CN1303276A - 包含紧密压实的固体药剂原料的药物释放系统 - Google Patents
包含紧密压实的固体药剂原料的药物释放系统 Download PDFInfo
- Publication number
- CN1303276A CN1303276A CN99806648A CN99806648A CN1303276A CN 1303276 A CN1303276 A CN 1303276A CN 99806648 A CN99806648 A CN 99806648A CN 99806648 A CN99806648 A CN 99806648A CN 1303276 A CN1303276 A CN 1303276A
- Authority
- CN
- China
- Prior art keywords
- delivery system
- drug delivery
- liposome
- tightly compacted
- medicament stock
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 63
- 239000007787 solid Substances 0.000 title claims abstract description 28
- 238000012377 drug delivery Methods 0.000 title claims abstract description 26
- 239000002502 liposome Substances 0.000 claims abstract description 61
- 239000002245 particle Substances 0.000 claims abstract description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 37
- 230000003213 activating effect Effects 0.000 claims description 32
- 229940079593 drug Drugs 0.000 claims description 19
- 230000002685 pulmonary effect Effects 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 108020004414 DNA Proteins 0.000 claims description 11
- 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 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 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 claims description 8
- 238000001415 gene therapy Methods 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229960005486 vaccine Drugs 0.000 claims description 6
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
- 239000000734 parasympathomimetic agent Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 4
- 229960002555 zidovudine Drugs 0.000 claims description 4
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 229940126575 aminoglycoside Drugs 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 3
- 239000003246 corticosteroid Substances 0.000 claims description 3
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 239000004005 microsphere Substances 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 238000002255 vaccination Methods 0.000 claims description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 2
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 2
- 102000055006 Calcitonin Human genes 0.000 claims description 2
- 108060001064 Calcitonin Proteins 0.000 claims description 2
- 229930186147 Cephalosporin Natural products 0.000 claims description 2
- 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 claims description 2
- 102000053602 DNA Human genes 0.000 claims description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 2
- 229930182566 Gentamicin Natural products 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 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 claims description 2
- 102000004877 Insulin Human genes 0.000 claims description 2
- 108090001061 Insulin Proteins 0.000 claims description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
- 201000005505 Measles Diseases 0.000 claims description 2
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 claims description 2
- UZIQYAYUUNMDMU-UHFFFAOYSA-N N.[Br+] Chemical compound N.[Br+] UZIQYAYUUNMDMU-UHFFFAOYSA-N 0.000 claims description 2
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 2
- 229930182555 Penicillin Natural products 0.000 claims description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 2
- 201000005702 Pertussis Diseases 0.000 claims description 2
- 208000000474 Poliomyelitis Diseases 0.000 claims description 2
- 229920000153 Povidone-iodine Polymers 0.000 claims description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 claims description 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 2
- 102000013275 Somatomedins Human genes 0.000 claims description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
- 229960001391 alfentanil Drugs 0.000 claims description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 229960003060 bambuterol Drugs 0.000 claims description 2
- ANZXOIAKUNOVQU-UHFFFAOYSA-N bambuterol Chemical compound CN(C)C(=O)OC1=CC(OC(=O)N(C)C)=CC(C(O)CNC(C)(C)C)=C1 ANZXOIAKUNOVQU-UHFFFAOYSA-N 0.000 claims description 2
- 229960004495 beclometasone Drugs 0.000 claims description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 229960004436 budesonide Drugs 0.000 claims description 2
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims description 2
- 229960001736 buprenorphine Drugs 0.000 claims description 2
- 229960004015 calcitonin Drugs 0.000 claims description 2
- 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 2
- 210000003850 cellular structure Anatomy 0.000 claims description 2
- 229940124587 cephalosporin Drugs 0.000 claims description 2
- 150000001780 cephalosporins Chemical class 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 229960003405 ciprofloxacin Drugs 0.000 claims description 2
- 206010013023 diphtheria Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 229960001022 fenoterol Drugs 0.000 claims description 2
- 229960002428 fentanyl Drugs 0.000 claims description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims description 2
- 229960002714 fluticasone Drugs 0.000 claims description 2
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 claims description 2
- 229960002848 formoterol Drugs 0.000 claims description 2
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims description 2
- 229960002963 ganciclovir Drugs 0.000 claims description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 239000000745 gonadal hormone Substances 0.000 claims description 2
- 239000002271 gyrase inhibitor Substances 0.000 claims description 2
- 229960002897 heparin Drugs 0.000 claims description 2
- 229920000669 heparin Polymers 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 2
- 229960001410 hydromorphone Drugs 0.000 claims description 2
- 229940125396 insulin Drugs 0.000 claims description 2
- 229920002521 macromolecule Polymers 0.000 claims description 2
- 229960005181 morphine Drugs 0.000 claims description 2
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 claims description 2
- 229960004398 nedocromil Drugs 0.000 claims description 2
- 229960001699 ofloxacin Drugs 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 229960001609 oxitropium bromide Drugs 0.000 claims description 2
- LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 claims description 2
- 229960002085 oxycodone Drugs 0.000 claims description 2
- 229940049954 penicillin Drugs 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 229960001621 povidone-iodine Drugs 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 150000003233 pyrroles Chemical class 0.000 claims description 2
- 201000005404 rubella Diseases 0.000 claims description 2
- 229960002052 salbutamol Drugs 0.000 claims description 2
- 230000003637 steroidlike Effects 0.000 claims description 2
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 claims description 2
- 229960004739 sufentanil Drugs 0.000 claims description 2
- 229960000195 terbutaline Drugs 0.000 claims description 2
- 239000005495 thyroid hormone Substances 0.000 claims description 2
- 229940036555 thyroid hormone Drugs 0.000 claims description 2
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 claims description 2
- 229960000707 tobramycin Drugs 0.000 claims description 2
- 210000000605 viral structure Anatomy 0.000 claims description 2
- 239000002132 β-lactam antibiotic Substances 0.000 claims description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract description 5
- 239000012876 carrier material Substances 0.000 abstract 1
- 239000000443 aerosol Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000000843 powder Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 201000003883 Cystic fibrosis Diseases 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 238000012387 aerosolization Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 230000001804 emulsifying effect Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 210000001132 alveolar macrophage Anatomy 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 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
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 230000000622 irritating effect Effects 0.000 description 2
- 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 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000004549 pulsed laser deposition Methods 0.000 description 2
- 229960000329 ribavirin Drugs 0.000 description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 239000004594 Masterbatch (MB) Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283898 Ovis Species 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 235000012489 doughnuts Nutrition 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000002474 experimental method Methods 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
- 238000009472 formulation Methods 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000003230 hygroscopic agent Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000012383 pulmonary drug delivery Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012475 sodium chloride buffer Substances 0.000 description 1
- -1 sodium nitride Chemical class 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229930195727 α-lactose Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- 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
-
- 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
- A61P31/06—Antibacterial agents for tuberculosis
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Anesthesiology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
包含紧密压实的固体药剂原料的药物释放系统,该原料具有包含一种活性剂的、基本上各向同性的固态结构,该原料适合于产生含有所述活性剂的可吸入粒子,其中该紧密压实的固体药剂原料包含至少一种与微粒载体物料联合的活性剂,尤其包含脂质体。
Description
本发明涉及包含紧密压实的固体药剂原料的药物释放系统、该药剂原料的制备方法以及本发明的固体药剂原料的用途。
通过药物物质的吸入或吹入而给肺部用药的方法，例如将所需药物作为气雾剂或以粉末吸入给药目前已经实现。由于气雾剂常常是基于氟代烃或其他烃类的，因此通常需要用粉末吸入代替气雾剂。
EP 0407028公开了一种以粉末形式通过吸入法给药的装置。该装置和药物的缺点是由于用于压实的压力很低，固体药库不能安全地进行操作，而且压实体是脆性的，如果操作不小心，可能崩溃。
WO94/14490和WO93/24165公开的是一种粉末或微粒的吸入用药系统。WO93/24165的装置可从具有各向同性结构的压实片中产生粒子。WO94/14490的紧密压实的药物是通过施加高达500MPa的压力而制备的，因此比EP0407028所用压力高几个数量级。WO94/14490的压制体优于根据EP0407028的压制体。例如，由于紧密，不会崩溃，因此易于操作。而且，与EP0407028的压制体相比，它不会吸水。
脂质体是熟知的药物组合物载体。药物应用脂质体的优点已经得到很多人的认可。脂质体用在肺部已在治疗传染病和哮喘方面取得很大进展(例如参看H.Schreier，脂质体的肺部用药，“医用脂质体”，Paphadjopoulos &Lasic(eds.),Elsevier,1997；R.J.Gonzalez-Rothi & H.Schreier,脂质体胶囊在哮喘治疗中的肺部药物释放，Clin.Immunother.4,331-337,1995；H.Schreier,R.J.Gonzalez-Rothi,A.A.Stecenko,在肺部释放的脂质体，J.Controlled Release 24,209-223,1993)。有病的肺特别容易接受药物气雾剂通过吸入法进行局部治疗(H.Schreier & S.M.Sawyer,囊性纤维变性基因治疗用的脂质体DNA载体，最新应用、限制、及今后的发展方向，Adv.Drug Del.Rev.19,73-87,1996；L.Gagne & H.Schreier,质粒DNA的气雾化，溶质冷凝剂的保护作用，以及脂质体的载体，Proceed.Inten.Symp.Control.Rel.Bioact.Mater.,1997)。尽管用计量吸入剂(MDI)释放抗哮喘剂和抗过敏反应剂得到了广泛使用，但气雾化抗微生物剂，例如用于囊性纤维变性治疗的氨基苷类、用于婴儿呼吸道合胞体病毒感染治疗的利巴韦林和用于免疫损伤患者肺部卡氏肺囊虫感染治疗的戊双脒也只是在最近才引入使用(WO96/27393,H.Schreier,K.J.McNicol,M.Ausborn,D.W.Soucy,H.Derendorf,A.A.Stecenko,R.J.Gonzalez-Rothi,羊肺部的脂质体释放及急性脂质体毒性，Int.J.Pharmaceut.87,183-193,1992)。
本领域中已报道过与脂质体相当的其他微粒载体。它们包括微球体、纳粒子、大多孔粒子、脉冲激光聚合包衣的分子、人工病毒包膜等。
使用这些可供替换的微粒载体时，其制备方法通常是本领域已知的。例如，广范围释放的治疗药或美容药的微球体是如WO95/15118所述进行制备的。
在某些情况下可以使用纳粒子，只要它们能够按照本发明负载足量的活性剂并可向下呼吸道给药。它们可以按照本领域已知的方法制备，例如Heyder(GSF Munchen)，“药物在肺部的释放”，Abstracts IV,Hilton HeadIsland Converence,May 1998。
使用脉冲激光沉积(PLD)仪器和在短期不含水的过程中对药物粉末进行聚合物包衣的方法也都适合于形成本发明的微粒制剂。这些方法已有报道，例如Talton等“Novel Coating Method for Improved Dry Delivery”,Univ.ofFlorida UF 1997(1998)。
进一步适合的释放系统是利用大的多孔粒子，公开在David A.Edwards等“Large Porous Particles for Pulmonary Drug Delivery”(Science,20.June1997,Vol.276,p.1868-1871)。
下文是对脂质体进行说明，不过应当认为，本发明可以结合使用或替换为适合的其它微粒载体进行操作。
药物在肺部释放的复杂性在于：(ⅰ)需要训练患者协调呼吸和吸入气雾剂，(ⅱ)大多数药物吸收快速因而必须频繁给药，而频繁给药常常与全身副作用有关，(ⅲ)药物的水溶性差，可导致气道内的局部刺激作用和炎性作用，或者妨碍气雾剂的完全使用，和(ⅳ)治疗细胞内病原体的药物的胞溶性渗透作用差。这些问题举例来说，利巴韦林气雾剂的使用是有争论的，它要求过度的气雾化作用(“气雾剂帷幕(aerosoltent)”)、阀门的频繁监控、管道系统的改变、和气管内的管吸作用，以防止药物沉淀，同时在临床能达到最佳结果。肺部药物释放在治疗学上另一种不希望出现的问题是大多数药物在肺中快速吸收，必须要频繁给药，例如支气管扩张药和皮质甾类。微粒载体、尤其是脂质体，缓和了一些在常规气雾剂释放中所遇到的这些问题，因为它们能够(ⅰ)充当溶解性差的活性剂的增溶基质；(ⅱ)起到肺部缓释药库的作用；和(ⅲ)促进药物的细胞内释放，具体释放到肺泡巨噬细胞中。因此，脂质体可以提供一种手段，目的是(ⅰ)防止对肺组织的局部刺激作用，减少对肺的毒性，(ⅱ)延长局部治疗用药水平，和(ⅲ)产生较高细胞内药物浓度，例如在被感染的肺泡巨噬细胞中。已经认为是经脂质体进行肺部释放的药物包括抗癌药(抗微生物剂、肽、酶、抗哮喘和抗过敏反应的化合物以及色甘酸钠)。还包括免疫调节剂、免疫抑制剂、抗病毒剂和抗分支杆菌剂以及基因构成物。
本发明的一个目的是提供一种药物释放系统，用于活性剂的肺部释放，该系统与脂质体或其他微粒载体联合使用。本发明的另一个目的是提供一种紧密的固体药剂原料，适合于产生含有活性剂的可吸入粒子。
本发明的药物释放系统包含紧密压实的固体药剂原料，该原料包含一种活性剂，基本上是各向同性的固态结构，并且该原料适合于产生含有所述活性剂的可吸入粒子，其中该紧密压实的固体药剂原料包含至少一种与微粒载体例如脂质体联合的活性剂。本发明特别是基于这样一个意外的发现，即脂质体经得起高压，这是为形成含有脂质体的紧密固体药剂原料所必须的。还令人惊奇的是，当含有脂质体的粉末例如是通过用WO93/24165(引用作为本发明参考文献)中公开的装置进行研磨而从该紧密的药剂原料产生时，负载活性剂或与活性剂联合的载体(尤其是脂质体)不是空的或完全被破坏的。按照WO94/14490(也引用作为本发明参考文献)最好施加高达500MPa的压力。
令人惊奇的是，与活性剂联合的脂质体在压紧过程(同WO94/14490)和研磨过程(同WO93/24165)中都保持相当完整，外表没有变化。
按照本发明优选的是，与载体联合的活性剂排列在所述载体内和/或上。例如优选的是，活性剂结合在脂质体内，或者脂质体载有活性剂，即活性剂被脂质体包封。不过，在负载过程中，容易发生活性剂也结合在包封脂质体的外膜内，或者甚至在脂质体膜的外表面上，使活性剂在这种情况下不仅从脂质体的内部释放，而且也从脂质体的外膜或外壳释放。
微粒载体、尤其是脂质体的性质对本发明的药物释放系统来说不是主要关键。各种脂质体都可以压成本发明的紧密压实的药剂原料，包括带负电的、中性和阳离子脂质体以及如WO96/27393所述的脂质配合物。可以利用如我们早期申请、现在的EP0639373所述的脂质体来实施本发明。
优选的是，与至少一种活性剂联合的脂质体与至少一种辅助物料组合，例如填充物料。该辅助物料优选是一种药学上可接受的填充物料，例如选自生理学上可接受的糖或盐。特别优选的辅助物料选自乳糖、海藻糖、葡萄糖、甘露糖(mannit)、氮化钠和它们的组合。优选使用乳糖作为辅助物料，对一重量份脂质体的比例至少为一百重量份乳糖。在优选的实施方式中，本发明的药物释放系统的药剂原料是用50至500MPa的压力均匀压实的。
上述至少一种活性剂基本上可以是任何能显示出药学或生物学作用的活性剂，其范围例如包括从小分子到人造的人染色体，只要它们能够载在脂质体中或与脂质体联合即可。特别是至少一种选自下组的活性剂，包括：
-短效β2-拟交感神经剂，例如沙丁胺醇、特布他林、非诺特罗、班布特罗，
-长效β2-拟交感神经剂，例如沙美特罗、福莫特罗，
-吸入用皮质甾类，例如布地奈德、倍氯米松、氟替卡松，
-抗胆碱能剂，例如依托溴铵、氧托溴铵，
-非甾体抗变态反应剂，例如DSCG、奈多罗米，
-抗炎剂，尤其是抗生素和/或抗菌剂，例如聚维酮碘，
和它们的组合。
进而，本发明的药物释放系统的药剂原料中的至少一种活性剂可以选自：
-β-内酰胺抗生素，例如青霉素、头孢菌素、亚胺培南；氨基苷类，例如妥布霉素、庆大霉素；促旋酶抑制剂，例如氧氟沙星、环丙沙星，
-抗病毒剂，例如更昔洛韦、叠氮胸苷，
-抗霉菌剂，例如polyeme、吡咯，
-抗麻疹、风疹、白喉、百日咳、脊髓灰质炎等的疫苗，
-主要由病毒或细菌组分组成的疫苗，
-含有编码产生特异性抗原的DNA的疫苗，
-用于疼痛缓解和治疗的阿片样物质，例如吗啡、氧可酮、氢吗啡酮、丁丙诺啡、芬太尼、阿芬太尼、舒芬太尼等，
-抗感染剂，例如低聚/聚核糖-和/或低聚/聚脱氧核糖核酸，
-肽、多肽，例如胰岛素、低和高分子肝素，
-激素，例如生长因子、甲状腺的激素、性激素、降钙素，
和它们的组合。
除非采取额外的预防措施，本发明可能不太适合于吸湿剂、容易氧化的活性剂、和某些遇光不稳定的活性剂。不过，常常可能的做法是把适当的保护性物质加入到形成两亲物质的脂质体膜中、加入到脂质体的内部物质中、和/或加入到助剂或载体物质中，以充分保护和稳定本发明所用的如此敏感的活性剂。
为了从本发明的紧密压实的药剂原料中产生微粒物料，可以利用任何适合于从固体母料中产生粉末的方法。特别优选的方法例如微粉化或研磨的方法，尤其公开在EP0407028(引用作为本发明参考文献)以及WO94/14490(引用作为本发明参考文献)。
在肺部用药时，从紧密压实的药剂原料中产生的粒子粒径优选为0.1至50μm，更优选为1至8μm。在鼻部用药时，其相应粒径优选为1至15μm。
用在根据本发明的药物释放系统中的药剂原料的制备方法包括制备微粒载体、尤其是脂质体，和以本身已知的方式进行负载的步骤。将负载的载体粒子可以任选与至少一种辅助物料混合，随后均匀压制成一定形状的物体。优选地，所用压力在50至500MPa范围内。成形的物体优选使用公开在WO93/24165中的装置进行成形。该形状尤其是公开在WO94/14490中的一种环形片。
当载体是脂质体物料时，例如可以将磷脂酰胆碱和磷脂酰甘油的干燥脂质膜分散在一种水溶液中，优选为生理溶液。相关的活性剂也存在在同一的溶液中，也可以有或没有辅助物料。例如通过摇动，使分散系成分充分混合。然后对分散系进行一次或多次冻熔，并优选通过膜挤出法进行乳化。冻熔和乳化循环重复若干次。为了除去没有被包封的活性剂，使用把脂质体与活性药物分离的方法。这些方法对技术人员来说是已知的，并且根据所要包封的活性剂大小加以选择。例如，如果必须从脂质体分散系中分离小分子量活性剂，那么可以通过透析混合物进行分离。最终的分散系例如再进行冷冻和冷冻干燥等进一步操作。将优选通过冻干法制备的固体物料研制，得到脂质体粗颗粒。将该颗粒与辅助物料混合，随后在50与500MPa之间的压力下压制。通过这些操作得到具有平滑表面的固体、非脆性片剂。
用在本发明的药物释放系统中的紧密压实的固体药剂原料可用于产生能够通过吹入法和/或吸入法给药的粒子。紧密压实的固体药剂可用在呼吸道疾病与障碍以及器官疾病与障碍的常规疗法中。本发明的药剂原料也可用在基因疗法和/或疫苗接种中。
基因疗法正在形成一种临床上可用的治疗方案，用于遗传性、肿瘤和传染性疾病。一个突出的例子是囊性纤维变性，这是一种由囊性纤维变性跨膜电导调节(CFTR)基因引起的遗传性疾病。有鉴于此，基因构成物的脂质体载体的肺部释放最近已经受到更多关注。不过，实验已经显示，用或不用脂质体进行的DNA通过常规喷雾器的反复循环操作对DNA是有害的，导致自喷雾开始后数分钟内完全降解。除此以外，并且考虑到其他通常有关脂质体的稳定性，基因疗法要求相对浓缩剂量的DNA配合物或者包封在脂质体内释放。不过，DNA/脂质配合物的浓溶液趋于聚集和沉淀，因此不能实现含水分散系的雾化作用。不过，本发明的药物释放系统由于使用了本发明的紧密压实的药剂原料，能够克服现有技术已知的其他DNA/脂质体给药方法的缺点。其他基因疗法的目的可能是医治Ⅸ因子和α1-抗胰蛋白酶基因缺乏，以及治疗与Ⅷ因子产生不足或其他在凝血级联中起到重要作用的蛋白质产生不足有关的血友病。当然，不言而喻的是，所提到的上述基因疗法的目标仅供举例说明之用。它们不应限制本发明的范围。
用本发明的药物释放系统也可以通过相关结构或物质的释放来实现疫苗接种。在这种情况下，用于诱导免疫应答的常规载体可以借助于本发明的紧密压实的药剂原料中存在的脂质体等载体给药。
下列实施例用于详细解释本发明，而不用于限定或限制本发明的范围。
实施例Ⅰ
将由5.76克磷脂酰胆碱和0.64克磷脂酰甘油组成的干燥脂质膜分散在含有3.8克荧光素异硫氰酸酯-葡聚糖(FITC-葡聚糖)和28.8克α-乳糖的160ml磷酸盐缓冲盐水(PBS)中。该分散体系用手摇动2小时，然后进行冻熔，再利用EmulsiFex-C5(Avestin)均化器，在不超过3000psi下，通过100nm孔径膜(Poretic)挤出法乳化10分钟。冻熔和挤出循环重复三次。为了除去没有被包封的FITC-葡聚糖，利用分子量截留值为18000的中空纤维药筒，将脂质体分散体系对乳糖溶液(1800克α-乳糖/10L PBS)进行透析，流速为8-10ml/分。三个透析循环之后，荧光浓度保持恒定，为原始浓度的大约50％，用Hitachi F-2000荧光分光光度计进行测量。将最终的分散液在干冰与乙醇的混合物中冷冻，转移到冻干器(Edwars Supermodulyo)中。将冷冻后的制剂在-40℃和0.07毫巴下冷冻干燥48小时，然后在25℃下再次干燥4小时。用干燥氮气代替真空。产量为41.7克。研制冻干后的饼，得到自由流动的、脂质体粗颗粒。将该颗粒以1∶10w/w比例与乳糖混合，在150MPa下均匀压制约60秒。制得具有光滑表面的固体、非脆性片剂，装在根据WO93/24165的装置的塑料夹具上，在塑料容器中在室温下贮藏。片剂驱动20次。测定每次驱动从片剂表面刮下的总质量和每次驱动的FITC-萄聚糖含量。总的释放质量为9.66+/-0.99mg，含有208+/-63 F.U.的FITC-萄聚糖。
实施例Ⅱ
使用按照EP0639373制备的脂质体重复上述操作如下：
在具有用来增加表面的玻璃珠的1000ml烧瓶中，将51.9mg胆固醇和213mg氢化大豆卵磷脂溶于足量甲醇与氯仿的2∶1混合物。然后在真空下蒸发溶剂，直到在烧瓶内表面上和玻璃珠上形成一层膜。
另将2.4gPVP碘(含有约10％可利用的碘)溶于12ml水。
再在另一个容器内，将8.77g氯化钠和1.78g Na2HPO4·2H2O溶于400ml水。进一步加入水，使总体积达到980ml，然后加入大约12ml 1N氢氯酸，调pH至7.4。该溶液然后加满水，至精确的1000ml。
在第四个容器内，将900mg蔗糖和57mg琥珀酸二钠溶于12ml水。
然后在烧瓶内向脂质膜加入PVP碘溶液，摇动混合物，直到膜溶解。这样在烧瓶内从水合的脂质生成脂质体。将产物离心，弃去上清液。加入约12ml蔗糖溶液，产物再次离心。然后再次弃去上清液。在该阶段，可以使用进一步的、用蔗糖溶液或氯化钠缓冲溶液洗涤的步骤。
在最后一步离心和弃去上清液后，加入约12ml氯化钠缓中溶液，脂质体均匀地分布其中。然后将产物分装在小瓶内，每瓶含有2ml脂质体分散液，然后将小瓶冷冻干燥。
冷冻干燥后，每瓶包含约40mg固体。
然后如实施例Ⅰ所述，将固体脂质体与乳糖压实。
借助WO93/24165的研磨装置，使用环形片，每次驱动释放总共大约10mg粉末。粉末中的PVP碘含量相当于理论(计算)值，在实验误差界限内。
Claims (14)
1．包含紧密压实的固体药剂原料的药物释放系统，该原料具有包含一种活性剂的基本上是各向同性的固态结构，该原料适合于产生含有所述活性剂的可吸入粒子，其中该紧密压实的固体药剂原料包含至少一种与脂质体或类似微粒载体联合的活性剂。
2．权利要求1的药物释放系统，其中包含在该紧密压实的药剂原料中的至少一种活性剂是包封在所述脂质体膜中的和/或与之联合的。
3．权利要求1和/或2的药物释放系统，其中所述紧密压实的固体药剂原料含有所述脂质体，以及辅助物料例如填充物料。
5．权利要求1至3任意一项的药物释放系统，其中包含在该紧密压实的固体药剂原料中的所述至少一种活性剂选自
-短效β2-拟交感神经剂，例如沙丁胺醇、特布他林、非诺特罗、班布特罗，
-长效β2-拟交感神经剂，例如沙美特罗、福莫特罗，
-吸入用皮质甾类，例如布地奈德、倍氯米松、氟替卡松，
-抗胆碱能剂，例如依托溴铵、氧托溴铵，
-非甾体抗变态反应剂，例如DSCG、奈多罗米，
-抗炎剂，尤其是抗生素和/或抗菌剂，例如聚维酮碘，
和它们的组合。
5．权利要求1至3任意一项的药物释放系统，其中包含在该紧密压实的固体药剂原料中的所述至少一种活性剂选自
-β-内酰胺抗生素，例如青霉素、头孢菌素、亚胺培南；氨基苷类，例如妥布霉素、庆大霉素；促旋酶抑制剂，例如氧氟沙星、环丙沙星，
-抗病毒剂，例如更昔洛韦、叠氮胸苷，
-抗霉菌剂，例如polyeme、吡咯，
-抗麻疹、风疹、白喉、百日咳、脊髓灰质炎等的疫苗，
-主要由病毒或细菌组分组成的疫苗，
-含有编码产生特异性抗原的DNA的疫苗，
-用于疼痛缓解和治疗的阿片样物质，例如吗啡、氧可酮、氢吗啡酮、丁丙诺啡、芬太尼、阿芬太尼、舒芬太尼等，
-抗感染剂，例如低聚/聚核糖-和/或低聚/聚脱氧核糖核酸，
-肽、多肽，例如胰岛素、低和高分子肝素，
-激素，例如生长因子、甲状腺的激素、性激素、降钙素，
和它们的组合。
6．权利要求1至5任意一项的药物释放系统，其中该紧密压实的固体药剂原料已经用50至500MPa的压力均匀压实。
7．权利要求1至6任意一项的药物释放系统，其中该紧密压实的固体药剂原料中的辅助物料选自乳糖、海藻糖、葡萄糖、甘露糖、氯化钠和它们的组合。
8．权利要求1至7任意一项的药物释放系统，其中该脂质体与乳糖的混合比例为每1重量份脂质体至少100重量份乳糖。
9．权利要求1至5任意一项的药物释放系统，其中该紧密压实的药剂原料经过适当处理产生粒子，例如微粉化或研磨作用。
10．权利要求9的药物释放系统，其中所产生的粒子粒径为0.1至50μm，特别是在肺部用药时为1至8μm，在鼻部用药时为1至15μm。
11．权利要求1的药物释放系统，其中该微粒载体选自微球体、纳粒子、大多孔粒子、人造病毒包膜和类似的药学上可接受的物料。
12．权利要求1至11任意一项的药物释放系统的紧密压实的固体药剂原料的制备方法，其中该脂质体是按已知方式制备或负载的，可任选地与至少一种辅助物料混合，随后通过均匀压制形成具有一定形状的物体。
13．权利要求12的方法，其中该均匀压制法是用50至500MPa的压力进行的。
14．权利要求1至11任意一项的药物释放系统中的紧密压实的固体药剂原料在呼吸道疾病和障碍以及器官疾病与障碍的疗法、基因疗法和/或疫苗接种中的用途，用于产生能够通过吹入和/或吸入给药的粒子。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8689598P | 1998-05-27 | 1998-05-27 | |
| US60/086,895 | 1998-05-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1303276A true CN1303276A (zh) | 2001-07-11 |
Family
ID=22201600
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99806578A Pending CN1303272A (zh) | 1998-05-27 | 1999-05-27 | 施用于上呼吸道和/或耳部的消炎剂,特别是抗菌剂和/或促进伤口愈合活性剂的制剂 |
| CN99806577A Pending CN1303271A (zh) | 1998-05-27 | 1999-05-27 | 施用于下呼吸道的消炎剂,特别是抗菌剂和/或促进伤口愈合活性剂的制剂 |
| CN99806648A Pending CN1303276A (zh) | 1998-05-27 | 1999-05-27 | 包含紧密压实的固体药剂原料的药物释放系统 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99806578A Pending CN1303272A (zh) | 1998-05-27 | 1999-05-27 | 施用于上呼吸道和/或耳部的消炎剂,特别是抗菌剂和/或促进伤口愈合活性剂的制剂 |
| CN99806577A Pending CN1303271A (zh) | 1998-05-27 | 1999-05-27 | 施用于下呼吸道的消炎剂,特别是抗菌剂和/或促进伤口愈合活性剂的制剂 |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US20080038330A1 (zh) |
| EP (3) | EP1079806B1 (zh) |
| JP (3) | JP2002516269A (zh) |
| KR (3) | KR100445146B1 (zh) |
| CN (3) | CN1303272A (zh) |
| AT (3) | ATE319427T1 (zh) |
| AU (3) | AU752018C (zh) |
| BR (3) | BR9911070A (zh) |
| CA (3) | CA2332371A1 (zh) |
| CY (1) | CY1105834T1 (zh) |
| DE (6) | DE29923766U1 (zh) |
| DK (2) | DK1079807T3 (zh) |
| ES (2) | ES2273493T3 (zh) |
| HK (2) | HK1035335A1 (zh) |
| HU (3) | HU226710B1 (zh) |
| IL (4) | IL139231A0 (zh) |
| PT (2) | PT1079806E (zh) |
| RU (3) | RU2212884C2 (zh) |
| WO (3) | WO1999060999A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108743537A (zh) * | 2012-05-21 | 2018-11-06 | 英斯麦德公司 | 治疗肺部感染的系统 |
| CN111700883A (zh) * | 2020-07-23 | 2020-09-25 | 深圳大佛药业股份有限公司 | 一种硫酸沙丁胺醇缓释型吸入制剂及其生产工艺 |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
| ES2341532T3 (es) * | 1999-05-27 | 2010-06-22 | Euro-Celtique S.A. | Preparacion con povidona yodada para el tratamiento de heridas. |
| US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
| WO2000072823A1 (en) | 1999-05-27 | 2000-12-07 | Euroceltique S.A. | Preparations for the application of anti-inflammatory agents |
| EP2517710B1 (en) * | 2000-02-08 | 2015-03-25 | Euro-Celtique S.A. | Tamper-resistant oral opioid agonist formulations |
| US6989157B2 (en) * | 2000-07-27 | 2006-01-24 | Nucryst Pharmaceuticals Corp. | Dry powders of metal-containing compounds |
| MXPA03005655A (es) | 2000-12-21 | 2004-12-03 | Nektar Therapeutics | Liberacion pulmonar de agentes antifungicos de polieno. |
| US6667344B2 (en) | 2001-04-17 | 2003-12-23 | Dey, L.P. | Bronchodilating compositions and methods |
| US20030055026A1 (en) | 2001-04-17 | 2003-03-20 | Dey L.P. | Formoterol/steroid bronchodilating compositions and methods of use thereof |
| DE10125731A1 (de) * | 2001-05-17 | 2003-03-06 | A I D Autoimmun Diagnostika Gm | Darreichungsform von immunologischen Wirkstoffen |
| DE10141650C1 (de) * | 2001-08-24 | 2002-11-28 | Lohmann Therapie Syst Lts | Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen |
| KR20040093155A (ko) * | 2002-03-18 | 2004-11-04 | 야마노우치세이야쿠 가부시키가이샤 | 흡입용 분말 의약조성물 및 이의 제조방법 |
| US7718189B2 (en) | 2002-10-29 | 2010-05-18 | Transave, Inc. | Sustained release of antiinfectives |
| EP1561467A4 (en) * | 2002-11-11 | 2008-06-25 | Kowa Co | COMPOSITION FOR RECOVERING DAMAGED SKIN |
| EP1631259A4 (en) | 2002-12-18 | 2006-08-02 | Hough Ear Inst | OTOLOGICAL NANOTECHNOLOGY |
| EP1449520A1 (en) * | 2003-02-24 | 2004-08-25 | Euro-Celtique S.A. | Use of PVP-Iodine liposomes for treatment of herpes |
| DK1479379T3 (da) * | 2003-05-19 | 2008-01-02 | Euro Celtique Sa | Törre, liposomale PVP-iod-sammensætninger |
| US7344491B1 (en) | 2003-11-26 | 2008-03-18 | Nanobiomagnetics, Inc. | Method and apparatus for improving hearing |
| US8651113B2 (en) | 2003-06-18 | 2014-02-18 | Swr&D Inc. | Magnetically responsive nanoparticle therapeutic constructs and methods of making and using |
| US7723311B2 (en) | 2003-06-18 | 2010-05-25 | Nanobiomagnetics, Inc. | Delivery of bioactive substances to target cells |
| TWI359675B (en) | 2003-07-10 | 2012-03-11 | Dey L P | Bronchodilating β-agonist compositions |
| US20050058673A1 (en) | 2003-09-09 | 2005-03-17 | 3M Innovative Properties Company | Antimicrobial compositions and methods |
| US9028852B2 (en) | 2004-09-07 | 2015-05-12 | 3M Innovative Properties Company | Cationic antiseptic compositions and methods of use |
| FR2878746B1 (fr) | 2004-12-02 | 2007-02-23 | Vetoquinol Sa Sa | Nouvelle composition pharmaceutique utilisable dans le domaine des vaccins |
| EP1858482B1 (en) | 2005-03-10 | 2014-04-23 | 3M Innovative Properties Company | Methods of reducing microbial contamination |
| TW200724134A (en) | 2005-03-10 | 2007-07-01 | 3M Innovative Properties Co | Antimicrobial compositions and methods |
| AU2006322076C1 (en) | 2005-12-08 | 2013-11-14 | Insmed Incorporated | Lipid-based compositions of antiinfectives for treating pulmonary infections |
| DE102006011314A1 (de) | 2006-03-11 | 2007-10-18 | Peter Dr. Engels | Kosmetische Zubereitungen mit einem Zusatz aus der Baobab-Pflanze |
| US20080057129A1 (en) * | 2006-04-03 | 2008-03-06 | Lerner E I | Drug microparticles |
| RU2315593C1 (ru) * | 2006-08-02 | 2008-01-27 | Открытое Акционерное Общество Завод Экологической Техники И Экопитания "Диод" | Липосомальная композиция антиоксидантов для ингаляций при заболеваниях легких и верхних дыхательных путей |
| US8071127B2 (en) | 2006-10-24 | 2011-12-06 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| US8119156B2 (en) | 2006-10-24 | 2012-02-21 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| US8268347B1 (en) * | 2006-10-24 | 2012-09-18 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| JP5551442B2 (ja) | 2006-10-27 | 2014-07-16 | スリーエム イノベイティブ プロパティズ カンパニー | 抗菌剤組成物 |
| US20100196455A1 (en) | 2007-05-04 | 2010-08-05 | Transave, Inc. | Compositions of Multicationic Drugs for Reducing Interactions with Polyanionic Biomolecules and Methods of Use Thereof |
| US9333214B2 (en) | 2007-05-07 | 2016-05-10 | Insmed Incorporated | Method for treating pulmonary disorders with liposomal amikacin formulations |
| US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
| US9114081B2 (en) | 2007-05-07 | 2015-08-25 | Insmed Incorporated | Methods of treating pulmonary disorders with liposomal amikacin formulations |
| ES2402618T3 (es) * | 2007-11-23 | 2013-05-07 | Pharmalundensis Ab | Usos y medios para obtener relajación bronquial |
| WO2009085651A1 (en) | 2007-12-20 | 2009-07-09 | Nucryst Pharmaceuticals Corp. | Metal carbonate particles for use in medicine and methods of making thereof |
| KR20100048751A (ko) * | 2008-10-31 | 2010-05-11 | 주식회사 동성바이오레인 | 스프레이 가능한 캡슐화된 기능성 미립자 조성물과 그 제조방법 |
| NL2002442C2 (nl) | 2009-01-22 | 2010-07-26 | Weezenbeek Specialties B V Van | Werkwijze voor het verjongen van een bitumen bevattende samenstelling. |
| EP2226073A1 (en) | 2009-03-02 | 2010-09-08 | Euro-Celtique S.A. | Topical pharmaceutical composition comprising an antiseptic and arginine for wound healing |
| US20110086084A1 (en) * | 2009-10-13 | 2011-04-14 | David William Koenig | Active Agent Containing Polymer Network Delivery Composition and Articles Using the Same |
| LT2722053T (lt) | 2010-12-30 | 2017-12-11 | Aktsionernoye Obshchestvo "Nauchnyi Tsentr Protivoinfektsionnyh Preparatov" | Antibakterinis agentas, skirtas bakterinės kilmės infekcinių ligų gydymui |
| WO2013059622A1 (en) * | 2011-10-19 | 2013-04-25 | President And Fellows Of Harvard College | Treatments for mycobacterium tuberculosis |
| KR101860485B1 (ko) * | 2011-11-03 | 2018-07-02 | (주)아모레퍼시픽 | 미세 유화 입자를 포함하는 미용 티슈, 그 제조방법 및 사용방법 |
| US10124066B2 (en) | 2012-11-29 | 2018-11-13 | Insmed Incorporated | Stabilized vancomycin formulations |
| RU2538433C1 (ru) * | 2013-06-11 | 2015-01-10 | Закрытое акционерное общество "ФИРН М" (ЗАО ФИРН М") | Фармацевтическая композиция для профилактики и лечения инфекционно-воспалительных заболеваний различной этиологии путем оромукозного введения |
| US9987227B2 (en) | 2013-10-22 | 2018-06-05 | Aradigm Corporation | Inhaled surfactant-modified liposomal formulations providing both an immediate and sustained release profile |
| RU2550932C1 (ru) * | 2014-03-18 | 2015-05-20 | Александр Александрович Кролевец | Способ получения нанокапсул цефалоспориновых антибиотиков в ксантановой камеди |
| WO2015156904A1 (en) * | 2014-04-08 | 2015-10-15 | Aradigm Corporation | Liposomes that form drug nanocrystals after freeze-thaw |
| US20160120806A1 (en) * | 2014-04-08 | 2016-05-05 | Aradigm Corporation | Nanocrystals formed in a microenvironment |
| WO2015157038A1 (en) | 2014-04-08 | 2015-10-15 | Aradigm Corporation | Liposomal ciprofloxacin formulations with activity against non-tuberculous mycobacteria |
| SI3466432T1 (sl) | 2014-05-15 | 2020-11-30 | Insmed Incorporated | Postopek zdravljenja pljučnih netuberkuloznih mikobakterijskih okužb |
| WO2016011496A1 (en) | 2014-07-23 | 2016-01-28 | Firebrick Pharma Pty Ltd | Treatment and prevention of the common cold using povidone-iodine |
| KR102086150B1 (ko) | 2017-04-10 | 2020-03-06 | 부산대학교 산학협력단 | 하이드로겔화 되는 창상 치료용 파우더 조성물 및 이의 제조방법 |
| FR3066115B1 (fr) | 2017-05-10 | 2019-06-28 | Universite de Bordeaux | Comprimes de vecteurs d'acides nucleiques |
| KR101935250B1 (ko) * | 2017-07-04 | 2019-01-04 | 김대황 | 요오드제 및 삼투성 미각제를 포함하는 눈, 구강용, 비강용 또는 흡입용 항바이러스 및 항균 조성물 |
| WO2019009630A1 (ko) * | 2017-07-04 | 2019-01-10 | 김대황 | 수용해성이 향상된 요오드제 및 염화나트륨을 포함하는 고체 조성물 및 이의 수용액을 포함하는 눈, 구강용, 비강용 또는 흡입용 항바이러스 및 항균 조성물 |
| US20200289552A1 (en) * | 2017-07-04 | 2020-09-17 | Fluchem Ltd | Solid composition comprising iodine agent and sodium chloride having improved water solubility, and antiviral and antimicrobial composition for eye, oral cavity, nasal cavity or inhalation containing aqueous solution thereof |
| KR102026805B1 (ko) | 2017-12-12 | 2019-11-04 | 주식회사 크로파세 | 항염 화장료 조성물 |
| US11571386B2 (en) | 2018-03-30 | 2023-02-07 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
| EP3781151A1 (en) * | 2018-04-17 | 2021-02-24 | Université de Caen Normandie | Bambuterol for the treatment of alzheimer's disease |
| RU2730834C1 (ru) * | 2020-01-17 | 2020-08-26 | Александр Александрович Кролевец | Способ получения нанокапсул тимола |
| WO2021201310A1 (ko) * | 2020-03-30 | 2021-10-07 | 현대바이오사이언스 주식회사 | 비타민과 덱스판테놀이 봉입된 에토좀 조성물 및 이의 제조방법 |
| JP2022151438A (ja) * | 2021-03-26 | 2022-10-07 | 均 石井 | 外耳炎と中耳炎と内耳炎の治療薬。 |
| JP2022151426A (ja) * | 2021-03-26 | 2022-10-07 | 均 石井 | 上気道炎治療薬。 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE615889A (zh) * | 1952-04-15 | 1900-01-01 | ||
| US4113857A (en) * | 1977-05-16 | 1978-09-12 | The Purdue Frederick Company | Process for the preparation of iodophor compounds and methods for stabilizing iodophor pharmaceutical compositions containing the same |
| US4675009A (en) * | 1977-11-07 | 1987-06-23 | Lec Tec Corporation | Drug dispensing device for transdermal delivery of medicaments |
| US4235871A (en) * | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| FR2536278A1 (fr) * | 1982-11-18 | 1984-05-25 | Dupont Michele | Nouvelle composition therapeutique utile notamment pour la cicatrisation des plaies |
| US4704383A (en) * | 1983-12-29 | 1987-11-03 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| FR2581542B1 (fr) * | 1985-05-07 | 1988-02-19 | Oreal | Compositions topiques destinees au traitement de la peau a base de derives de l'acide salicylique |
| FR2591105B1 (fr) * | 1985-12-11 | 1989-03-24 | Moet Hennessy Rech | Composition pharmaceutique, notamment dermatologique, ou cosmetique, a base de phases lamellaires lipidiques hydratees ou de liposomes contenant un retinoide ou un analogue structural dudit retinoide tel qu'un carotenoide. |
| SE8603812D0 (sv) * | 1986-09-12 | 1986-09-12 | Draco Ab | Administration of liposomes to mammals |
| US5049388A (en) * | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
| US4938965A (en) * | 1987-07-22 | 1990-07-03 | Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence Of Her Majesty's Canadian Government | Ocular delivery of prophylactic agents |
| US5246708A (en) * | 1987-10-28 | 1993-09-21 | Pro-Neuron, Inc. | Methods for promoting wound healing with deoxyribonucleosides |
| DE3826946C1 (zh) * | 1988-08-09 | 1990-03-15 | A. Nattermann & Cie Gmbh, 5000 Koeln, De | |
| US4906476A (en) * | 1988-12-14 | 1990-03-06 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs in lungs |
| US5006343A (en) * | 1988-12-29 | 1991-04-09 | Benson Bradley J | Pulmonary administration of pharmaceutically active substances |
| US5232692A (en) * | 1989-04-28 | 1993-08-03 | Research And Education Institute, Inc. | Povidone-iodine neonatal ophthalmic antimicrobial prophylactic agent |
| EP0407028B2 (en) * | 1989-05-31 | 1999-07-07 | FISONS plc | Medicament inhalation device and formulation |
| US5089389A (en) * | 1989-08-25 | 1992-02-18 | Eastman Kodak Company | Buffered composition, coated article test device and a method for their use |
| US5128139A (en) * | 1991-02-15 | 1992-07-07 | Nu Skin International, Inc. | Composition containing liposome-entrapped grapefruit seed extract and method for making |
| DE4111982C2 (de) * | 1991-04-12 | 1998-12-24 | Merz & Co Gmbh & Co | Stabile kleinpartikuläre Liposomenzubereitungen, deren Herstellung und Verwendung |
| EP0580860B2 (en) * | 1991-04-16 | 2004-12-15 | Nippon Shinyaku Company, Limited | Method of manufacturing solid dispersion |
| ATE221379T1 (de) * | 1991-05-01 | 2002-08-15 | Jackson H M Found Military Med | Verfahren zur behandlung infektiöser respiratorischer erkrankungen |
| AU4066693A (en) * | 1992-12-23 | 1994-07-19 | Bernhard Hugemann | Compacted drug body for use in the mechanical generation of inhalable active-substance particles |
| US5552158A (en) * | 1993-02-23 | 1996-09-03 | Norac Technologies Inc. | Skin care composition |
| DE4306475A1 (de) * | 1993-03-02 | 1994-09-08 | Ensenat Pedro Gonzalez | Liposomen, enthaltend Chlorhexidindiacetat oder Chlorhexidindigluconat |
| WO1994028876A1 (en) * | 1993-06-07 | 1994-12-22 | Advanced Therapies, Inc. | Liposome powders |
| US5512269A (en) * | 1993-06-09 | 1996-04-30 | Burroughs Wellcome, Co. | Method of treating retained pulmonary secretions |
| US5456904A (en) * | 1993-06-28 | 1995-10-10 | The Procter & Gamble Company | Photoprotection compositions comprising certain chelating agents |
| US5863556A (en) * | 1993-08-20 | 1999-01-26 | Euro-Celtique, S.A. | Preparations for the external application of antiseptic agents and/or agents promoting the healing of wounds |
| DE9312509U1 (de) * | 1993-08-20 | 1993-10-28 | Euro-Celtique S.A., Luxemburg/Luxembourg | Präparate zur äußeren Verabreichung von antiseptischen und/oder die Wundheilung fördernden Wirkstoffen |
| EP0789584B1 (de) * | 1994-11-04 | 2001-09-19 | Polymun Scientific Immunbiologische Forschung GmbH | Applikation von sod in liposomen |
| US5744457A (en) * | 1995-03-31 | 1998-04-28 | Hamilton Civic Hospitals Research Development Inc. | Compositions and methods for inhibiting thrombogenesis |
| JPH08301774A (ja) * | 1995-05-08 | 1996-11-19 | Kowa Co | 喉用殺菌消毒薬 |
| US20010055610A1 (en) * | 1997-06-06 | 2001-12-27 | Shunji Nagata | Medicament administration system |
| US7297344B1 (en) * | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
| ES2341532T3 (es) * | 1999-05-27 | 2010-06-22 | Euro-Celtique S.A. | Preparacion con povidona yodada para el tratamiento de heridas. |
| US7300667B1 (en) * | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
| WO2000072823A1 (en) * | 1999-05-27 | 2000-12-07 | Euroceltique S.A. | Preparations for the application of anti-inflammatory agents |
| US6497896B2 (en) * | 2001-02-12 | 2002-12-24 | Supergen, Inc. | Method for administering camptothecins via injection of a pharmaceutical composition comprising microdroplets containing a camptothecin |
| DK1479379T3 (da) * | 2003-05-19 | 2008-01-02 | Euro Celtique Sa | Törre, liposomale PVP-iod-sammensætninger |
| US8435261B2 (en) * | 2009-07-15 | 2013-05-07 | Regents Of The University Of Minnesota | Treatment and placement device for sinusitis applications |
-
1999
- 1999-05-27 ES ES99926448T patent/ES2273493T3/es not_active Expired - Lifetime
- 1999-05-27 JP JP2000550463A patent/JP2002516269A/ja active Pending
- 1999-05-27 WO PCT/EP1999/003681 patent/WO1999060999A1/en active IP Right Grant
- 1999-05-27 WO PCT/EP1999/003677 patent/WO1999060998A1/en active IP Right Grant
- 1999-05-27 CN CN99806578A patent/CN1303272A/zh active Pending
- 1999-05-27 KR KR10-2000-7013259A patent/KR100445146B1/ko not_active IP Right Cessation
- 1999-05-27 CN CN99806577A patent/CN1303271A/zh active Pending
- 1999-05-27 CA CA002332371A patent/CA2332371A1/en not_active Abandoned
- 1999-05-27 BR BR9911070-9A patent/BR9911070A/pt not_active IP Right Cessation
- 1999-05-27 EP EP99926446A patent/EP1079806B1/en not_active Expired - Lifetime
- 1999-05-27 CA CA002332389A patent/CA2332389C/en not_active Expired - Lifetime
- 1999-05-27 HU HU0102337A patent/HU226710B1/hu unknown
- 1999-05-27 DK DK99926448T patent/DK1079807T3/da active
- 1999-05-27 PT PT99926446T patent/PT1079806E/pt unknown
- 1999-05-27 RU RU2000132713/14A patent/RU2212884C2/ru active
- 1999-05-27 HU HU0102892A patent/HUP0102892A3/hu unknown
- 1999-05-27 RU RU2000132711/14A patent/RU2211693C2/ru active
- 1999-05-27 JP JP2000550459A patent/JP4741726B2/ja not_active Expired - Fee Related
- 1999-05-27 BR BR9911071-7A patent/BR9911071A/pt not_active Application Discontinuation
- 1999-05-27 AU AU43706/99A patent/AU752018C/en not_active Expired
- 1999-05-27 DE DE29923766U patent/DE29923766U1/de not_active Expired - Lifetime
- 1999-05-27 BR BR9911072-5A patent/BR9911072A/pt not_active Application Discontinuation
- 1999-05-27 AU AU43704/99A patent/AU759264B2/en not_active Expired
- 1999-05-27 KR KR1020007013257A patent/KR100613706B1/ko not_active IP Right Cessation
- 1999-05-27 EP EP99953285A patent/EP1083886B1/en not_active Expired - Lifetime
- 1999-05-27 AT AT99926446T patent/ATE319427T1/de active
- 1999-05-27 DE DE69906518T patent/DE69906518D1/de not_active Expired - Lifetime
- 1999-05-27 AT AT99953285T patent/ATE235895T1/de not_active IP Right Cessation
- 1999-05-27 DE DE29923847U patent/DE29923847U1/de not_active Expired - Lifetime
- 1999-05-27 DE DE29923848U patent/DE29923848U1/de not_active Expired - Lifetime
- 1999-05-27 IL IL13923199A patent/IL139231A0/xx not_active IP Right Cessation
- 1999-05-27 AU AU42667/99A patent/AU747877B2/en not_active Ceased
- 1999-05-27 CN CN99806648A patent/CN1303276A/zh active Pending
- 1999-05-27 DK DK99926446T patent/DK1079806T3/da active
- 1999-05-27 KR KR1020007013258A patent/KR20010043820A/ko not_active Application Discontinuation
- 1999-05-27 EP EP99926448A patent/EP1079807B1/en not_active Expired - Lifetime
- 1999-05-27 HU HU0102899A patent/HU226729B1/hu unknown
- 1999-05-27 PT PT99926448T patent/PT1079807E/pt unknown
- 1999-05-27 DE DE69933208T patent/DE69933208T2/de not_active Expired - Lifetime
- 1999-05-27 IL IL13922999A patent/IL139229A0/xx unknown
- 1999-05-27 RU RU2000131695/14A patent/RU2202340C2/ru not_active IP Right Cessation
- 1999-05-27 ES ES99926446T patent/ES2260915T3/es not_active Expired - Lifetime
- 1999-05-27 IL IL13923099A patent/IL139230A0/xx active IP Right Grant
- 1999-05-27 AT AT99926448T patent/ATE339187T1/de active
- 1999-05-27 WO PCT/EP1999/003680 patent/WO1999061003A1/en not_active Application Discontinuation
- 1999-05-27 JP JP2000550460A patent/JP4741727B2/ja not_active Expired - Fee Related
- 1999-05-27 DE DE69930259T patent/DE69930259T2/de not_active Expired - Lifetime
- 1999-05-27 CA CA002332369A patent/CA2332369A1/en not_active Abandoned
-
2000
- 2000-10-24 IL IL139230A patent/IL139230A/en not_active IP Right Cessation
-
2001
- 2001-09-04 HK HK01106239A patent/HK1035335A1/xx not_active IP Right Cessation
- 2001-09-04 HK HK01106240A patent/HK1035336A1/xx not_active IP Right Cessation
-
2006
- 2006-12-06 CY CY20061101759T patent/CY1105834T1/el unknown
-
2007
- 2007-10-11 US US11/974,419 patent/US20080038330A1/en not_active Abandoned
-
2011
- 2011-09-22 US US13/240,232 patent/US20120009253A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108743537A (zh) * | 2012-05-21 | 2018-11-06 | 英斯麦德公司 | 治疗肺部感染的系统 |
| CN108743537B (zh) * | 2012-05-21 | 2021-06-11 | 英斯麦德公司 | 治疗肺部感染的系统 |
| CN111700883A (zh) * | 2020-07-23 | 2020-09-25 | 深圳大佛药业股份有限公司 | 一种硫酸沙丁胺醇缓释型吸入制剂及其生产工艺 |
| CN111700883B (zh) * | 2020-07-23 | 2021-04-06 | 深圳大佛药业股份有限公司 | 一种硫酸沙丁胺醇缓释型吸入制剂及其生产工艺 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1303276A (zh) | 包含紧密压实的固体药剂原料的药物释放系统 | |
| Courrier et al. | Pulmonary drug delivery systems: recent developments and prospects | |
| JP5797217B2 (ja) | 即時放出および持続放出の両方の特性を提供する二重作用吸入製剤 | |
| RU2000131695A (ru) | Система доставки лекарства | |
| CN100358494C (zh) | 一种吸入给药系统 | |
| AU2019236630A1 (en) | Mast cell stabilizers treatment for systemic disorders | |
| Goel et al. | Exploring targeted pulmonary delivery for treatment of lung cancer | |
| US20040247628A1 (en) | Kit for the preparation of a pharmaceutical composition | |
| Gaspar et al. | Inhaled liposomes–current strategies and future challenges | |
| CA2803672C (en) | Liposomes for pulmonary administration | |
| JPS63500175A (ja) | リポソ−ム吸入法および吸入システム | |
| Jin et al. | RETRACTED: Pulmonary route of administration is instrumental in developing therapeutic interventions against respiratory diseases | |
| WO2004052333A1 (en) | Pharmaceutical compositions for the pulmonary delivery of aztreonam | |
| Swaminathan et al. | Liposomes for pulmonary drug delivery | |
| JP2006511617A (ja) | 製薬用多孔質粒子 | |
| US20220241271A1 (en) | Inhalable dry powders | |
| Bi et al. | Liposomes as a carrier for pulmonary delivery of peptides and proteins | |
| TW202228792A (zh) | 吸入用奈米載體製劑 | |
| MXPA00011650A (en) | Drug delivery system comprising a tightly compacted solid medicament stock | |
| AU2012211514B2 (en) | Concentrated, inhalable ciprofloxacin formulation | |
| CIPOLLA et al. | Sommaire du brevet 2667494 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |