CA2263765A1 - Methods for the production of protein particles useful for delivery of pharmacological agents - Google Patents
Methods for the production of protein particles useful for delivery of pharmacological agentsInfo
- Publication number
- CA2263765A1 CA2263765A1 CA002263765A CA2263765A CA2263765A1 CA 2263765 A1 CA2263765 A1 CA 2263765A1 CA 002263765 A CA002263765 A CA 002263765A CA 2263765 A CA2263765 A CA 2263765A CA 2263765 A1 CA2263765 A1 CA 2263765A1
- Authority
- CA
- Canada
- Prior art keywords
- protein
- factor
- particles
- pharmacologically active
- dna
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 23
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 15
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 15
- 239000002245 particle Substances 0.000 title claims abstract 10
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 239000002831 pharmacologic agent Substances 0.000 title 1
- 238000003505 heat denaturation Methods 0.000 claims abstract 5
- 108020004414 DNA Proteins 0.000 claims abstract 4
- 150000001768 cations Chemical class 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract 3
- 229910052791 calcium Inorganic materials 0.000 claims abstract 3
- 239000011575 calcium Substances 0.000 claims abstract 3
- 108020004707 nucleic acids Proteins 0.000 claims abstract 3
- 102000039446 nucleic acids Human genes 0.000 claims abstract 3
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract 2
- 102000053642 Catalytic RNA Human genes 0.000 claims abstract 2
- 108090000994 Catalytic RNA Proteins 0.000 claims abstract 2
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract 2
- 230000015572 biosynthetic process Effects 0.000 claims abstract 2
- 150000004676 glycans Chemical class 0.000 claims abstract 2
- 108091033319 polynucleotide Proteins 0.000 claims abstract 2
- 102000040430 polynucleotide Human genes 0.000 claims abstract 2
- 239000002157 polynucleotide Substances 0.000 claims abstract 2
- 229920001282 polysaccharide Polymers 0.000 claims abstract 2
- 239000005017 polysaccharide Substances 0.000 claims abstract 2
- 108091092562 ribozyme Proteins 0.000 claims abstract 2
- -1 caesin Proteins 0.000 claims 4
- 239000000463 material Substances 0.000 claims 4
- 102000009027 Albumins Human genes 0.000 claims 3
- 108010088751 Albumins Proteins 0.000 claims 3
- 239000013543 active substance Substances 0.000 claims 3
- 108010054147 Hemoglobins Proteins 0.000 claims 2
- 102000001554 Hemoglobins Human genes 0.000 claims 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 2
- 102000019197 Superoxide Dismutase Human genes 0.000 claims 2
- 108010012715 Superoxide dismutase Proteins 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 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 2
- 239000000243 solution Substances 0.000 claims 2
- JSWWYAITRNDLLQ-HBJDUEGVSA-N (3s,3ar,6s,6as)-3,6,6a-trihydroxy-6-(5-methylfuran-2-yl)-3,3a-dihydro-2h-furo[3,2-b]furan-5-one Chemical compound O1C(C)=CC=C1[C@]1(O)[C@@]2(O)OC[C@H](O)[C@H]2OC1=O JSWWYAITRNDLLQ-HBJDUEGVSA-N 0.000 claims 1
- MHFRGQHAERHWKZ-HHHXNRCGSA-N (R)-edelfosine Chemical compound CCCCCCCCCCCCCCCCCCOC[C@@H](OC)COP([O-])(=O)OCC[N+](C)(C)C MHFRGQHAERHWKZ-HHHXNRCGSA-N 0.000 claims 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 claims 1
- 102000055025 Adenosine deaminases Human genes 0.000 claims 1
- 239000004382 Amylase Substances 0.000 claims 1
- 102000013142 Amylases Human genes 0.000 claims 1
- 108010065511 Amylases Proteins 0.000 claims 1
- 101710081722 Antitrypsin Proteins 0.000 claims 1
- 102000055006 Calcitonin Human genes 0.000 claims 1
- 108060001064 Calcitonin Proteins 0.000 claims 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims 1
- JDVVGAQPNNXQDW-WCMLQCRESA-N Castanospermine Natural products O[C@H]1[C@@H](O)[C@H]2[C@@H](O)CCN2C[C@H]1O JDVVGAQPNNXQDW-WCMLQCRESA-N 0.000 claims 1
- JDVVGAQPNNXQDW-TVNFTVLESA-N Castinospermine Chemical compound C1[C@H](O)[C@@H](O)[C@H](O)[C@H]2[C@@H](O)CCN21 JDVVGAQPNNXQDW-TVNFTVLESA-N 0.000 claims 1
- 102100035882 Catalase Human genes 0.000 claims 1
- 108010053835 Catalase Proteins 0.000 claims 1
- 108090000317 Chymotrypsin Proteins 0.000 claims 1
- 102100022641 Coagulation factor IX Human genes 0.000 claims 1
- 108010035532 Collagen Proteins 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 claims 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 claims 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 claims 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- DYEFUKCXAQOFHX-UHFFFAOYSA-N Ebselen Chemical compound [se]1C2=CC=CC=C2C(=O)N1C1=CC=CC=C1 DYEFUKCXAQOFHX-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 101800003838 Epidermal growth factor Proteins 0.000 claims 1
