UA76085C2 - Aerosol particles resistant to hygroscopic growth - Google Patents

Aerosol particles resistant to hygroscopic growth Download PDF

Info

Publication number: UA76085C2
Authority: UA; Ukraine
Prior art keywords: particles; active substance; hygroscopic growth; growth inhibitor; cyclodextrin
Prior art date: 1998-09-14

Application number

UA2001031707A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Nektar Therapeutics

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-09-14

Filing date

1999-09-13

Publication date

2006-07-17

1999-09-13 Application filed by Nektar Therapeutics filed Critical Nektar Therapeutics

2006-07-17 Publication of UA76085C2 publication Critical patent/UA76085C2/uk

Links

239000002245 particle Substances 0.000 title claims description 157
239000000443 aerosol Substances 0.000 title description 16
239000000843 powder Substances 0.000 claims abstract description 174
239000013543 active substance Substances 0.000 claims abstract description 88
210000004072 lung Anatomy 0.000 claims abstract description 74
238000000034 method Methods 0.000 claims abstract description 33
239000000203 mixture Substances 0.000 claims abstract description 29
238000010521 absorption reaction Methods 0.000 claims description 61
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 claims description 60
239000003966 growth inhibitor Substances 0.000 claims description 59
238000002360 preparation method Methods 0.000 claims description 37
229920001612 Hydroxyethyl starch Polymers 0.000 claims description 31
229940050526 hydroxyethylstarch Drugs 0.000 claims description 31
102000004877 Insulin Human genes 0.000 claims description 30
108090001061 Insulin Proteins 0.000 claims description 30
229940125396 insulin Drugs 0.000 claims description 30
230000002685 pulmonary effect Effects 0.000 claims description 24
229920000858 Cyclodextrin Polymers 0.000 claims description 22
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 22
-1 sulfobutyl ester Chemical class 0.000 claims description 19
238000001694 spray drying Methods 0.000 claims description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
108090000623 proteins and genes Proteins 0.000 claims description 12
229920002774 Maltodextrin Polymers 0.000 claims description 11
102000004169 proteins and genes Human genes 0.000 claims description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
102000004196 processed proteins & peptides Human genes 0.000 claims description 9
108090000765 processed proteins & peptides Proteins 0.000 claims description 9
239000007787 solid Substances 0.000 claims description 9
229920001605 Dextranomer Polymers 0.000 claims description 7
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 7
229960002864 dextranomer Drugs 0.000 claims description 7
239000003112 inhibitor Substances 0.000 claims description 7
229920001184 polypeptide Polymers 0.000 claims description 7
102000055006 Calcitonin Human genes 0.000 claims description 6
108060001064 Calcitonin Proteins 0.000 claims description 6
229960004015 calcitonin Drugs 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
238000012387 aerosolization Methods 0.000 claims description 5
229940112141 dry powder inhaler Drugs 0.000 claims description 4
239000002904 solvent Substances 0.000 claims description 4
NZAQRZWBQUIBSF-UHFFFAOYSA-N 4-(4-sulfobutoxy)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCOCCCCS(O)(=O)=O NZAQRZWBQUIBSF-UHFFFAOYSA-N 0.000 claims description 3
239000001116 FEMA 4028 Substances 0.000 claims description 2
235000011175 beta-cyclodextrine Nutrition 0.000 claims description 2
229960004853 betadex Drugs 0.000 claims description 2
238000010348 incorporation Methods 0.000 claims description 2
ODLHGICHYURWBS-FOSILIAISA-N molport-023-220-444 Chemical compound CC(O)COC[C@@H]([C@@H]([C@H]([C@@H]1O)O)O[C@@H]2O[C@H]([C@H](O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O[C@@H]3O[C@@H](COCC(C)O)[C@@H]([C@H]([C@@H]3O)O)O3)[C@@H](O)[C@@H]2O)COCC(O)C)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O)[C@H]3O[C@H]1COCC(C)O ODLHGICHYURWBS-FOSILIAISA-N 0.000 claims 1
229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 claims 1
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims 1
238000009472 formulation Methods 0.000 abstract description 3
238000001179 sorption measurement Methods 0.000 abstract 1
239000003814 drug Substances 0.000 description 39
229940079593 drug Drugs 0.000 description 36
239000000126 substance Substances 0.000 description 29
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 24
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 21
239000001509 sodium citrate Substances 0.000 description 21
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 20
229930195725 Mannitol Natural products 0.000 description 20
239000000594 mannitol Substances 0.000 description 20
235000010355 mannitol Nutrition 0.000 description 20
229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 16
239000000463 material Substances 0.000 description 16
108010068072 salmon calcitonin Proteins 0.000 description 16
239000000546 pharmaceutical excipient Substances 0.000 description 15
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 13
210000002345 respiratory system Anatomy 0.000 description 13
229920002307 Dextran Polymers 0.000 description 12
239000004471 Glycine Substances 0.000 description 10
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 9
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
230000000694 effects Effects 0.000 description 9
235000018102 proteins Nutrition 0.000 description 9
239000000243 solution Substances 0.000 description 9
238000009826 distribution Methods 0.000 description 8
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 7
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 7
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 7
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 7
238000005259 measurement Methods 0.000 description 7
239000003102 growth factor Substances 0.000 description 6
239000000523 sample Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
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 5
102000008100 Human Serum Albumin Human genes 0.000 description 5
108091006905 Human Serum Albumin Proteins 0.000 description 5
239000005913 Maltodextrin Substances 0.000 description 5
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
230000008021 deposition Effects 0.000 description 5
239000007789 gas Substances 0.000 description 5
239000008103 glucose Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229940035034 maltodextrin Drugs 0.000 description 5
230000002093 peripheral effect Effects 0.000 description 5
229920001282 polysaccharide Polymers 0.000 description 5
230000009467 reduction Effects 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000011248 coating agent Substances 0.000 description 4
238000000576 coating method Methods 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
229940097362 cyclodextrins Drugs 0.000 description 4
239000003623 enhancer Substances 0.000 description 4
150000004676 glycans Chemical class 0.000 description 4
230000035699 permeability Effects 0.000 description 4
239000005017 polysaccharide Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
230000001839 systemic circulation Effects 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
229920000896 Ethulose Polymers 0.000 description 3
239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 description 3
102000018997 Growth Hormone Human genes 0.000 description 3
108010051696 Growth Hormone Proteins 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 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 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 description 3
230000009471 action Effects 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
229940024606 amino acid Drugs 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
230000000975 bioactive effect Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
238000004364 calculation method Methods 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
229960004106 citric acid Drugs 0.000 description 3
235000015165 citric acid Nutrition 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 3
239000000122 growth hormone Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
238000002483 medication Methods 0.000 description 3
238000002156 mixing Methods 0.000 description 3
108020004707 nucleic acids Proteins 0.000 description 3
150000007523 nucleic acids Chemical class 0.000 description 3
102000039446 nucleic acids Human genes 0.000 description 3
210000003300 oropharynx Anatomy 0.000 description 3
230000008569 process Effects 0.000 description 3
238000012545 processing Methods 0.000 description 3
238000003127 radioimmunoassay Methods 0.000 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 description 3
238000004062 sedimentation Methods 0.000 description 3
238000010254 subcutaneous injection Methods 0.000 description 3
239000007929 subcutaneous injection Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
229960005486 vaccine Drugs 0.000 description 3
ZVCVMOFMPFNDBB-UHFFFAOYSA-N 1-sulfonyl-4-(4-sulfonylbutoxy)butane Chemical compound O=S(=O)=CCCCOCCCC=S(=O)=O ZVCVMOFMPFNDBB-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical class OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
102000016911 Deoxyribonucleases Human genes 0.000 description 2
108010053770 Deoxyribonucleases Proteins 0.000 description 2
108090000394 Erythropoietin Proteins 0.000 description 2
102000003951 Erythropoietin Human genes 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
102000002265 Human Growth Hormone Human genes 0.000 description 2
108010000521 Human Growth Hormone Proteins 0.000 description 2
239000000854 Human Growth Hormone Substances 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
DNDWZFHLZVYOGF-KKUMJFAQSA-N Leu-Leu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O DNDWZFHLZVYOGF-KKUMJFAQSA-N 0.000 description 2
102000003982 Parathyroid hormone Human genes 0.000 description 2
108090000445 Parathyroid hormone Proteins 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
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 2
229930006000 Sucrose Natural products 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
241000700605 Viruses Species 0.000 description 2
238000001793 Wilcoxon signed-rank test Methods 0.000 description 2
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000002776 aggregation Effects 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
230000000845 anti-microbial effect Effects 0.000 description 2
239000001961 anticonvulsive agent Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
230000008859 change Effects 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
238000009792 diffusion process Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
210000002919 epithelial cell Anatomy 0.000 description 2
229940105423 erythropoietin Drugs 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
238000010304 firing Methods 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
210000003714 granulocyte Anatomy 0.000 description 2
230000003054 hormonal effect Effects 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
229960000310 isoleucine Drugs 0.000 description 2
108010049589 leucyl-leucyl-leucine Proteins 0.000 description 2
239000003055 low molecular weight heparin Substances 0.000 description 2
229940127215 low-molecular weight heparin Drugs 0.000 description 2
210000002540 macrophage Anatomy 0.000 description 2
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
229940071648 metered dose inhaler Drugs 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
150000002772 monosaccharides Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
235000015097 nutrients Nutrition 0.000 description 2
229920001542 oligosaccharide Polymers 0.000 description 2
229960001319 parathyroid hormone Drugs 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 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
230000000241 respiratory effect Effects 0.000 description 2
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
238000007873 sieving Methods 0.000 description 2
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
239000007921 spray Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
150000005846 sugar alcohols Chemical class 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
239000013589 supplement Substances 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
238000012360 testing method Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
239000004474 valine Substances 0.000 description 2
239000000811 xylitol Substances 0.000 description 2
235000010447 xylitol Nutrition 0.000 description 2
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
229960002675 xylitol Drugs 0.000 description 2
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 1
DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 1
JBOWUKRDBGMOJZ-UHFFFAOYSA-N 3-[2-amino-6-(2-methylphenyl)quinolin-3-yl]-n-cyclohexylpropanamide Chemical compound CC1=CC=CC=C1C1=CC=C(N=C(N)C(CCC(=O)NC2CCCCC2)=C2)C2=C1 JBOWUKRDBGMOJZ-UHFFFAOYSA-N 0.000 description 1
VUPOTURDKDMIGQ-UHFFFAOYSA-N 5-chloro-1-[(4-chlorophenyl)methyl]-3-phenylsulfanylindole-2-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2N(CC=2C=CC(Cl)=CC=2)C(C(=O)O)=C1SC1=CC=CC=C1 VUPOTURDKDMIGQ-UHFFFAOYSA-N 0.000 description 1
VCCNKWWXYVWTLT-CYZBKYQRSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCCNKWWXYVWTLT-CYZBKYQRSA-N 0.000 description 1
108060003345 Adrenergic Receptor Proteins 0.000 description 1
102000017910 Adrenergic receptor Human genes 0.000 description 1
FDQGNLOWMMVRQL-UHFFFAOYSA-N Allobarbital Chemical compound C=CCC1(CC=C)C(=O)NC(=O)NC1=O FDQGNLOWMMVRQL-UHFFFAOYSA-N 0.000 description 1
102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108010011485 Aspartame 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
241000282472 Canis lupus familiaris Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
102000009660 Cholinergic Receptors Human genes 0.000 description 1
108010009685 Cholinergic Receptors Proteins 0.000 description 1
244000248349 Citrus limon Species 0.000 description 1
235000005979 Citrus limon Nutrition 0.000 description 1
BIHBFAKMTBCPIB-UHFFFAOYSA-N Cl[C]F.[C] Chemical compound Cl[C]F.[C] BIHBFAKMTBCPIB-UHFFFAOYSA-N 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
108010036949 Cyclosporine Proteins 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical class OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
208000004232 Enteritis Diseases 0.000 description 1
101100082618 Escherichia coli (strain K12) pdeN gene Proteins 0.000 description 1
108010076282 Factor IX Proteins 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
108010010803 Gelatin Proteins 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
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
241000282418 Hominidae Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102000006992 Interferon-alpha Human genes 0.000 description 1
108010047761 Interferon-alpha Proteins 0.000 description 1
102000003996 Interferon-beta Human genes 0.000 description 1
108090000467 Interferon-beta Proteins 0.000 description 1
102000008070 Interferon-gamma Human genes 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
102000019223 Interleukin-1 receptor Human genes 0.000 description 1
108050006617 Interleukin-1 receptor Proteins 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102000010790 Interleukin-3 Receptors Human genes 0.000 description 1
108010038452 Interleukin-3 Receptors Proteins 0.000 description 1
102000004388 Interleukin-4 Human genes 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
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 1
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
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
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-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
102000009151 Luteinizing Hormone Human genes 0.000 description 1
108010073521 Luteinizing Hormone Proteins 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
108010025020 Nerve Growth Factor Proteins 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
108091092920 SmY RNA Proteins 0.000 description 1
241001237710 Smyrna Species 0.000 description 1
102000005157 Somatostatin Human genes 0.000 description 1
108010056088 Somatostatin Proteins 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
239000000150 Sympathomimetic Substances 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
108010078233 Thymalfasin Proteins 0.000 description 1
102400000800 Thymosin alpha-1 Human genes 0.000 description 1
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 1
239000007983 Tris buffer Substances 0.000 description 1
MKFFGUZYVNDHIH-UHFFFAOYSA-N [2-(3,5-dihydroxyphenyl)-2-hydroxyethyl]-propan-2-ylazanium;sulfate Chemical compound OS(O)(=O)=O.CC(C)NCC(O)C1=CC(O)=CC(O)=C1.CC(C)NCC(O)C1=CC(O)=CC(O)=C1 MKFFGUZYVNDHIH-UHFFFAOYSA-N 0.000 description 1
239000006096 absorbing agent Substances 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000003741 agents affecting lipid metabolism Substances 0.000 description 1
238000005054 agglomeration Methods 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
BNPSSFBOAGDEEL-UHFFFAOYSA-N albuterol sulfate Chemical compound OS(O)(=O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-UHFFFAOYSA-N 0.000 description 1
229940057282 albuterol sulfate Drugs 0.000 description 1
108010060162 alglucerase Proteins 0.000 description 1
108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
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 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
229940043377 alpha-cyclodextrin Drugs 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
230000000078 anti-malarial effect Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000002141 anti-parasite Effects 0.000 description 1
230000000648 anti-parkinson Effects 0.000 description 1
230000003097 anti-respiratory effect Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000003430 antimalarial agent Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
239000000939 antiparkinson agent Substances 0.000 description 1
239000002216 antistatic agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical class C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000000149 argon plasma sintering Methods 0.000 description 1
239000011668 ascorbic acid Chemical class 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
229950000210 beclometasone dipropionate Drugs 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 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
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
229960003237 betaine Drugs 0.000 description 1
239000003833 bile salt Substances 0.000 description 1
229940093761 bile salts Drugs 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
239000000168 bronchodilator agent Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
238000005354 coacervation Methods 0.000 description 1
239000000306 component Substances 0.000 description 1
229940124558 contraceptive agent Drugs 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
239000013068 control sample Substances 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 1
229960003662 desonide Drugs 0.000 description 1
229960002086 dextran Drugs 0.000 description 1
229940119744 dextran 40 Drugs 0.000 description 1
229940119743 dextran 70 Drugs 0.000 description 1
229940119742 dextran 75 Drugs 0.000 description 1
229920003045 dextran sodium sulfate Polymers 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003792 electrolyte Substances 0.000 description 1
238000001493 electron microscopy Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
229960001903 ergotamine tartrate Drugs 0.000 description 1
238000005530 etching Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
229960004222 factor ix Drugs 0.000 description 1
239000003925 fat Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229960000676 flunisolide Drugs 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
229960002714 fluticasone Drugs 0.000 description 1
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 1
235000013305 food Nutrition 0.000 description 1
235000013373 food additive Nutrition 0.000 description 1
239000002778 food additive Substances 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
229940080345 gamma-cyclodextrin Drugs 0.000 description 1
229940044627 gamma-interferon Drugs 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
239000000174 gluconic acid Chemical class 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
229950006191 gluconic acid Drugs 0.000 description 1
125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
239000003326 hypnotic agent Substances 0.000 description 1
230000000147 hypnotic effect Effects 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000001427 incoherent neutron scattering Methods 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
150000002484 inorganic compounds Chemical class 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
230000002608 insulinlike Effects 0.000 description 1
230000010354 integration Effects 0.000 description 1
229940028885 interleukin-4 Drugs 0.000 description 1
229960001361 ipratropium bromide Drugs 0.000 description 1
KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
229960005280 isotretinoin Drugs 0.000 description 1
238000010902 jet-milling Methods 0.000 description 1
239000000832 lactitol Substances 0.000 description 1
235000010448 lactitol Nutrition 0.000 description 1
VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
229960003451 lactitol Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000003580 lung surfactant Substances 0.000 description 1
229940040129 luteinizing hormone Drugs 0.000 description 1
239000000845 maltitol Substances 0.000 description 1
235000010449 maltitol Nutrition 0.000 description 1
VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
229940035436 maltitol Drugs 0.000 description 1
229960001855 mannitol Drugs 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229940042006 metaproterenol sulfate Drugs 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
239000003595 mist Substances 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
239000000178 monomer Substances 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
229940035363 muscle relaxants Drugs 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
229960004448 pentamidine Drugs 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000008103 phosphatidic acids Chemical class 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
229940067605 phosphatidylethanolamines Drugs 0.000 description 1
150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
230000006461 physiological response Effects 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
238000000163 radioactive labelling Methods 0.000 description 1
210000004994 reproductive system Anatomy 0.000 description 1
238000012552 review Methods 0.000 description 1
235000002020 sage Nutrition 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
238000009517 secondary packaging Methods 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
239000013049 sediment Substances 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229940083542 sodium Drugs 0.000 description 1
229960000999 sodium citrate dihydrate Drugs 0.000 description 1
229960000553 somatostatin Drugs 0.000 description 1
238000005507 spraying Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
230000003068 static effect Effects 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000001975 sympathomimetic effect Effects 0.000 description 1
239000011975 tartaric acid Chemical class 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
150000004044 tetrasaccharides Chemical class 0.000 description 1
NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
229960004231 thymalfasin Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000032258 transport Effects 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
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
150000004043 trisaccharides Chemical class 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000013603 viral vector Substances 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
239000002699 waste material Substances 0.000 description 1
230000003313 weakening effect Effects 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
230000004580 weight loss Effects 0.000 description 1

Classifications

- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- 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
- A61P31/04—Antibacterial agents

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pulmonology (AREA)
Epidemiology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Otolaryngology (AREA)
Inorganic Chemistry (AREA)
Medicinal Preparation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Solid-Sorbent Or Filter-Aiding Compositions (AREA)

UA2001031707A 1998-09-14 1999-09-13 Aerosol particles resistant to hygroscopic growth UA76085C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US10016398P	1998-09-14	1998-09-14
PCT/US1999/021109 WO2000015262A1 (fr)	1998-09-14	1999-09-13	Administration par voie pulmonaire d'un agent actif sous forme de poudre seche

Publications (1)

Publication Number	Publication Date
UA76085C2 true UA76085C2 (en)	2006-07-17

Family

ID=22278404

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2001031707A UA76085C2 (en)	1998-09-14	1999-09-13	Aerosol particles resistant to hygroscopic growth

Country Status (44)

Country	Link
EP (1)	EP1117442A1 (fr)
JP (1)	JP2002524535A (fr)
KR (1)	KR20010075063A (fr)
CN (1)	CN1317977A (fr)
AP (1)	AP1374A (fr)
AR (1)	AR022090A1 (fr)
AU (1)	AU753014B2 (fr)
BG (1)	BG105430A (fr)
BR (1)	BR9913722A (fr)
CA (1)	CA2343920A1 (fr)
CO (1)	CO5130023A1 (fr)
CZ (1)	CZ2001829A3 (fr)
DZ (1)	DZ2892A1 (fr)
EA (1)	EA003476B1 (fr)
EE (1)	EE200100151A (fr)
GE (1)	GEP20043257B (fr)
GT (1)	GT199900156A (fr)
HK (1)	HK1042231A1 (fr)
HN (1)	HN1999000159A (fr)
HR (1)	HRP20010189A2 (fr)
HU (1)	HUP0103837A3 (fr)
ID (1)	ID28845A (fr)
IL (2)	IL141562A0 (fr)
IS (1)	IS5878A (fr)
LT (1)	LT4897B (fr)
LV (1)	LV12658B (fr)
MA (1)	MA25590A1 (fr)
MY (1)	MY129282A (fr)
NO (1)	NO20011251L (fr)
NZ (1)	NZ510168A (fr)
OA (1)	OA11781A (fr)
PA (1)	PA8481901A1 (fr)
PE (1)	PE20001061A1 (fr)
PL (1)	PL195574B1 (fr)
SA (1)	SA99200718B1 (fr)
SK (1)	SK3442001A3 (fr)
TN (1)	TNSN99173A1 (fr)
TR (1)	TR200101182T2 (fr)
TW (1)	TWI226248B (fr)
UA (1)	UA76085C2 (fr)
UY (1)	UY25711A1 (fr)
WO (1)	WO2000015262A1 (fr)
YU (1)	YU24201A (fr)
ZA (1)	ZA200101995B (fr)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6956021B1 (en)	1998-08-25	2005-10-18	Advanced Inhalation Research, Inc.	Stable spray-dried protein formulations
HK1049621A1 (zh)	1999-06-09	2003-05-23	罗伯特‧E‧希弗斯	超临界流体辅助的喷雾和鼓泡乾燥
US6475468B2 (en) *	2001-02-15	2002-11-05	Aeropharm Technology Incorporated	Modulated release particles for aerosol delivery
JP2005503425A (ja) *	2001-05-24	2005-02-03	アレックザモレキュラーデリヴァリーコーポレイション	所定の吸入ルートによる薬剤エステルの送出
EG24184A (en) *	2001-06-15	2008-10-08	Otsuka Pharma Co Ltd	Dry powder inhalation system for transpulmonary
AU2002352836B2 (en)	2001-11-20	2005-09-29	Alkermes, Inc.	Improved particulate compositions for pulmonary delivery
CA2477245A1 (fr)	2002-02-25	2003-09-04	Diffusion Pharmaceuticals Llc	Sels carotenoides trans bipolaires et leurs utilisations
US7759506B2 (en)	2002-02-25	2010-07-20	Diffusion Pharmaceuticals Llc	Bipolar trans carotenoid salts and their uses
WO2004004798A2 (fr) *	2002-07-03	2004-01-15	The Brigham And Women's Hospital, Inc.	Introduction par les voies aeriennes centrales pour l'administration systemique d'agents therapeutiques
