SK11142002A3 - Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 - Google Patents

Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 Download PDF

Info

Publication number: SK11142002A3
Authority: SK; Slovakia
Prior art keywords: composition; dry powder; pulmonary inhalation; surfactant; polysorbate
Prior art date: 1999-12-30

Application number

SK1114-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Bao-Lu Chen

Maninder Hora

Original Assignee

Chiron Corporation

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.)

1999-12-30

Filing date

2000-12-27

Publication date

2004-09-08

2000-12-27 Application filed by Chiron Corporation filed Critical Chiron Corporation

2004-09-08 Publication of SK11142002A3 publication Critical patent/SK11142002A3/sk

Links

108010002350 Interleukin-2 Proteins 0.000 title claims abstract description 208
102000000588 Interleukin-2 Human genes 0.000 title claims abstract description 208
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 82
239000000203 mixture Substances 0.000 claims abstract description 207
230000002685 pulmonary effect Effects 0.000 claims abstract description 80
239000000843 powder Substances 0.000 claims abstract description 73
238000000034 method Methods 0.000 claims abstract description 70
239000004094 surface-active agent Substances 0.000 claims abstract description 45
238000010521 absorption reaction Methods 0.000 claims abstract description 27
239000000725 suspension Substances 0.000 claims abstract description 15
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 59
229920000053 polysorbate 80 Polymers 0.000 claims description 59
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 41
229940068968 polysorbate 80 Drugs 0.000 claims description 41
239000007788 liquid Substances 0.000 claims description 24
239000003814 drug Substances 0.000 claims description 23
239000002245 particle Substances 0.000 claims description 22
150000001413 amino acids Chemical class 0.000 claims description 19
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 19
239000004475 Arginine Substances 0.000 claims description 18
239000007900 aqueous suspension Substances 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 18
239000007864 aqueous solution Substances 0.000 claims description 17
230000001965 increasing effect Effects 0.000 claims description 15
239000000243 solution Substances 0.000 claims description 15
239000007921 spray Substances 0.000 claims description 15
229940071648 metered dose inhaler Drugs 0.000 claims description 14
239000000178 monomer Substances 0.000 claims description 14
239000006199 nebulizer Substances 0.000 claims description 13
239000004067 bulking agent Substances 0.000 claims description 10
239000000872 buffer Substances 0.000 claims description 9
235000000346 sugar Nutrition 0.000 claims description 8
229920001213 Polysorbate 20 Polymers 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 7
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 7
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 7
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 claims description 6
229930006000 Sucrose Natural products 0.000 claims description 6
229940112141 dry powder inhaler Drugs 0.000 claims description 6
229940068977 polysorbate 20 Drugs 0.000 claims description 6
239000005720 sucrose Substances 0.000 claims description 6
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 claims 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 claims description 3
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 claims description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
239000004472 Lysine Substances 0.000 claims description 3
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 claims description 3
UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose 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[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 claims 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 claims description 3
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 claims 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 claims description 3
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 claims description 3
239000000600 sorbitol Substances 0.000 claims description 3
UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose 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[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 claims description 3
102000015696 Interleukins Human genes 0.000 claims description 2
108010063738 Interleukins Proteins 0.000 claims description 2
229940124597 therapeutic agent Drugs 0.000 claims 1
238000002716 delivery method Methods 0.000 abstract 1
108090000765 processed proteins & peptides Proteins 0.000 description 64
102000004196 processed proteins & peptides Human genes 0.000 description 61
238000009472 formulation Methods 0.000 description 58
229920001184 polypeptide Polymers 0.000 description 54
238000007920 subcutaneous administration Methods 0.000 description 52
108090000623 proteins and genes Proteins 0.000 description 32
235000018102 proteins Nutrition 0.000 description 30
102000004169 proteins and genes Human genes 0.000 description 30
239000000443 aerosol Substances 0.000 description 22
235000001014 amino acid Nutrition 0.000 description 22
241001465754 Metazoa Species 0.000 description 20
108700025316 aldesleukin Proteins 0.000 description 20
125000003275 alpha amino acid group Chemical group 0.000 description 20
229940087463 proleukin Drugs 0.000 description 20
235000009697 arginine Nutrition 0.000 description 17
210000004072 lung Anatomy 0.000 description 16
241000700159 Rattus Species 0.000 description 14
239000000126 substance Substances 0.000 description 13
239000002253 acid Substances 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
150000003839 salts Chemical class 0.000 description 12
239000007787 solid Substances 0.000 description 12
230000000694 effects Effects 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 9
230000004071 biological effect Effects 0.000 description 9
239000003381 stabilizer Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
125000000539 amino acid group Chemical group 0.000 description 8
239000002585 base Substances 0.000 description 8
230000004048 modification Effects 0.000 description 8
238000012986 modification Methods 0.000 description 8
230000001225 therapeutic effect Effects 0.000 description 8
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 7
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 7
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
229930182817 methionine Natural products 0.000 description 7
230000036470 plasma concentration Effects 0.000 description 7
229920001223 polyethylene glycol Polymers 0.000 description 7
241000282414 Homo sapiens Species 0.000 description 6
239000012634 fragment Substances 0.000 description 6
229920001993 poloxamer 188 Polymers 0.000 description 6
230000009885 systemic effect Effects 0.000 description 6
-1 vapor Substances 0.000 description 6
CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 5
239000004471 Glycine Substances 0.000 description 5
229940044519 poloxamer 188 Drugs 0.000 description 5
238000001694 spray drying Methods 0.000 description 5
238000003860 storage Methods 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
238000011282 treatment Methods 0.000 description 5
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
241000124008 Mammalia Species 0.000 description 4
229930195725 Mannitol Natural products 0.000 description 4
230000037396 body weight Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
229940079593 drug Drugs 0.000 description 4
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 4
238000001990 intravenous administration Methods 0.000 description 4
239000000594 mannitol Substances 0.000 description 4
235000010355 mannitol Nutrition 0.000 description 4
239000002773 nucleotide Substances 0.000 description 4
125000003729 nucleotide group Chemical group 0.000 description 4
229920000136 polysorbate Polymers 0.000 description 4
230000008569 process Effects 0.000 description 4
238000011160 research Methods 0.000 description 4
238000010254 subcutaneous injection Methods 0.000 description 4
239000007929 subcutaneous injection Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 3
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 3
101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 3
108091028043 Nucleic acid sequence Proteins 0.000 description 3
229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000008901 benefit Effects 0.000 description 3
239000006172 buffering agent Substances 0.000 description 3
239000012876 carrier material Substances 0.000 description 3
238000012217 deletion Methods 0.000 description 3
230000037430 deletion Effects 0.000 description 3
210000000981 epithelium Anatomy 0.000 description 3
239000012530 fluid Substances 0.000 description 3
238000004108 freeze drying Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000006193 liquid solution Substances 0.000 description 3
239000006194 liquid suspension Substances 0.000 description 3
210000000214 mouth Anatomy 0.000 description 3
239000001509 sodium citrate Substances 0.000 description 3
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
241001227713 Chiron Species 0.000 description 2
239000004338 Dichlorodifluoromethane Substances 0.000 description 2
102400000686 Endothelin-1 Human genes 0.000 description 2
101800004490 Endothelin-1 Proteins 0.000 description 2
102000003951 Erythropoietin Human genes 0.000 description 2
108090000394 Erythropoietin Proteins 0.000 description 2
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 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
102000004877 Insulin Human genes 0.000 description 2
108090001061 Insulin Proteins 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
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 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
238000012387 aerosolization Methods 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
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 2
239000003833 bile salt Substances 0.000 description 2
229940093761 bile salts Drugs 0.000 description 2
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
238000004364 calculation method Methods 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000012377 drug delivery Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
229940105423 erythropoietin Drugs 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
230000013595 glycosylation Effects 0.000 description 2
238000006206 glycosylation reaction Methods 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
230000010224 hepatic metabolism Effects 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229940125396 insulin Drugs 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
238000011835 investigation Methods 0.000 description 2
239000012669 liquid formulation Substances 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
235000018977 lysine Nutrition 0.000 description 2
239000003226 mitogen Substances 0.000 description 2
230000035772 mutation Effects 0.000 description 2
108020004707 nucleic acids Proteins 0.000 description 2
102000039446 nucleic acids Human genes 0.000 description 2
150000007523 nucleic acids Chemical class 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
229950008882 polysorbate Drugs 0.000 description 2
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
239000003380 propellant Substances 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
238000012360 testing method Methods 0.000 description 2
239000004474 valine Substances 0.000 description 2
235000014393 valine Nutrition 0.000 description 2
229940070384 ventolin Drugs 0.000 description 2
239000008215 water for injection Substances 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
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-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
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
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 1
QCWJKJLNCFEVPQ-WHFBIAKZSA-N Asn-Gln Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O QCWJKJLNCFEVPQ-WHFBIAKZSA-N 0.000 description 1
CKAJHWFHHFSCDT-WHFBIAKZSA-N Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O CKAJHWFHHFSCDT-WHFBIAKZSA-N 0.000 description 1
239000004604 Blowing Agent Substances 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
241000206602 Eukaryota Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
VPZXBVLAVMBEQI-VKHMYHEASA-N Glycyl-alanine Chemical compound OC(=O)[C@H](C)NC(=O)CN VPZXBVLAVMBEQI-VKHMYHEASA-N 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000037357 HIV infectious disease Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
102000002265 Human Growth Hormone Human genes 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
239000000854 Human Growth Hormone Substances 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
102000008070 Interferon-gamma Human genes 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
208000008839 Kidney Neoplasms Diseases 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
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 1
NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
108010079364 N-glycylalanine Proteins 0.000 description 1
206010028980 Neoplasm Diseases 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
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108010043958 Peptoids Proteins 0.000 description 1
241000577979 Peromyscus spicilegus Species 0.000 description 1
APECKGGXAXNFLL-RNXOBYDBSA-N Phe-Trp-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 APECKGGXAXNFLL-RNXOBYDBSA-N 0.000 description 1
108010089814 Plant Lectins Proteins 0.000 description 1
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
241000288906 Primates Species 0.000 description 1
239000004365 Protease Substances 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
239000004147 Sorbitan trioleate Substances 0.000 description 1
241000282887 Suidae Species 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
230000006052 T cell proliferation Effects 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
206010054094 Tumour necrosis Diseases 0.000 description 1
108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
102400000015 Vasoactive intestinal peptide Human genes 0.000 description 1
TTZKGYULRVDFJJ-GIVMLJSASA-N [(2r)-2-[(2s,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-[(z)-octadec-9-enoyl]oxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1O TTZKGYULRVDFJJ-GIVMLJSASA-N 0.000 description 1
238000005299 abrasion Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000004931 aggregating effect Effects 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000013011 aqueous formulation Substances 0.000 description 1
230000001174 ascending effect Effects 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
108010038633 aspartylglutamate Proteins 0.000 description 1
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 1
230000015572 biosynthetic process Effects 0.000 description 1
230000007883 bronchodilation Effects 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
238000012937 correction Methods 0.000 description 1
229960000265 cromoglicic acid Drugs 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000000151 deposition Methods 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000013538 functional additive Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
RVRCFVVLDHTFFA-UHFFFAOYSA-N heptasodium;tungsten;nonatriacontahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[W].[W].[W].[W].[W].[W].[W].[W].[W].[W].[W] RVRCFVVLDHTFFA-UHFFFAOYSA-N 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
102000055277 human IL2 Human genes 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
230000004073 interleukin-2 production Effects 0.000 description 1
VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
229960002725 isoflurane Drugs 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
201000010982 kidney cancer Diseases 0.000 description 1
239000008101 lactose Substances 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000008263 liquid aerosol Substances 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229940127554 medical product Drugs 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
208000021039 metastatic melanoma Diseases 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
239000000693 micelle Substances 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000003595 mist Substances 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
229960002969 oleic acid Drugs 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
239000008363 phosphate buffer 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
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
239000003726 plant lectin Substances 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229960000502 poloxamer Drugs 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
235000019419 proteases Nutrition 0.000 description 1
230000004853 protein function Effects 0.000 description 1
238000011552 rat model Methods 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000002864 sequence alignment Methods 0.000 description 1
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate 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-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].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 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
VMSNAUAEKXEYGP-YEUHZSMFSA-M sodium glycodeoxycholate Chemical compound [Na+].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)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 VMSNAUAEKXEYGP-YEUHZSMFSA-M 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 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
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
229940083466 soybean lecithin Drugs 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
238000004544 sputter deposition Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008362 succinate buffer Substances 0.000 description 1
150000005846 sugar alcohols Chemical class 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000008961 swelling Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
210000003437 trachea Anatomy 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
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
230000009452 underexpressoin Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1
210000005253 yeast cell Anatomy 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
- A61K9/0075—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
- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Otolaryngology (AREA)
General Chemical & Material Sciences (AREA)
Pulmonology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Immunology (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Oil, Petroleum & Natural Gas (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK1114-2002A 1999-12-30 2000-12-27 Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 SK11142002A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US17392299P	1999-12-30	1999-12-30
US72481000A	2000-11-28	2000-11-28
PCT/US2000/035452 WO2001049274A2 (en)	1999-12-30	2000-12-27	Methods for pulmonary delivery of interleukin-2

Publications (1)

Publication Number	Publication Date
SK11142002A3 true SK11142002A3 (sk)	2004-09-08

Family

ID=26869690

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1114-2002A SK11142002A3 (sk)	1999-12-30	2000-12-27	Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2

Country Status (15)

Country	Link
US (2)	US20030198602A1 (de)
EP (1)	EP1244432A2 (de)
JP (1)	JP2003519175A (de)
CN (1)	CN100333790C (de)
AU (1)	AU783795B2 (de)
BR (1)	BR0016879A (de)
CA (1)	CA2395887A1 (de)
CZ (1)	CZ20022265A3 (de)
HU (1)	HUP0204136A3 (de)
IL (2)	IL150461A0 (de)
NO (1)	NO20023123L (de)
NZ (1)	NZ520379A (de)
PL (1)	PL356641A1 (de)
SK (1)	SK11142002A3 (de)
WO (1)	WO2001049274A2 (de)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030113271A1 (en) *	1997-01-29	2003-06-19	University Technology Corporation	Formulations for pulmonary delivery
US20060171899A1 (en) *	1998-12-10	2006-08-03	Akwete Adjei	Water-stabilized aerosol formulation system and method of making
US9006175B2 (en)	1999-06-29	2015-04-14	Mannkind Corporation	Potentiation of glucose elimination
JP2003524646A (ja) *	2000-01-25	2003-08-19	エアロファームテクノロジーインコーポレイテッド	医薬エアゾール製剤
JP4147234B2 (ja) *	2004-09-27	2008-09-10	キヤノン株式会社	吐出用液体、吐出方法、カートリッジ及び吐出装置
WO2003035051A2 (en) *	2001-10-19	2003-05-01	Inhale Therapeutic Systems, Inc.	The use of proton sequestering agents in drug formulations
ATE385193T1 (de)	2002-03-20	2008-02-15	Mannkind Corp	Inhalationsgerät
JP5057648B2 (ja) *	2002-09-26	2012-10-24	塩野義製薬株式会社	安定化されたタンパク組成物
EP1803445A3 (de) *	2003-01-08	2007-11-21	Novartis Vaccines and Diagnostics, Inc.	Stabilisierte lyophilisierte Zubereitungen mit Gewebefaktor-Inhibitor (TFPI) oder Varianten des Gewebefaktor-Inhibitors
CA2512680A1 (en) *	2003-01-08	2004-07-29	Chiron Corporation	Stabilized lyophilized compositions comprising tissue factor pathway inhibitor or tissue factor pathway inhibitor variants
BRPI0514263B8 (pt)	2004-08-20	2021-05-25	Mannkind Corp	método para a síntese de bis-3,6-[4-aminobutil]-2,5-dicetopiperazina n-protegida
CN104436170B (zh)	2004-08-23	2018-02-23	曼金德公司	用于药物输送的二酮哌嗪盐
JP4147235B2 (ja) *	2004-09-27	2008-09-10	キヤノン株式会社	吐出用液体、吐出方法、液滴化方法、液体吐出カートリッジ及び吐出装置
WO2006130943A1 (en) *	2005-06-10	2006-12-14	The Governors Of The University Of Alberta	Respirable dried powder formulation comprising drug loaded nanoparticles
AU2006290870B2 (en) *	2005-09-14	2013-02-28	Mannkind Corporation	Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces
TWI299993B (en) *	2005-12-15	2008-08-21	Dev Center Biotechnology	Aqueous inhalation pharmaceutical composition
JP5599975B2 (ja)	2006-02-22	2014-10-01	マンカインドコーポレイション	ジケトピペラジン及び活性薬剤を含有する微粒子の製剤特性の改善方法
CN101125199B (zh) *	2006-08-15	2010-07-21	北京四环生物制药有限公司	白介素2作为制备治疗鼻炎药物的应用
US8499757B2 (en)	2008-06-13	2013-08-06	Mannkind Corporation	Dry powder inhaler and system for drug delivery
US8485180B2 (en)	2008-06-13	2013-07-16	Mannkind Corporation	Dry powder drug delivery system
ES2904623T3 (es)	2008-06-20	2022-04-05	Mannkind Corp	Aparato interactivo para establecer un perfil en tiempo real de esfuerzos de inhalación
TWI614024B (zh)	2008-08-11	2018-02-11	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
US8538707B2 (en)	2009-03-11	2013-09-17	Mannkind Corporation	Apparatus, system and method for measuring resistance of an inhaler
RU2509555C2 (ru)	2009-06-12	2014-03-20	Маннкайнд Корпорейшн	Микрочастицы дикетопиперазина с определенными удельными площадями поверхности
CA2778698A1 (en)	2009-11-03	2011-05-12	Mannkind Corporation	An apparatus and method for simulating inhalation efforts
MX359281B (es)	2010-06-21	2018-09-21	Mannkind Corp	Sistema y metodos para suministrar un farmaco en polvo seco.
US8925726B2 (en)	2011-04-01	2015-01-06	Mannkind Corporation	Blister package for pharmaceutical cartridges
WO2012174472A1 (en)	2011-06-17	2012-12-20	Mannkind Corporation	High capacity diketopiperazine microparticles
EP2550863A1 (de) *	2011-07-27	2013-01-30	Bayer Intellectual Property GmbH	Aktivstoffhaltige Partikel auf Polyacrylat-Basis
BR112014009686A2 (pt)	2011-10-24	2018-08-07	Mannkind Corp	composição analgésica inalável, pó seco e método para tratar dor
MX354163B (es)	2012-07-12	2018-02-15	Mannkind Corp	Sistemas y métodos de suministro de fármaco en polvo seco.
EP2911690A1 (de)	2012-10-26	2015-09-02	MannKind Corporation	Inhalierbare influenza-impfstoffzusammensetzungen und verfahren
SG10201708090TA (en)	2013-03-15	2017-11-29	Mannkind Corp	Microcrystalline diketopiperazine compositions and methods
KR102321339B1 (ko)	2013-07-18	2021-11-02	맨카인드 코포레이션	열-안정성 건조 분말 약제학적 조성물 및 방법
CA2920488C (en)	2013-08-05	2022-04-26	Mannkind Corporation	Insufflation apparatus and methods
US10307464B2 (en)	2014-03-28	2019-06-04	Mannkind Corporation	Use of ultrarapid acting insulin
US10561806B2 (en)	2014-10-02	2020-02-18	Mannkind Corporation	Mouthpiece cover for an inhaler
US9585835B1 (en) *	2015-09-16	2017-03-07	Sansa Corporation (Barbados) Inc.	Inhalable nicotine formulations and methods of making and using the same
US11224594B2 (en) *	2015-09-16	2022-01-18	Philip Morris Products S.A.	Nicotine formulations and methods of making and using the same
WO2017068031A1 (en) *	2015-10-22	2017-04-27	Iltoo Pharma	Pharmaceutical compositions of il-2
MX385972B (es) *	2016-06-30	2025-03-18	Philip Morris Products Sa	Partículas y composiciones de nicotina.
AU2017350817B2 (en)	2016-10-25	2022-07-21	Marquette University	Storage media and powder formulations for avulsed teeth and explanted tissues comprising fibroblasts
BR112022022764A2 (pt) *	2020-05-11	2023-01-17	Alkermes Pharma Ireland Ltd	Composições de polipeptídeo de fusão de il-2 e métodos para fazer e usar as mesmas
WO2022087458A1 (en)	2020-10-23	2022-04-28	Asher Biotherapeutics, Inc.	Fusions with cd8 antigen binding molecules for modulating immune cell function
TW202227122A (zh) *	2020-11-13	2022-07-16	大陸商江蘇恆瑞醫藥股份有限公司	一種包含人白細胞介素２變體或其衍生物的醫藥組成物及其用途
CN121466042A (zh) *	2026-01-09	2026-02-06	苏州市立医院	一种吸入用药物组合物及其用途

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4604377A (en) *	1984-03-28	1986-08-05	Cetus Corporation	Pharmaceutical compositions of microbially produced interleukin-2
US5037644A (en) *	1986-10-27	1991-08-06	Cetus Corporation	Pharmaceutical compositions of recombinant interleukin-2 and formulation processes
US4927850A (en) *	1988-04-08	1990-05-22	Bayless Robert K	Antioxidant compositions and methods for ameliorating inflammatory symptoms of respiratory disease
US5078997A (en) *	1988-07-13	1992-01-07	Cetus Corporation	Pharmaceutical composition for interleukin-2 containing physiologically compatible stabilizers
US5780012A (en) *	1990-06-21	1998-07-14	Huland; Edith	Method for reducing lung afflictions by inhalation of cytokine solutions
EP0462305B1 (de) *	1990-06-21	1994-11-02	Huland, Edith, Dr. Dr.	Verwendung zytokinhaltiger Aerosole und zytokinhaltige Aerosole selbst
JP3507486B2 (ja) *	1991-03-15	2004-03-15	アムジエン・インコーポレーテツド	顆粒球コロニー刺激因子の肺内投与
US5354934A (en) *	1993-02-04	1994-10-11	Amgen Inc.	Pulmonary administration of erythropoietin
EP0710102A1 (de) *	1993-07-19	1996-05-08	Amgen Inc.	Stabilisierung von proteinen in aerosolform
EP1462096B1 (de) *	1994-03-07	2008-12-10	Nektar Therapeutics	Verfahren und Zusammensetzung für die pulmonale Darreichung von Insulin
US5985309A (en) *	1996-05-24	1999-11-16	Massachusetts Institute Of Technology	Preparation of particles for inhalation
US5874064A (en) *	1996-05-24	1999-02-23	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
US5855913A (en) *	1997-01-16	1999-01-05	Massachusetts Instite Of Technology	Particles incorporating surfactants for pulmonary drug delivery
HUP0203133A3 (en) *	1999-10-04	2005-07-28	Chiron Corp Emeryville	Stabilized liquid polypeptide-containing pharmaceutical compositions

2000
- 2000-12-27 EP EP00989539A patent/EP1244432A2/de not_active Withdrawn
- 2000-12-27 CA CA002395887A patent/CA2395887A1/en not_active Abandoned
- 2000-12-27 AU AU26037/01A patent/AU783795B2/en not_active Ceased
- 2000-12-27 SK SK1114-2002A patent/SK11142002A3/sk not_active Application Discontinuation
- 2000-12-27 HU HU0204136A patent/HUP0204136A3/hu unknown
- 2000-12-27 BR BR0016879-3A patent/BR0016879A/pt not_active IP Right Cessation
- 2000-12-27 WO PCT/US2000/035452 patent/WO2001049274A2/en not_active Ceased
- 2000-12-27 IL IL15046100A patent/IL150461A0/xx active IP Right Grant
- 2000-12-27 JP JP2001549642A patent/JP2003519175A/ja active Pending
- 2000-12-27 CZ CZ20022265A patent/CZ20022265A3/cs unknown
- 2000-12-27 PL PL00356641A patent/PL356641A1/xx not_active Application Discontinuation
- 2000-12-27 CN CNB008192537A patent/CN100333790C/zh not_active Expired - Fee Related
- 2000-12-27 NZ NZ520379A patent/NZ520379A/en unknown
2002
- 2002-06-27 NO NO20023123A patent/NO20023123L/no not_active Application Discontinuation
- 2002-06-27 IL IL150461A patent/IL150461A/en not_active IP Right Cessation
2003
- 2003-04-07 US US10/408,648 patent/US20030198602A1/en not_active Abandoned
2007
- 2007-07-10 US US11/827,086 patent/US20080003294A1/en not_active Abandoned

Also Published As

Publication number	Publication date
US20080003294A1 (en)	2008-01-03
WO2001049274A3 (en)	2002-02-14
CN1437466A (zh)	2003-08-20
JP2003519175A (ja)	2003-06-17
EP1244432A2 (de)	2002-10-02
BR0016879A (pt)	2002-12-03
HUP0204136A3 (en)	2005-09-28
CN100333790C (zh)	2007-08-29
NO20023123L (no)	2002-08-07
NZ520379A (en)	2004-05-28
NO20023123D0 (no)	2002-06-27
IL150461A (en)	2008-11-26
HUP0204136A2 (hu)	2003-03-28
US20030198602A1 (en)	2003-10-23
PL356641A1 (en)	2004-06-28
WO2001049274A2 (en)	2001-07-12
CA2395887A1 (en)	2001-07-12
AU2603701A (en)	2001-07-16
CZ20022265A3 (cs)	2004-01-14
AU783795B2 (en)	2005-12-08
IL150461A0 (en)	2002-12-01

Legal Events

Date	Code	Title	Description
2011-05-06	FC9A	Refused patent application

Publication	Publication Date	Title
AU783795B2 (en)	2005-12-08	Methods for pulmonary delivery of interleukin-2
JP4338214B2 (ja)	2009-10-07	エリトロポエチンの肺投与
US6565841B1 (en)	2003-05-20	Pulmonary administration of granulocyte colony stimulating factor
US7300919B2 (en)	2007-11-27	Pulmonary delivery of active fragments of parathyroid hormone
EP0505123B1 (de)	1997-01-08	Verabreichung von G-CSF über die Lungen
US6737045B2 (en)	2004-05-18	Methods and compositions for the pulmonary delivery insulin
EP0477386A1 (de)	1992-04-01	Aerosolformulierung feste polypeptid mikroteilchen enthaltend und verfahren zu ihrer herstellung.
US20090203576A1 (en)	2009-08-13	Methods and compositons for pulmonary delivery of insulin
Siekmeier et al.	2009	Treatment of systemic diseases by inhalation of biomolecule aerosols
AU2006200923A1 (en)	2006-03-30	Methods for pulmonary delivery of interleukin-2
CN1853725A (zh)	2006-11-01	白细胞介素－2经肺部的输递方法