DE69725312T2 - Verbesserte elektrophoretische verabreichung von therapeutischen wirkstoffen mit polybasischen anionischen gegenionen - Google Patents
Verbesserte elektrophoretische verabreichung von therapeutischen wirkstoffen mit polybasischen anionischen gegenionen Download PDFInfo
- Publication number
- DE69725312T2 DE69725312T2 DE69725312T DE69725312T DE69725312T2 DE 69725312 T2 DE69725312 T2 DE 69725312T2 DE 69725312 T DE69725312 T DE 69725312T DE 69725312 T DE69725312 T DE 69725312T DE 69725312 T2 DE69725312 T2 DE 69725312T2
- Authority
- DE
- Germany
- Prior art keywords
- reservoir
- active ingredient
- citrate
- solution
- compound
- 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.)
- Expired - Fee Related
Links
- 239000013543 active substance Substances 0.000 title claims description 26
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 125000000129 anionic group Chemical group 0.000 claims abstract description 22
- 150000001768 cations Chemical class 0.000 claims abstract description 19
- 238000012384 transportation and delivery Methods 0.000 claims abstract description 18
- 150000001450 anions Chemical class 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims description 63
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 46
- 239000000243 solution Substances 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 32
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical group OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000011787 zinc oxide Substances 0.000 claims description 23
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 19
- 239000000920 calcium hydroxide Substances 0.000 claims description 19
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 19
- 239000011159 matrix material Substances 0.000 claims description 17
- -1 acetylacetonate alkoxide Chemical class 0.000 claims description 16
- 229910052751 metal Inorganic materials 0.000 claims description 15
- 239000002184 metal Substances 0.000 claims description 15
- 229960004207 fentanyl citrate Drugs 0.000 claims description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical group [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052782 aluminium Inorganic materials 0.000 claims description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 229910052725 zinc Chemical group 0.000 claims description 8
- 239000011701 zinc Chemical group 0.000 claims description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052791 calcium Inorganic materials 0.000 claims description 7
- 239000011575 calcium Chemical group 0.000 claims description 7
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 7
- 238000010668 complexation reaction Methods 0.000 claims description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
- OJCZPLDERGDQRJ-UHFFFAOYSA-N Sufentanil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 OJCZPLDERGDQRJ-UHFFFAOYSA-N 0.000 claims description 5
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical group [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 5
- 229910017052 cobalt Inorganic materials 0.000 claims description 5
- 239000010941 cobalt Chemical group 0.000 claims description 5
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical group [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 5
- 229910052802 copper Inorganic materials 0.000 claims description 5
- 239000010949 copper Chemical group 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
- 229910052759 nickel Inorganic materials 0.000 claims description 5
- 229960001204 sufentanil citrate Drugs 0.000 claims description 5
- 239000010936 titanium Chemical group 0.000 claims description 5
- 229910052719 titanium Inorganic materials 0.000 claims description 5
- CNFIIGJQEIQCSX-UHFFFAOYSA-N n-[1-[2-(4-ethyl-5-oxotetrazol-1-yl)ethyl]-4-(methoxymethyl)piperidin-4-yl]-n-phenylpropanamide;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 CNFIIGJQEIQCSX-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 150000004703 alkoxides Chemical class 0.000 claims description 3
- 150000004678 hydrides Chemical class 0.000 claims description 3
- 230000000536 complexating effect Effects 0.000 claims description 2
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 claims 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 claims 2
- 229920000058 polyacrylate Polymers 0.000 claims 2
- 229920000193 polymethacrylate Polymers 0.000 claims 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 2
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 32
- 239000003795 chemical substances by application Substances 0.000 abstract description 11
- 150000002736 metal compounds Chemical class 0.000 abstract description 10
- 229940124597 therapeutic agent Drugs 0.000 abstract description 9
- 150000001457 metallic cations Chemical class 0.000 abstract description 3
- 239000000017 hydrogel Substances 0.000 description 36
- 229940079593 drug Drugs 0.000 description 23
- 229960002428 fentanyl Drugs 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000000499 gel Substances 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 17
- 210000003491 skin Anatomy 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 14
- 229910021645 metal ion Inorganic materials 0.000 description 13
- 230000009918 complex formation Effects 0.000 description 12
- AAZQQCFJUMQNKW-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylate;1-methylpiperidin-1-ium Chemical compound C[NH+]1CCCCC1.C[NH+]1CCCCC1.C[NH+]1CCCCC1.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O AAZQQCFJUMQNKW-UHFFFAOYSA-N 0.000 description 10
- 230000001070 adhesive effect Effects 0.000 description 10
- 238000006386 neutralization reaction Methods 0.000 description 10
- 229940127240 opiate Drugs 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000000853 adhesive Substances 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 9
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000002843 carboxylic acid group Chemical group 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001860 citric acid derivatives Chemical class 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229960004739 sufentanil Drugs 0.000 description 6
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 6
- YLXIPWWIOISBDD-NDAAPVSOSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;4-[(1r)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CNC[C@H](O)C1=CC=C(O)C(O)=C1 YLXIPWWIOISBDD-NDAAPVSOSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 4
- 229960001391 alfentanil Drugs 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229960003157 epinephrine bitartrate Drugs 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- AWQJMEDEHSUZIK-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;1-methylpiperidine Chemical compound CN1CCCCC1.OC(=O)CC(O)(C(O)=O)CC(O)=O AWQJMEDEHSUZIK-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- BWKOZPVPARTQIV-UHFFFAOYSA-N azanium;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical class [NH4+].OC(=O)CC(O)(C(O)=O)CC([O-])=O BWKOZPVPARTQIV-UHFFFAOYSA-N 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 235000011118 potassium hydroxide Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 3
- 239000011746 zinc citrate Substances 0.000 description 3
- 235000006076 zinc citrate Nutrition 0.000 description 3
- 229940068475 zinc citrate Drugs 0.000 description 3
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 2
- GWZMWHWAWHPNHN-UHFFFAOYSA-N 2-hydroxypropyl prop-2-enoate Chemical compound CC(O)COC(=O)C=C GWZMWHWAWHPNHN-UHFFFAOYSA-N 0.000 description 2
- PGNKBEARDDELNB-UHFFFAOYSA-N Diethylcarbamazine citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCN(CC)C(=O)N1CCN(C)CC1 PGNKBEARDDELNB-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- 229920000569 Gum karaya Polymers 0.000 description 2
- 229920000161 Locust bean gum Polymers 0.000 description 2
- CNCOEDDPFOAUMB-UHFFFAOYSA-N N-Methylolacrylamide Chemical compound OCNC(=O)C=C CNCOEDDPFOAUMB-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 241000934878 Sterculia Species 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 2
- 239000001354 calcium citrate Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229920003086 cellulose ether Polymers 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229960004837 diethylcarbamazine citrate Drugs 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000005370 electroosmosis Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000231 karaya gum Substances 0.000 description 2
- 235000010494 karaya gum Nutrition 0.000 description 2
- 229940039371 karaya gum Drugs 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000711 locust bean gum Substances 0.000 description 2
- 235000010420 locust bean gum Nutrition 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- OMNKZBIFPJNNIO-UHFFFAOYSA-N n-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical compound CC(=O)CC(C)(C)NC(=O)C=C OMNKZBIFPJNNIO-UHFFFAOYSA-N 0.000 description 2
- 231100000435 percutaneous penetration Toxicity 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 235000013337 tricalcium citrate Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- ACRMUSVWIFZVSM-JTHHODAVSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(3s)-3-methyl-4-morpholin-4-yl-2,2-diphenyl-1-pyrrolidin-1-ylbutan-1-one Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C([C@@H](C)C(C(=O)N1CCCC1)(C=1C=CC=CC=1)C=1C=CC=CC=1)N1CCOCC1 ACRMUSVWIFZVSM-JTHHODAVSA-N 0.000 description 1
- VENXSELNXQXCNT-OHAABKCISA-N 3-[(1r,2s)-2-amino-1-hydroxypropyl]phenol;(2r,3s)-2,3-dihydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O.C[C@H](N)[C@H](O)C1=CC=CC(O)=C1 VENXSELNXQXCNT-OHAABKCISA-N 0.000 description 1
- JLDOUEIDNZKSQH-YDYUUSCQSA-N 3-[(1r,2s)-2-amino-1-hydroxypropyl]phenol;oxalic acid Chemical compound OC(=O)C(O)=O.C[C@H](N)[C@H](O)C1=CC=CC(O)=C1 JLDOUEIDNZKSQH-YDYUUSCQSA-N 0.000 description 1
- CVQFAMQDTWVJSV-LQGIQHHOSA-N 3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=CNC3=C1 CVQFAMQDTWVJSV-LQGIQHHOSA-N 0.000 description 1
- 241001535291 Analges Species 0.000 description 1
- CKCVTPQYFOMHFD-HPJCWFBOSA-N Brovincamine fumarate Chemical compound OC(=O)\C=C\C(O)=O.BrC1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 CKCVTPQYFOMHFD-HPJCWFBOSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
- 229960005054 acepromazine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229960000847 dextromoramide tartrate Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 239000013536 elastomeric material Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229920000831 ionic polymer Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960000418 lisuride maleate Drugs 0.000 description 1
- YQZBAXDVDZTKEQ-UHFFFAOYSA-N loxapine succinate Chemical compound [H+].[H+].[O-]C(=O)CCC([O-])=O.C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 YQZBAXDVDZTKEQ-UHFFFAOYSA-N 0.000 description 1
- 229960000589 loxapine succinate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229960002984 metaraminol bitartrate Drugs 0.000 description 1
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000000000 tetracarboxylic acids Chemical class 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Electrotherapy Devices (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1961896P | 1996-06-12 | 1996-06-12 | |
| US19618P | 1996-06-12 | ||
| PCT/US1997/009550 WO1997047354A1 (en) | 1996-06-12 | 1997-06-03 | Enhanced electrotransport of therapeutic agents having polybasic anionic counter-ions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69725312D1 DE69725312D1 (de) | 2003-11-06 |
| DE69725312T2 true DE69725312T2 (de) | 2004-07-15 |
Family
ID=21794143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69725312T Expired - Fee Related DE69725312T2 (de) | 1996-06-12 | 1997-06-03 | Verbesserte elektrophoretische verabreichung von therapeutischen wirkstoffen mit polybasischen anionischen gegenionen |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0910432B1 (enExample) |
| JP (1) | JP3916669B2 (enExample) |
| CN (1) | CN1108173C (enExample) |
| AT (1) | ATE250957T1 (enExample) |
| AU (1) | AU3227397A (enExample) |
| BR (1) | BR9709780A (enExample) |
| CA (1) | CA2252899A1 (enExample) |
| DE (1) | DE69725312T2 (enExample) |
| DK (1) | DK0910432T3 (enExample) |
| ES (1) | ES2208911T3 (enExample) |
| PT (1) | PT910432E (enExample) |
| WO (1) | WO1997047354A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6719997B2 (en) | 2000-06-30 | 2004-04-13 | Dermatrends, Inc. | Transdermal administration of pharmacologically active amines using hydroxide-releasing agents as permeation enhancers |
| US6673363B2 (en) | 1999-12-16 | 2004-01-06 | Dermatrends, Inc. | Transdermal and topical administration of local anesthetic agents using basic enhancers |
| WO2007027892A1 (en) * | 2005-08-31 | 2007-03-08 | Alza Corporation | Cathode for electrotransport delivery of anionic drug |
| US20090105632A1 (en) * | 2007-10-18 | 2009-04-23 | Padmanabhan Rama V | Electrotransport Of Lisuride |
| CN101792564B (zh) * | 2010-03-04 | 2012-05-02 | 吉林大学 | 一种抗刮擦涂层及其制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5810066A (ja) * | 1981-07-10 | 1983-01-20 | 株式会社アドバンス | イオントフオレ−ゼ用プラスタ−構造体 |
| US4731049A (en) * | 1987-01-30 | 1988-03-15 | Ionics, Incorporated | Cell for electrically controlled transdermal drug delivery |
| IE64873B1 (en) * | 1990-03-15 | 1995-09-20 | Becton Dickinson Co | Method and composition for iontophoresis |
| US5298017A (en) * | 1992-12-29 | 1994-03-29 | Alza Corporation | Layered electrotransport drug delivery system |
| JP4090072B2 (ja) * | 1994-07-13 | 2008-05-28 | アルザ・コーポレーション | 経皮電気的移送式作用剤投与を促進するための組成物と方法 |
-
1997
- 1997-06-03 DK DK97927937T patent/DK0910432T3/da active
- 1997-06-03 ES ES97927937T patent/ES2208911T3/es not_active Expired - Lifetime
- 1997-06-03 DE DE69725312T patent/DE69725312T2/de not_active Expired - Fee Related
- 1997-06-03 WO PCT/US1997/009550 patent/WO1997047354A1/en not_active Ceased
- 1997-06-03 CA CA002252899A patent/CA2252899A1/en not_active Abandoned
- 1997-06-03 PT PT97927937T patent/PT910432E/pt unknown
- 1997-06-03 EP EP97927937A patent/EP0910432B1/en not_active Expired - Lifetime
- 1997-06-03 AU AU32273/97A patent/AU3227397A/en not_active Abandoned
- 1997-06-03 AT AT97927937T patent/ATE250957T1/de not_active IP Right Cessation
- 1997-06-03 BR BR9709780A patent/BR9709780A/pt not_active Application Discontinuation
- 1997-06-03 JP JP50166598A patent/JP3916669B2/ja not_active Expired - Fee Related
- 1997-06-03 CN CN97195459.3A patent/CN1108173C/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0910432B1 (en) | 2003-10-01 |
| JP2000512181A (ja) | 2000-09-19 |
| ES2208911T3 (es) | 2004-06-16 |
| JP3916669B2 (ja) | 2007-05-16 |
| EP0910432A1 (en) | 1999-04-28 |
| DK0910432T3 (da) | 2004-02-09 |
| PT910432E (pt) | 2004-01-30 |
| CN1222093A (zh) | 1999-07-07 |
| BR9709780A (pt) | 1999-08-10 |
| DE69725312D1 (de) | 2003-11-06 |
| ATE250957T1 (de) | 2003-10-15 |
| AU3227397A (en) | 1998-01-07 |
| WO1997047354A1 (en) | 1997-12-18 |
| CN1108173C (zh) | 2003-05-14 |
| CA2252899A1 (en) | 1997-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3225748C2 (enExample) | ||
| AT409088B (de) | Elektrotransport-medikamentenverabreichung | |
| DE69202872T2 (de) | Vorrichtung und Verfahren zur Erneuerung von Elektroden während der Iontophorese. | |
| DE69535556T2 (de) | Zusammensetzungen, vorrichtung und verfahren zur elektrotransport-wirkstoffabgabe | |
| DE69212468T2 (de) | Gerät zur verminderung der empfindung während der iontophoretischen arneimittelverabreichung | |
| DE69632131T2 (de) | Vorrichtung zur transdermalen iontophoretischen verabreichung von fentanyl und sufentanil | |
| DE69519393T2 (de) | Zusammensetzung und verfahren zur förderung von transdermaler elektrotransport-darreichung | |
| DE60202677T2 (de) | Implantierbare medizinische vorrichtung mit kontrollierter freigabe von gasförmigen mitteln | |
| DE3789035T2 (de) | Vorrichtung zur transdermalen Applikation von wirksamen Substanzen. | |
| DE69631766T2 (de) | Vorrichtung zur verabreichnung von medikamenten durch elektrotransport | |
| DE3785789T2 (de) | Apparat zur Verabreichung von Medikamenten durch Iontophorese. | |
| DE69431189T2 (de) | Iontophoresegerät | |
| DE69613113T2 (de) | Unhabhängige vorrichtung zur transdermalen verabreichung von medikamenten | |
| DE69115471T2 (de) | Gerät zur iontophoretischen verabreichung von medikamenten | |
| DE69031083T2 (de) | Gerät zur iontophoretischen verabreichung von medikamenten | |
| DE69502281T2 (de) | Verminderung der hautreizung während einer iontophoretischen abgabe von medikamenten | |
| DE69823869T2 (de) | Pharmazeutische hydrogelformulierungen, vorrichtungen zur arzneistoffabgabe und verfahren | |
| DE69623608T2 (de) | Zusammensetzung zur verbesserten elektroübertragunslieferung von wirkstoff | |
| DE3785442T2 (de) | Geraet zur transkutanen verabreichung von heilmitteln. | |
| DE69732833T2 (de) | Iontophoretisches behandlungssystem | |
| DE60110245T2 (de) | Vorrichtung zur transdermalen verabreichung von medikamenten und entsprechendes herstellungsverfahren | |
| DE69605298T2 (de) | Herstellung von formulierungen zur arzneiverabreichung mittels elektrotransport | |
| DE19681421B4 (de) | Vorrichtung und Bereitstellungsverfahren für eine transdermale Elektrotransport-Abgabe von Fentanyl und Sufentanil | |
| DE69532477T2 (de) | Zusammensetzung, vorrichtung und verfahren zur verbesserten elektrotransport-wirkstoffabgabe | |
| HK1201763A1 (en) | Polyamine enhanced formulations for triptan compound iontophoresis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |