EP0969874A1 - Compositions pharmaceutiques contenant des derives de propanamine et de la cyclodextrine - Google Patents
Compositions pharmaceutiques contenant des derives de propanamine et de la cyclodextrineInfo
- Publication number
- EP0969874A1 EP0969874A1 EP98913968A EP98913968A EP0969874A1 EP 0969874 A1 EP0969874 A1 EP 0969874A1 EP 98913968 A EP98913968 A EP 98913968A EP 98913968 A EP98913968 A EP 98913968A EP 0969874 A1 EP0969874 A1 EP 0969874A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cyclodextrin
- propanamine
- methyl
- formula
- phenoxy
- 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.)
- Withdrawn
Links
- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 169
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 title claims abstract description 48
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 230000003287 optical effect Effects 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 229920000642 polymer Polymers 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 claims abstract description 3
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 68
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 62
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 47
- 229960004853 betadex Drugs 0.000 claims description 43
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 23
- WIQRCHMSJFFONW-UHFFFAOYSA-N norfluoxetine Chemical compound C=1C=CC=CC=1C(CCN)OC1=CC=C(C(F)(F)F)C=C1 WIQRCHMSJFFONW-UHFFFAOYSA-N 0.000 claims description 23
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 22
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 10
- 208000020401 Depressive disease Diseases 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000001694 spray drying Methods 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000000227 grinding Methods 0.000 claims description 3
- 238000004898 kneading Methods 0.000 claims description 3
- 238000003801 milling Methods 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- MIFVTYPADKEWAV-HGRQBIKSSA-N chembl407030 Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)OC3O[C@H](CO)C([C@@H]([C@H]3O)O)C3O[C@H](CO)C([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)C3O[C@@H]1CO MIFVTYPADKEWAV-HGRQBIKSSA-N 0.000 claims 1
- DGDFMXSZLYHLAC-UHFFFAOYSA-N n-methyl-3-phenyl-3-[2-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=CC=C1C(F)(F)F DGDFMXSZLYHLAC-UHFFFAOYSA-N 0.000 claims 1
- 229940097362 cyclodextrins Drugs 0.000 abstract description 20
- 230000001430 anti-depressive effect Effects 0.000 abstract description 3
- 229960002464 fluoxetine Drugs 0.000 description 60
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 150000001875 compounds Chemical class 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 230000036470 plasma concentration Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 230000007423 decrease Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000001116 FEMA 4028 Substances 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical group OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 201000004219 Meesmann corneal dystrophy Diseases 0.000 description 2
- 208000002463 Sveinsson chorioretinal atrophy Diseases 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- -1 methyl fluoxetine Chemical group 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229940035613 prozac Drugs 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 230000009182 swimming Effects 0.000 description 2
- SDRCTKVIHMUQIG-UHFFFAOYSA-N 3-phenyl-3-[2-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCN)OC1=CC=CC=C1C(F)(F)F SDRCTKVIHMUQIG-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229960001407 sodium bicarbonate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 238000010591 solubility diagram Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- DSDAICPXUXPBCC-MWDJDSKUSA-N trimethyl-β-cyclodextrin Chemical compound COC[C@H]([C@H]([C@@H]([C@H]1OC)OC)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O3)[C@H](OC)[C@H]2OC)COC)O[C@@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@@H]3O[C@@H]1COC DSDAICPXUXPBCC-MWDJDSKUSA-N 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Definitions
- Preferred new complexes according to the invention include the following: inclusion complexes of ( ⁇ ) -N-methyl- ⁇ - [4- (trifluoromethyl) - -?- phenoxy] benzene-propanamine and its salts with ⁇ cyclodextrin; inclusion complexes of (+) -N-methyl- ⁇ - [ 4- ( trifluoromethyl ) - phenoxy] benzene-propanamine and its salts with ⁇ cyclodextrin; inclusion complexes of (-) -N-methyl- ⁇ - [ 4- (trifluoromethyl) - phenoxy] benzene-propanamine and its salts and ⁇ cyclodextrin; inclusion complexes of ( ⁇ ) - ⁇ - [4- (trifluoromethyl) - phenoxy] benzene-propanamine and its salts with ⁇ cyclodextrin; inclusion complexes of (+) -N-methyl- ⁇ - [ 4- ( trifluoro
- a pharmaceutical composition containing as an active ingredient inclusion complexes of a propanamine of the general formula I and a cyclodextrin, wherein the molar ratio of the propanamine of formula I to the cyclodextrin is within the range of 1:1 to 1:6 preferably 1:1 and 1:2.
- Oral administration of 10 m/kg of fluoxetine in the form of fluoxetine .HCl or fluoxetine . HCl/ ⁇ CD causes a progressive diminution of the discharge frequency of serotonmergic neurons of the RD. This diminution is of the order of 45% after 30 minutes.
- AUC (0-48h) area under the curve calculated by the trapezoidal rule between T Oh and T 48h (ng*h/ml); AUC (O-oo) . area under the curve extrapolated until ⁇ (ng*h/ml); MRT: mean residence time of drug (h) ; t'/ ⁇ : terminal half time (h) ; volume of distribution (1); C1T: Total clearance (ml/mm) .
- Table XIV Summary of FLU and FLU/ ⁇ CD pharmacokmetic parameters
- Table XV Summary of norfluoxetine and norfluoxetme/CD pharmacokmetic parameters.
- Figure 7 Curves of plasma levels of N-FLU (Mean ⁇ SE) time in hours after administration as a function of concentration. Round spots N-FLU, square spots N-FLU/ ⁇ CD.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nanotechnology (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
L'invention concerne une composition pharmaceutique, un procédé de préparation de cette composition pharmaceutique, et une méthode de traitement antidépresseur au moyen de cette composition qui contient une propanamine de la formule générale (I) - dans laquelle R représente un hydrogène ou un méthyle - ou n'importe quel isomère optique et/ou un sel de ce dernier acceptable du point de vue pharmaceutique, ainsi que de la cyclodextrine, de préférence sous la forme d'un composé d'inclusion. Ladite composition peut aussi comprendre éventuellement des matières auxiliaires et supplémentaires acceptables dans des produits pharmaceutiques destinés à un usage oral, parentéral, transdermique, rectal ou tout autre usage médical. Les cyclodextrines sont de préférence une η-cyclodextrine, une α-, β- ou η-cyclodextrine méthylée, une α-, β- ou η-cyclodextrine hydroxypropylée, un polymère de α-, β- ou η-cyclodextrine ionique soluble dans l'eau, ou une α-, β- ou η-cyclodextrine maltosylée. L'invention concerne également les composés d'inclusion et leur préparation. Le composé d'inclusion idéal est celui contenant (±), (-) ou (+) η-[4-(trifluorométhyl)-phénoxy]benzène-propanamine et η-cyclodextrine.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9700632A HUP9700632A3 (en) | 1997-03-24 | 1997-03-24 | Pharmaceutical compositions containing propylamine derivative and cyclodextrine and process for producing the same |
| HU9700632 | 1997-03-24 | ||
| PCT/HU1998/000028 WO1998042382A1 (fr) | 1997-03-24 | 1998-03-23 | Compositions pharmaceutiques contenant des derives de propanamine et de la cyclodextrine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0969874A1 true EP0969874A1 (fr) | 2000-01-12 |
Family
ID=89994898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP98913968A Withdrawn EP0969874A1 (fr) | 1997-03-24 | 1998-03-23 | Compositions pharmaceutiques contenant des derives de propanamine et de la cyclodextrine |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0969874A1 (fr) |
| JP (1) | JP2002514210A (fr) |
| AR (1) | AR010910A1 (fr) |
| AU (1) | AU6848198A (fr) |
| HR (1) | HRP980155A2 (fr) |
| HU (1) | HUP9700632A3 (fr) |
| WO (1) | WO1998042382A1 (fr) |
| ZA (1) | ZA982457B (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7091192B1 (en) * | 1998-07-01 | 2006-08-15 | California Institute Of Technology | Linear cyclodextrin copolymers |
| ATE248165T1 (de) * | 1999-07-01 | 2003-09-15 | Italfarmaco Spa | Komplexe von paroxetin mit cyclodextrin oder cyclodextrin derivaten |
| EP1534340B1 (fr) | 2002-09-06 | 2011-11-16 | Cerulean Pharma Inc. | Polymeres a base de cyclodextrine pour l'administration de medicaments lies par liaison covalente |
| JP2006516642A (ja) * | 2003-02-03 | 2006-07-06 | シャイア ラボラトリーズ，インコーポレイテッド | 薬物製剤およびメチル化シクロデキストリン結晶を用いた送達 |
| JP2010516625A (ja) | 2007-01-24 | 2010-05-20 | インサート セラピューティクス， インコーポレイテッド | 制御された薬物送達のためのテザー基を有するポリマー−薬物コンジュゲート |
| WO2014055493A1 (fr) | 2012-10-02 | 2014-04-10 | Cerulean Pharma Inc. | Procédés et systèmes s'appliquant à la précipitation de polymères et à la génération de particules |
| US11464866B2 (en) | 2016-05-06 | 2022-10-11 | Biodynamic Research Foundation | Pharmaceutical composition containing macromolecular drug |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5002935A (en) * | 1987-12-30 | 1991-03-26 | University Of Florida | Improvements in redox systems for brain-targeted drug delivery |
| WO1991013100A1 (fr) * | 1990-03-02 | 1991-09-05 | Australian Commercial Research & Development Limited | Compositions a base de cyclodextrines |
-
1997
- 1997-03-24 HU HU9700632A patent/HUP9700632A3/hu unknown
-
1998
- 1998-03-23 EP EP98913968A patent/EP0969874A1/fr not_active Withdrawn
- 1998-03-23 AU AU68481/98A patent/AU6848198A/en not_active Abandoned
- 1998-03-23 ZA ZA982457A patent/ZA982457B/xx unknown
- 1998-03-23 WO PCT/HU1998/000028 patent/WO1998042382A1/fr not_active Application Discontinuation
- 1998-03-23 JP JP54325498A patent/JP2002514210A/ja active Pending
- 1998-03-23 HR HRP9700632A patent/HRP980155A2/hr not_active Application Discontinuation
- 1998-03-24 AR ARP980101328A patent/AR010910A1/es unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9842382A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| HU9700632D0 (en) | 1997-05-28 |
| WO1998042382A1 (fr) | 1998-10-01 |
| ZA982457B (en) | 1998-09-23 |
| HUP9700632A3 (en) | 1999-10-28 |
| AU6848198A (en) | 1998-10-20 |
| HUP9700632A2 (hu) | 1998-12-28 |
| JP2002514210A (ja) | 2002-05-14 |
| AR010910A1 (es) | 2000-07-12 |
| HRP980155A2 (en) | 1998-12-31 |
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