LT4897B - Sauso miltelių pavidalo aktyvaus agento įvedimas į plaučius - Google Patents

Sauso miltelių pavidalo aktyvaus agento įvedimas į plaučius Download PDF

Info

Publication number: LT4897B
Authority: LT; Lithuania
Prior art keywords: particles; active agent; powder; hygroscopic growth; growth inhibitor
Prior art date: 1998-09-14

Application number

LT2001021A

Other languages

English (en)

Lithuanian (lt)

Other versions

LT2001021A (en

Inventor

Andrew Clark

Mei Chang Kuo

Cecily Lalor

Barry John Aldous

Original Assignee

Inhale Therapeutic Systems,Inc.

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

2001-03-14

Publication date

2002-02-25

2001-03-14 Application filed by Inhale Therapeutic Systems,Inc. filed Critical Inhale Therapeutic Systems,Inc.

2001-11-26 Publication of LT2001021A publication Critical patent/LT2001021A/xx

2002-02-25 Publication of LT4897B publication Critical patent/LT4897B/lt

Links

239000000843 powder Substances 0.000 title claims description 169
239000013543 active substance Substances 0.000 title claims description 80
230000002685 pulmonary effect Effects 0.000 title claims description 3
238000000034 method Methods 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract description 5
239000002245 particle Substances 0.000 claims description 152
210000004072 lung Anatomy 0.000 claims description 97
239000000203 mixture Substances 0.000 claims description 67
239000003966 growth inhibitor Substances 0.000 claims description 50
238000010521 absorption reaction Methods 0.000 claims description 35
239000003795 chemical substances by application Substances 0.000 claims description 31
229920001612 Hydroxyethyl starch Polymers 0.000 claims description 28
229940050526 hydroxyethylstarch Drugs 0.000 claims description 28
238000001179 sorption measurement Methods 0.000 claims description 24
239000000443 aerosol Substances 0.000 claims description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
229920000858 Cyclodextrin Polymers 0.000 claims description 17
229920002307 Dextran Polymers 0.000 claims description 17
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 claims description 16
230000002401 inhibitory effect Effects 0.000 claims description 15
230000001965 increasing effect Effects 0.000 claims description 14
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
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 claims description 13
238000009826 distribution Methods 0.000 claims description 12
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 description 11
229920002774 Maltodextrin Polymers 0.000 claims description 10
238000001694 spray drying Methods 0.000 claims description 10
239000001116 FEMA 4028 Substances 0.000 claims description 7
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical group 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
235000011175 beta-cyclodextrine Nutrition 0.000 claims description 7
229960004853 betadex Drugs 0.000 claims description 7
229940097362 cyclodextrins Drugs 0.000 claims description 7
239000005913 Maltodextrin Substances 0.000 claims description 6
229920002678 cellulose Polymers 0.000 claims description 6
235000010980 cellulose Nutrition 0.000 claims description 6
229940035034 maltodextrin Drugs 0.000 claims description 6
229920001605 Dextranomer Polymers 0.000 claims description 5
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
239000001913 cellulose Substances 0.000 claims description 5
229960002864 dextranomer Drugs 0.000 claims description 5
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
229960002086 dextran Drugs 0.000 claims description 4
229940067631 phospholipid Drugs 0.000 claims description 4
150000003904 phospholipids Chemical class 0.000 claims description 4
208000007934 ACTH-independent macronodular adrenal hyperplasia Diseases 0.000 claims description 3
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
239000002904 solvent Substances 0.000 claims description 3
VKWZWOKLRQWMPC-UHFFFAOYSA-N 1-(2-hydroxybutoxy)butan-2-ol Chemical compound CCC(O)COCC(O)CC VKWZWOKLRQWMPC-UHFFFAOYSA-N 0.000 claims description 2
238000012387 aerosolization Methods 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
PVPBHKCSQBLDEW-ZQOBQRRWSA-N (1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecol 4-hydroxybutane-1-sulfonic acid Chemical compound OCCCCS(O)(=O)=O.OC[C@H]1O[C@@H]2O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@@H]6[C@@H](CO)O[C@H](O[C@@H]7[C@@H](CO)O[C@H](O[C@@H]8[C@@H](CO)O[C@H](O[C@H]1[C@H](O)[C@H]2O)[C@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O)[C@H](O)[C@H]3O PVPBHKCSQBLDEW-ZQOBQRRWSA-N 0.000 claims 3
BLUGYPPOFIHFJS-UUFHNPECSA-N (2s)-n-[(2s)-1-[[(3r,4s,5s)-3-methoxy-1-[(2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-[[(1s)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-3-methyl-2-(methylamino)butanamid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 BLUGYPPOFIHFJS-UUFHNPECSA-N 0.000 claims 1
229920000896 Ethulose Polymers 0.000 claims 1
239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 claims 1
235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 claims 1
239000003230 hygroscopic agent Substances 0.000 claims 1
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 58
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 32
102000004877 Insulin Human genes 0.000 description 29
108090001061 Insulin Proteins 0.000 description 29
229940125396 insulin Drugs 0.000 description 29
239000003814 drug Substances 0.000 description 28
238000009472 formulation Methods 0.000 description 27
229940079593 drug Drugs 0.000 description 23
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 21
229930195725 Mannitol Natural products 0.000 description 21
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 21
239000000594 mannitol Substances 0.000 description 21
235000010355 mannitol Nutrition 0.000 description 21
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
229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 20
108010068072 salmon calcitonin Proteins 0.000 description 20
239000004471 Glycine Substances 0.000 description 14
239000000463 material Substances 0.000 description 11
239000000546 pharmaceutical excipient Substances 0.000 description 11
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 10
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 10
108090000623 proteins and genes Proteins 0.000 description 9
210000002345 respiratory system Anatomy 0.000 description 9
239000000243 solution Substances 0.000 description 9
102000008100 Human Serum Albumin Human genes 0.000 description 8
108091006905 Human Serum Albumin Proteins 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
-1 fatty acid salts Chemical class 0.000 description 8
235000018102 proteins Nutrition 0.000 description 8
102000004169 proteins and genes Human genes 0.000 description 8
239000007787 solid Substances 0.000 description 8
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 7
230000000694 effects Effects 0.000 description 7
230000002093 peripheral effect Effects 0.000 description 7
102000004196 processed proteins & peptides Human genes 0.000 description 7
108090000765 processed proteins & peptides Proteins 0.000 description 7
239000000523 sample Substances 0.000 description 7
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 6
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 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000008021 deposition Effects 0.000 description 6
239000008103 glucose Substances 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
238000010348 incorporation Methods 0.000 description 5
229920001184 polypeptide Polymers 0.000 description 5
229920001282 polysaccharide Polymers 0.000 description 5
239000007921 spray Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
230000008859 change Effects 0.000 description 4
239000003623 enhancer Substances 0.000 description 4
239000000945 filler Substances 0.000 description 4
239000007789 gas Substances 0.000 description 4
150000004676 glycans Chemical class 0.000 description 4
230000001976 improved effect Effects 0.000 description 4
238000002156 mixing Methods 0.000 description 4
239000005017 polysaccharide Substances 0.000 description 4
238000003127 radioimmunoassay Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
ZVCVMOFMPFNDBB-UHFFFAOYSA-N 1-sulfonyl-4-(4-sulfonylbutoxy)butane Chemical compound O=S(=O)=CCCCOCCCC=S(=O)=O ZVCVMOFMPFNDBB-UHFFFAOYSA-N 0.000 description 3
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
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 3
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 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
239000004599 antimicrobial Substances 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
238000000576 coating method Methods 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
229940112141 dry powder inhaler Drugs 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000012530 fluid Substances 0.000 description 3
238000002221 gravimetric sorption analysis Methods 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000012545 processing Methods 0.000 description 3
230000009467 reduction Effects 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
238000010254 subcutaneous injection Methods 0.000 description 3
239000007929 subcutaneous injection Substances 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 2
SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-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 compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
235000005979 Citrus limon Nutrition 0.000 description 2
244000131522 Citrus pyriformis Species 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
102000003951 Erythropoietin Human genes 0.000 description 2
108090000394 Erythropoietin Proteins 0.000 description 2
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 2
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 2
239000000095 Growth Hormone-Releasing Hormone Substances 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
102000004889 Interleukin-6 Human genes 0.000 description 2
108090001005 Interleukin-6 Proteins 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
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
101710142969 Somatoliberin Proteins 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
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
239000000654 additive Substances 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
239000002260 anti-inflammatory agent Substances 0.000 description 2
229940121363 anti-inflammatory agent Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000011324 bead Substances 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
238000004364 calculation method Methods 0.000 description 2
150000001720 carbohydrates Chemical class 0.000 description 2
235000014633 carbohydrates Nutrition 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
229960004106 citric acid Drugs 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
229940119744 dextran 40 Drugs 0.000 description 2
229940039227 diagnostic agent Drugs 0.000 description 2
239000000032 diagnostic agent Substances 0.000 description 2
239000010432 diamond Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
238000009792 diffusion process Methods 0.000 description 2
210000002919 epithelial cell Anatomy 0.000 description 2
229940105423 erythropoietin Drugs 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
238000011049 filling Methods 0.000 description 2
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
229940028334 follicle stimulating hormone Drugs 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
230000036571 hydration Effects 0.000 description 2
238000006703 hydration reaction Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
229940100601 interleukin-6 Drugs 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
238000005259 measurement Methods 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
238000003801 milling Methods 0.000 description 2
150000002772 monosaccharides Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
108020004707 nucleic acids Proteins 0.000 description 2
150000007523 nucleic acids Chemical class 0.000 description 2
102000039446 nucleic acids Human genes 0.000 description 2
229920001542 oligosaccharide Polymers 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
230000005855 radiation Effects 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
230000000241 respiratory effect Effects 0.000 description 2
150000003839 salts Chemical class 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
238000012216 screening Methods 0.000 description 2
238000004062 sedimentation 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
150000005846 sugar alcohols Chemical class 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
238000012360 testing method Methods 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
229960005486 vaccine Drugs 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
NEZDNQCXEZDCBI-WJOKGBTCSA-N (2-aminoethoxy)[(2r)-2,3-bis(tetradecanoyloxy)propoxy]phosphinic acid Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-WJOKGBTCSA-N 0.000 description 1
DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 1
NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 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
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
SHCCKWGIFIPGNJ-NSUCVBPYSA-N 2-aminoethyl [(2r)-2,3-bis[(z)-octadec-9-enoxy]propyl] hydrogen phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC[C@H](COP(O)(=O)OCCN)OCCCCCCCC\C=C/CCCCCCCC SHCCKWGIFIPGNJ-NSUCVBPYSA-N 0.000 description 1
108060003345 Adrenergic Receptor Proteins 0.000 description 1
102000017910 Adrenergic receptor Human genes 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
101710081722 Antitrypsin Proteins 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
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical class CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
102000055006 Calcitonin Human genes 0.000 description 1
108060001064 Calcitonin Proteins 0.000 description 1
XWCDCDSDNJVCLO-UHFFFAOYSA-N Chlorofluoromethane Chemical compound FCCl XWCDCDSDNJVCLO-UHFFFAOYSA-N 0.000 description 1
102000009660 Cholinergic Receptors Human genes 0.000 description 1
108010009685 Cholinergic Receptors Proteins 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 Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
125000002353 D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 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
QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
108010053770 Deoxyribonucleases Proteins 0.000 description 1
102000016911 Deoxyribonucleases Human genes 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 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
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
108010076282 Factor IX Proteins 0.000 description 1
108010054218 Factor VIII Proteins 0.000 description 1
102000001690 Factor VIII Human genes 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
101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
108010008212 Integrin alpha4beta1 Proteins 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
229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
102000019223 Interleukin-1 receptor Human genes 0.000 description 1
108050006617 Interleukin-1 receptor Proteins 0.000 description 1
102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102000004388 Interleukin-4 Human genes 0.000 description 1
108090000978 Interleukin-4 Proteins 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
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
238000000134 MTT assay Methods 0.000 description 1
231100000002 MTT assay Toxicity 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
108010025020 Nerve Growth Factor Proteins 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
108010016076 Octreotide Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000005157 Somatostatin Human genes 0.000 description 1
108010056088 Somatostatin Proteins 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
239000000150 Sympathomimetic Substances 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
102000007501 Thymosin Human genes 0.000 description 1
108010046075 Thymosin Proteins 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
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000002776 aggregation Effects 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
102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
108010050122 alpha 1-Antitrypsin Proteins 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
238000004458 analytical method Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000001475 anti-trypsic effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
239000003472 antidiabetic 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
229940125687 antiparasitic agent Drugs 0.000 description 1
239000002216 antistatic agent Substances 0.000 description 1
239000003443 antiviral agent Substances 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
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 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
230000002238 attenuated effect Effects 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
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
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process 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 compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
229960004015 calcitonin Drugs 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
239000012159 carrier gas Substances 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
229940049197 cerezyme Drugs 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
DDPFHDCZUJFNAT-PZPWKVFESA-N chembl2104402 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=1N=CNC=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(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)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]1CCCCCC(=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 DDPFHDCZUJFNAT-PZPWKVFESA-N 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
238000005354 coacervation Methods 0.000 description 1
238000004590 computer program Methods 0.000 description 1
