TWI835310B - 抑制雙氯芬酸吲哚啉酮體之生成之方法 - Google Patents
抑制雙氯芬酸吲哚啉酮體之生成之方法 Download PDFInfo
- Publication number
- TWI835310B TWI835310B TW111136189A TW111136189A TWI835310B TW I835310 B TWI835310 B TW I835310B TW 111136189 A TW111136189 A TW 111136189A TW 111136189 A TW111136189 A TW 111136189A TW I835310 B TWI835310 B TW I835310B
- Authority
- TW
- Taiwan
- Prior art keywords
- diclofenac
- mass
- patch
- adhesive
- acid
- Prior art date
Links
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 title claims abstract description 83
- 229960001259 diclofenac Drugs 0.000 title claims abstract description 47
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 16
- 239000012790 adhesive layer Substances 0.000 claims abstract description 64
- 239000000853 adhesive Substances 0.000 claims abstract description 57
- 230000001070 adhesive effect Effects 0.000 claims abstract description 57
- 239000010410 layer Substances 0.000 claims abstract description 34
- 239000000203 mixture Substances 0.000 claims abstract description 34
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 13
- -1 polyethylene terephthalate Polymers 0.000 description 60
- 239000002585 base Substances 0.000 description 53
- 229920005989 resin Polymers 0.000 description 25
- 239000011347 resin Substances 0.000 description 25
- 239000013464 silicone adhesive Substances 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 235000014113 dietary fatty acids Nutrition 0.000 description 20
- 239000000194 fatty acid Substances 0.000 description 20
- 229930195729 fatty acid Natural products 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 20
- 229920001971 elastomer Polymers 0.000 description 19
- 239000005060 rubber Substances 0.000 description 19
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 13
- 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 12
- 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 12
- 239000003522 acrylic cement Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 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 12
- 230000000052 comparative effect Effects 0.000 description 11
- 229920001577 copolymer Polymers 0.000 description 11
- 229960001193 diclofenac sodium Drugs 0.000 description 10
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 10
- 229920002367 Polyisobutene Polymers 0.000 description 9
- 229920000139 polyethylene terephthalate Polymers 0.000 description 9
- 239000005020 polyethylene terephthalate Substances 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- 239000004744 fabric Substances 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 230000035699 permeability Effects 0.000 description 8
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 7
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 7
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 7
- 239000013032 Hydrocarbon resin Substances 0.000 description 7
- 239000005642 Oleic acid Substances 0.000 description 7
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 7
- 239000003655 absorption accelerator Substances 0.000 description 7
- 125000002723 alicyclic group Chemical group 0.000 description 7
- 229920006270 hydrocarbon resin Polymers 0.000 description 7
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 7
- 239000004014 plasticizer Substances 0.000 description 7
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- 150000003505 terpenes Chemical class 0.000 description 7
- 235000007586 terpenes Nutrition 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 125000005908 glyceryl ester group Chemical group 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920001296 polysiloxane Polymers 0.000 description 6
- 239000004814 polyurethane Substances 0.000 description 6
- 229920002635 polyurethane Polymers 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000004745 nonwoven fabric Substances 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000002759 woven fabric Substances 0.000 description 5
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 4
- WQNHWIYLCRZRLR-UHFFFAOYSA-N 2-(3-hydroxy-2,5-dioxooxolan-3-yl)acetic acid Chemical compound OC(=O)CC1(O)CC(=O)OC1=O WQNHWIYLCRZRLR-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229940057995 liquid paraffin Drugs 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 229920000098 polyolefin Polymers 0.000 description 4
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 3
- BTOVVHWKPVSLBI-UHFFFAOYSA-N 2-methylprop-1-enylbenzene Chemical compound CC(C)=CC1=CC=CC=C1 BTOVVHWKPVSLBI-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000005215 alkyl ethers Chemical class 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229930003658 monoterpene Natural products 0.000 description 3
- 235000002577 monoterpenes Nutrition 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- MSFGZHUJTJBYFA-UHFFFAOYSA-M sodium dichloroisocyanurate Chemical compound [Na+].ClN1C(=O)[N-]C(=O)N(Cl)C1=O MSFGZHUJTJBYFA-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 2
- XMGQYMWWDOXHJM-JTQLQIEISA-N (+)-α-limonene Chemical compound CC(=C)[C@@H]1CCC(C)=CC1 XMGQYMWWDOXHJM-JTQLQIEISA-N 0.000 description 2
- GRWFGVWFFZKLTI-IUCAKERBSA-N (-)-α-pinene Chemical compound CC1=CC[C@@H]2C(C)(C)[C@H]1C2 GRWFGVWFFZKLTI-IUCAKERBSA-N 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 description 2
- VSKJLJHPAFKHBX-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 VSKJLJHPAFKHBX-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- AOMUHOFOVNGZAN-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)dodecanamide Chemical compound CCCCCCCCCCCC(=O)N(CCO)CCO AOMUHOFOVNGZAN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000005062 Polybutadiene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000002240 Tennis Elbow Diseases 0.000 description 2
- 208000004760 Tenosynovitis Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
- 229920006271 aliphatic hydrocarbon resin Polymers 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 2
- 229920005549 butyl rubber Polymers 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 235000013985 cinnamic acid Nutrition 0.000 description 2
- 229930016911 cinnamic acid Natural products 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 229920003049 isoprene rubber Polymers 0.000 description 2
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940031957 lauric acid diethanolamide Drugs 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- UQDUPQYQJKYHQI-UHFFFAOYSA-N methyl laurate Chemical compound CCCCCCCCCCCC(=O)OC UQDUPQYQJKYHQI-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940055577 oleyl alcohol Drugs 0.000 description 2
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920003207 poly(ethylene-2,6-naphthalate) Polymers 0.000 description 2
- 229920002857 polybutadiene Polymers 0.000 description 2
- 239000011112 polyethylene naphthalate Substances 0.000 description 2
- 229920001195 polyisoprene Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229940026235 propylene glycol monolaurate Drugs 0.000 description 2
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 229940035044 sorbitan monolaurate Drugs 0.000 description 2
- 229920003048 styrene butadiene rubber Polymers 0.000 description 2
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- FQTLCLSUCSAZDY-UHFFFAOYSA-N (+) E(S) nerolidol Natural products CC(C)=CCCC(C)=CCCC(C)(O)C=C FQTLCLSUCSAZDY-UHFFFAOYSA-N 0.000 description 1
- WTARULDDTDQWMU-RKDXNWHRSA-N (+)-β-pinene Chemical compound C1[C@H]2C(C)(C)[C@@H]1CCC2=C WTARULDDTDQWMU-RKDXNWHRSA-N 0.000 description 1
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- WTARULDDTDQWMU-IUCAKERBSA-N (-)-Nopinene Natural products C1[C@@H]2C(C)(C)[C@H]1CCC2=C WTARULDDTDQWMU-IUCAKERBSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- ALBAONCGXKQWRY-UHFFFAOYSA-N (2-butylphenoxy)methanol Chemical compound CCCCC1=CC=CC=C1OCO ALBAONCGXKQWRY-UHFFFAOYSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- ARIWANIATODDMH-AWEZNQCLSA-N 1-lauroyl-sn-glycerol Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)CO ARIWANIATODDMH-AWEZNQCLSA-N 0.000 description 1
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 1
- XFOQWQKDSMIPHT-UHFFFAOYSA-N 2,3-dichloro-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)C(Cl)=N1 XFOQWQKDSMIPHT-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- IDGSXMQBQUGSRF-UHFFFAOYSA-N 2,4-dibutyl-3-methylphenol Chemical compound CCCCC1=CC=C(O)C(CCCC)=C1C IDGSXMQBQUGSRF-UHFFFAOYSA-N 0.000 description 1
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WDQMWEYDKDCEHT-UHFFFAOYSA-N 2-ethylhexyl 2-methylprop-2-enoate Chemical compound CCCCC(CC)COC(=O)C(C)=C WDQMWEYDKDCEHT-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 description 1
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- BGRXBNZMPMGLQI-UHFFFAOYSA-N 2-octyldodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC BGRXBNZMPMGLQI-UHFFFAOYSA-N 0.000 description 1
- CAWGQUPKYLTTNX-UHFFFAOYSA-N 3,4,5,6-tetrahydro-2,7-benzodioxecine-1,8-dione Chemical compound O=C1OCCCCOC(=O)C2=CC=CC=C12 CAWGQUPKYLTTNX-UHFFFAOYSA-N 0.000 description 1
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LKUNXBRZDFMZOK-GFCCVEGCSA-N Capric acid monoglyceride Natural products CCCCCCCCCC(=O)OC[C@H](O)CO LKUNXBRZDFMZOK-GFCCVEGCSA-N 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- 201000011275 Epicondylitis Diseases 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 239000005792 Geraniol Substances 0.000 description 1
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- CMBYOWLFQAFZCP-UHFFFAOYSA-N Hexyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCCCC CMBYOWLFQAFZCP-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- DTGKSKDOIYIVQL-MRTMQBJTSA-N Isoborneol Natural products C1C[C@@]2(C)[C@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-MRTMQBJTSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- FQTLCLSUCSAZDY-ATGUSINASA-N Nerolidol Chemical compound CC(C)=CCC\C(C)=C\CC[C@](C)(O)C=C FQTLCLSUCSAZDY-ATGUSINASA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229920005987 OPPANOL® Polymers 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- WTARULDDTDQWMU-UHFFFAOYSA-N Pseudopinene Natural products C1C2C(C)(C)C1CCC2=C WTARULDDTDQWMU-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- KGUHOFWIXKIURA-VQXBOQCVSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl dodecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCC)O[C@@H]1O[C@@]1(CO)[C@@H](O)[C@H](O)[C@@H](CO)O1 KGUHOFWIXKIURA-VQXBOQCVSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XGKPLOKHSA-N [2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XGKPLOKHSA-N 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 125000005396 acrylic acid ester group Chemical group 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- XCPQUQHBVVXMRQ-UHFFFAOYSA-N alpha-Fenchene Natural products C1CC2C(=C)CC1C2(C)C XCPQUQHBVVXMRQ-UHFFFAOYSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- MVNCAPSFBDBCGF-UHFFFAOYSA-N alpha-pinene Natural products CC1=CCC23C1CC2C3(C)C MVNCAPSFBDBCGF-UHFFFAOYSA-N 0.000 description 1
- WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940009868 aluminum magnesium silicate Drugs 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229930006722 beta-pinene Natural products 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 239000010624 camphor oil Substances 0.000 description 1
- 229960000411 camphor oil Drugs 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940074979 cetyl palmitate Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical class C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 239000002812 cholic acid derivative Substances 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229920006026 co-polymeric resin Polymers 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010227 cup method (microbiological evaluation) Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- SQIFACVGCPWBQZ-UHFFFAOYSA-N delta-terpineol Natural products CC(C)(O)C1CCC(=C)CC1 SQIFACVGCPWBQZ-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- 150000002195 fatty ethers Chemical class 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 201000010603 frozen shoulder Diseases 0.000 description 1
- LCWMKIHBLJLORW-UHFFFAOYSA-N gamma-carene Natural products C1CC(=C)CC2C(C)(C)C21 LCWMKIHBLJLORW-UHFFFAOYSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229940113087 geraniol Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940068939 glyceryl monolaurate Drugs 0.000 description 1
- 229960002389 glycol salicylate Drugs 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- 229940100463 hexyl laurate Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical class OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000005001 laminate film Substances 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- WASNIKZYIWZQIP-AWEZNQCLSA-N nerolidol Natural products CC(=CCCC(=CCC[C@@H](O)C=C)C)C WASNIKZYIWZQIP-AWEZNQCLSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 229940065472 octyl acrylate Drugs 0.000 description 1
- 229940073665 octyldodecyl myristate Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940060184 oil ingredients Drugs 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001921 poly-methyl-phenyl-siloxane Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920002215 polytrimethylene terephthalate Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- LKUNXBRZDFMZOK-UHFFFAOYSA-N rac-1-monodecanoylglycerol Chemical compound CCCCCCCCCC(=O)OCC(O)CO LKUNXBRZDFMZOK-UHFFFAOYSA-N 0.000 description 1
- GRWFGVWFFZKLTI-UHFFFAOYSA-N rac-alpha-Pinene Natural products CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940032085 sucrose monolaurate Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003784 tall oil Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229940116411 terpineol Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本發明揭示一種抑制貼附劑中之雙氯芬酸吲哚啉酮體之生成之方法。上述貼附劑係具備支持體層、及積層於上述支持體層上之黏著劑層之貼附劑，上述方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。又，以上述黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%～8質量%。
Description
本發明係關於一種抑制雙氯芬酸吲哚啉酮體之生成之方法。
關於含有作為一種非類固醇性消炎鎮痛劑之雙氯芬酸之貼附劑，已知其具有腰痛症、肩周炎、頸肩腕綜合征、腱/腱鞘炎、腱周圍炎、肱骨外上髁炎(網球肘等)、肌肉痛(肌肉/筋膜性腰痛症等)、及外傷後之腫脹/疼痛等疾病及症狀之鎮痛/消炎、各種癌之鎮痛等功效作用，迄今為止進行了大量研究。例如，專利文獻1中記載有一種貼附劑，其含有雙氯芬酸或其藥學上可容許之鹽、檸檬酸及二甲基亞碸，且雙氯芬酸或其藥學上可容許之鹽與檸檬酸之質量比、雙氯芬酸或其藥學上可容許之鹽與二甲基亞碸之質量比處於特定範圍內。又，專利文獻2中記載有一種含活性物質之黏著性貼附藥，其包含：不滲透性輔助膜；雙氯芬酸或其藥學上可容許之鹽；選自苯乙烯-異戊二烯-苯乙烯嵌段共聚物及乙烯-乙酸乙烯酯共聚物之基質形成聚合物；包含脂肪族烴樹脂及熱塑性萜烯樹脂之黏著性賦予劑；以及選自由油酸及其衍生物、脂肪酸烷基酯、以及N-烷基-吡咯啶酮所組成之群中之1種或1種以上之溶劑；以及可剝離之保護膜。
先前技術文獻
專利文獻
專利文獻1：國際公報第2013/191128號
專利文獻2：日本專利特表2004-508397號公報
[發明所欲解決之問題]
此前研究之含雙氯芬酸之貼附劑大多為含有雙氯芬酸之藥學上可容許之鹽(具體而言為雙氯芬酸鈉)之貼附劑。已知於含有雙氯芬酸之藥學上可容許之鹽之貼附劑中，會生成作為雙氯芬酸之一種分解物之雙氯芬酸吲哚啉酮體。為提供穩定性較高之貼附劑，抑制雙氯芬酸吲哚啉酮體之生成較為重要。因此，本發明之目的在於提供一種抑制貼附劑中之雙氯芬酸吲哚啉酮體之生成之方法。又，本發明之目的還在於提供一種雙氯芬酸吲哚啉酮體之生成得到抑制之貼附劑及其製造方法。
[解決問題之技術手段]
發明人等對含有雙氯芬酸游離酸之貼附劑進行了研究，結果發現，含有特定量之雙氯芬酸游離酸之貼附劑相較於含有雙氯芬酸鈉之貼附劑，更能夠抑制雙氯芬酸吲哚啉酮體之生成，從而完成了本發明。
即，本發明提供一種方法，其係於具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑中抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法，該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟，以黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%～8質量%。
本發明還提供一種方法，其係具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑之製造方法，該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟，以上述黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%～8質量%，本發明進而提供一種貼附劑，其具備支持體層、及積層於上述支持體層上之黏著劑層，上述黏著劑層含有雙氯芬酸游離酸及黏著基劑，以上述黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%～8質量%。
[發明之效果]
根據本發明，可於貼附劑中抑制雙氯芬酸吲哚啉酮體之生成(尤其是保存時之雙氯芬酸吲哚啉酮體之生成)。
以下，示出本發明之實施方式來詳細地說明本發明。
本發明之一實施方式之貼附劑具備支持體層、及積層於上述支持體層上之黏著劑層。上述黏著劑層含有雙氯芬酸游離酸及黏著基劑，以上述黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%～8質量%。
支持體層保持黏著劑層。支持體層較佳為將纖維製成布狀(織布、不織布、或編織布)而成者之單層體或積層體、或者無孔性或多孔性之膜(片材)之單層體或積層體。支持體層之材質較佳為選自聚酯(聚對苯二甲酸乙二酯、聚間苯二甲酸乙二酯、聚對苯二甲酸丙二酯、聚間苯二甲酸丙二酯、聚對苯二甲酸丁二酯、或聚萘二甲酸乙二酯等)、聚烯烴(乙烯、丙烯、乙酸乙烯酯、或丙烯腈等乙烯基系單體之聚合物或共聚物)、聚醯胺(尼龍或蠶絲等)、聚胺酯、或纖維素(棉紗或麻等)中之1種以上之材質。布(織布、不織布、或編織布)上可塗佈橡膠組合物。橡膠組合物包含橡膠系黏著基劑。橡膠系黏著基劑例如為聚異戊二烯、聚異丁烯、聚丁二烯、苯乙烯-丁二烯-苯乙烯嵌段共聚物、苯乙烯-異戊二烯-苯乙烯嵌段共聚物、苯乙烯-丁二烯橡膠、苯乙烯-異戊二烯橡膠、或該等之組合。橡膠組合物可包含黏著賦予樹脂。黏著賦予樹脂例如為脂環族飽和烴樹脂、氫化松香甘油酯、萜烯系樹脂、或該等之組合。又，橡膠組合物亦可進而包含塑化劑、填充劑等添加劑。支持體層之厚度例如為0.1 mm～2 mm。支持體層之單位面積重量例如為30 g/m
2～200 g/m
2。於本說明書中，支持體層之厚度及單位面積重量係依據JIS L 1906：2000之標準進行測定。
支持體層之透濕度較佳為400 g/m
2･24小時以上，更佳為1000 g/m
2･24小時以上，進而較佳為4000 g/m
2･24小時以上。若使用此種高透濕度之支持體層，則二甲基亞碸自應用於皮膚之貼附劑中逐漸揮散，因此貼附劑之黏著性提高，即便長時間應用貼附劑，亦不易剝落。透濕度之上限值可為20000 g/m
2･24小時。若支持體層之透濕度處於此種範圍內，則二甲基亞碸更易自黏著劑層中揮散，故而對貼附劑之黏著性之提高更有效。再者，支持體層之透濕度係指JIS Z0208：1976之標準(防濕包裝材料之透濕度試驗方法(杯式法))中定義之40℃下之透濕度。
於支持體層為布狀之情形時，支持體層之縱向(材料流動方向)及橫向(材料寬度方向)中之任一方向之50%模數(JIS L 1018：1999)均較佳為1 N/50 mm～12 N/50 mm。於50%模數為12 N/50 mm以下之情形時，由於皮膚之伸縮，貼附劑所受到之應力更小，因此對皮膚之附著性良好。
於支持體層為膜之情形時，材質較佳為如聚胺酯之高透濕性(高二甲基亞碸透過性)。包含聚胺酯之膜由於伸縮性優異，故而就提高貼附劑對皮膚之附著性及伸縮追隨性之觀點而言較佳。
支持體層較佳為例如包含聚胺酯之不織布或膜、包含聚對苯二甲酸乙二酯之編織布、不織布或膜、經橡膠組合物塗佈之聚酯之布、或該等之組合。更具體而言，支持體層更佳為包含聚胺酯之膜與包含聚胺酯之不織布之積層體、包含聚對苯二甲酸乙二酯之編織布或不織布、或經橡膠組合物塗佈之聚酯之布。
黏著劑層係由將雙氯芬酸游離酸、黏著基劑、及後述之任意成分混和所得之黏著劑組合物形成。就使貼附劑適當地黏著於皮膚之觀點而言，黏著劑層整體之膏體質量較佳為10 g/m
2～1000 g/m
2，更佳為30 g/m
2～300 g/m
2，進而較佳為100 g/m
2～250 g/m
2。
雙氯芬酸游離酸係亦稱為2-[(2,6-二氯苯基)胺基]苯乙酸之化合物。以黏著劑層之總質量為基準，雙氯芬酸游離酸之含量為0.5質量%～8質量%，亦可為1質量%～7質量%、1質量%～5質量%或1質量%～4.65質量%。
黏著基劑係用於對黏著劑層賦予黏著性者，例如可例舉：橡膠系黏著基劑、丙烯酸系黏著基劑、矽酮系黏著基劑等。黏著基劑較佳為選自由橡膠系黏著基劑、丙烯酸系黏著基劑及矽酮系黏著基劑所組成之群中之1種以上。黏著基劑較佳為不含水(非水系黏著基劑)。黏著基劑可為橡膠系黏著基劑、丙烯酸系黏著基劑及矽酮系黏著基劑中之任一者，亦可為該等之組合。以黏著劑層之總質量為基準，黏著基劑之總含量可設為10質量%～90質量%，亦可為20質量%～90質量%。
作為橡膠系黏著基劑，例如可例舉：天然橡膠、聚異丁烯、烷基乙烯基醚(共)聚合物、聚異戊二烯、聚丁二烯、苯乙烯-丁二烯共聚物、苯乙烯-異戊二烯共聚物、苯乙烯-異戊二烯-苯乙烯嵌段共聚物、苯乙烯-丁二烯-苯乙烯嵌段共聚物等。橡膠系黏著基劑可單獨使用該等中之1種，亦可組合2種以上使用。其中，作為本實施方式之橡膠系黏著基劑，就傾向於可發揮出黏著劑層之更充分之黏著力之觀點而言，較佳為選自由苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯所組成之群中之至少1種以上，更佳為苯乙烯-異戊二烯-苯乙烯嵌段共聚物、或者苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯。
作為橡膠系黏著基劑之具體例，可例舉：Quintac(註冊商標)3570C(商品名，日本瑞翁股份有限公司製造)、SIS5002、SIS5229、SIS5505、SIS5505P(商品名，JSR股份有限公司製造)、SIBSTAR(註冊商標)T102(商品名，Kaneka股份有限公司製造)等，又，聚異丁烯亦包含所謂之丁基橡膠(異丁烯-異戊二烯橡膠)，作為具體例，可例舉：Oppanol(註冊商標)N50、N80、N100、N150、B11、B12、B50、B80、B100、B120、B150、B220(商品名，BASF公司製造)、JSR(註冊商標)Butyl 065、268、365(商品名，JSR股份有限公司製造)、X_Butyl(註冊商標)RB100、101-3、301、402(商品名，ARLANXEO公司製造)、Exxon(註冊商標)Butyl 065、065S、068、068S、268、268S、365、365S(商品名，Exxon Mobile公司製造)等。
以黏著劑層之總質量為基準，橡膠系黏著基劑之含量可設為10質量%～90質量%，亦可為15質量%～60質量%、15質量%～40質量%、15質量%～30質量%。於使用苯乙烯-異戊二烯-苯乙烯嵌段共聚物及聚異丁烯之混合物作為橡膠系黏著基劑之情形時，兩者之質量比較佳為4：1～1：4、3：1～1：1、或3：1～2：1。
丙烯酸系黏著基劑係對黏著劑層賦予黏著性之成分，例如為1種或2種以上之(甲基)丙烯酸烷基酯之(共)聚合物。作為(甲基)丙烯酸烷基酯，例如可例舉：(甲基)丙烯酸丁酯、(甲基)丙烯酸異丁酯、(甲基)丙烯酸己酯、(甲基)丙烯酸辛酯、(甲基)丙烯酸2-乙基己酯、(甲基)丙烯酸癸酯等。再者，於本說明書中，｢(甲基)丙烯酸｣這一用語係指丙烯酸及甲基丙烯酸之任一者或兩者，類似表達以同樣之方式來定義。
丙烯酸系黏著基劑可為由(甲基)丙烯酸烷基酯(主單體)與共聚單體所形成之共聚物。作為主單體，例如可例舉：(甲基)丙烯酸甲酯、(甲基)丙烯酸乙酯、(甲基)丙烯酸丁酯、(甲基)丙烯酸己酯、(甲基)丙烯酸庚酯、(甲基)丙烯酸辛酯、(甲基)丙烯酸2-乙基己酯等，可單獨使用該等中之1種，亦可組合2種以上使用。共聚單體只要為可與(甲基)丙烯酸烷基酯共聚之成分即可。作為共聚單體，例如可例舉：(甲基)丙烯酸羥烷基酯、乙烯、丙烯、苯乙烯、乙酸乙烯酯、N-乙烯基吡咯啶酮、(甲基)丙烯酸、(甲基)丙烯醯胺等。共聚單體可為單獨1種或組合2種以上而成者。
作為丙烯酸系黏著基劑之具體例，可例舉：丙烯酸/丙烯酸辛酯共聚物、丙烯酸2-乙基己酯/乙烯基吡咯啶酮共聚物溶液、丙烯酸酯/乙酸乙烯酯共聚物、丙烯酸2-乙基己酯/甲基丙烯酸2-乙基己酯/甲基丙烯酸十二烷基酯共聚物、丙烯酸甲酯/丙烯酸2-乙基己酯共聚樹脂乳液、丙烯酸樹脂烷醇胺液中含有之丙烯酸系高分子等。作為此種丙烯酸系黏著基劑之具體例，可例舉：DURO-TAK(註冊商標)387-2510、DURO-TAK(註冊商標)87-2510、DURO-TAK(註冊商標)387-2287、DURO-TAK(註冊商標)87-2287、DURO-TAK(註冊商標)87-4287、DURO-TAK(註冊商標)387-2516、DURO-TAK(註冊商標)87-2516、DURO-TAK(註冊商標)87-2074、DURO-TAK(註冊商標)87-900A、DURO-TAK(註冊商標)87-901A、DURO-TAK(註冊商標)87-9301、DURO-TAK(註冊商標)87-4098等DURO-TAK系列(Henkel公司製造)；GELVA(註冊商標)GMS 788、GELVA(註冊商標)GMS 3083、GELVA(註冊商標)GMS 3253等GELVA系列(Henkel公司製造)；MAS811(商品名)、MAS683(商品名)等MAS系列(CosMED Pharmaceutical股份有限公司製造)；Eudragit(註冊商標)系列(Evonik公司製造)、Nikasol(註冊商標)系列(日本電石工業股份有限公司製造)、ULTRAZORU(註冊商標)系列(Aica Kogyo股份有限公司製造)。
以黏著劑層之總質量為基準，丙烯酸系黏著基劑之含量可設為10質量%～90質量%，亦可為20質量%～90質量%。
矽酮系黏著基劑為具有有機聚矽氧烷骨架之化合物。作為矽酮系黏著基劑，例如可例舉：二甲基聚矽氧烷、聚甲基乙烯基矽氧烷、聚甲基苯基矽氧烷。作為具體之矽酮系黏著基劑，例如可例舉：MD7-4502矽酮黏合劑(Silicone Adhesive)、MD7-4602矽酮黏合劑等MD系列(DuPont Toray Specialty Materials股份有限公司製造)；BIO-PSA(註冊商標)7-4301矽酮黏合劑、BIO-PSA(註冊商標)7-4302矽酮黏合劑、BIO-PSA(註冊商標)7-4201矽酮黏合劑、BIO-PSA(註冊商標)7-4202矽酮黏合劑、BIO-PSA(註冊商標)7-4101矽酮黏合劑、BIO-PSA(註冊商標)7-4102矽酮黏合劑、BIO-PSA(註冊商標)7-4601矽酮黏合劑、BIO-PSA(註冊商標)7-4602矽酮黏合劑、BIO-PSA(註冊商標)7-4501矽酮黏合劑、BIO-PSA(註冊商標)7-4502矽酮黏合劑、BIO-PSA(註冊商標)7-4401矽酮黏合劑、BIO-PSA(註冊商標)7-4402矽酮黏合劑等BIO-PSA系列(DuPont Toray Specialty Materials股份有限公司製造)、Dow Corning(註冊商標)7-9800A、Dow Corning(註冊商標)7-9800B、Dow Corning(註冊商標)7-9700A、Dow Corning(註冊商標)7-9700B。
以黏著劑層之總質量為基準，矽酮系黏著基劑之含量可設為10質量%～90質量%，亦可為20質量%～90質量%。
出於使雙氯芬酸游離酸溶解以提高其皮膚透過性等目的，黏著劑層可進而含有二甲基亞碸。以黏著劑層之總質量為基準，二甲基亞碸之含量較佳為1質量%～20質量%、1質量%～7質量%、2質量%～10質量%、3質量%～10質量%、或4質量%～8質量%。
就提昇雙氯芬酸游離酸之皮膚透過性之觀點、及防止雙氯芬酸之結晶析出之觀點而言，雙氯芬酸游離酸與二甲基亞碸之比較佳為1：0.3～1：14、1：0.4～1：7、1：0.6～1：3、或1：0.7～1：3。
黏著劑層可進而任意含有其他添加劑。作為其他添加劑，例如可例舉：黏著賦予樹脂、塑化劑、吸收促進劑、溶解劑、穩定劑、填充劑、香料等。
黏著賦予樹脂係調整黏著劑層之黏著性之成分。作為黏著賦予樹脂，例如可例舉：石油系樹脂、萜烯系樹脂、松香系樹脂、酚系樹脂及二甲苯系樹脂等。作為石油系樹脂，例如可例舉脂環族系石油樹脂(脂環族飽和烴樹脂等)、脂肪族系石油樹脂(脂肪族烴樹脂等)、芳香族系石油樹脂等，更具體而言，可例舉：Arkon P-70、Arkon P-85、Arkon P-90、Arkon P-100、Arkon P-115、Arkon P-125、Arkon M-70、Arkon M-85、Arkon M-90、Arkon M-100、Arkon M-115、Arkon M-125(以上為商品名，荒川化學工業股份有限公司製造)、Escorez 8000(商品名，埃索(Esso)石油化學股份有限公司製造)等。作為萜烯系樹脂，例如可例舉：蒎烯聚合物(α-蒎烯聚合物、β-蒎烯聚合物等)、萜烯聚合物、雙戊烯聚合物、萜烯-苯酚聚合物、芳香族改性萜烯聚合物、蒎烯-苯酚共聚物，更具體而言，可例舉：YS Resin(YS Resin PXN(1150N、300N)、YS Resin PX1000、YS Resin TO125、YS Resin TO105等)、Clearon P105、Clearon M115、Clearon K100(以上為商品名，Yasuhara Chemical股份有限公司製造)、Tamanol 901(商品名，荒川化學工業股份有限公司製造)。作為松香系樹脂，例如可例舉：氫化松香甘油酯、超淺色松香、超淺色松香酯、酸改性超淺色松香，更具體而言，可例舉：Pine Crystal(KE-311、PE-590、KE-359、KE-100等)(商品名，荒川化學工業股份有限公司製造)等。黏著賦予樹脂可單獨使用該等中之1種，亦可組合2種以上使用。其中，較佳為脂環族飽和烴樹脂、萜烯系樹脂、氫化松香甘油酯或該等之組合，更佳為脂環族飽和烴樹脂、氫化松香甘油酯或該等之組合。於黏著劑層含有黏著賦予樹脂之情形時，以黏著劑層之總質量為基準，黏著賦予樹脂之含量可設為15質量%～80質量%，亦可為30質量%～65質量%。於使用脂環族飽和烴樹脂及氫化松香甘油酯作為黏著賦予樹脂之情形時，兩者之質量比較佳為4：1～1：4、4：1～2：3、或3：1～2：1。
作為塑化劑，例如可例舉：石蠟油(液態石蠟等)、角鯊烷、角鯊烯、植物油類(橄欖油、山茶油、蓖麻油、妥爾油、花生油、綠薄荷油、桉葉油、荷荷芭油、白樟油、葵花籽油、橙油等)、油脂類(鄰苯二甲酸二丁酯、鄰苯二甲酸二辛酯等)、及液狀橡膠(液狀聚丁烯、液狀異戊二烯橡膠等)。較佳之塑化劑為液態石蠟。塑化劑可單獨使用1種，亦可組合2種以上使用。於黏著劑層含有塑化劑之情形時，以黏著劑層之總質量為基準，塑化劑之含量例如為3質量%～50質量%、5質量%～30質量%、或7質量%～20質量%。
吸收促進劑只要為先前已知具有經皮吸收促進作用之化合物即可。作為吸收促進劑，例如可例舉：有機酸及其鹽(例如，碳原子數為6～20之脂肪族羧酸(以下，亦稱為｢脂肪酸｣)及其鹽、肉桂酸及其鹽)、有機酸酯(例如，脂肪酸酯、肉桂酸酯)、有機酸醯胺(例如，脂肪酸醯胺)、脂肪族醇、多元醇、醚(例如，脂肪族醚、聚氧乙烯烷基醚)等。該等吸收促進劑可具有不飽和鍵，亦可為環狀、直鏈狀或支鏈狀之化學結構。又，吸收促進劑可為單萜系化合物、倍半萜系化合物、及植物油(例如，橄欖油)。該等吸收促進劑可單獨使用1種，亦可組合2種以上使用。
作為相關有機酸，可例舉：脂肪族(單、二或三)羧酸(例如，乙酸、丙酸、異丁酸、己酸、辛酸、脂肪酸、乳酸、馬來酸、丙酮酸、草酸、琥珀酸、酒石酸等)、芳香族羧酸(例如，苯二甲酸、水楊酸、苯甲酸、乙醯水楊酸等)、肉桂酸、烷烴磺酸(例如，甲磺酸、乙磺酸、丙磺酸、丁磺酸)、烷磺酸衍生物(例如，聚氧乙烯烷基醚磺酸、N-2-羥乙基哌𠯤-N'-2-乙磺酸)、膽酸衍生物(例如，去氫膽酸等)。該等有機酸可為鈉鹽等鹼金屬鹽。其中，較佳為脂肪族羧酸、芳香族羧酸或該等之鹽，尤佳為乙酸或乙酸鈉。作為脂肪酸，例如可例舉月桂酸、肉豆蔻酸、棕櫚酸、硬脂酸、異硬脂酸、油酸、亞麻油酸、次亞麻油酸。
於另一實施方式中，黏著劑層不含檸檬酸(包括檸檬酸酐)及其鹽。具備不含檸檬酸及其鹽之黏著劑層之貼附劑能夠進一步抑制雙氯芬酸吲哚啉酮體之生成。
作為有機酸酯，例如可例舉：乙酸乙酯、乙酸丙酯、乳酸鯨蠟酯、乳酸月桂酯、水楊酸甲酯、乙二醇水楊酸酯、肉桂酸甲酯、脂肪酸酯。作為脂肪酸酯，例如可例舉：月桂酸甲酯、月桂酸己酯、肉豆蔻酸異丙酯、肉豆蔻酸肉豆蔻酯、肉豆蔻酸辛基十二烷基酯、棕櫚酸異丙酯、棕櫚酸鯨蠟酯。脂肪酸酯可為甘油脂肪酸酯、丙二醇脂肪酸酯、山梨醇酐脂肪酸酯、聚乙二醇山梨醇酐脂肪酸酯、聚乙二醇脂肪酸酯、蔗糖脂肪酸酯、或聚氧乙烯氫化蓖麻油。作為脂肪酸酯之具體例，可例舉：甘油單辛酸酯、甘油單癸酸酯、甘油單月桂酸酯、甘油單油酸酯、山梨醇酐單月桂酸酯、蔗糖單月桂酸酯、聚山梨糖醇酯20、丙二醇單月桂酸酯、聚乙二醇單月桂酸酯、聚乙二醇單硬脂酸酯、Span40、Span60、Span80、Span120(商品名，Croda Japan股份有限公司製造)、Tween(註冊商標)20、Tween(註冊商標)21、Tween(註冊商標)40、Tween(註冊商標)60、Tween(註冊商標)80、NIKKOL(註冊商標)HCO-60(商品名，Nikko Chemicals股份有限公司製造)。
作為有機酸醯胺，例如可例舉：脂肪酸醯胺(例如，月桂酸二乙醇醯胺)、六氫-1-十二烷基-2H-氮呯-2-酮(亦稱為Azone)及其衍生物、吡咯硫代癸烷。
脂肪醇係指碳原子數為6～20之脂肪族醇。作為脂肪醇，例如可例舉：月桂醇、肉豆蔻醇、油醇、異硬脂醇、鯨蠟醇。作為多元醇，例如可例舉丙二醇。
脂肪醚係指具有碳原子數為6～20之脂肪族基(例如，烷基、烯基)之醚。作為聚氧乙烯烷基醚，例如可例舉聚氧乙烯月桂醚。
作為單萜系化合物，例如可例舉：香葉草醇、瑞香草酚、松油醇、l-薄荷腦、冰片、d-檸檬烯、異冰片、橙花醇、dl-樟腦。作為單萜系化合物，亦可使用薄荷油。
於黏著劑層含有吸收促進劑之情形時，以黏著劑層之總質量為基準，吸收促進劑之含量可設為2質量%～40質量%。
溶解劑係使雙氯芬酸游離酸容易溶解於黏著劑組合物中之成分。作為溶解劑，例如可例舉：脂肪酸烷基酯(例如，肉豆蔻酸異丙酯、棕櫚酸異丙酯)、脂肪酸多元醇酯(例如，單月桂酸丙二醇酯、單月桂酸甘油酯、單油酸甘油酯、山梨醇酐單月桂酸酯)、脂肪酸醯胺(例如，月桂酸二乙醇醯胺)、脂肪族醇(例如，辛基十二烷醇、異硬脂醇、油醇)、多元醇(例如，丙二醇、二丙二醇、聚乙二醇)、吡咯啶酮衍生物(例如，N-甲基-2-吡咯啶酮)、胺(例如，三乙醇胺、二乙醇胺、單乙醇胺、二異丙醇胺、胺丁三醇、葡甲胺)。溶解劑可單獨使用1種，亦可組合2種以上使用。於黏著劑層含有溶解劑之情形時，以黏著劑層之總質量為基準，溶解劑之含量可設為2質量%～40質量%。
穩定劑只要為可抑制因紫外線等光線、熱或活性化學物種之作用而產生之自由基之生成及其連鎖反應之進行者即可。作為穩定劑，例如可例舉：維生素E及其酯衍生物、抗壞血酸及其酯衍生物、2,6-二丁基羥基甲苯、丁基羥基甲氧苯、2-硫醇基苯并咪唑等。穩定劑可單獨使用1種，亦可組合2種以上使用。於黏著劑層含有穩定劑之情形時，以黏著劑層之總質量為基準，穩定劑之含量可設為0.05質量%～3質量%，亦可為0.05質量%～1質量%、0.05質量%～0.25質量%或0.1質量%～0.25質量%。
作為填充劑，例如可例舉：金屬化合物(氧化鋁、氫氧化鋁、氧化鋅、氧化鈦、碳酸鈣等)、陶瓷(滑石、黏土、高嶺土、二氧化矽、羥磷石灰、合成矽酸鋁、矽酸鋁鎂等)或有機化合物(纖維素粉末、硬脂酸鹽等)之粉末或包含該等之樹脂之短纖維。填充劑可單獨使用1種，亦可組合2種以上使用。於黏著劑層含有填充劑之情形時，以黏著劑層之總質量為基準，填充劑之含量可設為0.1質量%～20質量%。
貼附劑可進而具備剝離襯墊。剝離襯墊積層於黏著劑層之與支持體為相反側之面。若具備剝離襯墊，則傾向於可減少保存時污物等附著於黏著劑層之情況。剝離襯墊之與黏著劑層相接之面較佳為已利用矽酮或氟化聚烯烴等進行離型處理。
作為剝離襯墊之素材，並無特別限定，可使用本領域技術人員公知之襯墊。作為剝離襯墊，例如可例舉：紙；聚對苯二甲酸乙二酯、聚萘二甲酸乙二酯等聚酯；聚乙烯、聚丙烯等聚烯烴；聚氯乙烯、聚偏二氯乙烯、尼龍、鋁等之膜。剝離襯墊可為高級紙與聚烯烴之層壓膜。作為剝離襯墊之材質，較佳為由聚丙烯或聚對苯二甲酸乙二酯製造之膜。
本發明之一實施方式之貼附劑之製造方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。更具體而言，貼附劑例如可藉由以下方法進行製造。首先，將構成黏著劑層之各成分以特定之比率混合而獲得均勻之溶解物(黏著劑組合物)。然後，使黏著劑組合物以特定之膏體質量於可剝離之膜(剝離襯墊)或支持體層上延展而形成黏著劑層。繼而，以黏著劑層夾於可剝離之膜與支持體層之間之方式，將黏著劑層壓接於支持體層或可剝離之膜。最後，切斷為所需之形狀，藉此可獲得貼附劑。於此情形時，剝離襯墊於應用貼附劑時去除。
本發明之一實施方式之抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟。更具體而言，可藉由與上述之貼附劑之製造方法相同之方法來實施。
貼附劑之面積可為5～200 cm
2，亦可為30～100 cm
2。貼附劑之形狀及尺寸例如可為短邊3～14 cm且長邊7～20 cm之矩形、或直徑1～10 cm之圓形。
[實施例]
實驗1：使用橡膠系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
按照下述表1，混合各成分，獲得黏著劑組合物。以每單位面積之膏體質量為214 g/m
2之方式，使所得之黏著劑組合物於剝離襯墊(經實施離型處理之聚對苯二甲酸乙二酯製膜)上延展，形成黏著劑層。於所得之黏著劑層之與上述相反之面上積層支持體層(聚對苯二甲酸乙二酯製編織布)，獲得依序積層有支持體層/黏著劑層/剝離襯墊之貼附劑。
2.雙氯芬酸吲哚啉酮體含量之測定
雙氯芬酸吲哚啉酮體之含量係使用剛製造後之貼附劑、及製造後於60℃下在鋁製包裝袋中保存1週後之貼附劑，按以下順序進行測定。
首先，取出貼附劑之黏著劑層，浸漬於2 mL丙酮中，提取有機物。
然後，加入6 mL稀釋溶液(0.1%磷酸水溶液/甲醇＝60/40(v/v))，使總量為8 mL，過濾不溶物後，藉由以下之分析條件下之高效液相層析法來獲得雙氯芬酸游離酸及雙氯芬酸吲哚啉酮體之峰分離之層析圖。雙氯芬酸吲哚啉酮體之含量係將雙氯芬酸游離酸之理論量設為100，根據雙氯芬酸吲哚啉酮體所對應之峰曲線下面積之值而算出。
＜分析條件＞
管柱：YMC-PacK Pro C8
流動相：0.1%磷酸水溶液/甲醇＝60/40(v/v)
測定波長：275 nm
流量：1 mL/min
試樣注入量：30 μL
管柱溫度：40℃
[表1]
| 比較例1 | 實施例1 | 實施例2 | 實施例3 | 實施例4 | 比較例2 | |
| 雙氯芬酸游離酸 | - | 1.00 | 3.00 | 4.65 | 7.00 | 10.00 |
| 雙氯芬酸鈉 | 5.00 | - | - | - | - | - |
| 苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 19.15 | 20.89 | 20.32 | 19.85 | 19.18 | 18.33 |
| 聚異丁烯 | 8.21 | 8.96 | 8.71 | 8.51 | 8.24 | 7.86 |
| 脂環族飽和烴樹脂 | 27.00 | 29.45 | 28.65 | 27.99 | 27.05 | 25.84 |
| 氫化松香甘油酯 | 10.00 | 10.00 | 10.00 | 10.00 | 10.00 | 10.00 |
| 液態石蠟 | 12.53 | 13.66 | 13.30 | 12.99 | 12.55 | 11.99 |
| 油酸 | 5.00 | 5.00 | 5.00 | 5.00 | 5.00 | 5.00 |
| 二甲基亞碸 | 7.00 | 7.00 | 7.00 | 7.00 | 7.00 | 7.00 |
| 檸檬酸酐 | 2.11 | - | - | - | - | - |
| 其他 | 4.00 | 4.04 | 4.02 | 4.01 | 4.0 | 3.98 |
| 合計 | 100 | 100 | 100 | 100 | 100 | 100 |
| 剛製造後之吲哚啉酮體之生成率(%) | 0.84 | 0.13 | 0.15 | 0.21 | 0.22 | 0.42 |
| 於60℃下保存1週後之吲哚啉酮體之生成率(%) | 2.18 | 0.33 | 0.55 | 0.65 | 1.36 | 2.57 |
確認到，相較於含有雙氯芬酸鈉之比較例1之貼附劑，含有雙氯芬酸游離酸之實施例1～4之貼附劑更能夠抑制雙氯芬酸吲哚啉酮體之生成。又，確認到，於比較例2之貼附劑之情形時，無法抑制雙氯芬酸吲哚啉酮體之生成，於上述比較例2之貼附劑中，以黏著劑層之總質量為基準，雙氯芬酸游離酸之含量為10質量%。
實驗2：使用丙烯酸系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
按照下述表2，混合各成分，獲得黏著劑組合物。以每單位面積之膏體質量為120 g/m
2之方式，使所得之黏著劑組合物於剝離襯墊(經實施離型處理之聚對苯二甲酸乙二酯製膜)上延展，將溶劑乾燥去除而形成黏著劑層。於所得之黏著劑層之與上述相反之面上積層支持體層(聚對苯二甲酸乙二酯製膜)，獲得依序積層有支持體層/黏著劑層/剝離襯墊之貼附劑。
2.雙氯芬酸吲哚啉酮體含量之測定
以與實驗1相同之方式進行測定。
[表2]
| 比較例3 | 實施例5 | |
| 雙氯芬酸游離酸 | - | 4.65 |
| 雙氯芬酸鈉 | 5.00 | - |
| 丙烯酸系黏著基劑(MAS811B) | 77.89 | 80.35 |
| 油酸 | 5.00 | 5.00 |
| 二甲基亞碸 | 7.00 | 7.00 |
| 檸檬酸酐 | 2.11 | - |
| 其他 | 3.00 | 3.00 |
| 合計 | 100 | 100 |
| 剛製造後之吲哚啉酮體之生成率(%) | 0.09 | 0.06 |
| 於60℃下保存1週後之吲哚啉酮體之生成率(%) | 2.05 | 0.84 |
確認到，即便於使用丙烯酸系黏著基劑之情形時，相較於含有雙氯芬酸鈉之比較例3之貼附劑，含有雙氯芬酸游離酸之實施例5之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。
實驗3：使用矽酮系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗2相同之方式，按照下述表3之組成製造貼附劑。但是，於本實施例中，以每單位面積之膏體質量為160 g/m
2之方式進行延展。
2.雙氯芬酸吲哚啉酮體含量之測定
以與實驗1相同之方式進行測定。
[表3]
| 比較例4 | 實施例6 | |
| 雙氯芬酸游離酸 | - | 4.65 |
| 雙氯芬酸鈉 | 5.00 | - |
| 矽酮系黏著基劑(BIO-PSA 7-4202) | 77.89 | 80.35 |
| 油酸 | 5.00 | 5.00 |
| 二甲基亞碸 | 7.00 | 7.00 |
| 檸檬酸酐 | 2.11 | - |
| 其他 | 3.00 | 3.00 |
| 合計 | 100 | 100 |
| 剛製造後之吲哚啉酮體之生成率(%) | 0.21 | 0.06 |
| 於60℃下保存1週後之吲哚啉酮體之生成率(%) | 5.32 | 1.23 |
確認到，即便於使用矽酮系黏著基劑之情形時，相較於含有雙氯芬酸鈉之比較例4之貼附劑，含有雙氯芬酸游離酸之實施例6之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。
實驗4：不含聚異丁烯之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗1相同之方式，按照下述表4之組成製造貼附劑。
2.雙氯芬酸吲哚啉酮體之含量之測定
以與實驗1相同之方式進行測定。
[表4]
| 實施例7 | |
| 雙氯芬酸游離酸 | 4.65 |
| 苯乙烯-異戊二烯-苯乙烯嵌段共聚物 | 22.76 |
| 聚異丁烯 | - |
| 脂環族飽和烴樹脂 | 32.10 |
| 氫化松香甘油酯 | 10.00 |
| 液態石蠟 | 14.89 |
| 油酸 | 5.00 |
| 二甲基亞碸 | 7.00 |
| 其他 | 3.60 |
| 合計 | 100 |
| 剛製造後之吲哚啉酮體之生成率(%) | 0.17 |
| 於60℃下保存1週後之吲哚啉酮體之生成率(%) | 1.03 |
確認到，即便於不含聚異丁烯之情形時，相較於含有雙氯芬酸鈉之比較例1之貼附劑，含有雙氯芬酸游離酸之實施例7之貼附劑亦更能夠抑制雙氯芬酸吲哚啉酮體之生成。又，確認到實施例7之貼附劑與實施例1～4之貼附劑相比，雙氯芬酸吲哚啉酮體之生成率亦為同等程度。
實驗5：使用丙烯酸系黏著基劑或矽酮系黏著基劑之貼附劑中之雙氯芬酸吲哚啉酮體之生成率之評估
1.貼附劑之製備
以與實驗2相同之方式，按照下述表5之組成製造實施例8～9之貼附劑。又，以與實驗3相同之方式，按照下述表5之組成製造實施例10～11之貼附劑。
2.雙氯芬酸吲哚啉酮體之含量之測定
以與實驗1相同之方式進行測定。
[表5]
| 實施例8 | 實施例9 | 實施例10 | 實施例11 | |
| 雙氯芬酸游離酸 | 1.00 | 7.00 | 1.00 | 4.65 |
| 丙烯酸系黏著基劑(MAS811B) | 84.00 | 78.00 | - | - |
| 矽酮系黏著基劑(BIO-PSA 7-4202) | - | - | 90.00 | - |
| 矽酮系黏著基劑(BIO-PSA 7-4502) | - | - | - | 80.35 |
| 油酸 | 5.00 | 5.00 | 5.00 | 5.00 |
| 二甲基亞碸 | 7.00 | 7.00 | 1.00 | 7.00 |
| 其他 | 3.00 | 3.00 | 3.00 | 3.00 |
| 合計 | 100 | 100 | 100 | 100 |
| 剛製造後之吲哚啉酮體之生成率(%) | 0.00 | 0.04 | 0.00 | 0.18 |
| 於60℃下保存1週後之吲哚啉酮體之生成率(%) | 0.29 | 1.34 | 0.57 | 0.48 |
確認到，即便於使用丙烯酸系黏著基劑或矽酮系黏著劑之情形時，實施例8～10之貼附劑與含有雙氯芬酸鈉之比較例3或4之貼附劑相比，亦能夠抑制雙氯芬酸吲哚啉酮體之生成，於上述實施例8～10中，使以黏著劑層之總質量為基準之雙氯芬酸游離酸之含量於0.5質量%～8質量%之範圍內變化。又，確認到，使用有與實施例6不同之矽酮系黏著基劑之實施例11之貼附劑相較於含有雙氯芬酸鈉之比較例4之貼附劑，更能夠抑制雙氯芬酸吲哚啉酮體之生成。
Claims (1)
- 一種方法，其係於具備支持體層、及積層於上述支持體層上之黏著劑層的貼附劑中抑制黏著劑層中之雙氯芬酸吲哚啉酮體之生成之方法，該方法包括將雙氯芬酸游離酸與黏著基劑混合以獲得黏著劑組合物之步驟、及形成上述黏著劑組合物以獲得上述貼附劑之步驟，以上述黏著劑層之總質量為基準，上述雙氯芬酸游離酸之含量為0.5質量%~8質量%。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021156757 | 2021-09-27 | ||
| JP2021-156757 | 2021-09-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW202329923A TW202329923A (zh) | 2023-08-01 |
| TWI835310B true TWI835310B (zh) | 2024-03-11 |
Family
ID=85720755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111136189A TWI835310B (zh) | 2021-09-27 | 2022-09-23 | 抑制雙氯芬酸吲哚啉酮體之生成之方法 |
Country Status (2)
| Country | Link |
|---|---|
| TW (1) | TWI835310B (zh) |
| WO (1) | WO2023048192A1 (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040037872A1 (en) * | 2000-09-18 | 2004-02-26 | Liebschutz Isabelle Francine | Tropical composition |
| TW201406411A (zh) * | 2012-06-20 | 2014-02-16 | Hisamitsu Pharmaceutical Co | 貼附劑 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003520191A (ja) * | 1998-09-08 | 2003-07-02 | ワトソン ファーマシューティカルズ， インコーポレイテッド | 薬物の親水性塩類を含有する感圧接着剤マトリックスパッチの製造方法 |
| TWI337086B (en) * | 2003-09-03 | 2011-02-11 | Hisamitsu Pharmaceutical Co | Transdermal formulation containing nonsteroidal antiinflammatory drug |
| US8852628B1 (en) * | 2009-07-13 | 2014-10-07 | Noven Pharmaceuticals, Inc. | Transdermal drug delivery system for diclofenac |
-
2022
- 2022-09-21 WO PCT/JP2022/035204 patent/WO2023048192A1/ja active Application Filing
- 2022-09-23 TW TW111136189A patent/TWI835310B/zh active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040037872A1 (en) * | 2000-09-18 | 2004-02-26 | Liebschutz Isabelle Francine | Tropical composition |
| TW201406411A (zh) * | 2012-06-20 | 2014-02-16 | Hisamitsu Pharmaceutical Co | 貼附劑 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW202329923A (zh) | 2023-08-01 |
| WO2023048192A1 (ja) | 2023-03-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003211297B2 (en) | Percutaneous absorption type plaster | |
| EP2078524B1 (en) | Adhesive skin patch | |
| KR102090411B1 (ko) | 첩부제 | |
| JP4354678B2 (ja) | 貼付剤 | |
| EP2143445B1 (en) | Medicated patch | |
| TWI835310B (zh) | 抑制雙氯芬酸吲哚啉酮體之生成之方法 | |
| JP7222155B1 (ja) | ジクロフェナクインドリノン体の生成を抑制する方法 | |
| TWI825512B (zh) | 抑制阿申那平(asenapine)之分解之方法 | |
| TWI805535B (zh) | 含有利多卡因之貼附劑 | |
| JP2024077214A (ja) | ジクロフェナクインドリノン体の生成を抑制する方法 | |
| TWI830086B (zh) | 含有阿申那平(asenapine)之貼附劑 | |
| TWI796445B (zh) | 含派醋甲酯貼附劑 | |
| JP2023123395A (ja) | ビソプロロール含有貼付剤 | |
| JP2024078015A (ja) | ビソプロロール含有貼付剤 | |
| JP2023011534A (ja) | ブロナンセリン含有貼付剤 | |
| JP2023024350A (ja) | ブロナンセリン含有貼付剤 | |
| EP4052703A1 (en) | Method for suppressing production of asenapine-n-oxide | |
| JP2024077124A (ja) | ブロナンセリン含有貼付剤 | |
| JP2023041781A (ja) | フェンタニル含有貼付剤 |