HRP20010141A2 - Method for administering insulinotropic peptides - Google Patents

Method for administering insulinotropic peptides

Info

Publication number: HRP20010141A2
Authority: HR; Croatia
Prior art keywords: glp; molecule; released; val8; patient
Prior art date: 1998-08-28

Application number

HR20010141A

Other languages

English (en)

Croatian (hr)

Inventor

Benjamin Lee Hughes

Ronald Keith Wolff

Original Assignee

Lilly Co Eli

Priority date (The priority date 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 date listed.)

1998-08-28

Filing date

2001-02-27

Publication date

2002-02-28

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26794577&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20010141(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2001-02-27 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2002-02-28 Publication of HRP20010141A2 publication Critical patent/HRP20010141A2/hr

Links

238000000034 method Methods 0.000 title claims description 52
108090000765 processed proteins & peptides Proteins 0.000 title description 37
102000004196 processed proteins & peptides Human genes 0.000 title description 6
230000002473 insulinotropic effect Effects 0.000 title description 5
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 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 description 186
101800000224 Glucagon-like peptide 1 Proteins 0.000 claims description 129
102100040918 Pro-glucagon Human genes 0.000 claims description 129
239000002245 particle Substances 0.000 claims description 36
210000004072 lung Anatomy 0.000 claims description 32
230000002685 pulmonary effect Effects 0.000 claims description 30
239000000443 aerosol Substances 0.000 claims description 22
239000000843 powder Substances 0.000 claims description 20
238000002360 preparation method Methods 0.000 claims description 20
238000000151 deposition Methods 0.000 claims description 10
239000007921 spray Substances 0.000 claims description 10
239000006199 nebulizer Substances 0.000 claims description 9
206010012601 diabetes mellitus Diseases 0.000 claims description 7
229940112141 dry powder inhaler Drugs 0.000 claims description 7
201000001421 hyperglycemia Diseases 0.000 claims description 5
229940071648 metered dose inhaler Drugs 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
239000000725 suspension Substances 0.000 claims description 5
239000012736 aqueous medium Substances 0.000 claims description 3
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 3
BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 claims 3
208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 claims 3
239000003937 drug carrier Substances 0.000 claims 3
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 36
239000000203 mixture Substances 0.000 description 32
235000018102 proteins Nutrition 0.000 description 31
102000004169 proteins and genes Human genes 0.000 description 31
108090000623 proteins and genes Proteins 0.000 description 31
241001465754 Metazoa Species 0.000 description 23
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical group NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 19
102000004877 Insulin Human genes 0.000 description 18
108090001061 Insulin Proteins 0.000 description 18
229940125396 insulin Drugs 0.000 description 18
150000001875 compounds Chemical class 0.000 description 16
238000009472 formulation Methods 0.000 description 16
239000000243 solution Substances 0.000 description 16
239000004094 surface-active agent Substances 0.000 description 16
-1 alkyl amide Chemical class 0.000 description 13
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 12
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 12
239000008103 glucose Substances 0.000 description 11
241000282472 Canis lupus familiaris Species 0.000 description 10
150000001408 amides Chemical class 0.000 description 10
235000001014 amino acid Nutrition 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 9
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 9
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 9
229940024606 amino acid Drugs 0.000 description 9
150000001413 amino acids Chemical class 0.000 description 9
210000004369 blood Anatomy 0.000 description 9
239000008280 blood Substances 0.000 description 9
239000000872 buffer Substances 0.000 description 9
150000003839 salts Chemical class 0.000 description 9
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 8
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical group C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 8
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 8
238000010521 absorption reaction Methods 0.000 description 8
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
238000005070 sampling Methods 0.000 description 8
238000006467 substitution reaction Methods 0.000 description 8
239000004471 Glycine Substances 0.000 description 7
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical group CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 7
239000000654 additive Substances 0.000 description 7
235000004279 alanine Nutrition 0.000 description 7
230000008021 deposition Effects 0.000 description 7
238000007920 subcutaneous administration Methods 0.000 description 7
238000002560 therapeutic procedure Methods 0.000 description 7
239000004475 Arginine Substances 0.000 description 6
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 6
101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 6
102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 description 6
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical group CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 6
239000004472 Lysine Substances 0.000 description 6
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
235000009582 asparagine Nutrition 0.000 description 6
229960001230 asparagine Drugs 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
235000018417 cysteine Nutrition 0.000 description 6
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
239000003380 propellant Substances 0.000 description 6
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
239000004474 valine Substances 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 5
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
239000004473 Threonine Substances 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
230000000996 additive effect Effects 0.000 description 5
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 5
230000037396 body weight Effects 0.000 description 5
229960002885 histidine Drugs 0.000 description 5
229960000310 isoleucine Drugs 0.000 description 5
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229930182817 methionine Natural products 0.000 description 5
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
239000003755 preservative agent Substances 0.000 description 5
238000010254 subcutaneous injection Methods 0.000 description 5
239000007929 subcutaneous injection Substances 0.000 description 5
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 4
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 4
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 4
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-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
229930195725 Mannitol Natural products 0.000 description 4
238000007792 addition Methods 0.000 description 4
125000003275 alpha amino acid group Chemical group 0.000 description 4
235000003704 aspartic acid Nutrition 0.000 description 4
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
150000001720 carbohydrates Chemical class 0.000 description 4
235000014633 carbohydrates Nutrition 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
239000003814 drug Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
239000012530 fluid Substances 0.000 description 4
235000013922 glutamic acid Nutrition 0.000 description 4
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
239000008101 lactose Substances 0.000 description 4
239000000787 lecithin Substances 0.000 description 4
235000010445 lecithin Nutrition 0.000 description 4
229940067606 lecithin Drugs 0.000 description 4
210000000265 leukocyte Anatomy 0.000 description 4
239000000594 mannitol Substances 0.000 description 4
235000010355 mannitol Nutrition 0.000 description 4
239000000813 peptide hormone Substances 0.000 description 4
230000036470 plasma concentration Effects 0.000 description 4
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
229920000053 polysorbate 80 Polymers 0.000 description 4
230000000241 respiratory effect Effects 0.000 description 4
210000002345 respiratory system Anatomy 0.000 description 4
208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 3
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
229930006000 Sucrose Natural products 0.000 description 3
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
229960001231 choline Drugs 0.000 description 3
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
239000004220 glutamic acid Chemical group 0.000 description 3
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
231100000824 inhalation exposure Toxicity 0.000 description 3
230000002335 preservative effect Effects 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000001694 spray drying Methods 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 2
102000009027 Albumins Human genes 0.000 description 2
108010088751 Albumins Proteins 0.000 description 2
108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
241001269524 Dura Species 0.000 description 2
101800004295 Glucagon-like peptide 1(7-36) Proteins 0.000 description 2
102400000325 Glucagon-like peptide 1(7-36) Human genes 0.000 description 2
206010022489 Insulin Resistance Diseases 0.000 description 2
HGNRJCINZYHNOU-LURJTMIESA-N Lys-Gly Chemical group NCCCC[C@H](N)C(=O)NCC(O)=O HGNRJCINZYHNOU-LURJTMIESA-N 0.000 description 2
102000003982 Parathyroid hormone Human genes 0.000 description 2
108090000445 Parathyroid hormone Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
229920001214 Polysorbate 60 Polymers 0.000 description 2
102000035554 Proglucagon Human genes 0.000 description 2
108010058003 Proglucagon Proteins 0.000 description 2
102000007327 Protamines Human genes 0.000 description 2
108010007568 Protamines Proteins 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
239000013543 active substance Substances 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
230000002411 adverse Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000000889 atomisation Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000004067 bulking agent Substances 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
125000003636 chemical group Chemical group 0.000 description 2
238000007385 chemical modification Methods 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
229940079593 drug Drugs 0.000 description 2
230000000694 effects Effects 0.000 description 2
210000000981 epithelium Anatomy 0.000 description 2
210000003743 erythrocyte Anatomy 0.000 description 2
230000030136 gastric emptying Effects 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000003914 insulin secretion Effects 0.000 description 2
239000007951 isotonicity adjuster Substances 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
108010064235 lysylglycine Chemical group 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000002184 metal Substances 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
238000003801 milling Methods 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
210000003739 neck Anatomy 0.000 description 2
231100000062 no-observed-adverse-effect level Toxicity 0.000 description 2
QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
230000006919 peptide aggregation Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
229940068977 polysorbate 20 Drugs 0.000 description 2
229940068968 polysorbate 80 Drugs 0.000 description 2
230000000291 postprandial effect Effects 0.000 description 2
239000002243 precursor Substances 0.000 description 2
229940048914 protamine Drugs 0.000 description 2
230000009325 pulmonary function Effects 0.000 description 2
238000003127 radioimmunoassay Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
230000036387 respiratory rate Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
230000007017 scission Effects 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
IZUAHLHTQJCCLJ-UHFFFAOYSA-N (2-chloro-1,1,2,2-tetrafluoroethyl) hypochlorite Chemical compound FC(F)(Cl)C(F)(F)OCl IZUAHLHTQJCCLJ-UHFFFAOYSA-N 0.000 description 1
AJFGLTPLWPTALJ-SSDOTTSWSA-N (2s)-2-azaniumyl-2-(fluoromethyl)-3-(1h-imidazol-5-yl)propanoate Chemical compound FC[C@@](N)(C(O)=O)CC1=CN=CN1 AJFGLTPLWPTALJ-SSDOTTSWSA-N 0.000 description 1
MSECZMWQBBVGEN-LURJTMIESA-N (2s)-2-azaniumyl-4-(1h-imidazol-5-yl)butanoate Chemical compound OC(=O)[C@@H](N)CCC1=CN=CN1 MSECZMWQBBVGEN-LURJTMIESA-N 0.000 description 1
UYEGXSNFZXWSDV-BYPYZUCNSA-N (2s)-3-(2-amino-1h-imidazol-5-yl)-2-azaniumylpropanoate Chemical group OC(=O)[C@@H](N)CC1=CNC(N)=N1 UYEGXSNFZXWSDV-BYPYZUCNSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
WPRAXAOJIODQJR-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C(C)=C1 WPRAXAOJIODQJR-UHFFFAOYSA-N 0.000 description 1
PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
OHMHBGPWCHTMQE-UHFFFAOYSA-N 2,2-dichloro-1,1,1-trifluoroethane Chemical compound FC(F)(F)C(Cl)Cl OHMHBGPWCHTMQE-UHFFFAOYSA-N 0.000 description 1
OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
WADQOGCINABPRT-UHFFFAOYSA-N 3-chloro-2-methylphenol Chemical compound CC1=C(O)C=CC=C1Cl WADQOGCINABPRT-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
102400000113 Calcitonin Human genes 0.000 description 1
108060001064 Calcitonin Proteins 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
229930028154 D-arginine Natural products 0.000 description 1
HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical group OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 description 1
229930195721 D-histidine Chemical group 0.000 description 1
KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
206010052804 Drug tolerance Diseases 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
PZOHPVWRSNXCRP-QRCCJXOFSA-N GPL-1 Chemical class C([C@@H](NC(=O)CC(O)CCCCCCCCCCCCCCCCCCCCCCCCCCCCC)C(=O)N[C@H]([C@@H](C)OC1[C@@H]([C@H](O)[C@H](O)[C@H](C)O1)O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)C(=O)N[C@H](C)C(=O)N[C@@H](C)COC1[C@@H]([C@H](OC)[C@@H](OC)[C@H](C)O1)O)C1=CC=CC=C1 PZOHPVWRSNXCRP-QRCCJXOFSA-N 0.000 description 1
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
101000788682 Homo sapiens GATA-type zinc finger protein 1 Proteins 0.000 description 1
101000886868 Homo sapiens Gastric inhibitory polypeptide Proteins 0.000 description 1
101500028774 Homo sapiens Glucagon-like peptide 1 Proteins 0.000 description 1
101500028773 Homo sapiens Glucagon-like peptide 1(7-37) Proteins 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
101100395023 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-7 gene Proteins 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
239000004147 Sorbitan trioleate Substances 0.000 description 1
PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
BNPSSFBOAGDEEL-UHFFFAOYSA-N albuterol sulfate Chemical compound OS(O)(=O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-UHFFFAOYSA-N 0.000 description 1
108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
HRRYYCWYCMJNGA-ZETCQYMHSA-N alpha-methyl-L-histidine Chemical compound OC(=O)[C@](N)(C)CC1=CN=CN1 HRRYYCWYCMJNGA-ZETCQYMHSA-N 0.000 description 1
210000002821 alveolar epithelial cell Anatomy 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003178 anti-diabetic effect Effects 0.000 description 1
239000003472 antidiabetic agent Substances 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000036528 appetite Effects 0.000 description 1
235000019789 appetite Nutrition 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000001483 arginine derivatives Chemical group 0.000 description 1
210000003651 basophil Anatomy 0.000 description 1
230000008901 benefit Effects 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
229960003872 benzethonium Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000004820 blood count Methods 0.000 description 1
230000035565 breathing frequency Effects 0.000 description 1
229940028978 brevital Drugs 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
229960004015 calcitonin Drugs 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
210000004298 cerebral vein Anatomy 0.000 description 1
238000002144 chemical decomposition reaction Methods 0.000 description 1
229960003260 chlorhexidine Drugs 0.000 description 1
KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000013480 data collection Methods 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000002716 delivery method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical group OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 description 1
SIYLLGKDQZGJHK-UHFFFAOYSA-N dimethyl-(phenylmethyl)-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]ammonium Chemical compound C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
230000005684 electric field Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
210000003158 enteroendocrine cell Anatomy 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
210000003979 eosinophil Anatomy 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000010579 first pass effect Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000011888 foil Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
230000006870 function Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
230000004190 glucose uptake Effects 0.000 description 1
125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
230000002641 glycemic effect Effects 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
230000026781 habituation Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
150000002410 histidine derivatives Chemical group 0.000 description 1
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
238000001794 hormone therapy Methods 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
230000003345 hyperglycaemic effect Effects 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
238000010902 jet-milling Methods 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
239000000832 lactitol Substances 0.000 description 1
VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
235000010448 lactitol Nutrition 0.000 description 1
229960003451 lactitol Drugs 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
239000000845 maltitol Substances 0.000 description 1
235000010449 maltitol Nutrition 0.000 description 1
229940035436 maltitol Drugs 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229940127554 medical product Drugs 0.000 description 1
QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
KDXZREBVGAGZHS-UHFFFAOYSA-M methohexital sodium Chemical compound [Na+].CCC#CC(C)C1(CC=C)C(=O)N=C([O-])N(C)C1=O KDXZREBVGAGZHS-UHFFFAOYSA-M 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
238000007431 microscopic evaluation Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
230000000420 mucociliary effect Effects 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
238000010606 normalization Methods 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
229960001319 parathyroid hormone Drugs 0.000 description 1
238000003921 particle size analysis Methods 0.000 description 1
230000037361 pathway Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
210000003240 portal vein Anatomy 0.000 description 1
238000012545 processing Methods 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
238000012552 review Methods 0.000 description 1
230000028327 secretion Effects 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000005846 sugar alcohols Chemical class 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000008399 tap water Substances 0.000 description 1
235000020679 tap water Nutrition 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229960004906 thiomersal Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000032258 transport Effects 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940070384 ventolin Drugs 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
- 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
- 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)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Pulmonology (AREA)
Otolaryngology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Chemical Kinetics & Catalysis (AREA)
Obesity (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Emergency Medicine (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Dispersion Chemistry (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Peptides Or Proteins (AREA)

HR20010141A 1998-08-28 2001-02-27 Method for administering insulinotropic peptides HRP20010141A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US9827398P	1998-08-28	1998-08-28
US10001298P	1998-09-11	1998-09-11
PCT/US1999/019348 WO2000012116A1 (en)	1998-08-28	1999-08-24	Method for administering insulinotropic peptides

Publications (1)

Publication Number	Publication Date
HRP20010141A2 true HRP20010141A2 (en)	2002-02-28

Family

ID=26794577

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20010141A HRP20010141A2 (en)	1998-08-28	2001-02-27	Method for administering insulinotropic peptides

Country Status (21)

Country	Link
EP (1)	EP0997151B1 (ru)
JP (1)	JP2002523466A (ru)
KR (1)	KR20010073033A (ru)
CN (1)	CN1314818A (ru)
AR (1)	AR022368A1 (ru)
AT (1)	ATE347902T1 (ru)
AU (1)	AU764371B2 (ru)
BR (1)	BR9913284A (ru)
CA (1)	CA2341454A1 (ru)
CO (1)	CO5090908A1 (ru)
CZ (1)	CZ2001690A3 (ru)
DE (1)	DE69934380D1 (ru)
EA (1)	EA200100289A1 (ru)
HR (1)	HRP20010141A2 (ru)
HU (1)	HUP0103369A3 (ru)
IL (1)	IL141241A0 (ru)
NO (1)	NO20010982L (ru)
PE (1)	PE20001031A1 (ru)
PL (1)	PL346317A1 (ru)
TR (1)	TR200100600T2 (ru)
WO (1)	WO2000012116A1 (ru)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US9006175B2 (en)	1999-06-29	2015-04-14	Mannkind Corporation	Potentiation of glucose elimination
AU2353701A (en) *	2000-01-11	2001-07-24	Novo Nordisk A/S	Transepithelial delivery of glp-1 derivatives
US6540983B1 (en) *	2000-01-25	2003-04-01	Aeropharm Technology Incorporated	Medical aerosol formulation
AU2001264789A1 (en) *	2000-06-08	2001-12-17	Eli Lilly And Company	Protein powder for pulmonary delivery
NZ523693A (en) *	2000-07-10	2004-08-27	Chiron Corp	Macrolide formulations for inhalation and methods of treatment of endobronchial infections
EP1542712A2 (en) *	2001-06-01	2005-06-22	Eli Lilly And Company	Glp-1 formulations with protracted time action
IL160917A0 (en)	2001-10-18	2004-08-31	Bristol Myers Squibb Co	Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
US7238671B2 (en)	2001-10-18	2007-07-03	Bristol-Myers Squibb Company	Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
EP2277910A1 (en)	2001-12-21	2011-01-26	Human Genome Sciences, Inc.	Albumin fusion proteins
ES2425392T3 (es)	2002-03-20	2013-10-15	Mannkind Corporation	Cartucho para un aparato de inhalación
CA2493478C (en) *	2002-08-01	2014-11-18	Mannkind Corporation	Cell transport compositions and uses thereof
US8921311B2 (en)	2003-08-01	2014-12-30	Mannkind Corporation	Method for treating hyperglycemia
CA2549582A1 (en)	2003-12-18	2005-06-30	Novo Nordisk A/S	Novel glp-1 compounds
ES2385934T3 (es)	2004-08-20	2012-08-03	Mannkind Corporation	Catálisis de la síntesis de dicetopiperazina.
BRPI0514293B1 (pt)	2004-08-23	2022-07-19	Mannkind Corporation	Sistema microparticulado para distribuição de droga
KR100704447B1 (ko) *	2005-05-16	2007-04-09	정용현	3단계로 코팅되는 김치 유산균의 코팅방법 및 그로부터 제조된 코팅된 김치유산균 및 코팅된 김치 유산균이 함유된 조성물
BRPI0616071B8 (pt)	2005-09-14	2021-05-25	Mannkind Corp	métodos de revestir uma micropartícula cristalina pré-formada em suspensão com um agente ativo
LT1965823T (lt) *	2005-11-04	2016-10-10	Glaxosmithkline Llc	Hipoglikeminių agentų skyrimo būdai
ES2390286T3 (es)	2005-12-16	2012-11-08	Nektar Therapeutics	Conjugados poliméricos de GLP-1
MX360812B (es)	2006-02-22	2018-11-16	Mannkind Corp	Un método para mejorar las propiedades farmacéuticas de micropartículas que contienen dicetopiperazina y un agente activo.
PE20121528A1 (es) *	2006-09-13	2012-12-12	Smithkline Beecham Corp	Metodos para administrar agentes hipoglucemiantes de larga duracion
WO2008132224A2 (en)	2007-04-30	2008-11-06	Novo Nordisk A/S	Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein
JP2009019027A (ja) *	2007-07-16	2009-01-29	Hanmi Pharmaceutical Co Ltd	アミノ末端のアミノ酸が変異したインスリン分泌ペプチド誘導体
EP2211842B1 (en) *	2007-10-24	2015-08-12	MannKind Corporation	An inhalable dry powder formulation comprising glp-1 for use in the treatment of hyperglycemia and diabetes by pulmonary administration
CA3086027C (en)	2008-06-13	2022-05-17	Mannkind Corporation	A dry powder inhaler and system for drug delivery
US8485180B2 (en)	2008-06-13	2013-07-16	Mannkind Corporation	Dry powder drug delivery system
EP2609954B1 (en)	2008-06-20	2021-12-29	MannKind Corporation	An interactive apparatus for real-time profiling of inhalation efforts
TWI532497B (zh)	2008-08-11	2016-05-11	曼凱公司	超快起作用胰島素之用途
US8314106B2 (en)	2008-12-29	2012-11-20	Mannkind Corporation	Substituted diketopiperazine analogs for use as drug delivery agents
DK2379100T3 (en)	2009-01-08	2014-12-01	Mannkind Corp	Treatment of hyperglycemia with GLP-1
EP2405963B1 (en)	2009-03-11	2013-11-06	MannKind Corporation	Apparatus, system and method for measuring resistance of an inhaler
CN102647979B (zh)	2009-06-12	2015-03-04	曼金德公司	具有确定比表面积的二酮哌嗪颗粒
EP2496295A1 (en)	2009-11-03	2012-09-12	MannKind Corporation	An apparatus and method for simulating inhalation efforts
JP6385673B2 (ja)	2010-06-21	2018-09-05	マンカインドコーポレイション	乾燥粉末薬物送達システム
KR101940832B1 (ko)	2011-04-01	2019-01-21	맨카인드 코포레이션	의약 카트리지용 블리스터 패키지
WO2012174472A1 (en)	2011-06-17	2012-12-20	Mannkind Corporation	High capacity diketopiperazine microparticles
US9233159B2 (en)	2011-10-24	2016-01-12	Mannkind Corporation	Methods and compositions for treating pain
RU2650035C2 (ru)	2012-07-12	2018-04-06	Маннкайнд Корпорейшн	Системы и способы доставки сухих порошковых лекарств
WO2014066856A1 (en)	2012-10-26	2014-05-01	Mannkind Corporation	Inhalable influenza vaccine compositions and methods
EP2970149B1 (en)	2013-03-15	2019-08-21	MannKind Corporation	Microcrystalline diketopiperazine compositions and methods
MX2020009878A (es)	2013-07-18	2022-07-27	Mannkind Corp	Composiciones farmaceuticas en polvo seco estables al calor y metodos.
CA2920488C (en)	2013-08-05	2022-04-26	Mannkind Corporation	Insufflation apparatus and methods
WO2015148905A1 (en)	2014-03-28	2015-10-01	Mannkind Corporation	Use of ultrarapid acting insulin
US10561806B2 (en)	2014-10-02	2020-02-18	Mannkind Corporation	Mouthpiece cover for an inhaler
US11359267B2 (en)	2017-02-21	2022-06-14	Jfe Steel Corporation	High-carbon hot-rolled steel sheet and method for manufacturing the same
GB201917723D0 (en)	2019-12-04	2020-01-15	Nv Rose Llc	Stable liquid formulations of glucagon-like peptide 1 or analogues thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5545618A (en) *	1990-01-24	1996-08-13	Buckley; Douglas I.	GLP-1 analogs useful for diabetes treatment
DK36492D0 (da) *	1992-03-19	1992-03-19	Novo Nordisk As	Praeparat
NZ250844A (en) *	1993-04-07	1996-03-26	Pfizer	Treatment of non-insulin dependant diabetes with peptides; composition
US5512549A (en) *	1994-10-18	1996-04-30	Eli Lilly And Company	Glucagon-like insulinotropic peptide analogs, compositions, and methods of use
UA72181C2 (ru) *	1996-08-30	2005-02-15	Ново Нордіск А/С	Translated By PlajПРОИЗВОДНЫЕ ГЛЮКАГОНООБРАЗНОГО ПЕПТИДА-1
UA65549C2 (ru) *	1996-11-05	2004-04-15	Елі Ліллі Енд Компані	Применение аналогов и производных glp-1 для периферического введения для борьбы с ожирением
EP1019031A4 (en) *	1997-07-18	2003-02-05	Infimed Inc	BIODEGRADABLE MACROMERS FOR THE REGULATED RELEASE OF BIOLOGICALLY ACTIVE SUBSTANCES

1999
- 1999-08-24 AU AU55841/99A patent/AU764371B2/en not_active Ceased
- 1999-08-24 AR ARP990104231A patent/AR022368A1/es unknown
- 1999-08-24 JP JP2000567230A patent/JP2002523466A/ja not_active Withdrawn
- 1999-08-24 IL IL14124199A patent/IL141241A0/xx unknown
- 1999-08-24 CN CN99810174A patent/CN1314818A/zh active Pending
- 1999-08-24 PL PL99346317A patent/PL346317A1/xx not_active Application Discontinuation
- 1999-08-24 EA EA200100289A patent/EA200100289A1/ru unknown
- 1999-08-24 KR KR1020017002518A patent/KR20010073033A/ko not_active Application Discontinuation
- 1999-08-24 TR TR2001/00600T patent/TR200100600T2/xx unknown
- 1999-08-24 CZ CZ2001690A patent/CZ2001690A3/cs unknown
- 1999-08-24 BR BR9913284-2A patent/BR9913284A/pt not_active IP Right Cessation
- 1999-08-24 CA CA002341454A patent/CA2341454A1/en not_active Abandoned
- 1999-08-24 CO CO99053457A patent/CO5090908A1/es unknown
- 1999-08-24 HU HU0103369A patent/HUP0103369A3/hu unknown
- 1999-08-24 WO PCT/US1999/019348 patent/WO2000012116A1/en not_active Application Discontinuation
- 1999-08-25 PE PE1999000857A patent/PE20001031A1/es not_active Application Discontinuation
- 1999-08-25 EP EP99306733A patent/EP0997151B1/en not_active Revoked
- 1999-08-25 AT AT99306733T patent/ATE347902T1/de not_active IP Right Cessation
- 1999-08-25 DE DE69934380T patent/DE69934380D1/de not_active Expired - Lifetime
2001
- 2001-02-27 NO NO20010982A patent/NO20010982L/no not_active Application Discontinuation
- 2001-02-27 HR HR20010141A patent/HRP20010141A2/hr not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1314818A (zh)	2001-09-26
DE69934380D1 (de)	2007-01-25
EP0997151A3 (en)	2000-09-20
AR022368A1 (es)	2002-09-04
EA200100289A1 (ru)	2001-10-22
CA2341454A1 (en)	2000-03-09
NO20010982D0 (no)	2001-02-27
EP0997151B1 (en)	2006-12-13
ATE347902T1 (de)	2007-01-15
NO20010982L (no)	2001-04-27
IL141241A0 (en)	2002-03-10
PL346317A1 (en)	2002-01-28
KR20010073033A (ko)	2001-07-31
HUP0103369A2 (hu)	2002-02-28
BR9913284A (pt)	2001-05-15
TR200100600T2 (tr)	2001-07-23
AU764371B2 (en)	2003-08-14
WO2000012116A1 (en)	2000-03-09
JP2002523466A (ja)	2002-07-30
EP0997151A2 (en)	2000-05-03
PE20001031A1 (es)	2000-10-12
AU5584199A (en)	2000-03-21
HUP0103369A3 (en)	2002-03-28
CZ2001690A3 (cs)	2002-04-17
CO5090908A1 (es)	2001-10-30

Legal Events

Date	Code	Title	Description
2002-02-28	A1OB	Publication of a patent application
2004-09-10	OBST	Application withdrawn

Publication	Publication Date	Title
US6720407B1 (en)	2004-04-13	Method for administering insulinotropic peptides
AU764371B2 (en)	2003-08-14	Method for administering insulinotropic peptides
US6335316B1 (en)	2002-01-01	Method for administering acylated insulin
AU747619B2 (en)	2002-05-16	Method for administering ASPB28-human insulin
KR100419037B1 (ko)	2004-06-12	폐를통한인슐린의전달방법및그조성물
US20050043228A1 (en)	2005-02-24	Glp-1 formulations with protracted time action
WO2000064940A1 (en)	2000-11-02	Insulin crystals for pulmonary administration
JP2003519664A (ja)	2003-06-24	Ｇｌｐ−１誘導体の経上皮送達
WO2001000674A1 (en)	2001-01-04	Insulin crystals for pulmonary administration
EP1666054A1 (en)	2006-06-07	Method for administering insulinotropic peptides
MXPA01001905A (en)	2001-11-21	Method for administering insulinotropic peptides
US20040214747A1 (en)	2004-10-28	Method for administering monomeric insulin
WO2004054606A1 (en)	2004-07-01	Method of decreasing hepatic glucose output in diabetic patients
MXPA00006645A (en)	2001-07-03	Method for administering aspb28-human insulin
MXPA00006644A (en)	2001-07-03	Method for administering monomeric insulin analogs
ZA200101541B (en)	2002-05-23	Method for administering insulinotropic peptides.