229940124558 contraceptive agent Drugs 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
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
230000003247 decreasing effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
229940119742 dextran 75 Drugs 0.000 description 1
229920003045 dextran sodium sulfate Polymers 0.000 description 1
235000015872 dietary supplement Nutrition 0.000 description 1
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
150000002016 disaccharides Chemical class 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
238000009513 drug distribution Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000012636 effector Substances 0.000 description 1
108700032313 elcatonin Proteins 0.000 description 1
229960000756 elcatonin Drugs 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
238000005516 engineering process Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
230000029142 excretion Effects 0.000 description 1
229960004222 factor ix Drugs 0.000 description 1
229960000301 factor viii Drugs 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000011152 fibreglass Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
238000010304 firing Methods 0.000 description 1
239000000796 flavoring agent Substances 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
MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical class 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
229960002714 fluticasone Drugs 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 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
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
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
229950006191 gluconic acid Drugs 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
210000003714 granulocyte Anatomy 0.000 description 1
239000003102 growth factor Substances 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
230000003054 hormonal effect Effects 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
239000003326 hypnotic agent Substances 0.000 description 1
230000000147 hypnotic effect Effects 0.000 description 1
229940126904 hypoglycaemic agent Drugs 0.000 description 1
108010039650 imiglucerase Proteins 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
150000002484 inorganic compounds Chemical class 0.000 description 1
229960000367 inositol Drugs 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
230000010354 integration Effects 0.000 description 1
229960003130 interferon gamma Drugs 0.000 description 1
229960001388 interferon-beta Drugs 0.000 description 1
239000003407 interleukin 1 receptor blocking agent Substances 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 class 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
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
150000002632 lipids Chemical class 0.000 description 1
239000003580 lung surfactant Substances 0.000 description 1
230000001592 luteinising effect Effects 0.000 description 1
230000014759 maintenance of location Effects 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
239000011159 matrix material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229940042006 metaproterenol sulfate Drugs 0.000 description 1
229930182817 methionine Natural products 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
229940035363 muscle relaxants Drugs 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
229960002700 octreotide Drugs 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
239000003002 pH adjusting agent Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
230000035699 permeability Effects 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
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
150000008103 phosphatidic acids Chemical class 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
229940067605 phosphatidylethanolamines Drugs 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
229920000642 polymer Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940068965 polysorbates Drugs 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
239000003368 psychostimulant agent Substances 0.000 description 1
238000011158 quantitative evaluation Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000009877 rendering Methods 0.000 description 1
210000004994 reproductive system Anatomy 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 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
239000000932 sedative agent Substances 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000007873 sieving Methods 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
210000002460 smooth muscle Anatomy 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
239000005720 sucrose Substances 0.000 description 1
229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 1
238000004441 surface measurement Methods 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000001975 sympathomimetic effect Effects 0.000 description 1
229940064707 sympathomimetics Drugs 0.000 description 1
210000000225 synapse Anatomy 0.000 description 1
230000001839 systemic circulation Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000004044 tetrasaccharides Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
229940126585 therapeutic drug Drugs 0.000 description 1
LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=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(C)C)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(C)C)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)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
210000003437 trachea Anatomy 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
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
229960005294 triamcinolone Drugs 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
229940073585 tromethamine hydrochloride Drugs 0.000 description 1
239000002753 trypsin inhibitor Substances 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
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
239000003021 water soluble solvent Substances 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)

LT2001021A 1998-09-14 2001-03-14 Sauso miltelių pavidalo aktyvaus agento įvedimas į plaučius LT4897B (lt)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US10016398P	1998-09-14	1998-09-14

Publications (2)

Publication Number	Publication Date
LT2001021A LT2001021A (en)	2001-11-26
LT4897B true LT4897B (lt)	2002-02-25

Family

ID=22278404

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LT2001021A LT4897B (lt)	1998-09-14	2001-03-14	Sauso miltelių pavidalo aktyvaus agento įvedimas į plaučius

Country Status (44)

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

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
ATE555773T1 (de)	1999-06-09	2012-05-15	Sievers Robert E	Überkritische fluidgestützte verneblung und blasen trochnen
US6475468B2 (en) *	2001-02-15	2002-11-05	Aeropharm Technology Incorporated	Modulated release particles for aerosol delivery
CA2446904A1 (en) *	2001-05-24	2003-04-03	Alexza Pharmaceuticals, Inc.	Delivery of drug esters through an inhalation route
EG24184A (en) *	2001-06-15	2008-10-08	Otsuka Pharma Co Ltd	Dry powder inhalation system for transpulmonary
CA2465675C (en)	2001-11-20	2008-06-10	Advanced Inhalation Research, Inc.	Improved particulate compositions for pulmonary delivery
US7759506B2 (en)	2002-02-25	2010-07-20	Diffusion Pharmaceuticals Llc	Bipolar trans carotenoid salts and their uses
EA200401111A1 (ru)	2002-02-25	2005-02-24	Диффьюжн Фармасьютикалз Ллс	Биполярные соли транс-каротиноидов и их применение
AU2003232081B2 (en) *	2002-07-03	2009-02-05	Brandeis University	Central airway administration for systemic delivery of therapeutics
WO2004060352A1 (en) *	2002-12-19	2004-07-22	Pharmacia Corporation	Non-hygroscopic formulation comprising a hydroscopic drug
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
PL2708225T3 (pl) *	2004-04-23	2019-07-31	Cydex Pharmaceuticals, Inc.	Formulacja DPI zawierająca eter sulfoalkilowy cyklodekstryny
UA95903C2 (ru) *	2005-02-24	2011-09-26	Дифьюжен Фармасьютикалз Ллк	Транс-каротиноиды, их синтез, лекарственная форма и применение
RU2007137121A (ru) *	2005-03-09	2009-04-20	Оно Фармасьютикал Ко., Лтд. (Jp)	Частица и препарат, содержащий указанную частицу
DK1945228T4 (da)	2005-10-26	2015-01-12	Cydex Pharmaceuticals Inc	Sulfoalkyl-ether-cyclodextrin-sammensætninger og fremgangsmåder til fremstilling deraf
US7629331B2 (en)	2005-10-26	2009-12-08	Cydex Pharmaceuticals, Inc.	Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof
US20080035143A1 (en) *	2006-08-14	2008-02-14	Sievers Robert E	Human-powered dry powder inhaler and dry powder inhaler compositions
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 (de) *	2006-11-22	2008-05-28	Boehringer Ingelheim Pharma GmbH & Co. KG	Stabile Pulverformulierung enthaltend ein Anticholinergikum
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
JP2011502125A (ja)	2007-10-31	2011-01-20	ディフュージョン・ファーマシューティカルズ・エルエルシー	小分子拡散を促進する新しい種類の治療法
DK2432502T3 (en)	2009-05-20	2018-03-12	Aeras	STABLE, SPRAY DRIED, IMMUNOGENE, VIRUS COMPOSITIONS
KR101875843B1 (ko)	2009-06-22	2018-07-06	디퓨젼 파마슈티컬즈 엘엘씨	확산 촉진 화합물 및 그 화합물 단독 또는 혈전 용해제와 합쳐진 화합물의 용도
KR101891357B1 (ko)	2010-06-02	2018-08-24	디퓨젼 파마슈티컬즈 엘엘씨	양극성 트랜스 카로티노이드의 경구용 제형
NZ630040A (en)	2012-05-03	2016-10-28	Janssen Sciences Ireland Uc	Polyinosinic-polycytidylic acid (poly (i:c)) formulations for the treatment of upper respiratory tract infections
BR112015010601B1 (pt) *	2012-11-09	2022-07-19	Civitas Therapeutics, Inc.	Composição farmacêutica e uso da composição
WO2015042352A1 (en) *	2013-09-20	2015-03-26	Virginia Commonwealth University	Delivery of particles using hygroscopic excipients
WO2016067252A1 (en)	2014-10-31	2016-05-06	Glaxosmithkline Intellectual Property Development Limited	Powder formulation
US11185523B2 (en)	2016-03-24	2021-11-30	Diffusion Pharmaceuticals Llc	Use of bipolar trans carotenoids with chemotherapy and radiotherapy for treatment of cancer
US20220378727A1 (en) *	2021-05-14	2022-12-01	The University Of Hong Kong	Dry powder formulations of tamibarotene for pulmonary and intranasal delivery

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1997044013A1 (en)	1996-05-24	1997-11-27	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
WO1998031346A1 (en)	1997-01-16	1998-07-23	Massachusetts Institute Of Technology	Preparation of particles for inhalation

Family Cites Families (4)

* 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
ES2177544T3 (es) *	1992-06-12	2002-12-16	Teijin Ltd	Polvo ultrafinno para inhalar y metodo para su preparacion.
US6524557B1 (en) *	1994-12-22	2003-02-25	Astrazeneca Ab	Aerosol formulations of peptides and proteins
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 OA OA1200100063A patent/OA11781A/en unknown
- 1999-09-13 WO PCT/US1999/021109 patent/WO2000015262A1/en not_active Ceased
- 1999-09-13 EA EA200100300A patent/EA003476B1/ru active IP Right Revival
- 1999-09-13 IL IL14156299A patent/IL141562A0/xx not_active IP Right Cessation
- 1999-09-13 AP APAP/P/2001/002093A patent/AP1374A/en active
- 1999-09-13 ID IDW20010582A patent/ID28845A/id unknown
- 1999-09-13 CZ CZ2001829A patent/CZ2001829A3/cs unknown
- 1999-09-13 EP EP99969035A patent/EP1117442A1/en not_active Withdrawn
- 1999-09-13 TW TW088115876A patent/TWI226248B/zh not_active IP Right Cessation
- 1999-09-13 BR BR9913722-4A patent/BR9913722A/pt not_active IP Right Cessation
- 1999-09-13 PL PL99346768A patent/PL195574B1/pl not_active IP Right Cessation
- 1999-09-13 EE EEP200100151A patent/EE200100151A/xx unknown
- 1999-09-13 AU AU60397/99A patent/AU753014B2/en not_active Ceased
- 1999-09-13 HN HN1999000159A patent/HN1999000159A/es unknown
- 1999-09-13 PE PE1999000925A patent/PE20001061A1/es not_active Application Discontinuation
- 1999-09-13 HR HR20010189A patent/HRP20010189A2/hr not_active Application Discontinuation
- 1999-09-13 JP JP2000569846A patent/JP2002524535A/ja not_active Withdrawn
- 1999-09-13 NZ NZ510168A patent/NZ510168A/en unknown
- 1999-09-13 MY MYPI99003947A patent/MY129282A/en unknown
- 1999-09-13 GE GEAP19995857A patent/GEP20043257B/en unknown
- 1999-09-13 SK SK344-2001A patent/SK3442001A3/sk unknown
- 1999-09-13 UA UA2001031707A patent/UA76085C2/uk unknown
- 1999-09-13 ZA ZA200101995A patent/ZA200101995B/en unknown
- 1999-09-13 TR TR2001/01182T patent/TR200101182T2/xx unknown
- 1999-09-13 KR KR1020017003208A patent/KR20010075063A/ko not_active Ceased
- 1999-09-13 YU YU24201A patent/YU24201A/sh unknown
- 1999-09-13 AR ARP990104587A patent/AR022090A1/es unknown
- 1999-09-13 CN CN99810871A patent/CN1317977A/zh active Pending
- 1999-09-13 CA CA002343920A patent/CA2343920A1/en not_active Abandoned
- 1999-09-13 DZ DZ990192A patent/DZ2892A1/xx active
- 1999-09-13 HK HK02101738.3A patent/HK1042231A1/zh unknown
- 1999-09-13 HU HU0103837A patent/HUP0103837A3/hu unknown
- 1999-09-14 PA PA19998481901A patent/PA8481901A1/es unknown
- 1999-09-14 CO CO99058265A patent/CO5130023A1/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
- 1999-10-31 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 LT LT2001021A patent/LT4897B/lt not_active IP Right Cessation
- 2001-03-14 LV LV010041A patent/LV12658B/xx unknown
- 2001-04-10 BG BG105430A patent/BG105430A/xx unknown

