JPS6030651B2 - 経鼻投与用インスリ製剤 - Google Patents
経鼻投与用インスリ製剤Info
- Publication number
- JPS6030651B2 JPS6030651B2 JP51055965A JP5596576A JPS6030651B2 JP S6030651 B2 JPS6030651 B2 JP S6030651B2 JP 51055965 A JP51055965 A JP 51055965A JP 5596576 A JP5596576 A JP 5596576A JP S6030651 B2 JPS6030651 B2 JP S6030651B2
- Authority
- JP
- Japan
- Prior art keywords
- insulin
- solution
- acid
- surfactant
- value
- 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.)
- Expired
Links
- 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 title claims description 140
- 102000004877 Insulin Human genes 0.000 title claims description 68
- 108090001061 Insulin Proteins 0.000 title claims description 68
- 229940125396 insulin Drugs 0.000 title claims description 68
- 238000002360 preparation method Methods 0.000 title description 7
- 239000004094 surface-active agent Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 229940100656 nasal solution Drugs 0.000 claims description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 230000000694 effects Effects 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 150000001340 alkali metals Chemical class 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 125000001183 hydrocarbyl group Chemical group 0.000 description 7
- 210000002850 nasal mucosa Anatomy 0.000 description 7
- -1 alkali metal salts Chemical class 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 108010005991 Pork Regular Insulin Proteins 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- 150000007949 saponins Chemical class 0.000 description 4
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000003158 alcohol group Chemical group 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 description 2
- AFWTZXXDGQBIKW-UHFFFAOYSA-N C14 surfactin Natural products CCCCCCCCCCCC1CC(=O)NC(CCC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)O1 AFWTZXXDGQBIKW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010040576 Shock hypoglycaemic Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000002280 amphoteric surfactant Substances 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000003833 bile salt Substances 0.000 description 2
- 229940093761 bile salts Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 238000007391 self-medication Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- NJGWOFRZMQRKHT-UHFFFAOYSA-N surfactin Natural products CC(C)CCCCCCCCCC1CC(=O)NC(CCC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)O1 NJGWOFRZMQRKHT-UHFFFAOYSA-N 0.000 description 2
- NJGWOFRZMQRKHT-WGVNQGGSSA-N surfactin C Chemical compound CC(C)CCCCCCCCC[C@@H]1CC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)O1 NJGWOFRZMQRKHT-WGVNQGGSSA-N 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical class C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 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 1
- 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 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010007979 Glycocholic Acid Chemical class 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Chemical class C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 1
- 108010092217 Long-Acting Insulin Proteins 0.000 description 1
- 102000016261 Long-Acting Insulin Human genes 0.000 description 1
- 229940100066 Long-acting insulin Drugs 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Chemical class OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Chemical class OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 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
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin 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)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)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(C)C)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 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
- RPKLZQLYODPWTM-KBMWBBLPSA-N cholanoic acid Chemical class C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC(O)=O)C)[C@@]1(C)CC2 RPKLZQLYODPWTM-KBMWBBLPSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical class C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- 229940099347 glycocholic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical class C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical class [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical class C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- A61K38/28—Insulins
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB34576/75 | 1975-08-20 | ||
| GB34576/75A GB1527605A (en) | 1975-08-20 | 1975-08-20 | Insulin preparation for intranasal administration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5225013A JPS5225013A (en) | 1977-02-24 |
| JPS6030651B2 true JPS6030651B2 (ja) | 1985-07-17 |
Family
ID=10367351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51055965A Expired JPS6030651B2 (ja) | 1975-08-20 | 1976-05-14 | 経鼻投与用インスリ製剤 |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS6030651B2 (OSRAM) |
| BE (1) | BE841871A (OSRAM) |
| DE (1) | DE2620446A1 (OSRAM) |
| FR (1) | FR2321275A1 (OSRAM) |
| GB (1) | GB1527605A (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04126437U (ja) * | 1991-05-10 | 1992-11-18 | 八木アンテナ株式会社 | 光受信機 |
| EP0689052A2 (en) | 1994-06-24 | 1995-12-27 | Toa Medical Electronics Co., Ltd. | Insulin standard solution |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5145405A (ja) * | 1974-10-16 | 1976-04-17 | Unyusho Kowan Gijutsu Kenkyush | Jibankairyokoho |
| JPS53115510A (en) * | 1977-12-19 | 1978-10-09 | Kitagawa Iron Works Co | Support structure made by hardening weak soil |
| JPS53115509A (en) * | 1977-12-19 | 1978-10-09 | Kitagawa Iron Works Co | Method of changing weak ground into stable ground |
| DE2917535C2 (de) * | 1979-04-30 | 1986-10-30 | Hoechst Ag, 6230 Frankfurt | Gegen Denaturierung beständige Insulinlösungen |
| JPS58501125A (ja) * | 1981-07-17 | 1983-07-14 | ノルデイスク・インスリンラボラトリウム | 安定な水性治療性インシユリン製剤及びその製造方法 |
| CH657779A5 (de) * | 1982-10-05 | 1986-09-30 | Sandoz Ag | Galenische zusammensetzungen enthaltend calcitonin. |
| IE56483B1 (en) * | 1982-12-10 | 1991-08-14 | Syntex Inc | Lhrh preparations for intranasal administration |
| IL70489A0 (en) * | 1982-12-29 | 1984-03-30 | Armour Pharma | Pharmaceutical compositions containing calcitonin |
| JPS59163313A (ja) * | 1983-03-09 | 1984-09-14 | Teijin Ltd | 経鼻投与用ペプチドホルモン類組成物 |
| US4746508A (en) * | 1983-06-06 | 1988-05-24 | Beth Israel Hospital Assn. | Drug administration |
| US4548922A (en) * | 1983-06-06 | 1985-10-22 | Beth Israel Hospital | Drug administration |
| DE3443877A1 (de) * | 1984-06-09 | 1985-12-12 | Hoechst Ag | Insulinzubereitungen, verfahren zu deren herstellung und deren verwendung |
| US4658830A (en) * | 1984-08-08 | 1987-04-21 | Survival Technology, Inc. | Method and apparatus for initiating reperfusion treatment by an unattended individual undergoing heart attack symptoms |
| AU584184B2 (en) * | 1985-04-15 | 1989-05-18 | Eli Lilly And Company | An improved method for administering insulin |
| CA1274774A (en) * | 1985-04-15 | 1990-10-02 | Kenneth S. Su | Method for administering insulin |
| GB2177914B (en) * | 1985-06-04 | 1989-10-25 | Chugai Pharmaceutical Co Ltd | A pharmaceutical composition containing human erythropoietin and a surface active agent for nasal administration for the treatment of anemia |
| US4731360A (en) * | 1985-08-16 | 1988-03-15 | Merck & Co., Inc. | Acylcarnitines as absorption-enhancing agents for drug delivery through mucous membranes of the nasal, buccal, sublingual and vaginal compartments |
| US4692441A (en) * | 1985-08-16 | 1987-09-08 | Merck & Co., Inc. | Chorine esters as absorption-enhancing agents for drug delivery through mucous membranes of the nasal, buccal, sublingual and vaginal cavities |
| DK179286D0 (da) * | 1986-04-18 | 1986-04-18 | Nordisk Gentofte | Insulinpraeparat |
| CA1291036C (en) * | 1986-04-23 | 1991-10-22 | Edwin I. Stoltz | Nasal administration of drugs |
| US5179079A (en) * | 1986-12-16 | 1993-01-12 | Novo Nordisk A/S | Nasal formulation and intranasal administration therewith |
| NZ222907A (en) * | 1986-12-16 | 1990-08-28 | Novo Industri As | Preparation for intranasal administration containing a phospholipid absorption enhancing system |
| CA1335076C (en) * | 1987-04-01 | 1995-04-04 | Hanna R. Kowarski | Pharmaceutical composition and method for intranasal administration |
| US5112804A (en) * | 1987-04-01 | 1992-05-12 | Temple University Of The Commonwealth System Of Higher Education | Pharmaceutical composition and method of intranasal administration |
| US6645504B1 (en) | 1987-06-24 | 2003-11-11 | Autoimmune Inc. | Bystander suppression of type I diabetes by oral administration of glucagon |
| US4994439A (en) * | 1989-01-19 | 1991-02-19 | California Biotechnology Inc. | Transmembrane formulations for drug administration |
| JPH0713372B2 (ja) * | 1989-02-14 | 1995-02-15 | 鹿島建設株式会社 | 砂質土層における構造物基礎の構築方法 |
| IL99699A (en) * | 1990-10-10 | 2002-04-21 | Autoimmune Inc | Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes |
| US5795870A (en) * | 1991-12-13 | 1998-08-18 | Trustees Of Princeton University | Compositions and methods for cell transformation |
| US5693769A (en) * | 1991-12-13 | 1997-12-02 | Transcell Technologies, Inc. | Glycosylated steroid derivatives for transport across biological membranes and process for making and using same |
| US5338837A (en) * | 1991-12-13 | 1994-08-16 | The Trustees Of Princeton University | Glycosylated steroid derivatives for transport across biological membranes and process for making same |
| US6509006B1 (en) | 1992-07-08 | 2003-01-21 | Inhale Therapeutic Systems, Inc. | Devices compositions and methods for the pulmonary delivery of aerosolized medicaments |
| US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
| US5639866A (en) * | 1993-02-23 | 1997-06-17 | Princeton University | Single-step formation of multiple glycosidic linkages |
| IL108748A0 (en) * | 1993-02-23 | 1994-08-26 | Univ Princeton | Solution and solid-phase formation of glycosidic linkages |
| US5830853A (en) * | 1994-06-23 | 1998-11-03 | Astra Aktiebolag | Systemic administration of a therapeutic preparation |
| US6632456B1 (en) | 1993-06-24 | 2003-10-14 | Astrazeneca Ab | Compositions for inhalation |
| US5747445A (en) * | 1993-06-24 | 1998-05-05 | Astra Aktiebolag | Therapeutic preparation for inhalation |
| IS1796B (is) * | 1993-06-24 | 2001-12-31 | Ab Astra | Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband |
| TW402506B (en) | 1993-06-24 | 2000-08-21 | Astra Ab | Therapeutic preparation for inhalation |
| US6794357B1 (en) | 1993-06-24 | 2004-09-21 | Astrazeneca Ab | Compositions for inhalation |
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| JPH10501519A (ja) | 1994-03-07 | 1998-02-10 | インヘイル・セラピューティック・システムズ | インシュリンを肺に送給できる方法および組成物 |
| US6051256A (en) | 1994-03-07 | 2000-04-18 | Inhale Therapeutic Systems | Dispersible macromolecule compositions and methods for their preparation and use |
| US6165976A (en) | 1994-06-23 | 2000-12-26 | Astra Aktiebolag | Therapeutic preparation for inhalation |
| US6290991B1 (en) | 1994-12-02 | 2001-09-18 | Quandrant Holdings Cambridge Limited | Solid dose delivery vehicle and methods of making same |
| US6524557B1 (en) | 1994-12-22 | 2003-02-25 | Astrazeneca Ab | Aerosol formulations of peptides and proteins |
| SK81197A3 (en) | 1994-12-22 | 1997-11-05 | Astra Ab | Aerosol drug formulations, method for production thereof and its use |
| US5780014A (en) * | 1995-04-14 | 1998-07-14 | Inhale Therapeutic Systems | Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin |
| US20030203036A1 (en) | 2000-03-17 | 2003-10-30 | Gordon Marc S. | Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients |
| US7575761B2 (en) | 2000-06-30 | 2009-08-18 | Novartis Pharma Ag | Spray drying process control of drying kinetics |
| DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
| US6653492B2 (en) | 2001-05-02 | 2003-11-25 | Novo Nordick A/S | Preparation of bile acids |
| GB0216562D0 (en) | 2002-04-25 | 2002-08-28 | Bradford Particle Design Ltd | Particulate materials |
| US9339459B2 (en) | 2003-04-24 | 2016-05-17 | Nektar Therapeutics | Particulate materials |
| DE10227232A1 (de) | 2002-06-18 | 2004-01-15 | Aventis Pharma Deutschland Gmbh | Saure Insulinzubereitungen mit verbesserter Stabilität |
| DK3228320T3 (da) | 2008-10-17 | 2020-03-09 | Sanofi Aventis Deutschland | Kombination af et insulin og en glp-1-agonist |
| PL3417871T3 (pl) | 2009-11-13 | 2021-06-14 | Sanofi-Aventis Deutschland Gmbh | Kompozycja farmaceutyczna zawierająca agonistę GLP-1, insulinę i metioninę |
| CN102711804B (zh) | 2009-11-13 | 2015-09-16 | 赛诺菲-安万特德国有限公司 | 包含glp-1激动剂和甲硫氨酸的药物组合物 |
| RU2546520C2 (ru) | 2010-08-30 | 2015-04-10 | Санофи-Авентис Дойчланд Гмбх | Применение ave0010 для производства лекарственного средства для лечения сахарного диабета 2 типа |
| JP5906194B2 (ja) * | 2011-01-13 | 2016-04-20 | 株式会社カネカ | 皮膚外用剤 |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| BR112014004726A2 (pt) | 2011-08-29 | 2017-04-04 | Sanofi Aventis Deutschland | combinação farmacêutica para uso no controle glicêmico em pacientes de diabetes tipo 2 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| ES2949095T3 (es) | 2014-12-12 | 2023-09-25 | Sanofi Aventis Deutschland | Formulación de relación fija de insulina glargina/lixisenatida |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL62232C (OSRAM) * | 1900-01-01 | |||
| US3096249A (en) * | 1960-05-10 | 1963-07-02 | Samuel J Prigal | Emulsion composition |
-
1975
- 1975-08-20 GB GB34576/75A patent/GB1527605A/en not_active Expired
-
1976
- 1976-05-08 DE DE19762620446 patent/DE2620446A1/de not_active Withdrawn
- 1976-05-14 JP JP51055965A patent/JPS6030651B2/ja not_active Expired
- 1976-05-14 BE BE167070A patent/BE841871A/xx not_active IP Right Cessation
- 1976-05-14 FR FR7614707A patent/FR2321275A1/fr active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04126437U (ja) * | 1991-05-10 | 1992-11-18 | 八木アンテナ株式会社 | 光受信機 |
| EP0689052A2 (en) | 1994-06-24 | 1995-12-27 | Toa Medical Electronics Co., Ltd. | Insulin standard solution |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2321275B1 (OSRAM) | 1979-04-13 |
| JPS5225013A (en) | 1977-02-24 |
| GB1527605A (en) | 1978-10-04 |
| BE841871A (fr) | 1976-11-16 |
| DE2620446A1 (de) | 1977-03-03 |
| FR2321275A1 (fr) | 1977-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS6030651B2 (ja) | 経鼻投与用インスリ製剤 | |
| US4153689A (en) | Stable insulin preparation for nasal administration | |
| DE3880346T2 (de) | Insulinderivate. | |
| US4548922A (en) | Drug administration | |
| EP0147526B1 (de) | Verfahren zur Erhöhung der enteralen Resorbierbarkeit von Heparin sowie das so erhältliche Heparinpräparat | |
| DE2620483A1 (de) | Stabile waessrige insulinloesungen | |
| CS273139B1 (en) | Method of pharmaceutical agent production for intranasal feed | |
| DE19627392A1 (de) | Medikament zur Verabreichung durch die Nase | |
| EP0145209B1 (en) | A kit or device and method for administering gangliosides and derivatives thereof of inhalation and pharmaceutical compositions suitable therefor | |
| JPS61218510A (ja) | 毛髪用剤 | |
| US4789660A (en) | Insulin administration using methyl and propyl paraben | |
| AT396475B (de) | Säureadditionssalze aus amidiertem taurin oder glycin, deren herstellung und verwendung | |
| JPH0228121A (ja) | 経粘膜吸収促進剤及びこれを用いた経鼻投与剤 | |
| US6008189A (en) | Intravaginal preparation containing physiologically active peptide | |
| NL8203314A (nl) | Farmaceutische preparaten, die menselijk insuline en menselijk pro-insuline bevatten. | |
| US3914416A (en) | Certain monomethyl trisilanol mannuronate complexes for treating cellulitis | |
| DE3601923A1 (de) | Nasal applizierbares arzneimittel, verfahren zu seiner herstellung und seine verwendung | |
| DE3881254T2 (de) | Pharmazeutische zusammensetzung. | |
| US4389414A (en) | Prostaglandin compositions | |
| EP0324745B1 (de) | Prostacyclinderivate enthaltende mittel für die topische anwendung | |
| JPS62207226A (ja) | 経鼻投与用製剤 | |
| NL8203316A (nl) | Farmaceutische preparaten met menselijk pro-insuline. | |
| JP3534793B2 (ja) | グリチルリチン酸直腸製剤 | |
| CN1239436A (zh) | 用于将肽药物引入生物体的局部制剂 | |
| JPH01308235A (ja) | ヒト成長ホルモン経鼻剤 |