EP1575563B1 (fr) *	2002-12-19	2007-02-14	Pharmacia Corporation	Formulation a caractere non-hygroscopique comprenant un principe actif hydroscopique
DE10338403A1 (de) *	2003-08-18	2005-03-17	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Pulverformulierung, enthaltend den CGRP-Antagonisten 1-[N2-[3,5-Dibrom-N-[[4-(3,4-dihydro-2(1H)-oxochinazolin-3-yl]-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyrindinyl)-piperazin, Verfahren zu dessen Herstellung sowie dessen Verwendung als Inhalativum
GB0327723D0 (en) *	2003-09-15	2003-12-31	Vectura Ltd	Pharmaceutical compositions
US20070020299A1 (en)	2003-12-31	2007-01-25	Pipkin James D	Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
CN101098678A (zh)	2004-04-23	2008-01-02	锡德克斯公司	含有磺基烷基醚环糊精的dpi制剂
EP2540696B1 (fr)	2005-02-24	2020-01-01	Diffusion Pharmaceuticals LLC	Transcaroténoïdes, formulation les comprenant et leurs utilisations
BRPI0608844A2 (pt) *	2005-03-09	2010-02-02	Ono Pharmaceutical Co	partìcula e preparação que contém a partìcula
US7629331B2 (en)	2005-10-26	2009-12-08	Cydex Pharmaceuticals, Inc.	Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof
PT2583668E (pt)	2005-10-26	2015-01-05	Cydex Pharmaceuticals Inc	Composições de éter sulfoalquílico de ciclodextrina e métodos para a sua preparação
WO2008021451A2 (fr) *	2006-08-14	2008-02-21	Aktiv-Dry Llc	Inhalateur à poudre sèche actionné par l'homme et compositions à inhaler sous forme de poudre sèche
JP5315056B2 (ja) *	2006-10-25	2013-10-16	大日本住友製薬株式会社	固結抑制粒状製剤
EP1925295A1 (fr) *	2006-11-22	2008-05-28	Boehringer Ingelheim Pharma GmbH & Co. KG	Formule de poudre stable contenant un nouveau anticholinergique
CN101687757A (zh)	2007-04-13	2010-03-31	扩散药品有限公司	双极性反式类胡萝卜素作为预治疗及其在周围血管疾病的治疗中的应用
US12370352B2 (en)	2007-06-28	2025-07-29	Cydex Pharmaceuticals, Inc.	Nasal and ophthalmic delivery of aqueous corticosteroid solutions
KR20100083820A (ko)	2007-10-31	2010-07-22	디퓨젼 파마슈티컬즈 엘엘씨	저분자 확산을 촉진시키는 신규한 치료요법
ES2661215T3 (es)	2009-05-20	2018-03-28	Aeras	Composiciones víricas; inmunógenas; secadas por pulverización; estables
EP2445339B1 (fr)	2009-06-22	2019-08-07	Diffusion Pharmaceuticals LLC	Composé améliorant la diffusion et son utilisation avec un thrombolytique
AU2011262361A1 (en)	2010-06-02	2013-01-10	Diffusion Pharmaceuticals Llc	Oral formulations of bipolar trans carotenoids
KR102240042B1 (ko) *	2012-05-03	2021-04-14	얀센 사이언시즈 아일랜드 언리미티드 컴퍼니	상기도 감염 치료용 폴리이노신산-폴리사이티딜산(폴리 (i:c)) 제형
BR112015010601B1 (pt) *	2012-11-09	2022-07-19	Civitas Therapeutics, Inc.	Composição farmacêutica e uso da composição
US20180043585A9 (en) *	2013-09-20	2018-02-15	Virginia Commonwealth University	Delivery of particles using hygroscopic excipients
MX392636B (es)	2014-10-31	2025-03-24	Glaxosmithkline Ip Dev Ltd	Formulacion en polvo.
CA3018550A1 (fr)	2016-03-24	2017-09-28	Diffusion Pharmaceuticals Llc	Utilisation de carotenoides trans bipolaires avec une chimiotherapie et une radiotherapie en vue du traitement d'un cancer
US20220378727A1 (en) *	2021-05-14	2022-12-01	The University Of Hong Kong	Dry powder formulations of tamibarotene for pulmonary and intranasal delivery

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3155573A (en) *	1958-05-06	1964-11-03	Benger Lab Ltd	Inhalant composition and method of making same
CA2115065C (fr) *	1992-06-12	2000-10-03	Kiyoyuki Sakon	Poudre particulaire ultrafine pour inhalation et methode de production
US6524557B1 (en) *	1994-12-22	2003-02-25	Astrazeneca Ab	Aerosol formulations of peptides and proteins
US5874064A (en)	1996-05-24	1999-02-23	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
CA2277801C (fr) *	1997-01-16	2002-10-15	Massachusetts Institute Of Technology	Preparation de particules pour inhalation
US6086376A (en) *	1998-01-30	2000-07-11	Rtp Pharma Inc.	Dry aerosol suspension of phospholipid-stabilized drug microparticles in a hydrofluoroalkane propellant

1999
- 1999-09-09 MA MA25762A patent/MA25590A1/fr unknown
- 1999-09-13 HN HN1999000159A patent/HN1999000159A/es unknown
- 1999-09-13 DZ DZ990192A patent/DZ2892A1/fr active
- 1999-09-13 CA CA002343920A patent/CA2343920A1/fr not_active Abandoned
- 1999-09-13 HU HU0103837A patent/HUP0103837A3/hu unknown
- 1999-09-13 YU YU24201A patent/YU24201A/sh unknown
- 1999-09-13 CZ CZ2001829A patent/CZ2001829A3/cs unknown
- 1999-09-13 ID IDW20010582A patent/ID28845A/id unknown
- 1999-09-13 CN CN99810871A patent/CN1317977A/zh active Pending
- 1999-09-13 AP APAP/P/2001/002093A patent/AP1374A/en active
- 1999-09-13 PE PE1999000925A patent/PE20001061A1/es not_active Application Discontinuation
- 1999-09-13 TW TW088115876A patent/TWI226248B/zh not_active IP Right Cessation
- 1999-09-13 KR KR1020017003208A patent/KR20010075063A/ko not_active Ceased
- 1999-09-13 PL PL99346768A patent/PL195574B1/pl not_active IP Right Cessation
- 1999-09-13 IL IL14156299A patent/IL141562A0/xx not_active IP Right Cessation
- 1999-09-13 TR TR2001/01182T patent/TR200101182T2/xx unknown
- 1999-09-13 NZ NZ510168A patent/NZ510168A/en unknown
- 1999-09-13 ZA ZA200101995A patent/ZA200101995B/en unknown
- 1999-09-13 JP JP2000569846A patent/JP2002524535A/ja not_active Withdrawn
- 1999-09-13 OA OA1200100063A patent/OA11781A/en unknown
- 1999-09-13 EA EA200100300A patent/EA003476B1/ru active IP Right Revival
- 1999-09-13 SK SK344-2001A patent/SK3442001A3/sk unknown
- 1999-09-13 EP EP99969035A patent/EP1117442A1/fr not_active Withdrawn
- 1999-09-13 EE EEP200100151A patent/EE200100151A/xx unknown
- 1999-09-13 HK HK02101738.3A patent/HK1042231A1/zh unknown
- 1999-09-13 GE GEAP19995857A patent/GEP20043257B/en unknown
- 1999-09-13 MY MYPI99003947A patent/MY129282A/en unknown
- 1999-09-13 BR BR9913722-4A patent/BR9913722A/pt not_active IP Right Cessation
- 1999-09-13 AU AU60397/99A patent/AU753014B2/en not_active Ceased
- 1999-09-13 UA UA2001031707A patent/UA76085C2/uk unknown
- 1999-09-13 HR HR20010189A patent/HRP20010189A2/hr not_active Application Discontinuation
- 1999-09-13 WO PCT/US1999/021109 patent/WO2000015262A1/fr not_active Ceased
- 1999-09-13 AR ARP990104587A patent/AR022090A1/es unknown
- 1999-09-14 UY UY25711A patent/UY25711A1/es not_active Application Discontinuation
- 1999-09-14 TN TNTNSN99173A patent/TNSN99173A1/fr unknown
- 1999-09-14 GT GT199900156A patent/GT199900156A/es unknown
- 1999-09-14 PA PA19998481901A patent/PA8481901A1/es unknown
- 1999-09-14 CO CO99058265A patent/CO5130023A1/es unknown
- 1999-10-31 SA SA99200718A patent/SA99200718B1/ar unknown
2001
- 2001-02-21 IL IL141562A patent/IL141562A/en unknown
- 2001-03-05 IS IS5878A patent/IS5878A/is unknown
- 2001-03-13 NO NO20011251A patent/NO20011251L/no not_active Application Discontinuation
- 2001-03-14 LV LV010041A patent/LV12658B/xx unknown
- 2001-03-14 LT LT2001021A patent/LT4897B/lt not_active IP Right Cessation
- 2001-04-10 BG BG105430A patent/BG105430A/xx unknown

Also Published As

Publication number	Publication date
KR20010075063A (ko)	2001-08-09
TR200101182T2 (tr)	2001-09-21
NZ510168A (en)	2003-09-26
CO5130023A1 (es)	2002-02-27
ID28845A (id)	2001-07-05
MY129282A (en)	2007-03-30
OA11781A (en)	2005-07-26
HUP0103837A3 (en)	2002-11-28
NO20011251D0 (no)	2001-03-13
BG105430A (en)	2001-12-29
YU24201A (sh)	2003-08-29
AR022090A1 (es)	2002-09-04
AU753014B2 (en)	2002-10-03
LT2001021A (en)	2001-11-26
EA003476B1 (ru)	2003-06-26
EP1117442A1 (fr)	2001-07-25
PL195574B1 (pl)	2007-10-31
IL141562A (en)	2007-07-24
AP2001002093A0 (en)	2001-03-31
MA25590A1 (fr)	2002-12-31
TWI226248B (en)	2005-01-11
SK3442001A3 (en)	2001-11-06
LT4897B (lt)	2002-02-25
CZ2001829A3 (cs)	2001-09-12
PL346768A1 (en)	2002-02-25
EE200100151A (et)	2002-06-17
LV12658B (lv)	2001-09-20
UY25711A1 (es)	1999-11-17
JP2002524535A (ja)	2002-08-06
EA200100300A1 (ru)	2001-10-22
WO2000015262A1 (fr)	2000-03-23
NO20011251L (no)	2001-04-17
IL141562A0 (en)	2002-03-10
TNSN99173A1 (fr)	2005-11-10
GEP20043257B (en)	2004-06-25
GT199900156A (es)	2001-03-07
AP1374A (en)	2005-02-28
ZA200101995B (en)	2002-03-11
HRP20010189A2 (en)	2005-04-30
LV12658A (lv)	2001-05-20
IS5878A (is)	2001-03-05
SA99200718B1 (ar)	2006-11-04
BR9913722A (pt)	2001-05-29
PE20001061A1 (es)	2000-10-08
CN1317977A (zh)	2001-10-17
HK1042231A1 (zh)	2002-08-09
HUP0103837A2 (hu)	2002-05-29
DZ2892A1 (fr)	2003-12-15
HN1999000159A (es)	1999-11-11
PA8481901A1 (es)	2002-04-25
AU6039799A (en)	2000-04-03
CA2343920A1 (fr)	2000-03-23

Publication	Publication Date	Title
UA76085C2 (en)	2006-07-17	Aerosol particles resistant to hygroscopic growth
ES2213180T3 (es)	2004-08-16	Polvos y su uso en inhaladores de polvo seco.
US7625865B2 (en)	2009-12-01	Insulin highly respirable microparticles
ES2375007T3 (es)	2012-02-24	Mejoras en y relativas a partículas portadoras para su uso en inhaladores de polvo seco.
JP4859320B2 (ja)	2012-01-25	改良された分散性を有する乾燥粉末組成物
RU2275900C2 (ru)	2006-05-10	Способ высокоэффективной доставки аэрозоля с большой терапевтической массой
US6896906B2 (en)	2005-05-24	Storage stable powder compositions of interleukin-4 receptor
JP2003513031A5 (fr)	2011-02-24
Quarta et al.	2020	Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats
EP1485068A2 (fr)	2004-12-15	Preparations d'hormone de croissance humaine (hch) destinees a etre administrees par voie pulmonaire
CN101098671A (zh)	2008-01-02	最少化表面上的粉末滞留量
MXPA01002649A (en)	2001-12-04	Dry powder active agent pulmonary delivery
Arora et al.	2012	Liposome: a novel aerosol carrier of doxophylline in treatment of chronic asthma & chronic obstructive pulmonary disease
WO2025237925A1 (fr)	2025-11-20	Composition de poudre sèche comprenant un antagoniste de glp-1
HK1116391A (en)	2008-12-24	Minimizing powder retention on surfaces
HK1098078A (en)	2007-07-13	Highly efficient delivery of a large therapeutic mass aerosol