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1997044013A1 (en)	1996-05-24	1997-11-27	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
WO1998031346A1 (en)	1997-01-16	1998-07-23	Massachusetts Institute Of Technology	Preparation of particles for inhalation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GONDA I: "Aerosols for delivery of therapeutic and diagnostic agents to the respiratory tract", CRIT REV THER DRUG CARRIER SYST, 1990, pages 273 - 313, XP009099233

Also Published As

Publication number	Publication date
SK3442001A3 (en)	2001-11-06
HUP0103837A3 (en)	2002-11-28
MA25590A1 (fr)	2002-12-31
KR20010075063A (ko)	2001-08-09
EE200100151A (et)	2002-06-17
NO20011251L (no)	2001-04-17
LV12658A (lv)	2001-05-20
IL141562A0 (en)	2002-03-10
HK1042231A1 (zh)	2002-08-09
BG105430A (en)	2001-12-29
EA200100300A1 (ru)	2001-10-22
PL346768A1 (en)	2002-02-25
HUP0103837A2 (hu)	2002-05-29
UA76085C2 (en)	2006-07-17
LV12658B (lv)	2001-09-20
AR022090A1 (es)	2002-09-04
SA99200718B1 (ar)	2006-11-04
ID28845A (id)	2001-07-05
IL141562A (en)	2007-07-24
CZ2001829A3 (cs)	2001-09-12
GEP20043257B (en)	2004-06-25
TWI226248B (en)	2005-01-11
OA11781A (en)	2005-07-26
LT2001021A (en)	2001-11-26
DZ2892A1 (fr)	2003-12-15
AP2001002093A0 (en)	2001-03-31
WO2000015262A1 (en)	2000-03-23
CN1317977A (zh)	2001-10-17
PE20001061A1 (es)	2000-10-08
AU6039799A (en)	2000-04-03
NO20011251D0 (no)	2001-03-13
EP1117442A1 (en)	2001-07-25
CO5130023A1 (es)	2002-02-27
UY25711A1 (es)	1999-11-17
HRP20010189A2 (en)	2005-04-30
ZA200101995B (en)	2002-03-11
PL195574B1 (pl)	2007-10-31
GT199900156A (es)	2001-03-07
CA2343920A1 (en)	2000-03-23
PA8481901A1 (es)	2002-04-25
YU24201A (sh)	2003-08-29
HN1999000159A (es)	1999-11-11
AP1374A (en)	2005-02-28
BR9913722A (pt)	2001-05-29
AU753014B2 (en)	2002-10-03
JP2002524535A (ja)	2002-08-06
IS5878A (is)	2001-03-05
TNSN99173A1 (fr)	2005-11-10
NZ510168A (en)	2003-09-26
MY129282A (en)	2007-03-30
EA003476B1 (ru)	2003-06-26
TR200101182T2 (tr)	2001-09-21

Legal Events

Date	Code	Title	Description
2008-05-26	MM9A	Lapsed patents	Effective date: 20070913

Publication	Publication Date	Title
LT4897B (lt)	2002-02-25	Sauso miltelių pavidalo aktyvaus agento įvedimas į plaučius
US7625865B2 (en)	2009-12-01	Insulin highly respirable microparticles
KR100702878B1 (ko)	2007-04-04	개선된 분산성을 갖는 건조 분말 조성물
EP1296663B1 (en)	2007-03-21	Highly efficient delivery of a large therapeutic mass aerosol
US8586093B2 (en)	2013-11-19	Pulmonary delivery for levodopa
EP1487411B1 (en)	2019-01-02	Inhalable sustained therapeutic formulations
SK7772001A3 (en)	2001-12-03	Particles of amino acid, process for their preparation, powder containing same, process for the preparation of such powder, an inhalator containing such powder, and their use
JP2003513031A5 (is)	2011-02-24
US7754242B2 (en)	2010-07-13	Inhalable sustained therapeutic formulations
US20040009231A1 (en)	2004-01-15	hGH (human growth hormone) formulations for pulmonary administration
MXPA01002649A (en)	2001-12-04	Dry powder active agent pulmonary delivery
Batycky et al.	2002	The development of large porous particles for inhalation drug delivery
HK1098078A (en)	2007-07-13	Highly efficient delivery of a large therapeutic mass aerosol
HK1051139B (en)	2007-06-29	Highly efficient delivery of a large therapeutic mass aerosol