ZA200102068B - Insulin preparations for pulmonary delivery containing menthol. - Google Patents
Insulin preparations for pulmonary delivery containing menthol. Download PDFInfo
- Publication number
- ZA200102068B ZA200102068B ZA200102068A ZA200102068A ZA200102068B ZA 200102068 B ZA200102068 B ZA 200102068B ZA 200102068 A ZA200102068 A ZA 200102068A ZA 200102068 A ZA200102068 A ZA 200102068A ZA 200102068 B ZA200102068 B ZA 200102068B
- Authority
- ZA
- South Africa
- Prior art keywords
- insulin
- human insulin
- human
- des
- formulation according
- Prior art date
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 253
- 102000004877 Insulin Human genes 0.000 title claims description 120
- 108090001061 Insulin Proteins 0.000 title claims description 120
- 229940125396 insulin Drugs 0.000 title claims description 120
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 title claims description 23
- 229940041616 menthol Drugs 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 15
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 title claims 3
- 238000012384 transportation and delivery Methods 0.000 title description 8
- 230000002685 pulmonary effect Effects 0.000 title description 7
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 54
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 48
- 238000009472 formulation Methods 0.000 claims description 40
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 38
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 claims description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 239000004026 insulin derivative Substances 0.000 claims description 8
- 150000002500 ions Chemical class 0.000 claims description 8
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 8
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 108010008488 Glycylglycine Proteins 0.000 claims description 6
- 229940043257 glycylglycine Drugs 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 4
- 229910001414 potassium ion Inorganic materials 0.000 claims description 4
- 229910001415 sodium ion Inorganic materials 0.000 claims description 4
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 3
- 150000001768 cations Chemical class 0.000 claims description 3
- 229960002242 chlorocresol Drugs 0.000 claims description 3
- 235000012054 meals Nutrition 0.000 claims description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 239000005844 Thymol Substances 0.000 claims description 2
- 229940031956 chlorothymol Drugs 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- 239000004094 surface-active agent Substances 0.000 claims 1
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 21
- 239000011701 zinc Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229910052725 zinc Inorganic materials 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 150000002989 phenols Chemical class 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229930003836 cresol Natural products 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000006240 deamidation Effects 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WADQOGCINABPRT-UHFFFAOYSA-N 3-chloro-2-methylphenol Chemical compound CC1=C(O)C=CC=C1Cl WADQOGCINABPRT-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 108010092217 Long-Acting Insulin Proteins 0.000 description 2
- 102000016261 Long-Acting Insulin Human genes 0.000 description 2
- 229940100066 Long-acting insulin Drugs 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 206010061592 cardiac fibrillation Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000002600 fibrillogenic effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 235000007686 potassium Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 230000003019 stabilising effect Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000007056 transamidation reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- YBBOHZMBHYZMOV-DIEVJBPKSA-N (4S)-4-[[2-[[(1R,6R,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,50S,53S,56S,59S,62S,65S,68S,71S,74R,77S,80S,83S,88R)-88-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[(2-aminoacetyl)amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]-6-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-47-[[(1S)-3-amino-1-carboxy-3-oxopropyl]carbamoyl]-53-(2-amino-2-oxoethyl)-62-(3-amino-3-oxopropyl)-77-[(2S)-butan-2-yl]-24,56-bis(2-carboxyethyl)-83-[(1R)-1-hydroxyethyl]-12,71,80-tris(hydroxymethyl)-33,50,65-tris[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-5-ylmethyl)-27-methyl-18,30,36,59,68-pentakis(2-methylpropyl)-7,10,13,16,19,22,25,28,31,34,37,40,49,52,55,58,61,64,67,70,73,76,79,82,85,87-hexacosaoxo-21,39-di(propan-2-yl)-3,4,44,45,90,91-hexathia-8,11,14,17,20,23,26,29,32,35,38,41,48,51,54,57,60,63,66,69,72,75,78,81,84,86-hexacosazabicyclo[72.11.7]dononacontane-42-carbonyl]amino]acetyl]amino]-5-[[(2S)-5-carbamimidamido-1-[[2-[[(2S)-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopentan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3cnc[nH]3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC YBBOHZMBHYZMOV-DIEVJBPKSA-N 0.000 description 1
- DERSKOLBMUCHJB-UHFFFAOYSA-N 1-methyl-4-propan-2-ylcyclohexane-1-carbaldehyde Chemical compound CC(C)C1CCC(C)(C=O)CC1 DERSKOLBMUCHJB-UHFFFAOYSA-N 0.000 description 1
- ORVPXPKEZLTMNW-UHFFFAOYSA-N 1h-indol-7-ol Chemical compound OC1=CC=CC2=C1NC=C2 ORVPXPKEZLTMNW-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- 101100229963 Drosophila melanogaster grau gene Proteins 0.000 description 1
- 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 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010005991 Pork Regular Insulin Proteins 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000003857 carboxamides Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 108700042880 despentapeptide(B26-B30)- insulin Proteins 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 201000010064 diabetes insipidus Diseases 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940069330 human zinc insulin Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [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)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- 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)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199801326 | 1998-10-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200102068B true ZA200102068B (en) | 2001-10-12 |
Family
ID=8103609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200102068A ZA200102068B (en) | 1998-10-16 | 2001-03-13 | Insulin preparations for pulmonary delivery containing menthol. |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1121145B1 (uk) |
| JP (1) | JP2002527488A (uk) |
| KR (1) | KR20010080132A (uk) |
| CN (1) | CN1323220A (uk) |
| AT (1) | ATE216258T1 (uk) |
| AU (1) | AU758108B2 (uk) |
| BR (1) | BR9914568A (uk) |
| CA (1) | CA2346884A1 (uk) |
| CZ (1) | CZ20011133A3 (uk) |
| DE (1) | DE69901314T2 (uk) |
| DK (1) | DK1121145T3 (uk) |
| ES (1) | ES2177324T3 (uk) |
| HU (1) | HUP0103606A3 (uk) |
| IL (1) | IL142002A0 (uk) |
| NO (1) | NO20011841L (uk) |
| PL (1) | PL347171A1 (uk) |
| PT (1) | PT1121145E (uk) |
| UA (1) | UA67798C2 (uk) |
| WO (1) | WO2000023099A1 (uk) |
| ZA (1) | ZA200102068B (uk) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001026689A1 (fr) | 1999-10-14 | 2001-04-19 | Pola Chemical Industries Inc. | Compositions d'electroporation |
| CA2387370C (en) * | 1999-10-15 | 2008-12-23 | Pola Chemical Industries Inc. | Percutaneous sorbefacients for electroporation |
| DE10114178A1 (de) | 2001-03-23 | 2002-10-10 | Aventis Pharma Gmbh | Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität |
| EP3228320B1 (de) | 2008-10-17 | 2019-12-18 | Sanofi-Aventis Deutschland GmbH | Kombination von einem insulin und einem glp-1-agonisten |
| UY33025A (es) | 2009-11-13 | 2011-06-30 | Sanofi Aventis Deustschland Gmbh | Composicion farmaceutica que comprende un agonista de glp-1 metionina |
| AR080669A1 (es) | 2009-11-13 | 2012-05-02 | Sanofi Aventis Deutschland | Composicion farmaceutica que comprende un agonista de glp-1, una insulina y metionina |
| MX339614B (es) | 2010-08-30 | 2016-06-02 | Sanofi - Aventis Deutschland GmbH | Uso de ave0010 para la fabricacion de un medicamento para el tratamiento de la diabetes mellitus tipo 2. |
| 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 |
| RU2650616C2 (ru) | 2011-08-29 | 2018-04-16 | Санофи-Авентис Дойчланд Гмбх | Фармацевтическая комбинация для применения при гликемическом контроле у пациентов с сахарным диабетом 2 типа |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| CN107206058A (zh) | 2014-12-12 | 2017-09-26 | 赛诺菲-安万特德国有限公司 | 甘精胰岛素/利西拉来固定比率配制剂 |
| 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 (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| US5504188A (en) * | 1994-06-16 | 1996-04-02 | Eli Lilly And Company | Preparation of stable zinc insulin analog crystals |
| US5474978A (en) * | 1994-06-16 | 1995-12-12 | Eli Lilly And Company | Insulin analog formulations |
| US5635161A (en) * | 1995-06-07 | 1997-06-03 | Abbott Laboratories | Aerosol drug formulations containing vegetable oils |
| CN1198643C (zh) * | 1996-06-20 | 2005-04-27 | 诺沃挪第克公司 | 含碳水化合物的胰岛素制品 |
| AU6611998A (en) * | 1997-03-20 | 1998-10-20 | Novo Nordisk A/S | Therapeutic powder formulation for pulmonary administration, containing crystalline insulin |
-
1999
- 1999-10-15 DK DK99948726T patent/DK1121145T3/da active
- 1999-10-15 BR BR9914568-5A patent/BR9914568A/pt not_active IP Right Cessation
- 1999-10-15 IL IL14200299A patent/IL142002A0/xx unknown
- 1999-10-15 CA CA002346884A patent/CA2346884A1/en not_active Abandoned
- 1999-10-15 HU HU0103606A patent/HUP0103606A3/hu unknown
- 1999-10-15 CN CN99812209A patent/CN1323220A/zh active Pending
- 1999-10-15 WO PCT/DK1999/000557 patent/WO2000023099A1/en not_active Application Discontinuation
- 1999-10-15 ES ES99948726T patent/ES2177324T3/es not_active Expired - Lifetime
- 1999-10-15 AU AU61890/99A patent/AU758108B2/en not_active Ceased
- 1999-10-15 AT AT99948726T patent/ATE216258T1/de not_active IP Right Cessation
- 1999-10-15 UA UA2001042149A patent/UA67798C2/uk unknown
- 1999-10-15 DE DE69901314T patent/DE69901314T2/de not_active Expired - Fee Related
- 1999-10-15 EP EP99948726A patent/EP1121145B1/en not_active Expired - Lifetime
- 1999-10-15 KR KR1020017004638A patent/KR20010080132A/ko not_active Application Discontinuation
- 1999-10-15 JP JP2000576872A patent/JP2002527488A/ja not_active Withdrawn
- 1999-10-15 PL PL99347171A patent/PL347171A1/xx unknown
- 1999-10-15 PT PT99948726T patent/PT1121145E/pt unknown
- 1999-10-15 CZ CZ20011133A patent/CZ20011133A3/cs unknown
-
2001
- 2001-03-13 ZA ZA200102068A patent/ZA200102068B/en unknown
- 2001-04-10 NO NO20011841A patent/NO20011841L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1121145B1 (en) | 2002-04-17 |
| AU6189099A (en) | 2000-05-08 |
| WO2000023099A1 (en) | 2000-04-27 |
| UA67798C2 (uk) | 2004-07-15 |
| HUP0103606A2 (hu) | 2002-02-28 |
| IL142002A0 (en) | 2002-03-10 |
| KR20010080132A (ko) | 2001-08-22 |
| CZ20011133A3 (cs) | 2001-08-15 |
| PT1121145E (pt) | 2002-09-30 |
| AU758108B2 (en) | 2003-03-13 |
| NO20011841L (no) | 2001-06-15 |
| DE69901314D1 (de) | 2002-05-23 |
| EP1121145A1 (en) | 2001-08-08 |
| CN1323220A (zh) | 2001-11-21 |
| BR9914568A (pt) | 2001-07-03 |
| HUP0103606A3 (en) | 2002-05-28 |
| DK1121145T3 (da) | 2002-08-12 |
| PL347171A1 (en) | 2002-03-25 |
| JP2002527488A (ja) | 2002-08-27 |
| ATE216258T1 (de) | 2002-05-15 |
| CA2346884A1 (en) | 2000-04-27 |
| DE69901314T2 (de) | 2002-11-21 |
| NO20011841D0 (no) | 2001-04-10 |
| ES2177324T3 (es) | 2002-12-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6211144B1 (en) | Stable concentrated insulin preparations for pulmonary delivery | |
| EP1172114B1 (en) | Stable concentrated insulin preparations for pulmonary delivery | |
| US6489292B1 (en) | Stable aqueous insulin preparations without phenol and cresol | |
| EP1131089B1 (en) | Stable aqueous insulin preparations without phenol and cresol | |
| EP1969004B1 (en) | Compositions comprising an acylated insulin and zinc and method of making the said compositions | |
| AU2003238862B9 (en) | Formulations for amylin agonist peptides | |
| EP1121145B1 (en) | Insulin preparations for pulmonary delivery containing menthol | |
| US6635617B1 (en) | Insulin preparations for pulmonary delivery containing menthol | |
| MXPA01003777A (en) | Insulin preparations for pulmonary delivery containing menthol | |
| MXPA01003694A (es) | Preparaciones de insulina concentrada estable para suministro pulmonar | |
| JPS5846026A (ja) | ヒトインシユリン，ヒトｃ−ペプタイドおよびヒトプロインシユリン含有製剤 |