.000 claims 14
• 239000003960 organic solvent Substances 0.000 claims 14
• 239000002633 crown compound Substances 0.000 claims 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 9
• 239000012190 activator Substances 0.000 claims 6
• 239000003880 polar aprotic solvent Substances 0.000 claims 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 6
• 230000002209 hydrophobic Effects 0.000 claims 5
• 150000002632 lipids Chemical class 0.000 claims 5
• 239000000725 suspension Substances 0.000 claims 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 5
• 150000001768 cations Chemical class 0.000 claims 4
• ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical group NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims 4
• 150000002500 ions Chemical class 0.000 claims 4
• 150000003141 primary amines Chemical class 0.000 claims 4
• 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 4
• 239000000243 solution Substances 0.000 claims 4
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-Crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
• SECXISVLQFMRJM-UHFFFAOYSA-N n-methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 3
• 230000001264 neutralization Effects 0.000 claims 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
• ZAKBPRIDLSBYQQ-VHSXEESVSA-N 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical class CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OC[C@@H](O)CO ZAKBPRIDLSBYQQ-VHSXEESVSA-N 0.000 claims 2
• VJWXKKBAEQSRLE-UHFFFAOYSA-N 1,2-dihydroxy-2-(hydroxymethyl)dodecan-3-one Chemical compound CCCCCCCCCC(=O)C(O)(CO)CO VJWXKKBAEQSRLE-UHFFFAOYSA-N 0.000 claims 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 2
• FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 claims 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N Oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims 2
• 125000000129 anionic group Chemical group 0.000 claims 2
• 239000003125 aqueous solvent Substances 0.000 claims 2
• 239000007900 aqueous suspension Substances 0.000 claims 2
• 239000002152 aqueous-organic solution Substances 0.000 claims 2
• 238000006065 biodegradation reaction Methods 0.000 claims 2
• 125000002091 cationic group Chemical group 0.000 claims 2
• 238000001035 drying Methods 0.000 claims 2
• 150000004667 medium chain fatty acids Chemical class 0.000 claims 2
• 239000000813 peptide hormone Substances 0.000 claims 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
• 150000004666 short chain fatty acids Chemical class 0.000 claims 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
• VOYSKJXXUJMOBQ-ZETCQYMHSA-N (2S)-N-acetyl-2,6-diaminohexanamide Chemical compound CC(=O)NC(=O)[C@@H](N)CCCCN VOYSKJXXUJMOBQ-ZETCQYMHSA-N 0.000 claims 1
• DTHNMHAUYICORS-KTKZVXAJSA-N 107444-51-9 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 1
• 150000003990 18-crown-6 derivatives Chemical class 0.000 claims 1
• 229960000583 Acetic Acid Drugs 0.000 claims 1
• 239000005711 Benzoic acid Substances 0.000 claims 1
• PTMUSXLDYNJPJN-LURJTMIESA-N CC(=O)NC(=O)[C@@H](N)CCCNC(N)=N Chemical compound CC(=O)NC(=O)[C@@H](N)CCCNC(N)=N PTMUSXLDYNJPJN-LURJTMIESA-N 0.000 claims 1
• 108010011459 Exenatide Proteins 0.000 claims 1
• HTQBXNHDCUEHJF-XWLPCZSASA-N Exendin-4 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims 1
• 101710042131 GCG Proteins 0.000 claims 1
• 102100003818 GCG Human genes 0.000 claims 1
• 108010088406 Glucagon-Like Peptides Proteins 0.000 claims 1
• 108010019598 Liraglutide Proteins 0.000 claims 1
• 210000000214 Mouth Anatomy 0.000 claims 1
• FBUKVWPVBMHYJY-UHFFFAOYSA-N Nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims 1
• 239000005642 Oleic acid Substances 0.000 claims 1
• 229960004838 Phosphoric acid Drugs 0.000 claims 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-L Sulphite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims 1
• 229940046009 Vitamin E Drugs 0.000 claims 1
• 229930003427 Vitamin E Natural products 0.000 claims 1
• 230000002378 acidificating Effects 0.000 claims 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
• 235000010233 benzoic acid Nutrition 0.000 claims 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 claims 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 claims 1
• 229940043264 dodecyl sulfate Drugs 0.000 claims 1
• 230000002708 enhancing Effects 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• 229960001519 exenatide Drugs 0.000 claims 1
• 101710038873 glc-1 Proteins 0.000 claims 1
• YSDQQAXHVYUZIW-QCIJIYAXSA-N liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims 1
• 229960002701 liraglutide Drugs 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 239000006186 oral dosage form Substances 0.000 claims 1
• 235000006408 oxalic acid Nutrition 0.000 claims 1
• 239000000843 powder Substances 0.000 claims 1
• 230000000717 retained Effects 0.000 claims 1
• 229960004889 salicylic acid Drugs 0.000 claims 1
• 239000002904 solvent Substances 0.000 claims 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
• 235000002906 tartaric acid Nutrition 0.000 claims 1
• 239000011975 tartaric acid Substances 0.000 claims 1
• 229960001367 tartaric acid Drugs 0.000 claims 1
• 229940095064 tartrate Drugs 0.000 claims 1
• 235000019165 vitamin E Nutrition 0.000 claims 1
• 239000011709 vitamin E Substances 0.000 claims 1
• 150000003712 vitamin E derivatives Chemical class 0.000 claims 1