- 108090000394 Erythropoietin Proteins 0.000 claims 1
- 102000003951 Erythropoietin Human genes 0.000 claims 1
- 108010076282 Factor IX Proteins 0.000 claims 1
- 108010054218 Factor VIII Proteins 0.000 claims 1
- 102000001690 Factor VIII Human genes 0.000 claims 1
- 108010049003 Fibrinogen Proteins 0.000 claims 1
- 102000008946 Fibrinogen Human genes 0.000 claims 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims 1
- 108010067306 Fibronectins Proteins 0.000 claims 1
- 102000016359 Fibronectins Human genes 0.000 claims 1
- 229910052688 Gadolinium Inorganic materials 0.000 claims 1
- 102000000795 Galectin 1 Human genes 0.000 claims 1
- 108010001498 Galectin 1 Proteins 0.000 claims 1
- 108010010803 Gelatin Proteins 0.000 claims 1
- 102000004547 Glucosylceramidase Human genes 0.000 claims 1
- 108010017544 Glucosylceramidase Proteins 0.000 claims 1
- 108010051696 Growth Hormone Proteins 0.000 claims 1
- 102000007625 Hirudins Human genes 0.000 claims 1
- 108010007267 Hirudins Proteins 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102000004877 Insulin Human genes 0.000 claims 1
- 108090001061 Insulin Proteins 0.000 claims 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 1
- 102000008070 Interferon-gamma Human genes 0.000 claims 1
- 108010074328 Interferon-gamma Proteins 0.000 claims 1
- 102000014150 Interferons Human genes 0.000 claims 1
- 108010050904 Interferons Proteins 0.000 claims 1
- 102000000589 Interleukin-1 Human genes 0.000 claims 1
- 108010002352 Interleukin-1 Proteins 0.000 claims 1
- 102100020873 Interleukin-2 Human genes 0.000 claims 1
- 108010002350 Interleukin-2 Proteins 0.000 claims 1
- 102000004407 Lactalbumin Human genes 0.000 claims 1
- 108090000942 Lactalbumin Proteins 0.000 claims 1
- 108010085895 Laminin Proteins 0.000 claims 1
- 102000007547 Laminin Human genes 0.000 claims 1
- 102000004882 Lipase Human genes 0.000 claims 1
- 108090001060 Lipase Proteins 0.000 claims 1
- 239000004367 Lipase Substances 0.000 claims 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 claims 1
- 102000016943 Muramidase Human genes 0.000 claims 1
- 108010014251 Muramidase Proteins 0.000 claims 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims 1
- 102400000050 Oxytocin Human genes 0.000 claims 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims 1
- 101800000989 Oxytocin Proteins 0.000 claims 1
- 108090000284 Pepsin A Proteins 0.000 claims 1
- 102000057297 Pepsin A Human genes 0.000 claims 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 claims 1
- 108010076181 Proinsulin Proteins 0.000 claims 1
- 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 claims 1
- 102000013275 Somatomedins Human genes 0.000 claims 1
- 108010056088 Somatostatin Proteins 0.000 claims 1
- 102000005157 Somatostatin Human genes 0.000 claims 1
- 102100038803 Somatotropin Human genes 0.000 claims 1
- 108010023197 Streptokinase Proteins 0.000 claims 1
- 101710172711 Structural protein Proteins 0.000 claims 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims 1
- 102000004338 Transferrin Human genes 0.000 claims 1
- 108090000901 Transferrin Proteins 0.000 claims 1
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 1
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 1
- 108090000631 Trypsin Proteins 0.000 claims 1
- 102000004142 Trypsin Human genes 0.000 claims 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims 1
- 108010031318 Vitronectin Proteins 0.000 claims 1
- 102100035140 Vitronectin Human genes 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 229960004150 aciclovir Drugs 0.000 claims 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims 1
- 239000004411 aluminium Substances 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229960001280 amantadine hydrochloride Drugs 0.000 claims 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 claims 1
- 235000019418 amylase Nutrition 0.000 claims 1
- 230000000692 anti-sense effect Effects 0.000 claims 1
- 230000001475 anti-trypsic effect Effects 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 229910052788 barium Inorganic materials 0.000 claims 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims 1
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 claims 1
- 229960002495 buspirone Drugs 0.000 claims 1
- 229960004015 calcitonin Drugs 0.000 claims 1
- 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 1
- 229910001424 calcium ion Inorganic materials 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 229960002376 chymotrypsin Drugs 0.000 claims 1
- 239000010941 cobalt Substances 0.000 claims 1
- 229910017052 cobalt Inorganic materials 0.000 claims 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims 1
- 229920001436 collagen Polymers 0.000 claims 1
- 238000013270 controlled release Methods 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 229950010033 ebselen Drugs 0.000 claims 1
- 229950011461 edelfosine Drugs 0.000 claims 1
- 229950002798 enlimomab Drugs 0.000 claims 1
- 229940088598 enzyme Drugs 0.000 claims 1
- 229940116977 epidermal growth factor Drugs 0.000 claims 1
- 229940105423 erythropoietin Drugs 0.000 claims 1
- 229960004222 factor ix Drugs 0.000 claims 1
- 229960000301 factor viii Drugs 0.000 claims 1
- 229940012952 fibrinogen Drugs 0.000 claims 1
- 229940126864 fibroblast growth factor Drugs 0.000 claims 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims 1
- 229920000159 gelatin Polymers 0.000 claims 1
- 239000008273 gelatin Substances 0.000 claims 1
- 235000019322 gelatine Nutrition 0.000 claims 1
- 235000011852 gelatine desserts Nutrition 0.000 claims 1
- 238000001476 gene delivery Methods 0.000 claims 1
- 239000003862 glucocorticoid Substances 0.000 claims 1
- 239000000122 growth hormone Substances 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 229940006607 hirudin Drugs 0.000 claims 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 229940125721 immunosuppressive agent Drugs 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 229940125396 insulin Drugs 0.000 claims 1
- 229960003130 interferon gamma Drugs 0.000 claims 1
- 229940047124 interferons Drugs 0.000 claims 1
- 229910052742 iron Inorganic materials 0.000 claims 1
- 235000019421 lipase Nutrition 0.000 claims 1
- 229960000274 lysozyme Drugs 0.000 claims 1
- 239000004325 lysozyme Substances 0.000 claims 1
- 235000010335 lysozyme Nutrition 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229950000844 mizoribine Drugs 0.000 claims 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 claims 1
- 230000017074 necrotic cell death Effects 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- 229960001723 oxytocin Drugs 0.000 claims 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 claims 1
- 229940111202 pepsin Drugs 0.000 claims 1
- 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 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 229960000329 ribavirin Drugs 0.000 claims 1
- 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 claims 1
- 229960000553 somatostatin Drugs 0.000 claims 1
- 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 claims 1
- 229960005202 streptokinase Drugs 0.000 claims 1
- 229910052712 strontium Inorganic materials 0.000 claims 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims 1
- 229940037128 systemic glucocorticoids Drugs 0.000 claims 1
- 229960000187 tissue plasminogen activator Drugs 0.000 claims 1
- 238000001890 transfection Methods 0.000 claims 1
- 239000012581 transferrin Substances 0.000 claims 1
- 239000012588 trypsin Substances 0.000 claims 1
- 229960001322 trypsin Drugs 0.000 claims 1
- 239000002753 trypsin inhibitor Substances 0.000 claims 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims 1
- 229960005356 urokinase Drugs 0.000 claims 1
- 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 1
- 229960002555 zidovudine Drugs 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 150000002500 ions Chemical class 0.000 abstract 2
- 239000002105 nanoparticle Substances 0.000 abstract 2
- 102000008100 Human Serum Albumin Human genes 0.000 abstract 1
- 108091006905 Human Serum Albumin Proteins 0.000 abstract 1
- 102000007562 Serum Albumin Human genes 0.000 abstract 1
- 108010071390 Serum Albumin Proteins 0.000 abstract 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 238000000975 co-precipitation Methods 0.000 abstract 1
- 238000010348 incorporation Methods 0.000 abstract 1
- 239000011859 microparticle Substances 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 230000006920 protein precipitation Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
Abstract
A method has been developed for the formation of submicron particles (nanoparticles) by heat-denaturation of proteins (such as human serum albumin) in the presence of multivalent ions (such as calcium). Also provided are novel products produced by the invention method.
An appropriate concentration of multivalent ions, within a relatively narrow range of concentrations, induces the precipitation of protein in the form of colloidal particles, at a temperature which is well below the heat denaturation temperature of the protein (as low as 60 °C for serum albumin). Temperatures at which invention method operates are sufficiently low to permit incorporation of other molecules (e.g., by co-precipitation), into submicron particles according to the invention, including compounds which cannot withstand high temperatures.
Invention methods facilitate the production of protein nanoparticles and microparticles containing various molecules (such as nucleic acids, oligonucleotides, polynucleotides, DNA, RNA, polysaccharides, ribozymes, pharmacologically active compounds, and the like) useful for therapeutic, diagnostic and other purposes. The addition of multivalent cations serves both to induce precipitation, and to allow linking of negatively charged molecules, such as DNA, to the negatively charged protein.
An appropriate concentration of multivalent ions, within a relatively narrow range of concentrations, induces the precipitation of protein in the form of colloidal particles, at a temperature which is well below the heat denaturation temperature of the protein (as low as 60 °C for serum albumin). Temperatures at which invention method operates are sufficiently low to permit incorporation of other molecules (e.g., by co-precipitation), into submicron particles according to the invention, including compounds which cannot withstand high temperatures.
Invention methods facilitate the production of protein nanoparticles and microparticles containing various molecules (such as nucleic acids, oligonucleotides, polynucleotides, DNA, RNA, polysaccharides, ribozymes, pharmacologically active compounds, and the like) useful for therapeutic, diagnostic and other purposes. The addition of multivalent cations serves both to induce precipitation, and to allow linking of negatively charged molecules, such as DNA, to the negatively charged protein.
Claims (16)
1. A method for the preparation of protein particles having a diameter less than about 30 microns, said method comprising:
dissolving at least one protein, and optionally other non-proteinaceous materials, in a solution containing an amount of at least one multivalent cation sufficient to promote the formation of insoluble particles at a temperature below that of the heat denaturation temperature of said protein in purified form, and heating the solution to a temperature below that of the heat denaturation temperature of an aqueous solution of said protein in purified form for a period of time sufficient to form insoluble particles containing the protein and optional non-proteinaceous materials.
dissolving at least one protein, and optionally other non-proteinaceous materials, in a solution containing an amount of at least one multivalent cation sufficient to promote the formation of insoluble particles at a temperature below that of the heat denaturation temperature of said protein in purified form, and heating the solution to a temperature below that of the heat denaturation temperature of an aqueous solution of said protein in purified form for a period of time sufficient to form insoluble particles containing the protein and optional non-proteinaceous materials.
2. A method according to claim 1 wherein said particles have a diameter of less than about 2 µm.
3. A method according to claim 1 wherein said protein is a structural protein, an enzyme, an antibody, or a peptide.
4. A method according to claim 1 wherein said protein is albumin, collagen, gelatin, immunoglobulin, insulin, hemoglobin, transferrin, caesin, pepsin, trypsin, chymotrypsin, lysozyme, .alpha.-2-macroglobulin, fibronectin, vitronectin, fibrinogen, laminin, lipase, interleukin-1, interleukin-2, tissue necrosis factor, colony-stimulating factor, epidermal growth factor, transforming growth factors, fibroblast growth factor, insulin-like growth factors, hirudin, tissue plasminogen activator, urokinase, streptokinase, erythropoietin, Factor VIII, Factor IX, somatostatin, proinsulin, macrophage-inhibiting factor, macrophage-activating factor, muramyl dipeptide, interferons, glucocerebrosidase, calcitonin, oxytocin, growth hormone, .alpha.-1 antitrypsin, superoxide dismutase (SOD), catalase, adenosine deaminase, lactalbumin, ovalalbumin, amylase, hemoglobin or albumin.
5. A method according to claim 1 wherein said protein is albumin.
6. A method according to claim 1 wherein the multivalent cation is calcium, zinc, magnesium, barium, copper, iron, manganese, nickel, aluminium, gadolinium, technecium, strontium, cobalt, or mixtures of any two or more thereof.
7. A method according to claim 6 wherein the multivalent cation is calcium.
8. A method according to claim 7 wherein the concentration of calcium ions is between 0.1 mM and 10 mM.
9. A method according to claim 1 wherein the optional non-proteinaceous material is a nucleic acid, an oligonucleotide, a polynucleotide, DNA, RNA, a polysaccharide, a ribozyme or a pharmacologically active compound capable of inclusion within the protein particles.
10. A method according to claim 9 wherein said DNA is used for gene delivery and cell transfection.
11. A method according to claim 1 wherein the non-proteinaceous material is a pharmacologically active agent capable of inclusion within the protein particles.
12. A method according to claim 11 wherein said pharmacologically active agent is an antisense nucleic acid, an antiviral compound, an anticancer agent or an immunosuppressive agent.
13. A method according to claim 12 wherein said pharmacologically active agent is interferon gamma, zidovudine, amantadine hydrochloride, ribavirin, acyclovir, glucocorticoids, buspirone, castanospermine, ebselen, edelfosine, enlimomab, galaptin, methoxatone or mizoribine.
14. A method according to claim 1 wherein the heat denaturation is carried out at a temperature less than about 100°C.
15. The product produced by the method of claim 1.
16. A method for the controlled release delivery of drugs to a patient in need thereof, said method comprising administering to said patient an effective amount of said drug incorporated into a product according to claim 15.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2396896P | 1996-08-19 | 1996-08-19 | |
| US60/023,968 | 1996-08-19 | ||
| PCT/US1997/014661 WO1998007410A1 (en) | 1996-08-19 | 1997-08-19 | Methods for the production of protein particles useful for delivery of pharmacological agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2263765A1 true CA2263765A1 (en) | 1998-02-26 |
| CA2263765C CA2263765C (en) | 2010-03-30 |
Family
ID=21818165
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2263765A Expired - Lifetime CA2263765C (en) | 1996-08-19 | 1997-08-19 | Methods for the production of protein particles useful for delivery of pharmacological agents |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0938299A4 (en) |
| AU (1) | AU3916997A (en) |
| CA (1) | CA2263765C (en) |
| WO (1) | WO1998007410A1 (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6254890B1 (en) | 1997-12-12 | 2001-07-03 | Massachusetts Institute Of Technology | Sub-100nm biodegradable polymer spheres capable of transporting and releasing nucleic acids |
| EP1348034B1 (en) * | 2000-11-15 | 2016-07-20 | Minerva Biotechnologies Corporation | Oligonucleotide identifiers |
| US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
| US8067032B2 (en) | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
| AU2002245979A1 (en) * | 2001-04-05 | 2002-10-21 | Universite Laval | Process for making protein delivery matrix and uses thereof |
| CA2461349C (en) | 2001-09-26 | 2011-11-29 | Baxter International Inc. | Preparation of submicron sized nanoparticles via dispersion and solvent or liquid phase removal |
| US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
| JP4212921B2 (en) * | 2002-03-29 | 2009-01-21 | 独立行政法人科学技術振興機構 | Therapeutic agents using protein hollow nanoparticles presenting antibodies and protein hollow nanoparticles |
| IL150906A0 (en) | 2002-07-25 | 2003-02-12 | Yissum Res Dev Co | Diagnostic microspheres |
| DK1585548T3 (en) | 2002-12-09 | 2018-09-03 | Abraxis Bioscience Llc | COMPOSITIONS AND PROCEDURES FOR THE DELIVERY OF PHARMACOLOGICAL AGENTS |
| FR2902007B1 (en) * | 2006-06-09 | 2012-01-13 | Flamel Tech Sa | PHARMACEUTICAL FORMULATIONS FOR PROLONGED DELIVERY OF ACTIVE (S) PRINCIPLE (S) AND THEIR PARTICULARLY THERAPEUTIC APPLICATIONS |
| NZ604031A (en) | 2010-06-04 | 2015-05-29 | Abraxis Bioscience Llc | Methods of treatment of pancreatic cancer |
| EP2510930A1 (en) | 2011-04-15 | 2012-10-17 | Bionanoplus, S.L. | Nanoparticles comprising half esters of poly (methyl vinyl ether-co-maleic anhydride) and uses thereof |
| MX2017005692A (en) | 2014-10-31 | 2017-08-07 | Glaxosmithkline Ip Dev Ltd | Powder formulation. |
| CN110302364A (en) * | 2019-06-24 | 2019-10-08 | 浙江工商大学 | A kind of self assembly catalase nano particle and its preparation method and application |
| CN115154651B (en) * | 2022-06-23 | 2023-10-27 | 华中科技大学 | Biomineralization bovine serum albumin @ calcium selenium nanosphere, preparation method and application |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6020059B2 (en) * | 1980-09-16 | 1985-05-20 | 雪印乳業株式会社 | Method for producing microcapsules suitable for food or medicine |
| US5585112A (en) * | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
| GB9106686D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
| JP3482242B2 (en) * | 1994-06-10 | 2003-12-22 | 株式会社キティー | Fine particles enclosing a physiologically active substance and a method for producing the same |
-
1997
- 1997-08-19 EP EP97936517A patent/EP0938299A4/en not_active Withdrawn
- 1997-08-19 CA CA2263765A patent/CA2263765C/en not_active Expired - Lifetime
- 1997-08-19 AU AU39169/97A patent/AU3916997A/en not_active Abandoned
- 1997-08-19 WO PCT/US1997/014661 patent/WO1998007410A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0938299A1 (en) | 1999-09-01 |
| AU3916997A (en) | 1998-03-06 |
| CA2263765C (en) | 2010-03-30 |
| WO1998007410A1 (en) | 1998-02-26 |
| EP0938299A4 (en) | 2001-01-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2263765A1 (en) | Methods for the production of protein particles useful for delivery of pharmacological agents | |
| JP4927256B2 (en) | Polyamino acid-based particles and process for producing the same | |
| US5451410A (en) | Modified amino acids for encapsulating active agents | |
| US5811127A (en) | Desferrioxamine oral delivery system | |
| Dai et al. | Microencapsulation peptide and protein drugs delivery system | |
| CA2174961C (en) | Desferrioxamine oral delivery system | |
| Pitt | The controlled parenteral delivery of polypeptides and proteins | |
| Putney et al. | Improving protein therapeutics with sustained-release formulations | |
| EP2049560B1 (en) | Process for preparing particles of proteinaceous material | |
| EP0720471B1 (en) | Hydrophobic polymeric microparticles | |
| US4983581A (en) | Wound healing composition of IGF-I and TGF-β | |
| CN100536915C (en) | Neurotoxin implant | |
| US6939557B2 (en) | Slow release protein polymers | |
| Pawar et al. | Protein and peptide parenteral controlled delivery | |
| JP2002530323A5 (en) | ||
| JPH11513047A (en) | Sustained-release composition of drug encapsulated in fine particles of hyaluronic acid | |
| JP2009524667A (en) | Polymer microsphere preparation technology | |
| US20030082161A1 (en) | Gene preparations | |
| JP2002535108A (en) | Biocompatible materials made by nucleophilic addition to conjugated unsaturated groups | |
| JPH10504281A (en) | Bioerodible matrices for controlled release of drugs and assays for hydrolases | |
| EP1986611B1 (en) | Repeat sequence protein polymer nanoparticles optionally containing active agents and their preparation | |
| CN100528147C (en) | Method for preparing protein-polysaccharide vitreum slow release microsphere by using low-temperature aqueous-aqueous phase emulsion | |
| KR20010042079A (en) | Sustained-release preparation of physiologically active polypeptide and production thereof | |
| EP1683517A1 (en) | Methods for the production of protein particles useful for delivery of pharmacological agents | |
| US20100180464A1 (en) | Cores and microcapsules suitable for parenteral administration as well as process for their manufacture |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |