AU2005221151A1 - Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor - Google Patents
Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor Download PDFInfo
- Publication number
- AU2005221151A1 AU2005221151A1 AU2005221151A AU2005221151A AU2005221151A1 AU 2005221151 A1 AU2005221151 A1 AU 2005221151A1 AU 2005221151 A AU2005221151 A AU 2005221151A AU 2005221151 A AU2005221151 A AU 2005221151A AU 2005221151 A1 AU2005221151 A1 AU 2005221151A1
- Authority
- AU
- Australia
- Prior art keywords
- aat
- active portion
- functionally active
- unglycosylated
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 title claims description 79
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title claims description 20
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title claims description 15
- 238000011282 treatment Methods 0.000 title description 27
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 305
- 229940024142 alpha 1-antitrypsin Drugs 0.000 claims description 289
- 239000000203 mixture Substances 0.000 claims description 160
- 238000000034 method Methods 0.000 claims description 131
- -1 halide salt Chemical class 0.000 claims description 47
- 239000007788 liquid Substances 0.000 claims description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 33
- 239000000843 powder Substances 0.000 claims description 31
- 239000000779 smoke Substances 0.000 claims description 31
- 210000004072 lung Anatomy 0.000 claims description 30
- 235000019504 cigarettes Nutrition 0.000 claims description 22
- 239000003112 inhibitor Substances 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 241000208125 Nicotiana Species 0.000 claims description 18
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 18
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 claims description 17
- 239000011780 sodium chloride Substances 0.000 claims description 17
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 claims description 16
- 229940124630 bronchodilator Drugs 0.000 claims description 14
- 150000001720 carbohydrates Chemical class 0.000 claims description 14
- 239000003246 corticosteroid Substances 0.000 claims description 14
- 229940071648 metered dose inhaler Drugs 0.000 claims description 14
- 239000011159 matrix material Substances 0.000 claims description 9
- 239000006199 nebulizer Substances 0.000 claims description 9
- 102000005741 Metalloproteases Human genes 0.000 claims description 8
- 108010006035 Metalloproteases Proteins 0.000 claims description 8
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 claims description 8
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 claims description 8
- 150000003841 chloride salts Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 102100026261 Metalloproteinase inhibitor 3 Human genes 0.000 claims description 6
- 102100024289 Metalloproteinase inhibitor 4 Human genes 0.000 claims description 6
- 108050006579 Metalloproteinase inhibitor 4 Proteins 0.000 claims description 6
- 108010031429 Tissue Inhibitor of Metalloproteinase-3 Proteins 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 6
- 229940112141 dry powder inhaler Drugs 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 4
- NITYDPDXAAFEIT-DYVFJYSZSA-N ilomastat Chemical compound C1=CC=C2C(C[C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)CC(=O)NO)=CNC2=C1 NITYDPDXAAFEIT-DYVFJYSZSA-N 0.000 claims description 3
- 229960003696 ilomastat Drugs 0.000 claims description 3
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 claims 36
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 270
- 150000001413 amino acids Chemical group 0.000 description 35
- 102000004169 proteins and genes Human genes 0.000 description 35
- 108090000623 proteins and genes Proteins 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 34
- 206010014561 Emphysema Diseases 0.000 description 33
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 29
- 230000004927 fusion Effects 0.000 description 29
- 238000009472 formulation Methods 0.000 description 28
- 239000002245 particle Substances 0.000 description 25
- 108020001507 fusion proteins Proteins 0.000 description 24
- 102000037865 fusion proteins Human genes 0.000 description 24
- 101000615334 Homo sapiens Antileukoproteinase Proteins 0.000 description 22
- 102000035195 Peptidases Human genes 0.000 description 21
- 108091005804 Peptidases Proteins 0.000 description 21
- 239000004365 Protease Substances 0.000 description 21
