WO2001043724A1 - Microcapsulas para la liberacion prolongada de farmacos - Google Patents
Microcapsulas para la liberacion prolongada de farmacos Download PDFInfo
- Publication number
- WO2001043724A1 WO2001043724A1 PCT/ES2000/000475 ES0000475W WO0143724A1 WO 2001043724 A1 WO2001043724 A1 WO 2001043724A1 ES 0000475 W ES0000475 W ES 0000475W WO 0143724 A1 WO0143724 A1 WO 0143724A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microcapsules
- pharmaceutical preparation
- pharmaceutical
- analogue
- preparation according
- Prior art date
Links
- 239000003094 microcapsule Substances 0.000 title claims abstract description 33
- 229940079593 drug Drugs 0.000 title abstract description 22
- 239000003814 drug Substances 0.000 title abstract description 22
- 238000013268 sustained release Methods 0.000 title 1
- 239000012730 sustained-release form Substances 0.000 title 1
- 229920001577 copolymer Polymers 0.000 claims abstract 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 23
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
- 108010000817 Leuprolide Proteins 0.000 claims description 8
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical group CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 8
- -1 citric acid ester Chemical class 0.000 claims description 8
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 8
- 229960004338 leuprorelin Drugs 0.000 claims description 8
- 239000001069 triethyl citrate Substances 0.000 claims description 8
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 8
- 235000013769 triethyl citrate Nutrition 0.000 claims description 8
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical group C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical group OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 4
- 108010016076 Octreotide Proteins 0.000 claims description 4
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 claims description 3
- 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 3
- 229940045644 human calcitonin Drugs 0.000 claims description 3
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical group 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 description 3
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 claims description 2
- 108010037003 Buserelin Proteins 0.000 claims description 2
- 108010069236 Goserelin Proteins 0.000 claims description 2
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 2
- 102000005157 Somatostatin Human genes 0.000 claims description 2
- 108010056088 Somatostatin Proteins 0.000 claims description 2
- 108010050144 Triptorelin Pamoate Proteins 0.000 claims description 2
- 229960002719 buserelin Drugs 0.000 claims description 2
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 claims description 2
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims description 2
- 229960003230 cetrorelix Drugs 0.000 claims description 2
- 108700008462 cetrorelix Proteins 0.000 claims description 2
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 claims description 2
- 108700032313 elcatonin Proteins 0.000 claims description 2
- 229960000756 elcatonin Drugs 0.000 claims description 2
- JYSJVJJVLNYRKL-QPHHPWFVSA-N elcatonin 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(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)C1CCCCCC(=O)OC[C@H](N)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 JYSJVJJVLNYRKL-QPHHPWFVSA-N 0.000 claims description 2
- 229960002913 goserelin Drugs 0.000 claims description 2
- 229960002700 octreotide Drugs 0.000 claims description 2
- 108010068072 salmon calcitonin Proteins 0.000 claims description 2
- 229960000553 somatostatin Drugs 0.000 claims description 2
- 229940075620 somatostatin analogue Drugs 0.000 claims description 2
- 229960004824 triptorelin Drugs 0.000 claims description 2
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical group C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 2
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical group C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 claims 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229920000642 polymer Polymers 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 6
- 239000004014 plasticizer Substances 0.000 description 6
- 229920001296 polysiloxane Polymers 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HPPONSCISKROOD-OYLNGHKZSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-y Chemical compound CC(O)=O.C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 HPPONSCISKROOD-OYLNGHKZSA-N 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960001494 octreotide acetate Drugs 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229960000434 triptorelin acetate Drugs 0.000 description 2
- KGYXYKHTHJPEBX-UHFFFAOYSA-N 5-ethoxy-3-ethoxycarbonyl-3-hydroxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC(O)(CC(O)=O)C(=O)OCC KGYXYKHTHJPEBX-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229920003168 pharmaceutical polymer Polymers 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 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
- A61K9/14—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
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
Definitions
- the present invention relates to a new type of microcapsules for prolonged administration of drugs and their preparation process.
- These polymers have the peculiarity of slowly degrading inside the body releasing the drug that they have trapped inside, and the degradation products of these polymers (lactic acid and glycolic acid) are naturally present inside the body.
- the present invention also includes the preparation and use of said microcapsules.
- Citric acid esters useful for the purposes of the present invention are those commonly used as plasticizers for pharmaceutical polymers, such as triethyl citrate, tributyl citrate and acetyl tributyl citrate. The use of triethyl citrate is preferred.
- Peptides of pharmacological interest are understood as:
- - LHRH analogues such as triptorelin, Leuprolide, Goserelin, Buserelin or Cetrorelix
- a solution of the polymer is prepared together with the citric acid ester in a suitable solvent.
- the drug to be encapsulated is suspended and a non-solvent of the polymer is added to force the deposition of the polymer on the drug crystals. Examples of these procedures without using the plasticizer can also be found in documents such as ES 2009346 or EP 0 052 510
- the drug to be encapsulated is dissolved in water or in a solution of some other adjuvant and emulsified in a solution of the polymer and the citric acid ester in a suitable solvent such as dichloromethane.
- the resulting emulsion is in turn emulsified in water or in an aqueous solution of an emulsifier such as polyvinyl alcohol.
- an emulsifier such as polyvinyl alcohol.
- the drug to be encapsulated, the polymer and the citric acid ester are dissolved together in a suitable solvent.
- This solution is emulsified in water or in a solution of an emulsifier such as polyvinyl alcohol and the organic solvent is removed by evaporation or extraction.
- the resulting microcapsules are recovered by filtration. Examples of these procedures without using the plasticizer can also be found in documents such as USP 5,445,832 D) Solvent evaporation methods:
- the drug to be encapsulated, the polymer and the citric acid ester are dissolved together in a suitable solvent. This solution is evaporated and the resulting residue is micronized to the appropriate size. Examples of this procedure although without using the plasticizer can also be found in documents such as GB 2,209,937
- the citric acid ester is deposited together with the polymer, plasticizing and advantageously and substantially modifying the hydrophobicity, flexibility and the coating capacity of the polymer and the release profile of the obtained microcapsules. This is reducing the initial release of the encapsulated drug and making this release almost linear over time.
- EXAMPLE Nll Obtaining microcapsules, containing Leuprolide acetate that have a suitable drug release profile for one month.
- microcapsules are recovered by filtration and dried under vacuum for 48 hours.
- EXAMPLE Nl2 Obtaining microcapsules with release for one month containing Octreotide acetate
- microcapsules are recovered by filtration and dried under vacuum for 48 hours.
- EXAMPLE Nl3 Obtaining microcapsules with release for three months containing Triptorelin acetate
- microcapsules are recovered by filtration and dried under vacuum for 48 hours.
- EXAMPLE Nl4 In vitro determination of drug release by the microcapsules obtained.
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- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK00985267T DK1151746T3 (da) | 1999-12-17 | 2000-12-15 | Mikro-kapsler til vedvarende frigivelse af lægemidler |
AT00985267T ATE234608T1 (de) | 1999-12-17 | 2000-12-15 | Mikrokapseln mit verzögerter freisetzung von wirkstoffen |
BRPI0008197A BRPI0008197B8 (pt) | 1999-12-17 | 2000-12-15 | microcápsulas para a liberação prolongada de fármacos |
EP00985267A EP1151746B1 (en) | 1999-12-17 | 2000-12-15 | Microcapsules for sustained release of drugs |
JP2001544663A JP5021880B2 (ja) | 1999-12-17 | 2000-12-15 | 薬剤の徐放性放出のためのマイクロカプセル |
MXPA01008348A MXPA01008348A (es) | 1999-12-17 | 2000-12-15 | Microcapsulas para la liberacion prolongada de farmacos. |
DE60001717T DE60001717T2 (de) | 1999-12-17 | 2000-12-15 | Mikrokapseln mit verzögerter freisetzung von wirkstoffen |
CA002362769A CA2362769C (en) | 1999-12-17 | 2000-12-15 | Microcapsules for sustained release of drugs |
AU21735/01A AU774680B2 (en) | 1999-12-17 | 2000-12-15 | Microcapsules for sustained release of drugs |
US12/148,893 US9789064B2 (en) | 1999-12-17 | 2008-04-23 | Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES009902768A ES2169980B1 (es) | 1999-12-17 | 1999-12-17 | Microcapsulas para la liberacion prolongada de farmacos. |
ESP9902768 | 1999-12-17 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09913671 A-371-Of-International | 2000-12-15 | ||
US11/042,682 Division US20050123618A1 (en) | 1999-12-17 | 2005-01-25 | Method of producing micro-capsules for the sustained release of drugs |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001043724A1 true WO2001043724A1 (es) | 2001-06-21 |
Family
ID=8310957
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/ES2000/000475 WO2001043724A1 (es) | 1999-12-17 | 2000-12-15 | Microcapsulas para la liberacion prolongada de farmacos |
Country Status (13)
Country | Link |
---|---|
US (3) | US20020187196A1 (es) |
EP (1) | EP1151746B1 (es) |
JP (1) | JP5021880B2 (es) |
AT (1) | ATE234608T1 (es) |
AU (1) | AU774680B2 (es) |
BR (1) | BRPI0008197B8 (es) |
CA (1) | CA2362769C (es) |
DE (1) | DE60001717T2 (es) |
DK (1) | DK1151746T3 (es) |
ES (2) | ES2169980B1 (es) |
MX (1) | MXPA01008348A (es) |
PT (1) | PT1151746E (es) |
WO (1) | WO2001043724A1 (es) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040097419A1 (en) * | 2002-11-19 | 2004-05-20 | Holger Petersen | Organic compounds |
US20090110744A1 (en) * | 2005-03-01 | 2009-04-30 | Sun Pharma Advanced Research Company Limited | Sustained release pharmaceutical compositions |
KR20140133968A (ko) * | 2005-12-22 | 2014-11-20 | 노파르티스 아게 | 옥트레오티드 및 2종 이상의 폴리락티드-코-글리콜리드 중합체를 포함하는 서방형 제제 |
ES2324009B1 (es) * | 2007-11-23 | 2010-05-21 | Gp Pharm S.A. | Composicion farmaceutica de liberacion sostenida de somatostatina o un analogo suyo. |
CN105267153B (zh) * | 2015-11-27 | 2018-05-11 | 上海苏豪逸明制药有限公司 | 一种曲普瑞林缓释微粒及其制备方法 |
CN110954491B (zh) * | 2019-12-09 | 2022-11-15 | 北京博恩特药业有限公司 | 用于测量醋酸戈舍瑞林缓释植入剂体外溶出度的方法 |
JP7371519B2 (ja) | 2020-02-14 | 2023-10-31 | 村田機械株式会社 | 自動倉庫 |
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WO1997014408A1 (en) * | 1995-10-19 | 1997-04-24 | Biogram Ab | Sustained release particles |
DE19545257A1 (de) * | 1995-11-24 | 1997-06-19 | Schering Ag | Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln |
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-
1999
- 1999-12-17 ES ES009902768A patent/ES2169980B1/es not_active Expired - Fee Related
-
2000
- 2000-12-15 CA CA002362769A patent/CA2362769C/en not_active Expired - Lifetime
- 2000-12-15 ES ES00985267T patent/ES2194793T3/es not_active Expired - Lifetime
- 2000-12-15 PT PT00985267T patent/PT1151746E/pt unknown
- 2000-12-15 MX MXPA01008348A patent/MXPA01008348A/es active IP Right Grant
- 2000-12-15 AT AT00985267T patent/ATE234608T1/de active
- 2000-12-15 US US09/913,671 patent/US20020187196A1/en not_active Abandoned
- 2000-12-15 WO PCT/ES2000/000475 patent/WO2001043724A1/es active IP Right Grant
- 2000-12-15 DE DE60001717T patent/DE60001717T2/de not_active Expired - Lifetime
- 2000-12-15 DK DK00985267T patent/DK1151746T3/da active
- 2000-12-15 EP EP00985267A patent/EP1151746B1/en not_active Expired - Lifetime
- 2000-12-15 JP JP2001544663A patent/JP5021880B2/ja not_active Expired - Lifetime
- 2000-12-15 BR BRPI0008197A patent/BRPI0008197B8/pt not_active IP Right Cessation
- 2000-12-15 AU AU21735/01A patent/AU774680B2/en not_active Expired
-
2005
- 2005-01-25 US US11/042,682 patent/US20050123618A1/en not_active Abandoned
-
2008
- 2008-04-23 US US12/148,893 patent/US9789064B2/en not_active Expired - Fee Related
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WO1997014408A1 (en) * | 1995-10-19 | 1997-04-24 | Biogram Ab | Sustained release particles |
DE19545257A1 (de) * | 1995-11-24 | 1997-06-19 | Schering Ag | Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln |
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Also Published As
Publication number | Publication date |
---|---|
US20050123618A1 (en) | 2005-06-09 |
CA2362769A1 (en) | 2001-06-21 |
DK1151746T3 (da) | 2003-07-21 |
EP1151746A1 (en) | 2001-11-07 |
DE60001717T2 (de) | 2004-03-18 |
BRPI0008197B1 (pt) | 2017-05-09 |
US9789064B2 (en) | 2017-10-17 |
US20080233198A1 (en) | 2008-09-25 |
AU2173501A (en) | 2001-06-25 |
JP2003516960A (ja) | 2003-05-20 |
AU774680B2 (en) | 2004-07-01 |
ES2169980B1 (es) | 2003-11-01 |
DE60001717D1 (de) | 2003-04-24 |
ES2169980A1 (es) | 2002-07-16 |
CA2362769C (en) | 2008-09-09 |
BRPI0008197B8 (pt) | 2021-05-25 |
US20020187196A1 (en) | 2002-12-12 |
JP5021880B2 (ja) | 2012-09-12 |
BR0008197A (pt) | 2002-01-22 |
PT1151746E (pt) | 2003-07-31 |
ES2194793T3 (es) | 2003-12-01 |
ATE234608T1 (de) | 2003-04-15 |
EP1151746B1 (en) | 2003-03-19 |
MXPA01008348A (es) | 2004-03-19 |
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