CN107921043B - 含有酸捕捉剂的贴剂 - Google Patents
含有酸捕捉剂的贴剂 Download PDFInfo
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- CN107921043B CN107921043B CN201680049249.9A CN201680049249A CN107921043B CN 107921043 B CN107921043 B CN 107921043B CN 201680049249 A CN201680049249 A CN 201680049249A CN 107921043 B CN107921043 B CN 107921043B
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- CN
- China
- Prior art keywords
- acid
- potassium
- fatty acid
- salt
- patch
- 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.)
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- 239000002253 acid Substances 0.000 title claims abstract description 41
- 230000001070 adhesive effect Effects 0.000 title abstract description 19
- 239000000853 adhesive Substances 0.000 title abstract description 18
- 239000002516 radical scavenger Substances 0.000 title description 3
- 239000003814 drug Substances 0.000 claims abstract description 52
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 50
- 239000000194 fatty acid Substances 0.000 claims abstract description 50
- 229930195729 fatty acid Natural products 0.000 claims abstract description 50
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 239000012790 adhesive layer Substances 0.000 claims abstract description 32
- 239000002608 ionic liquid Substances 0.000 claims abstract description 30
- 229910001414 potassium ion Inorganic materials 0.000 claims abstract description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 21
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims abstract description 15
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims abstract description 10
- -1 amine compound Chemical class 0.000 claims description 19
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 claims description 19
- 229940043276 diisopropanolamine Drugs 0.000 claims description 19
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 claims description 14
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 claims description 12
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 11
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 9
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 8
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 8
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 8
- 239000005642 Oleic acid Substances 0.000 claims description 8
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 8
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 8
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 8
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 7
- 229940040102 levulinic acid Drugs 0.000 claims description 7
- 235000010199 sorbic acid Nutrition 0.000 claims description 7
- 239000004334 sorbic acid Substances 0.000 claims description 7
- 229940075582 sorbic acid Drugs 0.000 claims description 7
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical group [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
- ZWUKMNZJRDGCTQ-UHFFFAOYSA-N Tizanidine hydrochloride Chemical group Cl.ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 ZWUKMNZJRDGCTQ-UHFFFAOYSA-N 0.000 claims description 5
- 229960002388 tizanidine hydrochloride Drugs 0.000 claims description 5
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 claims description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 3
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims description 3
- 239000005639 Lauric acid Substances 0.000 claims description 3
- 235000021314 Palmitic acid Nutrition 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 0.000 claims description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000001103 potassium chloride Substances 0.000 claims description 3
- 235000011164 potassium chloride Nutrition 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- 229960000488 tizanidine Drugs 0.000 claims 2
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 claims 2
- 239000011230 binding agent Substances 0.000 claims 1
- 231100000245 skin permeability Toxicity 0.000 abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000014 opioid analgesic Substances 0.000 abstract description 6
- 229940005483 opioid analgesics Drugs 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 230000035515 penetration Effects 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 7
- 229940055577 oleyl alcohol Drugs 0.000 description 7
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229920001971 elastomer Polymers 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 239000005060 rubber Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 235000010241 potassium sorbate Nutrition 0.000 description 5
- 239000004302 potassium sorbate Substances 0.000 description 5
- 229940069338 potassium sorbate Drugs 0.000 description 5
- BQNSLJQRJAJITR-UHFFFAOYSA-N 1,1,2-trichloro-1,2-difluoroethane Chemical compound FC(Cl)C(F)(Cl)Cl BQNSLJQRJAJITR-UHFFFAOYSA-N 0.000 description 4
- DYUTXEVRMPFGTH-UHFFFAOYSA-N 4-(2,5-dimethylphenyl)-5-methyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC=C(C)C=2)C)=C1C DYUTXEVRMPFGTH-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 229960002738 hydromorphone hydrochloride Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229960003617 oxycodone hydrochloride Drugs 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 150000003388 sodium compounds Chemical class 0.000 description 4
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 4
- JOOXCMJARBKPKM-UHFFFAOYSA-M 4-oxopentanoate Chemical compound CC(=O)CCC([O-])=O JOOXCMJARBKPKM-UHFFFAOYSA-M 0.000 description 3
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 3
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 229910021485 fumed silica Inorganic materials 0.000 description 3
- ZTHYODDOHIVTJV-UHFFFAOYSA-N gallic acid propyl ester Natural products CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 3
- 229940058352 levulinate Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 229940049964 oleate Drugs 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical class C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 2
- AHOUBRCZNHFOSL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 2
- NBUHTTJGQKIBMR-UHFFFAOYSA-N 4,6-dimethylpyrimidin-5-amine Chemical compound CC1=NC=NC(C)=C1N NBUHTTJGQKIBMR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000003568 Sodium, potassium and calcium salts of fatty acids Substances 0.000 description 2
- 239000002998 adhesive polymer Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229960004379 fentanyl hydrochloride Drugs 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229940051129 meperidine hydrochloride Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229960005195 morphine hydrochloride Drugs 0.000 description 2
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 2
- 229940043348 myristyl alcohol Drugs 0.000 description 2
- LHCBOXPPRUIAQT-UHFFFAOYSA-N n-phenyl-n-[1-(2-phenylethyl)piperidin-4-yl]propanamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 LHCBOXPPRUIAQT-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 235000013966 potassium salts of fatty acid Nutrition 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000000473 propyl gallate Substances 0.000 description 2
- 235000010388 propyl gallate Nutrition 0.000 description 2
- 229940075579 propyl gallate Drugs 0.000 description 2
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 150000003505 terpenes Chemical class 0.000 description 2
- 235000007586 terpenes Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- SQUNAWUMZGQQJD-UHFFFAOYSA-N 1-(4-ethylphenyl)-2-methyl-3-(piperidin-1-yl)propan-1-one Chemical compound C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 SQUNAWUMZGQQJD-UHFFFAOYSA-N 0.000 description 1
- GLQPTZAAUROJMO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)benzaldehyde Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC=C(C=O)C=C1 GLQPTZAAUROJMO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- RJBSTXIIQYFNPX-UHFFFAOYSA-N 4-methoxy-6-phenyl-1,3,5-triazin-2-amine Chemical compound COC1=NC(N)=NC(C=2C=CC=CC=2)=N1 RJBSTXIIQYFNPX-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 229920002367 Polyisobutene Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- XDXHAEQXIBQUEZ-UHFFFAOYSA-N Ropinirole hydrochloride Chemical compound Cl.CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 XDXHAEQXIBQUEZ-UHFFFAOYSA-N 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N Ropinirole hydrochloride Natural products CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
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- PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 1
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- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
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- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
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- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
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- PHZLMBHDXVLRIX-UHFFFAOYSA-M potassium lactate Chemical compound [K+].CC(O)C([O-])=O PHZLMBHDXVLRIX-UHFFFAOYSA-M 0.000 description 1
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- OUDJDLBWLBEQBJ-UHFFFAOYSA-M potassium;4-oxopentanoate Chemical compound [K+].CC(=O)CCC([O-])=O OUDJDLBWLBEQBJ-UHFFFAOYSA-M 0.000 description 1
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- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
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- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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Abstract
本发明的目的在于,提供一种使用碱性药物酸加成盐作为原料,药物的皮肤渗透性优良的贴剂。本发明的贴剂是由在支承体的单面设置粘接剂层而成的贴剂,在所述粘接剂层中包含碱性药物、脂肪酸类离子液体以及钾盐和/或钾离子。所述钾盐和/或钾离子能够在粘接剂中通过所述碱性药物的酸加成盐与可生成钾离子的化合物反应而产生。作为碱性药物能够例示阿片类镇痛剂,作为酸加成盐能够例示盐酸盐。
Description
技术领域
本发明涉及将含有碱性药物的酸加成盐作为活性成分的贴剂,更详细而言,涉及通过含有添加至药物的酸捕捉剂而促进游离碱的生成的贴剂。
背景技术
作为促进药物经皮吸收的技术的一例,已知有在脂肪酸类离子液体中溶解药物的技术(专利文献1)。
另一方面,因稳定性以及操作性优良,所以碱性药物大多作为盐酸盐等酸加成盐流通。但是,已知与游离碱相比,这样的酸加成盐存在经皮吸收性较低的倾向。因此,提出了添加氢氧化钠等中和剂,在制剂中进行酸加成盐的脱离的方案(专利文献2)。虽然在该文献中,通过混合吸附剂解决了中和反应中产生的金属盐随时间而凝聚或生长的问题,但是无法对皮肤渗透性的提高带来满意的结果。
现有技术文献
专利文献
专利文献1:国际公开第2009/066457号公报
专利文献2:国际公开第2009/107479号公报
发明内容
发明要解决的技术问题
本发明的目的在于,提供一种使用碱性药物酸加成盐作为原料、药物的皮肤渗透性优良的贴剂。
用于解决上述技术问题的方案
本发明人专心研究后发现,将可生成钾离子的化合物添加至包含碱性药物酸加成盐以及脂肪酸类离子液体的粘接剂层,使钾离子捕捉碱性药物酸加成盐的酸作为钾盐,由此能够解决上述技术问题。
即,本发明提供下述(1)~(8)。
(1)一种贴剂,由在支承体的单面设置粘接剂层而成,在所述粘接剂层中包含碱性药物、脂肪酸类离子液体以及钾盐和/或钾离子。
(2)如上述(1)所述的贴剂,所述钾盐和/或钾离子是在粘接剂中,通过所述碱性药物的酸加成盐与可生成钾离子的化合物反应而产生的。
(3)如上述(1)或者(2)所述的贴剂,所述碱性药物为阿片类镇痛剂。
(4)如上述(1)~(3)中的任一项所述的贴剂,所述脂肪酸类离子液体选自油酸二异丙醇胺、乙酰丙酸二异丙醇胺、山梨酸二异丙醇胺的1种或2种以上。
(5)如上述(1)~(4)中的任一项所述的贴剂,所述碱性药物酸加成盐为碱性药物的盐酸盐,所述钾盐为氯化钾。
(6)一种贴剂用组合物,包含碱性药物的酸加成盐、脂肪酸类离子液体以及可生成钾离子的化合物。
(7)一种贴剂的制造方法,包括:
提供碱性药物的酸加成盐的工序;
提供用于生成脂肪酸类离子液体的脂肪酸以及有机胺化合物的工序;
提供可生成钾离子的化合物的工序;
以及在聚合物溶液中混合碱性药物的酸加成盐、脂肪酸、有机胺化合物以及可生成钾离子的化合物,生成用于形成粘接剂层的粘接剂组合物的工序。
(8)如上述(7)所述的贴剂的制造方法,预先将脂肪酸以及有机胺化合物混合作为脂肪酸类离子液体,提供得到的脂肪酸类离子液体代替脂肪酸以及有机胺化合物。
发明效果
根据本发明,能够提供经皮吸收性优良的碱性药物的贴剂。
具体实施方式
本发明的贴剂在支承体的单面设置有包含碱性药物、脂肪酸类离子液体以及钾盐和/或钾离子的粘接剂层。
[碱性药物]
能够使用通常以酸加成盐的形态流通的药物的任一种作为碱性药物。作为酸加成盐能够例示盐酸盐、硫酸盐、氢溴酸盐等无机酸盐、富马酸盐、马来酸盐、柠檬酸盐、酒石酸盐等有机酸盐。在本发明中,作为加成盐优选是无机酸盐,特别优选是盐酸盐。在使用了碱性药物的盐酸盐作为药物的情况下,粘接剂层所含的钾盐为氯化钾。
作为碱性药物盐酸盐的具体例,能够列举:盐酸吗啡、盐酸羟考酮、盐酸氢吗啡酮、盐酸芬太尼、盐酸哌替啶、盐酸纳洛酮等阿片类镇痛剂;盐酸利多卡因、盐酸丁卡因、盐酸普鲁卡因等局部麻醉剂;盐酸替扎尼定、盐酸乙哌立松等骨骼肌松弛剂;盐酸丙咪嗪、盐酸舍曲林、盐酸氟西汀、盐酸帕罗西汀等精神神经作用剂;盐酸哌甲酯、盐酸脱氧麻黄碱等兴奋、刺激剂;盐酸罗匹尼罗、盐酸金刚烷胺等抗帕金森病药;盐酸多奈哌齐等抗阿尔茨海默病药。在本发明中,优选地使用盐酸吗啡、盐酸羟考酮、盐酸氢吗啡酮、盐酸芬太尼、盐酸哌替啶等阿片类镇痛剂作为碱性药物,因盐酸羟考酮、盐酸氢吗啡酮对本发明的贴剂的皮肤渗透性提高效果较高,从而特别地优选使用。
[可生成钾离子的化合物]
本发明的贴剂的粘接剂层中所含的钾盐,是通过碱性药物的酸加成盐与可生成钾离子的化合物反应,在制造中和/或制造后的粘接剂中产生的。作为可生成钾离子的化合物,能够例示氢氧化钾;柠檬酸钾、乙酸钾、酒石酸钾、乳酸钾、C4-20脂肪酸的钾盐等有机酸钾盐;碳酸氢钾、磷酸二氢钾、磷酸氢二钾、磷酸三钾等无机酸钾盐。在C4-20脂肪酸的钾盐的例子中包括山梨酸钾、油酸钾、乙酰丙酸钾。在一实施方式中,能够使用氢氧化钾、脂肪酸钾盐的任一种、或者组合地使用两种。
以往,作为用于在制剂中中和碱性化合物的酸加成盐而生成游离碱的中和剂,优选是氢氧化钠等钠化合物。此外,已知脂肪酸类离子液体作为药物的溶解辅助剂以及经皮吸收促进剂是优异的。在含有脂肪酸类离子液体的有机溶剂中,即使想溶解碱性药物的酸加成盐以及氢氧化钠等钠化合物,药物也可能不会充分溶解于溶剂中。此外,即使在溶解了的情况下,与使用了钾化合物的情况相比,使用钠化合物制备的贴剂的药物的皮肤渗透性较差。认为原因之一在于酸加成物的脱离未充分地进行。另一方面,在可生成钾离子的化合物的存在下,碱性药物的酸加成盐在含有脂肪酸类离子液体的有机溶剂中不产生溶解残留而较好地溶解。使用得到的溶液制备的贴剂与使用了钠化合物的情况相比,药物的皮肤渗透性非常优良。
相对于碱性药物酸加成盐的酸1摩尔,可生成钾离子的化合物的含量可以是约0.6~约4.5摩尔、约0.8~约2.0摩尔、或者约0.8~约1.5摩尔的范围。
[脂肪酸类离子液体]
脂肪酸类离子液体是脂肪酸与有机胺化合物的盐。脂肪酸类离子液体可预先制备而添加至粘接剂中,也可以将脂肪酸以及有机胺化合物添加至粘接剂组合物中在该组合物中形成。作为上述脂肪酸可以使用碳原子数5~20的饱和或者不饱和脂肪酸。具体而言,能够例示癸酸、山梨酸、乙酰丙酸、月桂酸、肉豆蔻酸、软脂酸、硬脂酸、异硬脂酸、油酸等。作为上述有机胺化合物,能够使用碳原子数4~9的链烷醇胺。具体而言,能够例示单乙醇胺、单异丙醇胺、二乙醇胺、二异丙醇胺、三乙醇胺、三异丙醇胺、三羟甲基氨基甲烷等。
在脂肪酸类离子液体的例子中包括:乙酰丙酸与二异丙醇胺的等摩尔盐、癸酸与二异丙醇胺的等摩尔盐、异硬脂酸与二异丙醇胺的等摩尔盐、油酸与二异丙醇胺的等摩尔盐、山梨酸与二异丙醇胺的等摩尔盐等的含有二异丙醇胺的脂肪酸类离子液体;乙酰丙酸与三乙醇胺的等摩尔盐、己酸与三乙醇胺的等摩尔盐、异硬脂酸与三乙醇胺的等摩尔盐、油酸与三乙醇胺的等摩尔盐、山梨酸与三乙醇胺的等摩尔盐等的含有三乙醇胺的脂肪酸类离子液体;乙酰丙酸与二乙醇胺的等摩尔盐、癸酸与二乙醇胺的等摩尔盐、异硬脂酸与二乙醇胺的等摩尔盐、油酸与二乙醇胺的等摩尔盐、山梨酸与二乙醇胺的等摩尔盐等的含有二乙醇胺的脂肪酸类离子液体。制剂或者贴剂包含1种或者2种以上的脂肪酸类离子液体。
相对于1摩尔的碱性药物,脂肪酸类离子液体的含量能够从约0.2~约12摩尔、约0.4~约5摩尔、或者约0.5~约1.5摩尔的范围中选择。
在采用阿片类镇痛剂作为碱性药物的情况下,从提高经皮吸收性的观点来看,能够使用二异丙醇胺作为脂肪酸类离子液体。在该情况下,在一实施方式中,能够并用乙酰丙酸二异丙醇胺与油酸二异丙醇胺。
[粘接剂层]
粘接剂层由适当的粘接性聚合物构成。作为粘接性聚合物能够例示丙烯酸类聚合物、橡胶类聚合物、硅氧烷类聚合物、乙烯基醚类聚合物等。在本发明中,能够优选地使用苯乙烯-异戊二烯-苯乙烯嵌段共聚物、苯乙烯-丁二烯-苯乙烯嵌段共聚物、聚异戊二烯、聚异丁烯、聚丁二烯等的橡胶类聚合物。在使用橡胶类聚合物时,相对于粘接剂层的总重量,其含量可以在约5~约40重量%,或者约10~约30重量%的范围。
在粘接剂层由橡胶类聚合物构成的情况下,优选是粘接剂层还包括增粘剂、软化剂。作为增粘剂能够列举例如松香酯、氢化松香酯、马来松香、脂环族饱和烃树脂、萜烯树脂、聚烯烃树脂等。相对于粘接剂层的总重量,增粘树脂能够从约10~约35重量%、约20~约30重量%、或者约22~约28重量%的范围中选择。作为软化剂,能够列举环烷烃类加工油;山茶油、蓖麻油等植物油;液体聚丁烯、液体异戊二烯橡胶等液体橡胶;液态石蜡。
[其他的经皮吸收促进剂]
在一实施方式中,粘接剂层还能够包括1种或者2种以上的有机溶剂。在一实施方式中,上述有机溶剂具有经皮吸收促进效果。有机溶剂的例子包括脂肪酸、醇类、酯类等。作为脂肪酸能够使用与构成上述脂肪酸类离子液体的脂肪酸相同的脂肪酸。相对于1摩尔的脂肪酸类离子液体,脂肪酸的含量可以在约0.4~约5摩尔、约0.5~约3摩尔、或者约0.8~约1.5摩尔的范围。相对于粘接剂层的总重量,脂肪酸的含量可以在约0.5~约10重量%、或者约1.0~约6重量%的范围。
作为醇,能够例示辛醇、月桂醇、肉豆蔻醇、鲸蜡醇、硬脂醇、油醇等一元醇、丙二醇、丁二醇、聚乙二醇等二元醇、甘油等三元醇。相对于粘接剂层的总重量,醇的添加量可以在约5~约30重量%、约8~约25重量%、或者约10~约15重量%的范围。因油醇的经皮吸收性提高效果较高,所以能够在本发明中使用油醇。相对于粘接剂层的总重量,油醇的添加量可以在约3~约15重量%、或者约8~约12重量%的范围。油醇也能够与其他的醇组合地使用。
作为酯类能够例示碳酸丙烯酯等碳酸酯;癸二酸二乙酯、肉豆蔻酸异丙酯、己二酸二异丙酯、棕榈酸肉豆蔻酯、硬脂酸十八醇酯、中链脂肪酸甘油三酯等脂肪酸酯。
在一实施方式中,粘接剂层中还可以包括填充剂。若含有填充剂,则能够改善粘接剂层的粘接特性,并且提高药物的释放性。相对于粘接剂层的总重量,填充剂的含量可以在约0.5~约5重量%的范围。作为填充剂,能够使用水合二氧化硅、气相二氧化硅、滑石、结晶纤维素、淀粉、羧甲基纤维素、羧甲基纤维素金属盐等。在一实施方式中,能够使用气相二氧化硅作为填充剂。在一实施方式中,能够使用市售的气相二氧化硅艾罗西尔(注册商标AEROSIL)。
在粘接剂层还可以含有软化剂、抗氧化剂等用于贴剂的粘接剂层的添加剂。
[贴剂的制造方法]
示出本发明的贴剂的制造方法的一方案。将构成脂肪酸类离子液体的脂肪酸以及有机胺一起混合成为均匀的液体。在一实施方式中,根据需要在其中还添加有机溶剂。所述有机溶剂能够起到经皮吸收促进效果。添加碱性药物的酸加成盐以及可生成钾离子的化合物,使其溶解,从而制备贴剂用组合物(药物组合物)。在一实施方式中,也可以根据需要加热(例如45~60℃)溶液。在一实施方式中,也可以同时混合脂肪酸、有机胺、碱性药物的酸加成盐以及可生成钾离子的化合物。
在该药物组合物中,添加至碱性药物的酸脱离,产生碱性药物的游离碱。另一方面,通过脱离的酸与钾离子的反应生成钾盐。
这一连串的反应可以在碱性药物的溶液制备时就全部结束,也可以是一部分在与构成粘接剂层的材料混合的混合工序、向支承体的涂布、干燥工序中进行,也可以在贴剂制造结束后的粘接剂层中进行。碱性化合物的酸加成盐与钾盐一同存在于粘接剂层的贴剂也在本发明的范畴内。碱性药物的酸加成盐与钾离子一同存在的贴剂也在发明的范畴内。
制备的药物组合物与用于形成粘接剂层的材料混合。在一实施方式中,粘接剂层包含橡胶类聚合物。例如,将橡胶类聚合物以及增粘树脂与甲苯混合,加热(约60℃)为熔融液。将该熔融液与预先制备的药物组合物混合作为聚合物溶液。进而添加混合填充剂得到粘接剂组合物。进而,在支承体(纺织布、无纺布、PET薄膜等)上涂布该组合物。加热(约80℃)干燥除去甲苯,在支承体上形成粘接剂层。
实施例
以下,通过实施例对本发明更详细地进行说明,但本发明并不受到这些实施例的任何限定。
[含有羟考酮的贴剂]
以表1所示的组成(重量%)制造了贴剂。对由使用了弗朗茨扩散池的皮肤渗透性试验制造的贴剂的皮肤渗透性进行了评价。试验中所使用的是猪皮肤。在表1中一并示出各采样点中的累积皮肤渗透量。
[表1]
表1
实1-a | 实1-b | 实1-c | 实1-d | 实1-e | 比1 | |
M286 | M308 | M307 | M294 | M313 | ||
Oxyco.HCl·3H<sub>2</sub>O | 3.461 | 3.461 | 3.461 | 3.461 | 3.461 | 3.461 |
氢氧化钾 | 0.55 | 0.55 | 0.55 | |||
山梨酸钾 | 1.4 | 1.3 | ||||
氢氧化钠 | 0.34 | |||||
二异丙醇胺 | 1.5 | 1.5 | 1.5 | 0.7 | 1.5 | |
三乙醇胺 | 2.2 | |||||
乙酰丙酸 | 1.0 | 0.8 | 1.0 | 1.0 | 1.0 | |
油酸 | 4.0 | 4.0 | 3.0 | 4.0 | 4.0 | 4.0 |
油醇 | 10.0 | 10.0 | 10.0 | 8.0 | 10.0 | 10.0 |
甘油 | 3.0 | 4.0 | 4.0 | 2.5 | 3.0 | |
浓甘油 | 3.0 | |||||
碳酸丙稀酯 | 4.0 | 5.0 | 5.0 | 2.5 | 5.0 | 5.0 |
中链脂肪酸甘油三脂 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
液态石蜡 | 17.34 | 16.49 | 16.81 | 17.64 | 19.14 | 17.55 |
艾罗西尔(AEROSIL) | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
PX-1150N | 27.0 | 26.0 | 26.0 | 27.0 | 26.0 | 26.0 |
SIS-5002 | 15.0 | 15.0 | 15.0 | 15.0 | 14.0 | 15.0 |
焦亚硫酸钠 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
没食子酸丙酯 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
总计 | 100 | 100 | 100 | 97.001 | 100 | 100 |
2小时后皮肤渗透量(μg/cm<sup>2</sup>) | 1.72 | 0.5 | 0.3 | |||
4小时后皮肤渗透量(μg/cm<sup>2</sup>) | 12.5 | 2.2551 | 3.9967 | 1.86 | 5 | 1.8 |
6小时后皮肤渗透量(μg/cm<sup>2</sup>) | 40.32 | 7.0518 | 15.8 | 6.015 | 14.8 | 4 |
8小时后皮肤渗透量(μg/cm<sup>2</sup>) | 76.469 | 16.639 | 33.5 | 11.982 | 31.1 | 7.3 |
24小时后皮肤渗透量(μg/cm<sup>2</sup>) | 245.88 | 164.53 | 224.45 | 90.235 | 248.3 | 52.5 |
酸/碱 | 1.08 | 1.14 | 1.32 | 0.93 | 1.51 | 1.15 |
包含可生成钾离子的化合物作为原料的实施例1-a~1-e的贴剂均示出优良的皮肤渗透性。除氢氧化钾以外还包含氢氧化钠的比较例1的贴剂的皮肤渗透性不良。实施例1-d的贴剂因为不包含含有二异丙醇胺的脂肪酸类离子液体,所以与实施例1-a~1-c的贴剂相比,皮肤渗透性不良。实施例1-a以及实施例1-c的贴剂因为均包括乙酰丙酸二异丙醇胺与油酸二异丙醇胺,所以皮肤渗透性特别优良。
[包含氢吗啡酮的贴剂]
以表2所示的组成(重量%)制造了贴剂。对由使用了弗朗茨扩散池的皮肤渗透性试验制造的贴剂的皮肤渗透性进行了评价。试验中所使用的是猪皮肤。在表2中一并示出各采样点中的累积皮肤渗透量。
[表2]
表2
包含山梨酸钾的实施例2-a以及2-b的贴剂,与不含可生成钾离子的化合物的比较例2-a的贴剂相比,示出优良的皮肤渗透性。包含可生成钾离子的化合物的实施例2-c~2-f的贴剂,与不含该化合物的比较例2-b的贴剂相比,示出优良的皮肤渗透性。
[包含盐酸替扎尼定的贴剂]
以表3所示的组成(重量%)制造了贴剂。对由使用了弗朗茨扩散池的皮肤渗透性试验制造的贴剂的皮肤渗透性进行了评价。试验中所使用的是猪皮肤。在表3中一并示出各采样点中的累积皮肤渗透量。
[表3]
表3
实3-a | 实3-b | 实3-c | 实3-d | 实3-e | 实3-f | |
T651 | T695 | T697 | T700 | T702 | T696 | |
盐酸替扎尼定 | 1.72 | 1.72 | 1.72 | 1.72 | 1.72 | 1.72 |
山梨酸 | 0.66 | |||||
山梨酸钾 | 0.89 | 0.89 | 0.89 | 0.89 | 0.89 | 0.89 |
油酸 | 1.50 | 1.50 | 1.50 | 1.50 | 1.50 | |
三乙醇胺 | 0.5 | 0.5 | 0.4 | |||
油醇 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
肉豆蔻醇 | 3.0 | 3.0 | 3.0 | 3.0 | ||
甘油 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 |
DiPG | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 |
BG | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
中链脂肪酸甘油三酯 | 5.0 | |||||
艾罗西尔(AEROSIL) | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
液态石蜡 | 18.08 | 23.24 | 23.34 | 26.74 | 23.74 | 23.74 |
萜烯树脂 | 32.00 | 28.00 | 28.00 | 28.00 | 28.00 | 28.00 |
SIS5002 | 16.00 | 16.00 | 16.00 | 16.00 | 16.00 | 16.00 |
亚硫酸钠 | 0.10 | 0.10 | 0.10 | 0.10 | 0.10 | |
焦亚硫酸钠 | 0.10 | |||||
没食子酸丙酯 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 |
总计 | 100 | 100 | 100 | 100 | 100 | 100 |
4小时后皮肤渗透量 | 0.4 | 2.1 | 1.9 | 3.6 | 0.8 | 2.4 |
6小时后皮肤渗透量 | 1.6 | 5.8 | 5.7 | 7.0 | 2.7 | 8.5 |
8小时后皮肤渗透量 | 4.5 | 10.5 | 11.0 | 12.0 | 6.1 | 17.7 |
22小时后皮肤渗透量 | 84.0 | 51.2 | 54.5 | 68.7 | 57.8 | 105.2 |
24小时后皮肤渗透量 | 98.5 | 56.1 | 58.9 | 77.3 | 66.4 | 112.5 |
包含可生成钾离子的化合物即山梨酸钾的实施例3-a~3-f的贴剂均示出良好的皮肤渗透性。
工业实用性
本发明的贴剂的皮肤渗透性优良,特别是作为包含盐酸羟考酮、盐酸氢吗啡酮等的阿片类镇痛剂的贴剂而言,利用价值高。
Claims (3)
1.一种贴剂,由在支承体的单面设置粘接剂层而成,其特征在于,在所述粘接剂层中包含碱性药物、脂肪酸类离子液体以及钾盐和/或钾离子,
所述碱性药物是替扎尼定的酸加成盐,所述脂肪酸类离子液体是有机胺化合物和脂肪酸的盐,
所述有机胺化合物是从单乙醇胺、单异丙醇胺、二乙醇胺、二异丙醇胺、三乙醇胺、三异丙醇胺、三羟甲基氨基甲烷构成的组中选择的化合物,
所述脂肪酸是从癸酸、山梨酸、乙酰丙酸、月桂酸、肉豆蔻酸、软脂酸、硬脂酸、异硬脂酸、油酸构成的组中选择的酸,
所述钾盐和/或钾离子是在粘接剂中,通过替扎尼定的酸加成盐与可生成钾离子的化合物反应而产生的。
2.如权利要求1所述的贴剂,其特征在于,所述酸加成盐为盐酸替扎尼定,所述钾盐为氯化钾。
3.一种贴剂用组合物,其特征在于,包含碱性药物的酸加成盐、脂肪酸类离子液体以及通过与所述碱性药物的酸加成盐的反应可生成钾离子的化合物,所述碱性药物的酸加成盐是盐酸替扎尼定,所述脂肪酸类离子液体是有机胺化合物和脂肪酸的盐,
所述有机胺化合物是从单乙醇胺、单异丙醇胺、二乙醇胺、二异丙醇胺、三乙醇胺、三异丙醇胺、三羟甲基氨基甲烷构成的组中选择的化合物,
所述脂肪酸是从癸酸、山梨酸、乙酰丙酸、月桂酸、肉豆蔻酸、软脂酸、硬脂酸、异硬脂酸、油酸构成的组中选择的酸。
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JPPCT/JP2015/074552 | 2015-08-29 | ||
PCT/JP2015/074552 WO2017037812A1 (ja) | 2015-08-29 | 2015-08-29 | 酸捕捉剤を含有する貼付製剤 |
PCT/JP2016/075204 WO2017038768A1 (ja) | 2015-08-29 | 2016-08-29 | 酸捕捉剤を含有する貼付製剤 |
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JP (2) | JP6161142B1 (zh) |
CN (1) | CN107921043B (zh) |
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US10016502B2 (en) | 2015-08-29 | 2018-07-10 | Medrx Co., Ltd | Patch preparation containing an acid scavenger |
KR102302583B1 (ko) * | 2017-02-24 | 2021-09-14 | 히사미쓰 세이야꾸 가부시키가이샤 | 첩부제 및 그 포장체 |
JP2021028294A (ja) * | 2017-09-22 | 2021-02-25 | 株式会社 メドレックス | ヒドロモルホンを薬効成分とする外用剤組成物 |
CN115087445A (zh) * | 2020-02-19 | 2022-09-20 | 住友制药株式会社 | 经皮吸收制剂 |
US20240016758A1 (en) * | 2020-10-29 | 2024-01-18 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing patch and method for improving skin permeability of ropinirole |
WO2022196748A1 (ja) * | 2021-03-17 | 2022-09-22 | 国立大学法人九州大学 | 経皮吸収剤 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1591110A1 (en) * | 2003-01-22 | 2005-11-02 | Nichiban Company Limited | Percutaneous absorption preparation for treating ophthalmic disease, use thereof and method for migration of ophthalmic remedy into topical tissue in eye |
WO2010098230A1 (ja) * | 2009-02-27 | 2010-09-02 | 久光製薬株式会社 | 経皮投与製剤 |
EP2255809A1 (en) * | 2008-02-27 | 2010-12-01 | Hisamitsu Pharmaceutical Co., Inc. | Medicated patch |
EP2716287A1 (en) * | 2011-05-31 | 2014-04-09 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing adhesive skin patch and packaged product thereof |
EP2865376A1 (en) * | 2012-06-20 | 2015-04-29 | Medrx Co., Ltd. | Adhesive preparation composition obtained by blending drug, organic solvent, lipophilic ointment base, and powder |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR920010392B1 (ko) * | 1984-03-01 | 1992-11-27 | 산도즈 아크리엔 게젤샤프트 | 경피투여용 약학 조성물의 제조방법 |
JPH0720866B2 (ja) * | 1987-05-15 | 1995-03-08 | 三生製薬株式会社 | エペリゾン又はトルペリゾン或いはそれらの塩類含有経皮適用製剤 |
JP5333972B2 (ja) | 2007-11-22 | 2013-11-06 | 株式会社 メドレックス | 脂肪酸系イオン液体を有効成分とする外用剤組成物 |
WO2010073326A1 (ja) * | 2008-12-24 | 2010-07-01 | ニチバン株式会社 | 経皮吸収型製剤 |
US8784879B2 (en) * | 2009-01-14 | 2014-07-22 | Corium International, Inc. | Transdermal administration of tamsulosin |
-
2015
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-
2016
- 2016-08-29 EP EP16841800.2A patent/EP3342412A4/en not_active Withdrawn
- 2016-08-29 CN CN201680049249.9A patent/CN107921043B/zh active Active
- 2016-08-29 WO PCT/JP2016/075204 patent/WO2017038768A1/ja active Application Filing
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1591110A1 (en) * | 2003-01-22 | 2005-11-02 | Nichiban Company Limited | Percutaneous absorption preparation for treating ophthalmic disease, use thereof and method for migration of ophthalmic remedy into topical tissue in eye |
EP2255809A1 (en) * | 2008-02-27 | 2010-12-01 | Hisamitsu Pharmaceutical Co., Inc. | Medicated patch |
WO2010098230A1 (ja) * | 2009-02-27 | 2010-09-02 | 久光製薬株式会社 | 経皮投与製剤 |
EP2716287A1 (en) * | 2011-05-31 | 2014-04-09 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing adhesive skin patch and packaged product thereof |
EP2865376A1 (en) * | 2012-06-20 | 2015-04-29 | Medrx Co., Ltd. | Adhesive preparation composition obtained by blending drug, organic solvent, lipophilic ointment base, and powder |
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JP6161142B1 (ja) | 2017-07-12 |
JP2017178967A (ja) | 2017-10-05 |
WO2017037812A1 (ja) | 2017-03-09 |
JPWO2017038768A1 (ja) | 2017-09-07 |
WO2017038768A1 (ja) | 2017-03-09 |
CN107921043A (zh) | 2018-04-17 |
ES2966216T3 (es) | 2024-04-19 |
EP3342412A4 (en) | 2018-09-12 |
EP3342412A1 (en) | 2018-07-04 |
EP3756659B1 (en) | 2023-12-06 |
EP3756659A1 (en) | 2020-12-30 |
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