- 102100021253 Antileukoproteinase Human genes 0.000 description 20
- 101000879712 Streptomyces lividans Protease inhibitor Proteins 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 238000004108 freeze drying Methods 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 14
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 14
- 238000001035 drying Methods 0.000 description 14
- 235000000346 sugar Nutrition 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 11
- 229960004308 acetylcysteine Drugs 0.000 description 11
- 235000014633 carbohydrates Nutrition 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 238000011321 prophylaxis Methods 0.000 description 10
- 238000001694 spray drying Methods 0.000 description 9
- 238000003860 storage Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000000750 progressive effect Effects 0.000 description 8
- 230000002685 pulmonary effect Effects 0.000 description 8
- 150000008163 sugars Chemical class 0.000 description 8
- 230000007423 decrease Effects 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 108010088751 Albumins Proteins 0.000 description 6
- 102000009027 Albumins Human genes 0.000 description 6
- 102000004411 Antithrombin III Human genes 0.000 description 6
- 108090000935 Antithrombin III Proteins 0.000 description 6
- 229940122601 Esterase inhibitor Drugs 0.000 description 6
- 102000014702 Haptoglobin Human genes 0.000 description 6
- 108050005077 Haptoglobin Proteins 0.000 description 6
- 108010028275 Leukocyte Elastase Proteins 0.000 description 6
- 102100033174 Neutrophil elastase Human genes 0.000 description 6
- 229940122791 Plasmin inhibitor Drugs 0.000 description 6
- 229960005348 antithrombin iii Drugs 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000002329 esterase inhibitor Substances 0.000 description 6
- 229930182817 methionine Natural products 0.000 description 6
- 239000006187 pill Substances 0.000 description 6
- 239000002806 plasmin inhibitor Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000000391 smoking effect Effects 0.000 description 6
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 6
- 229940110309 tiotropium Drugs 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 108010067372 Pancreatic elastase Proteins 0.000 description 5
- 102000016387 Pancreatic elastase Human genes 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 230000007613 environmental effect Effects 0.000 description 5
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000007425 progressive decline Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical group SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- 102000012479 Serine Proteases Human genes 0.000 description 4
- 108010022999 Serine Proteases Proteins 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000000168 bronchodilator agent Substances 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 239000003172 expectorant agent Substances 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 229960001888 ipratropium Drugs 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 3
- 206010013975 Dyspnoeas Diseases 0.000 description 3
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical group CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 101000909992 Papio hamadryas Chymase Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108010082545 Secretory Leukocyte Peptidase Inhibitor Proteins 0.000 description 3
- 102000004002 Secretory Leukocyte Peptidase Inhibitor Human genes 0.000 description 3
- 208000032023 Signs and Symptoms Diseases 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 3
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 238000002663 nebulization Methods 0.000 description 3
- BULVZWIRKLYCBC-UHFFFAOYSA-N phorate Chemical compound CCOP(=S)(OCC)SCSCC BULVZWIRKLYCBC-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229940099982 prolastin Drugs 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229960002052 salbutamol Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 235000019505 tobacco product Nutrition 0.000 description 3
- 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 2
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 2
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 2
- 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 2
- 101710081722 Antitrypsin Proteins 0.000 description 2
- 101710110426 Aspartyl protease inhibitor Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108090000617 Cathepsin G Proteins 0.000 description 2
- 102100025975 Cathepsin G Human genes 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 102000015833 Cystatin Human genes 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 108700034637 EC 3.2.-.- Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108010026132 Gelatinases Proteins 0.000 description 2
- 102000013382 Gelatinases Human genes 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 101000741967 Homo sapiens Presequence protease, mitochondrial Proteins 0.000 description 2
- 102000001399 Kallikrein Human genes 0.000 description 2
- 108060005987 Kallikrein Proteins 0.000 description 2
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 2
- 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 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical group CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 2
- 102100038632 Presequence protease, mitochondrial Human genes 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 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 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 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 2
- 239000002253 acid Substances 0.000 description 2
- 238000012387 aerosolization Methods 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000003915 air pollution Methods 0.000 description 2
- 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 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001475 anti-trypsic effect Effects 0.000 description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 229940038528 aralast Drugs 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000003696 aspartic proteinase inhibitor Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 229960004436 budesonide Drugs 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 108050004038 cystatin Proteins 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 229940066493 expectorants Drugs 0.000 description 2
- 229960001022 fenoterol Drugs 0.000 description 2
- 229960002714 fluticasone Drugs 0.000 description 2
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 2
- 229960002848 formoterol Drugs 0.000 description 2
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 210000002175 goblet cell Anatomy 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 102000051410 human SLPI Human genes 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 229960005127 montelukast Drugs 0.000 description 2
- 230000000510 mucolytic effect Effects 0.000 description 2
- 229940066491 mucolytics Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 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 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 238000013125 spirometry Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 229940032528 zemaira Drugs 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GWNVDXQDILPJIG-CCHJCNDSSA-N 11-trans-Leukotriene C4 Chemical compound CCCCC\C=C/C\C=C\C=C\C=C\[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-CCHJCNDSSA-N 0.000 description 1
- RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 description 1
- 208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 description 1
- 241001156002 Anthonomus pomorum Species 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000010918 Cysteinyl leukotriene receptors Human genes 0.000 description 1
- 108050001116 Cysteinyl leukotriene receptors Proteins 0.000 description 1
- 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 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 101150014058 MMP1 gene Proteins 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- YPFLFUJKZDAXRA-UHFFFAOYSA-N [3-(carbamoylamino)-2-(2,4-dichlorobenzoyl)-1-benzofuran-6-yl] methanesulfonate Chemical group O1C2=CC(OS(=O)(=O)C)=CC=C2C(NC(N)=O)=C1C(=O)C1=CC=C(Cl)C=C1Cl YPFLFUJKZDAXRA-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009798 acute exacerbation Effects 0.000 description 1
- 235000016127 added sugars Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960003556 aminophylline Drugs 0.000 description 1
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 230000007883 bronchodilation Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical group COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 1
- 208000013116 chronic cough Diseases 0.000 description 1
- 229950001653 cilomilast Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 108700004333 collagenase 1 Proteins 0.000 description 1
- 229960003950 combination of corticosteroids Drugs 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000003869 coulometry Methods 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000005750 disease progression Effects 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
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000002849 elastaseinhibitory effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 231100000516 lung damage Toxicity 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229940124624 oral corticosteroid Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical compound CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
- 229960000797 oxitropium Drugs 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical group FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000007560 sedimentation technique Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 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
- 210000003934 vacuole Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- MWLSOWXNZPKENC-UHFFFAOYSA-N zileuton Chemical compound C1=CC=C2SC(C(N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-UHFFFAOYSA-N 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical group C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
- 229940052267 zyflo Drugs 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
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
- A24D1/00—Cigars; Cigarettes
- A24D1/002—Cigars; Cigarettes with additives, e.g. for flavouring
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
- A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
- A24D3/06—Use of materials for tobacco smoke filters
- A24D3/14—Use of materials for tobacco smoke filters of organic materials as additive
-
- 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
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Toxicology (AREA)
- Organic Chemistry (AREA)
- Materials Engineering (AREA)
- Otolaryngology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55185604P | 2004-03-09 | 2004-03-09 | |
| US60/551,856 | 2004-03-09 | ||
| PCT/US2005/007959 WO2005086915A2 (en) | 2004-03-09 | 2005-03-09 | Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2005221151A1 true AU2005221151A1 (en) | 2005-09-22 |
Family
ID=34976236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005221151A Abandoned AU2005221151A1 (en) | 2004-03-09 | 2005-03-09 | Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7914771B2 (enExample) |
| EP (1) | EP1737499A4 (enExample) |
| JP (1) | JP2007528409A (enExample) |
| AU (1) | AU2005221151A1 (enExample) |
| CA (1) | CA2559062A1 (enExample) |
| WO (1) | WO2005086915A2 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060257324A1 (en) | 2000-05-22 | 2006-11-16 | Chiesi Farmaceutici S.P.A. | Pharmaceutical solution formulations for pressurised metered dose inhalers |
| JP2007528409A (ja) * | 2004-03-09 | 2007-10-11 | アリバ ファーマシューティカルズ, インコーポレイテッド | プロテアーゼインヒビターの低用量吸入による慢性閉塞性肺疾患の処置 |
| US7973005B2 (en) * | 2006-02-09 | 2011-07-05 | Kamada Ltd. | Alpha-1 antitrypsin for treating exacerbation episodes of pulmonary diseases |
| WO2008053199A1 (en) * | 2006-10-30 | 2008-05-08 | Astrazeneca Ab | Combination therapy for the treatment of respiratory diseases |
| GB0716026D0 (en) * | 2007-08-16 | 2007-09-26 | Norton Healthcare Ltd | An inhalable medicament |
| UA124083C2 (uk) * | 2011-06-28 | 2021-07-21 | ІНГІБРЕКС, Інк. | Злитий серпіновий поліпептид і спосіб його застосування |
| US10400029B2 (en) | 2011-06-28 | 2019-09-03 | Inhibrx, Lp | Serpin fusion polypeptides and methods of use thereof |
| BR112013033801A2 (pt) | 2011-06-28 | 2017-12-19 | Inhibrx Llc | proteína de fusão isolada, e, método para tratar ou aliviar um sintoma de uma doença ou distúrbio inflamatórios |
| GB201200525D0 (en) | 2011-12-19 | 2012-02-29 | Teva Branded Pharmaceutical Prod R & D Inc | An inhalable medicament |
| EP2758065B1 (en) * | 2011-12-30 | 2021-06-23 | Grifols, S.A. | Alpha1-proteinase inhibitor for use in delaying the onset or progression of pulmonary exacerbations |
| US20160011207A1 (en) * | 2012-12-07 | 2016-01-14 | Virginia Commonwealth University | Diagnosis and therapy of chronic inflammation-induced disorders |
| EA201690335A1 (ru) * | 2013-08-05 | 2016-09-30 | Герард Форман | Новые средства для уменьшения негативных последствий курения |
| US10034866B2 (en) | 2014-06-19 | 2018-07-31 | Teva Branded Pharmaceutical Products R&D, Inc. | Inhalable medicament comprising tiotropium |
| US20210085764A1 (en) * | 2016-12-22 | 2021-03-25 | Kamada Ltd. | Dry powder formulations of alpha-1 antitrypsin |
| EP3915574A1 (en) * | 2020-05-27 | 2021-12-01 | Grifols Worldwide Operations Limited | Method for the treatment of cytokine release syndrome |
| CA3202852A1 (en) | 2020-12-01 | 2022-06-09 | Reverspah Llc | Methods and compositions for treating chronic obstructive pulmonary disease, asthma, pneumonia, bronchitis, cystic fibrosis and pulmonary edema, interstitial lung disease, sarcoidosis, idiopathic pulmonary fibrosis, a cute respiratory distress syndrome, and pulmonary arterial hypertension |
| US11324694B1 (en) * | 2021-10-28 | 2022-05-10 | Cmpd Licensing, Llc | Nebulization formulations for delivery to lower respiratory tract |
| WO2023091081A2 (en) * | 2021-11-16 | 2023-05-25 | Agency For Science, Technology And Research | Inhalable recombinant protein powder formulation for treating genetic and autoimmune disorders |
| EP4480493A1 (en) | 2023-06-22 | 2024-12-25 | AATEC Medical GmbH | A recombinant human alpha-1 antitrypsin glycoprotein for treating non-viral inflammatory diseases of the lung |
Family Cites Families (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4083372A (en) | 1976-05-24 | 1978-04-11 | Robert Boden | Cigarette-simulating inhaler |
| US4393884A (en) | 1981-09-25 | 1983-07-19 | Jacobs Allen W | Demand inhaler for oral administration of tobacco, tobacco-like, or other substances |
| AU577259B2 (en) * | 1982-08-13 | 1988-09-22 | Zymogenetics Inc. | Glycolytic promters for regulated protein expression protease inhibitor |
| US4870008A (en) * | 1983-08-12 | 1989-09-26 | Chiron Corporation | Secretory expression in eukaryotes |
| US4752576A (en) * | 1984-06-14 | 1988-06-21 | Chiron Corporation | Expression of α-1 antitrypsin in yeast |
| US4732973A (en) * | 1984-06-14 | 1988-03-22 | Chiron Corporation | Active site modified protease α-1-antitrypsin inhibitors |
| US4837148A (en) * | 1984-10-30 | 1989-06-06 | Phillips Petroleum Company | Autonomous replication sequences for yeast strains of the genus pichia |
| US4735217A (en) | 1986-08-21 | 1988-04-05 | The Procter & Gamble Company | Dosing device to provide vaporized medicament to the lungs as a fine aerosol |
| US4765348A (en) | 1986-12-12 | 1988-08-23 | Brown & Williamson Tobacco Corporation | Non-combustible simulated cigarette device |
| US5217951A (en) * | 1986-12-24 | 1993-06-08 | John Lezdey | Treatment of inflammation |
| US5166134A (en) * | 1986-12-24 | 1992-11-24 | John Lezdey | Treatment of allergic rhinitis |
| US5114917A (en) * | 1986-12-24 | 1992-05-19 | John Lezdey | Treatment of inflammation using alpha 1-antichymotrypsin |
| US5008242A (en) * | 1986-12-24 | 1991-04-16 | John Lezdey | Treatment of inflammation using 1-antichymotrypsin |
| US5290762A (en) * | 1986-12-24 | 1994-03-01 | John Lezdey | Treatment of inflammation |
| JP2656944B2 (ja) * | 1987-04-30 | 1997-09-24 | クーパー ラボラトリーズ | タンパク質性治療剤のエアロゾール化 |
| US5159940A (en) | 1988-07-22 | 1992-11-03 | Philip Morris Incorporated | Smoking article |
| US4892109A (en) | 1989-03-08 | 1990-01-09 | Brown & Williamson Tobacco Corporation | Simulated smoking article |
| US6068994A (en) * | 1989-08-07 | 2000-05-30 | Chiron Corporation | Ubiquitin expression system |
| US5113855A (en) | 1990-02-14 | 1992-05-19 | Newhouse Michael T | Powder inhaler |
| US5134119A (en) * | 1990-10-16 | 1992-07-28 | Lezdey John | Treatment of inflammation using 358 substituted alpha-antitrypsin |
| US5189178A (en) | 1990-11-21 | 1993-02-23 | Galardy Richard E | Matrix metalloprotease inhibitors |
| US5239078A (en) | 1990-11-21 | 1993-08-24 | Glycomed Incorporated | Matrix metalloprotease inhibitors |
| US5114953A (en) | 1990-11-21 | 1992-05-19 | University Of Florida | Treatment for tissue ulceration |
| US5892112A (en) * | 1990-11-21 | 1999-04-06 | Glycomed Incorporated | Process for preparing synthetic matrix metalloprotease inhibitors |
| US5268384A (en) * | 1990-11-21 | 1993-12-07 | Galardy Richard E | Inhibition of angiogenesis by synthetic matrix metalloprotease inhibitors |
| US5256657A (en) * | 1991-08-19 | 1993-10-26 | Sterling Winthrop, Inc. | Succinamide derivative matrix-metalloprotease inhibitors |
| US5287850A (en) | 1991-08-20 | 1994-02-22 | Habley Medical Technology Corporation | Timing and velocity controlled powered pharmaceutical inhaler |
| GB9215665D0 (en) | 1992-07-23 | 1992-09-09 | British Bio Technology | Compounds |
| FR2696080B1 (fr) | 1992-09-30 | 1994-12-23 | Jesus Covarrubias | Filtre à cigarette pour l'administration de taurine par inhalation. |
| US5441060A (en) | 1993-02-08 | 1995-08-15 | Duke University | Dry powder delivery system |
| AU671724B2 (en) | 1993-03-16 | 1996-09-05 | British Biotech Pharmaceuticals Limited | Hydroxamic acid derivatives as metalloproteinase inhibitors |
| CA2160139A1 (en) | 1993-04-07 | 1994-10-13 | Richard Edward Galardy | Synthetic matrix metalloprotease inhibitors and uses thereof |
| US5594106A (en) * | 1993-08-23 | 1997-01-14 | Immunex Corporation | Inhibitors of TNF-α secretion |
| US6562596B1 (en) | 1993-10-06 | 2003-05-13 | Amgen Inc. | Tissue inhibitor of metalloproteinase type three (TIMP-3) composition and methods |
| GB9320660D0 (en) | 1993-10-07 | 1993-11-24 | British Bio Technology | Inhibition of cytokine production |
| US6037472A (en) | 1993-11-04 | 2000-03-14 | Syntex (U.S.A.) Inc. | Matrix metalloprotease inhibitors |
| US5780014A (en) | 1995-04-14 | 1998-07-14 | Inhale Therapeutic Systems | Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin |
| DE19541873A1 (de) | 1995-11-09 | 1997-05-15 | Rhodia Ag Rhone Poulenc | Filterzigarette |
| AU2645497A (en) | 1996-05-06 | 1997-11-26 | Zeneca Limited | Thio derivatives of hydroxamic acids |
| USRE37053E1 (en) * | 1996-05-24 | 2001-02-13 | Massachusetts Institute Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5780440A (en) * | 1996-06-17 | 1998-07-14 | Protease Sciences Inc. | Treatment of pulmonary disease with protease inhibitors |
| GB9715962D0 (en) | 1996-08-23 | 1997-10-01 | Zeneca Ltd | Sulfonamides |
| US6610683B2 (en) * | 1996-09-12 | 2003-08-26 | Idun Pharmaceuticals, Inc. | Treatment of infectious disease using interleukin-1β-converting enzyme (ICE)/CED-3 family inhibitors |
| NZ334908A (en) | 1996-10-02 | 2000-10-27 | Novartis Ag | 3-imino-4-oxo-1,7-dioic acid (7-N-hydroxy) diamide derivatives characterised by the presence of an oxymethyl group on the 6-position for supression of TNF and treatment of inflammation |
| AU6843498A (en) | 1997-03-28 | 1998-10-22 | Zeneca Limited | Process for the preparation of n-(3-hydroxy-succinyl)-amino acid derivatives |
| FR2762315B1 (fr) | 1997-04-22 | 1999-05-28 | Logeais Labor Jacques | Derives d'amino-acides inhibiteurs des metalloproteases de la matrice extracellulaire et de la liberation du tnf alpha |
| US6124257A (en) * | 1997-08-28 | 2000-09-26 | Lezdey; John | Method of treatment |
| US20010006939A1 (en) | 1997-10-03 | 2001-07-05 | Ralph W. Niven | Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions |
| US5972986A (en) * | 1997-10-14 | 1999-10-26 | G.D. Searle & Co. | Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of neoplasia |
| US6133304A (en) | 1997-12-23 | 2000-10-17 | Warner-Lambert Company | ACE inhibitor-MMP inhibitor combinations |
| US5996589A (en) | 1998-03-03 | 1999-12-07 | Brown & Williamson Tobacco Corporation | Aerosol-delivery smoking article |
| GB9804504D0 (en) | 1998-03-03 | 1998-04-29 | Leo Pharm Prod Ltd | Matrix metalloproteinase inhibitors |
| EP1137633A2 (en) | 1998-12-09 | 2001-10-04 | American Home Products Corporation | Acetamide and substituted acetamide-containing thiourea inhibitors of herpes viruses |
| WO2000051623A2 (en) * | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide-induced clinical conditions |
| HUP0203323A3 (en) | 1999-10-19 | 2004-01-28 | Merck & Co Inc | Tyrosine kinase inhibitors and pharmaceutical compositions containing them |
| WO2001028993A2 (en) | 1999-10-19 | 2001-04-26 | Merck & Co. Inc. | Tyrosine kinase inhibitors |
| WO2001057025A1 (en) * | 2000-01-31 | 2001-08-09 | Pfizer Products Inc. | Pyrimidine carboxamides useful as inhibitors of pde4 isozymes |
| GB0004531D0 (en) * | 2000-02-25 | 2000-04-19 | Richards Andrew J M | The treatment of respiratory diseases |
| GB0008660D0 (en) * | 2000-04-07 | 2000-05-31 | Arakis Ltd | The treatment of respiratory diseases |
| US6637430B1 (en) | 2000-06-16 | 2003-10-28 | Ponwell Enterprises Limited | Respiratory delivery system with power/medicament recharge assembly |
| US20020099013A1 (en) * | 2000-11-14 | 2002-07-25 | Thomas Piccariello | Active agent delivery systems and methods for protecting and administering active agents |
| US7247704B2 (en) * | 2000-12-18 | 2007-07-24 | Arriva Pharmaceuticals, Inc. | Multifunctional protease inhibitors and their use in treatment of disease |
| WO2002050287A2 (en) | 2000-12-18 | 2002-06-27 | Arriva Pharmaceuticals, Inc. | Multifunctional protease inhibitors and their use in treatment of disease |
| EP1351678A2 (en) | 2001-01-02 | 2003-10-15 | Elizabeth Shanahan-Prendergast | Treatment for inhibiting neoplastic lesions using incensole and/or furanogermacrens |
| PA8539301A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Inhibidores de la metaloproteinasa de la matriz |
| US6544497B2 (en) * | 2001-02-15 | 2003-04-08 | Aeropharm Technology Incorporated | Modulated release particles for aerosol delivery |
| US6789546B2 (en) | 2001-06-26 | 2004-09-14 | Technion Research & Development Foundation Ltd. | Filters for preventing or reducing tobacco smoke-associated injury in the aerodigestive tract of a subject |
| JP4219810B2 (ja) * | 2001-10-26 | 2009-02-04 | 塩野義製薬株式会社 | Mmp阻害作用を有するスルホンアミド誘導体 |
| US20030211548A1 (en) * | 2002-01-29 | 2003-11-13 | Oncolmmunin, Inc. | Visualization and quantitiation of cellular cytotoxicity using cell-permeable fluorogenic protease substrates and caspase activity indicator markers |
| AU2003205898A1 (en) | 2002-02-18 | 2003-09-04 | University Of Southampton | Combination therapy for respiratory disorders |
| WO2003075959A1 (en) | 2002-03-08 | 2003-09-18 | Novartis Ag | Matrix metalloproteinase inhibitors in combination with hypothermia and/or radiotherapy for the treatment of cancer |
| AU2003235121A1 (en) * | 2002-04-26 | 2003-11-10 | Takeda Pharmaceutical Company Limited | Novel thiol derivative, process for producing the same and use thereof |
| US7165362B2 (en) * | 2002-07-15 | 2007-01-23 | Apple Computer, Inc. | Glass support member |
| US6810883B2 (en) | 2002-11-08 | 2004-11-02 | Philip Morris Usa Inc. | Electrically heated cigarette smoking system with internal manifolding for puff detection |
| CA2526222A1 (en) | 2003-05-16 | 2004-12-02 | Arriva Pharmaceuticals, Inc. | Treatment of respiratory disease associated with matrix metalloprotease inhibitors |
| EP1638579A2 (en) | 2003-07-02 | 2006-03-29 | Emory University | Compositions and methods for use of a protease inhibitor and adenosine for preventing organ ischemia and reperfusion injury |
| PL1684719T3 (pl) * | 2003-11-14 | 2012-11-30 | Baxalta Inc | Kompozycje alfa 1-antytrypsyny i sposoby leczenia z zastosowaniem takich kompozycji |
| JP2007528409A (ja) * | 2004-03-09 | 2007-10-11 | アリバ ファーマシューティカルズ, インコーポレイテッド | プロテアーゼインヒビターの低用量吸入による慢性閉塞性肺疾患の処置 |
-
2005
- 2005-03-09 JP JP2007503004A patent/JP2007528409A/ja active Pending
- 2005-03-09 CA CA002559062A patent/CA2559062A1/en not_active Abandoned
- 2005-03-09 WO PCT/US2005/007959 patent/WO2005086915A2/en not_active Ceased
- 2005-03-09 US US11/077,276 patent/US7914771B2/en not_active Expired - Fee Related
- 2005-03-09 EP EP05725249A patent/EP1737499A4/en not_active Withdrawn
- 2005-03-09 AU AU2005221151A patent/AU2005221151A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20050201951A1 (en) | 2005-09-15 |
| CA2559062A1 (en) | 2005-09-22 |
| WO2005086915A2 (en) | 2005-09-22 |
| WO2005086915A3 (en) | 2006-03-23 |
| JP2007528409A (ja) | 2007-10-11 |
| EP1737499A4 (en) | 2009-07-22 |
| US7914771B2 (en) | 2011-03-29 |
| EP1737499A2 (en) | 2007-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7914771B2 (en) | Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor | |
| JP2656944B2 (ja) | タンパク質性治療剤のエアロゾール化 | |
| US10125191B2 (en) | Compositions comprising an anti-C5 antibody | |
| ES2664624T3 (es) | Alfa-I antitripsina para tratar episodios de exacerbación de enfermedades pulmonares | |
| Demkow et al. | Role of elastases in the pathogenesis of chronic obstructive pulmonary disease: implications for treatment | |
| US20100124536A1 (en) | Hemophilia Treatment by Inhalation of Coagulation Factors | |
| JP2001518518A (ja) | 分泌性白血球プロテアーゼインヒビターの乾燥粉末薬学的組成物 | |
| AU691514B2 (en) | Stabilization of aerosolized proteins | |
| ES2887358T3 (es) | Inhibidor de Alfa1-Proteinasa para demorar el comienzo o progresión de exacerbaciones pulmonares | |
| Vogelmeier et al. | The intrapulmonary half-life and safety of aerosolized alpha1-protease inhibitor in normal volunteers. | |
| Garcia-Contreras et al. | Aerosol treatment of cystic fibrosis | |
| AU2004288854B2 (en) | Dry recombinant human alpha 1-antitrypsin formulation | |
| WO2005049801A2 (en) | Dry protein formulation | |
| Stockleyb et al. | Neutrophil elastase inhibitors | |
| MXPA00003231A (en) | Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |