CN1349794A - 经皮吸收制剂 - Google Patents
经皮吸收制剂 Download PDFInfo
- Publication number
- CN1349794A CN1349794A CN01131289.0A CN01131289A CN1349794A CN 1349794 A CN1349794 A CN 1349794A CN 01131289 A CN01131289 A CN 01131289A CN 1349794 A CN1349794 A CN 1349794A
- Authority
- CN
- China
- Prior art keywords
- adhesive phase
- transdermal formulation
- binding agent
- key
- medicine
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title abstract description 22
- 239000000853 adhesive Substances 0.000 claims abstract description 103
- 230000001070 adhesive effect Effects 0.000 claims abstract description 103
- 239000003814 drug Substances 0.000 claims abstract description 82
- -1 polysiloxane Polymers 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 54
- 239000011230 binding agent Substances 0.000 claims description 49
- 238000009472 formulation Methods 0.000 claims description 44
- 229920002367 Polyisobutene Polymers 0.000 claims description 23
- CERQOIWHTDAKMF-UHFFFAOYSA-N alpha-methacrylic acid Natural products CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 23
- 239000007788 liquid Substances 0.000 claims description 17
- 229920001577 copolymer Polymers 0.000 claims description 14
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 14
- 239000000194 fatty acid Substances 0.000 claims description 14
- 229930195729 fatty acid Natural products 0.000 claims description 14
- 229920001971 elastomer Polymers 0.000 claims description 10
- 239000002985 plastic film Substances 0.000 claims description 10
- 229920006255 plastic film Polymers 0.000 claims description 10
- 239000005060 rubber Substances 0.000 claims description 10
- 150000004665 fatty acids Chemical class 0.000 claims description 9
- 239000004568 cement Substances 0.000 claims description 6
- 229920000642 polymer Polymers 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 229920001195 polyisoprene Polymers 0.000 claims description 4
- 239000013464 silicone adhesive Substances 0.000 claims description 4
- 241001597008 Nomeidae Species 0.000 claims description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- 229920001296 polysiloxane Polymers 0.000 claims description 2
- 239000004705 High-molecular-weight polyethylene Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 abstract description 7
- 239000012790 adhesive layer Substances 0.000 abstract 2
- 239000010410 layer Substances 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 26
- 239000002585 base Substances 0.000 description 26
- 125000000217 alkyl group Chemical group 0.000 description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 15
- 239000011248 coating agent Substances 0.000 description 14
- 238000000576 coating method Methods 0.000 description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 239000004745 nonwoven fabric Substances 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 229940117958 vinyl acetate Drugs 0.000 description 9
- 229920002799 BoPET Polymers 0.000 description 8
- 239000005041 Mylar™ Substances 0.000 description 8
- 230000035699 permeability Effects 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000004698 Polyethylene Substances 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 229920000573 polyethylene Polymers 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 239000010409 thin film Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229920003023 plastic Polymers 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 5
- UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 5
- 229960004536 betahistine Drugs 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000010408 film Substances 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010040880 Skin irritation Diseases 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000036556 skin irritation Effects 0.000 description 4
- 231100000475 skin irritation Toxicity 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
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- ONKUXPIBXRRIDU-UHFFFAOYSA-N Diethyl decanedioate Chemical compound CCOC(=O)CCCCCCCCC(=O)OCC ONKUXPIBXRRIDU-UHFFFAOYSA-N 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-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
- 239000004743 Polypropylene Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000003302 alkenyloxy group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 125000002769 thiazolinyl group Chemical group 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-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
- KANZWHBYRHQMKZ-UHFFFAOYSA-N 2-ethenylpyrazine Chemical compound C=CC1=CN=CC=N1 KANZWHBYRHQMKZ-UHFFFAOYSA-N 0.000 description 2
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000790917 Dioxys <bee> Species 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000004699 Ultra-high molecular weight polyethylene Substances 0.000 description 2
- 239000003655 absorption accelerator Substances 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 229920006243 acrylic copolymer Polymers 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- MTAZNLWOLGHBHU-UHFFFAOYSA-N butadiene-styrene rubber Chemical compound C=CC=C.C=CC1=CC=CC=C1 MTAZNLWOLGHBHU-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960004022 clotrimazole Drugs 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical group CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- YPHQUSNPXDGUHL-UHFFFAOYSA-N n-methylprop-2-enamide Chemical compound CNC(=O)C=C YPHQUSNPXDGUHL-UHFFFAOYSA-N 0.000 description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- QJBZDBLBQWFTPZ-UHFFFAOYSA-N pyrrolnitrin Chemical compound [O-][N+](=O)C1=C(Cl)C=CC=C1C1=CNC=C1Cl QJBZDBLBQWFTPZ-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 229920003051 synthetic elastomer Polymers 0.000 description 2
- 239000005061 synthetic rubber Substances 0.000 description 2
- 229960005294 triamcinolone Drugs 0.000 description 2
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 2
- 229920000785 ultra high molecular weight polyethylene Polymers 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-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
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 description 1
- DCRYNQTXGUTACA-UHFFFAOYSA-N 1-ethenylpiperazine Chemical compound C=CN1CCNCC1 DCRYNQTXGUTACA-UHFFFAOYSA-N 0.000 description 1
- PBGPBHYPCGDFEZ-UHFFFAOYSA-N 1-ethenylpiperidin-2-one Chemical class C=CN1CCCCC1=O PBGPBHYPCGDFEZ-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- SZLZWPPUNLXJEA-UHFFFAOYSA-N 11,17-dimethoxy-18-[3-(3,4,5-trimethoxy-phenyl)-acryloyloxy]-yohimbane-16-carboxylic acid methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(OC)C1OC(=O)C=CC1=CC(OC)=C(OC)C(OC)=C1 SZLZWPPUNLXJEA-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- MZNSQRLUUXWLSB-UHFFFAOYSA-N 2-ethenyl-1h-pyrrole Chemical compound C=CC1=CC=CN1 MZNSQRLUUXWLSB-UHFFFAOYSA-N 0.000 description 1
- ZDHWTWWXCXEGIC-UHFFFAOYSA-N 2-ethenylpyrimidine Chemical compound C=CC1=NC=CC=N1 ZDHWTWWXCXEGIC-UHFFFAOYSA-N 0.000 description 1
- GWZMWHWAWHPNHN-UHFFFAOYSA-N 2-hydroxypropyl prop-2-enoate Chemical compound CC(O)COC(=O)C=C GWZMWHWAWHPNHN-UHFFFAOYSA-N 0.000 description 1
- KXGFMDJXCMQABM-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound [CH]OC1=CC=CC([CH])=C1O KXGFMDJXCMQABM-UHFFFAOYSA-N 0.000 description 1
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AGBXYHCHUYARJY-UHFFFAOYSA-N 2-phenylethenesulfonic acid Chemical compound OS(=O)(=O)C=CC1=CC=CC=C1 AGBXYHCHUYARJY-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-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
- CFZDMXAOSDDDRT-UHFFFAOYSA-N 4-ethenylmorpholine Chemical compound C=CN1CCOCC1 CFZDMXAOSDDDRT-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- BKYKPTRYDKTTJY-UHFFFAOYSA-N 6-chloro-3-(cyclopentylmethyl)-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1CCCC1 BKYKPTRYDKTTJY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Chemical class C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- KFYRPLNVJVHZGT-UHFFFAOYSA-N Amitriptyline hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KFYRPLNVJVHZGT-UHFFFAOYSA-N 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WJUUZHQWGKSLIJ-UHFFFAOYSA-N Bupranolol hydrochloride Chemical compound Cl.CC1=CC=C(Cl)C(OCC(O)CNC(C)(C)C)=C1 WJUUZHQWGKSLIJ-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000004258 Ethoxyquin Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- GYCMBHHDWRMZGG-UHFFFAOYSA-N Methylacrylonitrile Chemical compound CC(=C)C#N GYCMBHHDWRMZGG-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 229920005987 OPPANOL® Polymers 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- SZLZWPPUNLXJEA-FMCDHCOASA-N Rescinnamine Natural products O=C(O[C@H]1[C@@H](OC)[C@@H](C(=O)OC)[C@@H]2[C@H](C1)CN1[C@@H](c3[nH]c4c(c3CC1)ccc(OC)c4)C2)/C=C/c1cc(OC)c(OC)c(OC)c1 SZLZWPPUNLXJEA-FMCDHCOASA-N 0.000 description 1
- MJNIWUJSIGSWKK-BBANNHEPSA-N Riboflavin butyrate Chemical compound CCCC(=O)OC[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)CN1C2=CC(C)=C(C)C=C2N=C2C1=NC(=O)NC2=O MJNIWUJSIGSWKK-BBANNHEPSA-N 0.000 description 1
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Chemical class 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 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- 239000004098 Tetracycline Substances 0.000 description 1
- LCXXNKZQVOXMEH-UHFFFAOYSA-N Tetrahydrofurfuryl methacrylate Chemical compound CC(=C)C(=O)OCC1CCCO1 LCXXNKZQVOXMEH-UHFFFAOYSA-N 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
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical class C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 229960005142 alclofenac Drugs 0.000 description 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229960005119 amitriptyline hydrochloride Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 229940098184 amytal Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- CIJVBYRUFLGDHY-UHFFFAOYSA-N bucumolol Chemical compound O1C(=O)C=CC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2C CIJVBYRUFLGDHY-UHFFFAOYSA-N 0.000 description 1
- 229950002568 bucumolol Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- BOOMOFPAGCSKKE-UHFFFAOYSA-N butane-2-sulfonic acid;prop-2-enamide Chemical compound NC(=O)C=C.CCC(C)S(O)(=O)=O BOOMOFPAGCSKKE-UHFFFAOYSA-N 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229960002925 clonidine hydrochloride Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- WTYGAUXICFETTC-UHFFFAOYSA-N cyclobarbital Chemical compound C=1CCCCC=1C1(CC)C(=O)NC(=O)NC1=O WTYGAUXICFETTC-UHFFFAOYSA-N 0.000 description 1
- 229960004138 cyclobarbital Drugs 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 229950003988 decil Drugs 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- MZNZKBJIWPGRID-UHFFFAOYSA-N diphenylphosphorylmethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)CP(C=1C=CC=CC=1)C1=CC=CC=C1 MZNZKBJIWPGRID-UHFFFAOYSA-N 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- OPUNQOCLIVUKMO-UHFFFAOYSA-N dodecyl 2-oxopyrrolidine-1-carboxylate Chemical compound CCCCCCCCCCCCOC(=O)N1CCCC1=O OPUNQOCLIVUKMO-UHFFFAOYSA-N 0.000 description 1
- 229960001253 domperidone Drugs 0.000 description 1
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 229960004842 ephedrine sulfate Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- YDLRCMNQRQILLP-UHFFFAOYSA-N ethane-1,2-diol;nitric acid Chemical compound OCCO.O[N+]([O-])=O YDLRCMNQRQILLP-UHFFFAOYSA-N 0.000 description 1
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 description 1
- 229940093500 ethoxyquin Drugs 0.000 description 1
- 235000019285 ethoxyquin Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- RBVLUTAXWVILBT-UHFFFAOYSA-N ethyl prop-2-eneperoxoate Chemical compound CCOOC(=O)C=C RBVLUTAXWVILBT-UHFFFAOYSA-N 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- RGUQWGXAYZNLMI-UHFFFAOYSA-N flumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O RGUQWGXAYZNLMI-UHFFFAOYSA-N 0.000 description 1
- 229960003028 flumethiazide Drugs 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 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 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- MPGBPFMOOXKQRX-UHFFFAOYSA-N indenolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C=CC2 MPGBPFMOOXKQRX-UHFFFAOYSA-N 0.000 description 1
- 229950008838 indenolol Drugs 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229940095990 inderal Drugs 0.000 description 1
- 230000000053 inderal effect Effects 0.000 description 1
- 229940089536 indocin Drugs 0.000 description 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920003049 isoprene rubber Polymers 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- KJBLQGHJOCAOJP-UHFFFAOYSA-N metoclopramide hydrochloride Chemical compound O.Cl.CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC KJBLQGHJOCAOJP-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- AUCNMQYOQYTGPE-UHFFFAOYSA-N n-(hydroxymethyl)-n-methylprop-2-enamide Chemical compound OCN(C)C(=O)C=C AUCNMQYOQYTGPE-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- YRVUCYWJQFRCOB-UHFFFAOYSA-N n-butylprop-2-enamide Chemical compound CCCCNC(=O)C=C YRVUCYWJQFRCOB-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 1
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 description 1
- 229960001907 nitrofurazone Drugs 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- VJTXQHYNRDGLON-LTGZKZEYSA-N octotiamine Chemical compound COC(=O)CCCCC(SC(C)=O)CCSS\C(CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N VJTXQHYNRDGLON-LTGZKZEYSA-N 0.000 description 1
- 229950011324 octotiamine Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 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
- 229960005489 paracetamol Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- 239000005011 phenolic resin Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229950000845 politef Drugs 0.000 description 1
- 229920002857 polybutadiene Polymers 0.000 description 1
- 150000003097 polyterpenes Chemical class 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- DWCSHJVWTDQUCJ-UHFFFAOYSA-N prop-1-ene;pyrrolidin-2-one Chemical compound CC=C.O=C1CCCN1 DWCSHJVWTDQUCJ-UHFFFAOYSA-N 0.000 description 1
- UIIIBRHUICCMAI-UHFFFAOYSA-N prop-2-ene-1-sulfonic acid Chemical compound OS(=O)(=O)CC=C UIIIBRHUICCMAI-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 229960002132 pyrrolnitrin 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
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- SMSAPZICLFYVJS-QEGASFHISA-N rescinnamine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)\C=C\C1=CC(OC)=C(OC)C(OC)=C1 SMSAPZICLFYVJS-QEGASFHISA-N 0.000 description 1
- 229960001965 rescinnamine Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 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
- 239000003381 stabilizer Substances 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229940063650 terramycin Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical group C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 229960002044 tolmetin sodium Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Chemical class OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229940102566 valproate Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- 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
- A61K9/7061—Polyacrylates
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明提供了一种经皮吸收制剂,该经皮吸收制剂包括载体和具有释放控制层的粘合剂层,该粘合剂层形成在载体的至少一面上,其中粘合剂层含有粘合剂和0.5～60wt%的除1,2－乙二醇衍生物外的药物。
Description
技术领域
本发明涉及一种经皮吸收制剂，该制剂含有特定量的除1，2-乙二醇衍生物外的药物，该制剂可使药物持续地经皮吸收进入体内，并且该制剂可抑制由药物引起的对皮肤的刺激。
背景技术
对于给药，药物粘合片形式的制剂，即所谓的经皮吸收制剂，由于其具有可行的给药方法，易于控制给药等优点，最近几年已引起大家的注意，其中制剂是通过粘合剂的作用粘贴到皮肤上的。
但是，皮肤的功能本来是作为一个屏障体系，来保护身体不受外部环境的影响，并能有效地阻止外界物质对身体的入侵。为了使经皮吸收的药物的药理学作用完全发挥出来，需要开发一种具有穿越这种屏障功能的皮肤渗透性的经皮吸收制剂。
为改善皮肤的渗透性，人们做了如下尝试：经常向粘合剂中加入一种经皮吸收促进剂；使用离子电渗疗法，其中通过向皮肤通电而使离子化的药物被经皮吸收；通过利用超声波作用的扩音听诊器使药物被物理经皮吸收；等。
另一方面，已报道有很多化合物在被经皮吸收时会引起对皮肤的刺激。因为经皮吸收制剂的目标是将药物经皮吸收进入体内，所以会引起对皮肤的刺激的药物的经皮吸收，要求在不会对皮肤产生刺激的浓度下，身体能够经皮吸收足够量的药物，这意味着该制剂应具有相反的作用。
发明内容
发明概述
因此本发明的一个目的是提供一种经皮吸收制剂，该制剂能够持续地使药物经皮吸收进入体内，足以产生所需的药理学效果，并且该制剂能够抑制由药物引起的对皮肤的刺激。
根据本发明，具有释放控制层的粘合剂层形成在载体的至少一侧，以控制粘合剂层中含有的药物的释放量和释放速率，由此实现药物的持续经皮吸收，其吸收量足以发挥药理学作用，并提供一种药物对皮肤刺激较小的经皮吸收制剂。
因此，本发明提供如下的经皮吸收制剂：(1)一种经皮吸收制剂，含有载体和具有释放控制层的粘合剂层，该粘
合剂层形成在载体的至少一侧，其中粘合剂层含有粘合剂和0.5-
60wt％的除1，2-乙二醇衍生物以外的药物。(2)上述(1)中的经皮吸收制剂，其中所述的粘合剂选自下列粘合剂中
至少之一：丙烯酸粘合剂，该粘合剂含有一种聚合物作为主要组分，
该聚合物含有作为聚合组分的(甲基)丙烯酸C2-18烷基酯，其含量
不低于40wt％；橡胶粘合剂，该粘合剂含有选自聚异丁烯，聚异戊
二烯，和苯乙烯-二烯-苯乙烯共聚物中的至少一种作为主要组分；
和硅氧烷粘合剂，该粘合剂包含含有二甲基硅氧烷单元的聚有机硅
氧烷作为主要组分。(3)上述(1)中的经皮吸收制剂，其中粘合剂层含有至少一种选自二元
醇，脂肪和油脂，脂肪酸，醇和脂肪酸酯的有机液体组分。(4)上述(1)中的经皮吸收制剂，其中粘合剂是含有聚异丁烯作为主要
组分的橡胶粘合剂，并且粘合剂层还含有高级脂肪酸的低级烷基
酯。(5)上述(1)中的经皮吸收制剂，其中释放控制层是多孔塑料薄膜。(6)上述(5)中的经皮吸收制剂，其中多孔塑料薄膜是由高分子量聚乙
烯制成的。(7)上述(5)或(6)中的经皮吸收制剂，其中多孔塑料薄膜的孔隙率为
20-60％。(8)上述(1)中的经皮吸收制剂，其中具有释放控制层的粘合剂层，从
载体一侧开始具有由粘合剂层A/释放控制层/粘合剂层B构成的层压
结构。(9)上述(8)中的经皮吸收制剂，其中粘合剂层B的药物含量不超过
200μg/cm2。
附图说明
图1是显示测试实施例1中的水下释放试验结果的曲线。
发明详述
本发明的经皮吸收制剂含有载体和具有释放控制层的粘合剂层，该粘合剂层形成在载体的至少一侧，其中的粘合剂层含有粘合剂和除1，2-乙二醇衍生物外的药物。
用于本发明的药物可以是除1，2-乙二醇衍生物外的任何药物，并依治疗的目的而定。其实例包括皮质类固醇(例如氢化可的松，强的松龙，倍氯美松丙酸酯(becloinetasone propionate)，氟甲松，去炎松，去炎松丙酮，氟轻松，氟轻松丙酮，醋酸氟轻松丙酮，丙酸氯氟美松等)，抗炎镇痛剂(例如对乙酰氨基酚，甲灭酸，氟灭酸，消炎痛，1-薄荷醇，樟脑，苏灵大，联苯丁酮酸，保泰松，布洛芬，甲苯酰吡酸钠，双氯酚酸，双氯酚酸钠，烯氯苯乙酸，羟基保泰松，萘普生，氟联苯丙酸，酮丙酸，水杨酸，水杨酸甲酯等)，hypnosedatives(例如苯巴比妥，异戊巴比妥，环巴比妥，氯羟去甲安定，氟哌啶醇等)，镇静剂(例如氟非那嗪，甲硫哒嗪，安定，氟硝安定，氯丙嗪等)，抗高血压剂(例如可乐定，盐酸可乐定，心得静，心得安(盐酸盐)，氯甲苯心安，茚心安，布库洛尔，硝苯吡啶等)，利尿降血剂(例如双氢氯噻嗪，下氟噻嗪，环戊氯噻嗪等)，抗生素(例如青霉素，四环素，土霉素，硫酸新霉素，红霉素，氯霉素等)，麻醉剂(例如利多卡因，苯佐卡因，氨苯甲酸乙酯等)，抗菌剂(例如氯苄烷铵，呋喃西林，制霉菌素，磺胺乙酰钠，克霉唑等)，防霉剂(例如pentimycin，两性霉素B，硝吡咯菌素，克霉唑等)，维生素(例如维生素A，维生素D2，维生素D3，辛硫胺，丁酸核黄素等)，冠状血管舒张剂(例如硝酸甘油，硝酸乙二醇，硝酸异山梨醇酯等)，抗组胺剂(例如苯海拉明(盐酸盐)，氯苯吡胺等)，止咳药(例如美沙芬，叔丁喘宁，麻黄碱，麻黄碱盐酸盐等)，性激素(例如黄体酮，雌二醇等)，抗抑郁剂(例如丙咪嗪(盐酸盐)，阿密曲替林盐酸盐等)，改善大脑循环的制剂，止吐药物(例如灭吐灵，哌双咪酮等)，抗癌制剂(例如5-氟尿嘧啶等)，抗癫病药(例如硝基安定，安宁，氯硝安定，2-丙基戊酸钠等)，抗头晕药(例如甲胺乙吡啶等)等。这些药物可单独使用或组合使用。
上面提到的不能用在本发明中的1，2-乙二醇衍生物具有如下的通式(I)：
其中R1是任选取代的杂环基，R2为氢原子，低级烷基，低级烷氧基或任选保护羟基，R3为氢原子或低级烷基，在数字n内的R4和R5可相同，也可不同，并且各自为氢原子或低级烷基，R6为任选取代的氨基或含氮的杂环基，或氨复盐基，并且n为0-6的整数。
在上述通式(I)中，除非另外特别指出，每个符号代表下列含义：
卤原子是指氟原子，氯原子，溴原子或碘原子。
低级烷基是指C1-6烷基，如甲基，乙基，正丙基，异丙基，正丁基，异丁基，叔丁基，戊基和己基。
低级烯基是指C2-6烯基，如乙烯基，丙烯基，丁烯基，戊烯基和己烯基。
低级链烯氧基是指C2-6烯基-O-基。
环烷基是指C3-6环烷基，如环丙基，环丁基，环戊基和环己基。
低级烷氧基是指C1-6烷基-O-基。
低级烷硫基是指C1-6烷基-S-基。
芳基是指苯基，萘基，2，3-二氢化茚基或茚基。
芳氧基是指芳基-O-基。
芳基(低级)烷基是指芳基(C1-4)烷基，例如苄基，二苯甲基，三苯甲基和苯乙基。
芳基(低级)烯基是指芳基(C2-6)烯基，例如苯乙烯基，肉桂基等。
芳基(低级)烷氧基是指芳基(C1-4)烷基-O-基。
芳基(低级)烷硫基是指芳基(C1-4)烷基-S-基。
低级亚烷基二氧基是指C1-4亚烷基二氧基，例如亚甲基二氧基和亚乙基二氧基。
低级酰基是指C1-6烷基-CO-基，例如甲酰基，乙酰基和丁酰基。
芳酰基是指芳基-CO-基。
低级烷基磺酰基是指C1-6烷基-SO2-基。
芳基(低级)烷基磺酰基是指芳基(C1-6)烷基-SO2-基。
芳基磺酰基是指芳基-SO2-基。
低级烷基磺酰氧基是指C1-6烷基-SO2-O-基。
芳基磺酰氧基是指芳基-SO2-O-基。
芳基磺酰氨基是指芳基-SO2NH-基。
低级烷基磺酰氨基是指C1-6烷基-SO2NH-基。
二低级烷基氨基是指二C1-6烷基氨基。
氨复盐基是指三C1-6烷基氨复盐基，如三甲基氨复盐基和三乙基氨复盐基。
含氮的杂环基是指5元或6元稠合环或桥联环的杂环基，其含有一个或多个氮原子和一个或多个氧原子或硫原子作为形成环的杂原子，实例有吡咯基，吡咯烷基，哌啶基，哌嗪基，咪唑基，吡唑基，吡啶基，四氢吡啶基，嘧啶基，吗啉基，硫代吗啉基，喹啉基，喹嗪基，四氢喹啉基，四氢异喹啉基，奎宁环基，噻唑基，四唑基，噻二唑基，吡咯啉基，咪唑啉基，咪唑烷基，吡唑啉基，吡唑烷基，嘌呤基和吲唑基。
杂环基是指上述含氮杂环基，或含有一个或多个氧原子和/或硫原子作为形成环的杂原子的5元或6元稠合环或桥联环的杂环基，其实例有呋喃基，噻吩基，苯并呋喃基，苯并噻吩基，异苯并呋喃基，吡喃基，苯并二氢吡喃基，苯并吡喃基，黄嘌呤基，硫代吡喃基，噻蒽基，吩黄嘌呤基等。
杂环羰基是指杂环-CO-基。
在通式(I)中“任选取代的杂环基”R1的取代基的实例为卤原子；任选取代的氨基，低级烷基，芳基，芳基(低级)烷基，低级烷氧基，芳基(低级)烷氧基，芳氧基，氨基甲酰氧基，低级烷硫基，低级烯基，低级链烯氧基，芳基(低级)烷硫基，芳基(低级)烷基磺酰基，芳基磺酰基，低级烷基磺酰氨基，芳基磺酰氨基和杂环基；保护的氨基；任选保护的羟基；硝基；氧基；和低级亚烷基二氧基，这些取代基可单独使用或组合使用。
作为在通式(I)中“任选取代的杂环基”R1的取代基的“任选取代的低级烷基，芳基，芳基(低级)烷基，低级烷氧基，芳基(低级)烷氧基，芳氧基，氨基甲酰氧基，低级烷硫基，低级烯基，低级链烯氧基，芳基(低级)烷硫基，芳基(低级)烷基磺酰基，芳基磺酰基，低级烷基磺酰氨基，芳基磺酰氨基和杂环基”的取代基，及在通式(I)中“任选取代的含氮的杂环基”R6的取代基的实例有卤原子，任选保护的羟基，保护的羧基，任选保护的氨基，用任选保护的羟基任选取代的低级烷基，用卤原子任选取代的芳基，用卤原子任选取代的芳酰基，用低级烷氧基任选取代的低级烷氧基，低级酰基，芳基(低级)烷基，芳基(低级)烯基，杂环基，杂环羰基，氧基，低级烷基磺酰基和芳基磺酰基，这些取代基可单独使用或组合使用。
作为在通式(I)中“任选取代的杂环基”R1的取代基的“任选取代的氨基”的取代基，及在通式(I)中“任选取代的氨基”R6的取代基的实例有任选保护的羟基，用任选保护的羟基和/或保护的羧基任选取代的低级烷基，环烷基，芳基，低级酰基，芳基(低级)烷基，杂环基，被氧基任选取代的杂环羰基，金刚烷基，低级烷基磺酰基和芳基磺酰基，这些取代基可单独使用或组合使用。
在通式(I)中“任选保护的羟基”R2，作为在通式(I)中“任选取代的杂环基”R1的取代基的“保护的氨基”和“任选保护的羟基”，及所有作为在通式(I)中“任选取代的氨基或含氮的杂环基”R6的取代基的“任选保护的羟基”，“保护的羧基”，“任选保护的氨基”，“任选保护的羟基”或“被任选保护的羟基任选取代的低级烷基”，及“用保护的羧基任选取代的低级烷基”中的“保护的羧基”的保护基，可以是在“Protective Groups in Organic Synthesis” [TheodraW.Creen(1991)，John Wiley & Sons.Inc.]中描述的羟基，羧基和氨基的典型的保护基。具体而言，羟基的保护基是例如低级烷基，低级酰基，2-四氢吡喃基，或芳基(低级)烷基，例如任选取代的苄基。
当本发明中使用的药物可以形成盐时，其可以是自由形式或药物可接受的盐。药物可接受的盐的实例包括与酸形成的盐，所述酸可以是例如无机酸(例如盐酸，氢溴酸，硫酸，磷酸等)，有机酸(例如羧酸，如甲酸，乙酸，草酸，琥珀酸，富马酸，马来酸，乳酸，苹果酸，酒石酸，天冬氨酸等；磺酸，如甲磺酸，苯磺酸，对甲苯磺酸，萘磺酸等)等，碱盐，例如钠盐，铵盐等。
在本发明中，药物可接受的盐可以通过加一种盐的释放剂，而在粘合剂层中释放出来。释放剂的实例包括碱，例如氢氧化钠，氢氧化钾，三乙胺，四乙基铵，氨，辛酸钠等，酸，例如盐酸，琥珀酸，乙酸等。对于经皮吸收，包含在粘合剂层中的药物的经皮吸收性能的顺序为：自由形式的药物＞在粘合剂层中释放的药物＞药物的可接受的盐。
本发明中使用的药物在粘合剂层中的含量为0.5～60wt％，优选1～30wt％。当含量少于0.5wt％时，很难有有效量的药物被吸收以发挥药效。相反，当含量超过60wt％时，所述粘合剂层对皮肤的粘合力很低，不能确保粘合在皮肤上，或者不能得到药物量增加所带来的药效提高的效果，而这在经济上是不利的。
在本发明的粘合剂层中包含的粘合剂是一种粘合剂膏，该粘合剂膏可以粘合到皮肤上，使粘合剂层中包含的药物可以从皮肤表面经皮给药，并且该粘合剂膏在常温下具有粘性。
作为这类粘合剂，使用的是在涂敷到皮肤上后对皮肤无刺激性等的药用粘合剂，例如丙烯酸粘合剂，天然橡胶粘合剂，合成橡胶粘合剂(含有作为主要组分的合成橡胶组分，例如合成异戊二烯橡胶，聚异丁烯橡胶，苯乙烯/丁二烯橡胶，苯乙烯/异戊二烯/苯乙烯橡胶，苯乙烯/丁二烯/苯乙烯橡胶等)，硅氧烷粘合剂，乙烯酯粘合剂，乙烯醚粘合剂等是优选的。
在上述粘合剂中，考虑到性能的稳定和粘合剂性能控制的容易性，优选使用选自如下粘合剂中的至少一种粘合剂：丙烯酸酯粘合剂，该粘合剂含有一种聚合物作为主要组分，该聚合物含有作为聚合组分的(甲基)丙烯酸C2-18烷基酯，其含量不低于40wt％；橡胶粘合剂，该粘合剂含有聚异丁烯，聚异戊二烯，和苯乙烯-二烯-苯乙烯共聚物中的至少一种作为主要组分；和硅氧烷粘合剂，该粘合剂含有具有二甲基硅氧烷单元的聚有机硅氧烷作为主要组分。特别地，考虑到药物的稳定性，优选使用含有聚异丁烯作为主要组分的橡胶粘合剂。
上述丙烯酸粘合剂没有任何特别的限制，只要其具有上述组成。从粘合剂性能容易控制等角度考虑，由50～98wt％的一种或多种(甲基)丙烯酸C2-18烷基酯，和2～50wt％的一种或多种共聚单体共聚得到的共聚物是优选的。
上述(甲基)丙烯酸C2-18烷基酯的实例包括：由含有2～18，优选4～12个碳原子的烷基的一级，二级，或三级醇，和丙烯酸或甲基丙烯酸得到的酯。
上述共聚单体的实例包括具有至少一个参与共聚反应的不饱和双键，并且在侧链上具有官能团的单体，所述官能团是例如羧基[例如(甲基)丙烯酸，衣康酸，马来酸，马来酸酐等]；羟基[例如(甲基)丙烯酸羟乙酯，(甲基)丙烯酸羟丙酯等]；磺基[例如苯乙烯磺酸，烯丙基磺酸，(甲基)丙烯酸磺基丙基酯，(甲基)丙烯酰氧基萘磺酸，丙烯酰胺甲基丙磺酸等]；氨基[例如(甲基)丙烯酸氨乙酯，(甲基)丙烯酸二甲胺乙基酯，(甲基)丙烯酸叔丁基氨乙酯等]；酰胺基(例如(甲基)丙烯酰胺，二甲基(甲基)丙烯酰胺，N-丁基丙烯酰胺，N-羟甲基(甲基)丙烯酰胺，N-羟甲基丙烷(甲基)丙烯酰胺等)；烷氧基[例如(甲基)丙烯酸甲氧基乙基酯，(甲基)丙烯酸乙氧基乙基酯，(甲基)丙烯酸甲氧基乙二醇酯，(甲基)丙烯酸甲氧基二乙二醇酯，(甲基)丙烯酸甲氧基聚乙二醇酯，(甲基)丙烯酸四氢化糠基酯等]等。
除上述外的其它共聚单体的实例包括(甲基)丙烯腈，醋酸乙烯酯，丙酸乙烯酯，N-乙烯基-2-吡咯烷酮，甲基乙烯基吡咯烷酮，乙烯基吡啶，乙烯基哌啶酮，乙烯基嘧啶，乙烯基哌嗪，乙烯基吡嗪，乙烯基吡咯，乙烯基咪唑，乙烯基己内酰胺，乙烯基噁唑，乙烯基吗啉等。
可以使用一种或多种上述共聚单体。考虑到粘合剂的粘性和内聚力，包含在粘合剂层中的药物的释放性能等，共聚物中至少包括含羧基的单体和含羟基的单体中的一种，含量为1～50wt％，优选3～20wt％，并且在需要时，共聚物中优选含有上面列举的其它共聚单体，例如乙烯基单体(如醋酸乙烯酯，和N-乙烯基-2-吡咯烷酮)，含量不超过40wt％，优选不超过30wt％。
丙烯酸粘合剂的实例包括丙烯酸(2-乙基己基)酯和丙烯酸的共聚物，丙烯酸(2-乙基己基)酯和丙烯酸(2-羟乙基)酯的共聚物，丙烯酸(2-乙基己基)酯和丙烯酸(2-甲氧基乙基)酯，醋酸乙烯酯的共聚物，丙烯酸(2-乙基己基)酯和乙烯基吡咯烷酮的共聚物，丙烯酸(2-乙基己基)酯和乙烯基吡咯烷酮和丙烯酸的共聚物，等等。
按照本发明，所述粘合剂层优选含有至少一种有机液体组分，该有机液体组分选自二元醇，脂肪和油，脂肪酸，醇和脂肪酸酯。当粘合剂层含有有机液体组分时，可进一步改善对皮肤的粘性，药物的皮肤渗透性，和在剥离时对皮肤刺激性的降低等。换句话说，可以改善药物的皮肤渗透性；由于有机液体组分与粘合剂层中的粘合剂增塑剂的相容性，使粘合剂制备物在粘合到皮肤上时产生一种软的感觉；通过交联处理赋予合适的内聚力，并且可以降低使用后剥离时对皮肤的刺激。
上述二元醇的实例包括乙二醇，二甘醇，三甘醇，聚乙二醇，丙二醇，聚丙二醇等。具有高分子量的那些二元醇，例如聚乙二醇，聚丙二醇等，优选重均分子量为200～1000。
上述脂肪和油的实例包括橄榄油，蓖麻油，角鲨烯，角鲨烷，橙油，矿物油等。
上述脂肪酸的实例包括总碳数为6～20的一癸酸，油酸，辛酸，月桂酸，十一碳烯酸，异硬脂酸，亚油酸等。
上述醇的实例包括除上述二元醇外的，具有1～20个碳原子的醇，例如乙醇，甲醇，辛醇，乙氧化十八烷醇，1，3-丁二醇，癸醇，桉树脑，油醇等。
上述脂肪酸酯的实例包括总碳数为6～20的肉豆蔻酸异丙酯，癸二酸二乙酯，油酸乙酯，邻苯二甲酸二乙酯，己二酸二异丙酯，丙二醇脂肪酸酯，烟酸月桂酯，吡咯烷酮羧酸月桂酯等。
上述有机液体组分的含量优选为：每100份(重量)粘合剂，含有3～200份(重量)，更优选10～180份(重量)，最优选20～100份(重量)。当有机液体组分的含量太低时，将起不到效果。当含量太高时，粘合剂层塑化太严重，这将造成低的内聚力。这样还有一个结果，即交联处理将不可避免地在皮肤表面留下胶状残留物，并且可能增加在剥离时对皮肤的刺激。
如上所述，为了药物的稳定性，本发明优选使用含有聚异丁烯作为主要组分的橡胶粘合剂。在这种情况下，优选含有高级脂肪酸的低级烷基酯作为上述有机液体组分。
具体而言，对于涂敷到皮肤上后粘合剂性能(粘合力，内聚力，粘着性等)的平衡，优选一种合适的组合物，该组合物包括作为聚异丁烯的粘均分子量(Mv)为900,000～2,100,000的高分子量的聚异丁烯，Mv为10,000～200,000的中分子量的聚异丁烯，Mv为500～4,000的低分子量的聚异丁烯。
上述各聚异丁烯的混合比优选为：高分子量聚异丁烯，10～80wt％，优选20～70wt％；中分子量聚异丁烯，0～90wt％，优选10～80wt％；低分子量聚异丁烯，0～80wt％，优选0～60wt％。通过使各聚异丁烯的含量在上述范围内，得到的聚异丁烯粘合剂具有优异的粘合剂性能平衡，这将有效实现本发明药物的经皮吸收。
作为有机液体组分的高级脂肪酸低级烷基酯的实例包括具有10～14个碳原子的高级脂肪酸与具有1～3个碳原子的低级醇的酯化产物，例如肉豆蔻酸异丙酯，癸二酸二乙酯等。这些有机液体组分的含量优选为3～80份(重量)，更优选10～40份(重量)，基于每100份(重量)含有聚异丁烯作为主要组分的橡胶粘合剂。在这一范围内的含量，将降低药物对皮肤的刺激性，并改善药物的经皮吸收性能。
而且按照本发明，当需要增加粘合剂层的粘度时，可以与粘合剂一起使用一种增粘剂。增粘剂的实例包括松香，松香衍生物，多萜树脂，苯并二氢吡喃-茚树脂，石油树脂，萜苯酚树脂等。
在本发明中，当需要时，粘合剂层可以含有添加剂，例如抗氧化剂，颜料，填料，经皮吸收促进剂，药物稳定剂，药物加溶剂，药物降溶剂等。一般地，这些添加剂的含量通常为粘合剂层的约0.1～50wt％，优选1～10wt％。
按照本发明，所述粘合剂层含有一个释放控制层。该释放控制层的目的是，在粘合剂层中含有的药物由于铺展扩散，从粘合剂层的表面释放到与该层接触的皮肤表面时，控制药物的释放量和释放速度，并具有防止自由扩散的屏障功能。
本发明的含有释放控制层的粘合剂层，具有一种层叠结构，例如粘合剂层A/释放控制层/粘合剂层B，该顺序是从载体侧开始。在这种结构中，粘合剂层A和粘合剂层B的组成可以相同或不同，其中所包含的粘合剂，有机液体组分等的种类和量，及加入的药物的量可以变化。
上述释放控制层可以是纸，无纺布，纺织布，有孔的塑料薄膜等，并且如果药物可以溶解在其中，也可以使用没有孔的塑料薄膜(例如聚乙烯薄膜，聚丙烯薄膜，乙烯/醋酸乙烯酯共聚物薄膜)。当使用无孔塑料薄膜时，所述药物从粘合剂层A的释放速度可能降低，降低粘合剂层A中的药物的有效利用率，并且所述薄膜会由于有机液体组分的作用而溶涨，这样会产生皱纹。因此，优选使用有孔的塑料薄膜，特别是多孔的塑料薄膜。尽管对多孔塑料薄膜的厚度没有特别的限制，但是优选不超过100微米，以降低将其粘合在皮肤上所产生的不舒适感，即硬感。
可用于本发明的多孔塑料薄膜的例子为由如下材料制成的多孔薄膜：聚乙烯，聚丙烯，聚四氟乙烯，乙烯/醋酸乙烯酯共聚物，醋酸乙烯酯/氯乙烯共聚物，塑性氯乙烯，聚氨酯，聚(1，1-二氯乙烯)，聚酯等。在这些材料中，优选使用高分子量的聚乙烯，超高分子量的聚乙烯等，它们对上述有机液体组分具有足够的抵抗力(例如非溶涨性等)。
为了控制药物的释放，上述多孔塑料薄膜的孔隙率优选为约20～60％，更优选25～55％。孔的大小优选不超过50微米，更优选为20～35微米。
按照本发明，所述粘合剂层有一个释放控制层。通过这种结构，可以按照本发明的目标控制释放的量和释放的速度，由此实现药物被身体持续经皮吸收，并且可以抑制药物对皮肤的刺激。具体而言，药物在粘合剂层B(与皮肤接触一侧)的含量优选控制为不超过200μg/cm2，更优选为75～150μg/cm2，并且药物从粘合剂层A(载体侧)迁移到粘合剂层B的速率优选控制为不超过120μg/cm2/t1/2，更优选为70～120μg/cm2/t1/2。
因为粘合剂层B位于与皮肤接触的一侧，所以在粘合剂层B中包含的药物，在敷于皮肤上后立即释放到皮肤上。当粘合剂层B的药物含量太高时，将很难控制其释放到皮肤上的量。因此，粘合剂层B的药物含量优选设定为不超过200μg/cm2。另外，药物从粘合剂层B的释放速度优选控制为不超过180μg/cm2/t1/2，更优选不超过10～150μg/cm2/t1/2。通过调节粘合剂层的厚度和组成，药物的总含量和浓度，及有机液体组分的含量，可以控制释放速度。
在粘合剂层A中包含的药物在释放到皮肤上前，需要通过释放控制层，这涉及到持续的释放。当释放控制层的透过率太高时，在短时间内大量的药物释放到皮肤上，不能实现持续释放。因此，药物从粘合剂层A迁移到粘合剂层B的速度优选控制为不超过120μg/cm2/t1/2，更优选为70～120μg/cm2/t1/2。通过调节粘合剂层的组成，释放控制层的材料和厚度，可以控制迁移速度。
对本发明中使用的载体没有任何特别的限制，只要其可以承载粘合剂层并改善粘合性能。其实例包括：由聚酯，聚乙烯，聚丙烯，聚氯乙烯，聚(1，1-二氯乙烯)，乙烯/醋酸乙烯酯共聚物，乙酸纤维素，乙基纤维素，醋酸乙烯/氯乙烯共聚物，聚氨酯等制成的塑料薄膜，纸，纺织布，无纺布，及其层压物，这些材料和金属箔的层压物，等。
上述载体的厚度为，当本发明的经皮吸收制剂附着在皮肤表面时，不会引起不舒适感，并且在从皮肤表面剥离该制剂时能够提供足够的机械强度以保持该制剂完整的厚度。该厚度一般为1～50微米，优选1～30微米。
按照本发明，含有上述释放控制层的粘合剂层，优选通过包藏涂敷技术等，直接或间接形成在载体的至少一面上，以改善操作性能，对皮肤的粘接性，经皮吸收性，所述间接形成是指通过用于改善固定效果的底物等。
本发明的经皮吸收制剂可以按照如下方法得到。将一种形成粘合剂层的涂敷溶液涂布在脱模衬(例如经过脱模处理后的薄膜等)上并干燥(形成粘合剂层B)。分开地，将一种形成粘合剂层的涂敷溶液涂布在载体上并干燥(形成粘合剂层A)。将在脱模衬上的粘合剂层B和在载体上的粘合剂层A分别粘附在释放控制层的两面，并除去脱模衬，给出一种结构为载体/粘合剂层A/释放控制层/粘合剂层B的经皮吸收制剂。
尽管对本发明的经皮吸收制剂的形状无特殊的限制，但是优选具有优异可操作性的带状。
具体实施方式
下面参考实施例详细阐述本发明。无论如何，本发明不局限于这些实施例，而是可以做各种改变，只要这些改变未脱离本发明的技术概念。在下列叙述中，份数是指重量份，％是指wt％。
实施例1
将丙烯酸粘合剂(75份，丙烯酸(2-乙基己基)酯/丙烯酸共聚物，丙烯酸(2-乙基己基)酯/丙烯酸＝95/5(重量比))溶解在乙酸乙酯中。向其中加入癸二酸二乙酯(20份)和自由形式的甲胺乙吡啶(5份)，得到形成粘合剂层的涂敷溶液。将该涂敷溶液涂布到经过脱模处理的聚酯薄膜上，使干燥后的厚度为30微米，并干燥(形成粘合剂层B)。分开地，将上述涂敷溶液涂布在载体无纺布(6微米厚的聚酯薄膜和基础重量为8g/m2的聚酯无纺布的层压物)上，使干燥后的厚度为60微米，并干燥(形成粘合剂层A)。
作为释放控制层，使用一个50微米厚的高分子量多孔聚乙烯薄膜(孔隙率：45％，由NITTO DENKO CORPORATION生产的聚乙烯薄膜，商标为BREATHRON)。在该薄膜的两面粘附经过脱模处理的聚酯薄膜上的粘合剂层B，和在载体上的粘合剂层A，并剥离该经过脱模处理的聚酯薄膜，得到结构为载体/粘合剂层A/释放控制层/粘合剂层B的经皮吸收制剂。
实施例2
将一种聚异丁烯粘合剂(60份，为粘均分子量为1,400,000的聚异丁烯(100份)与粘均分子量为60,000的聚异丁烯(100份)的混合物)溶解在己烷中。加入肉豆蔻酸异丙酯(30份)和自由形式的甲胺乙吡啶(10份)，得到形成粘合剂层的涂敷溶液。将该涂敷溶液涂布到经过脱模处理的聚酯薄膜上，使干燥后的厚度为20微米，并干燥(形成粘合剂层B)。分开地，将上述涂敷溶液涂布在载体无纺布(6微米厚的聚酯薄膜和基础重量为8g/m2的聚酯无纺布的层压物)上，使干燥后的厚度为30微米，并干燥(形成粘合剂层A)。
作为释放控制层，使用一个50微米厚的超高分子量多孔聚乙烯薄膜(孔隙率：30％，由NITTO DENKO CORPORATION生产的超高分子量聚乙烯薄膜，商标为SUNMAP)。在该薄膜的两面粘附经过脱模处理的聚酯薄膜上的粘合剂层B，和在载体上的粘合剂层A，并剥离该经过脱模处理的聚酯薄膜，得到结构为载体/粘合剂层A/释放控制层/粘合剂层B的经皮吸收制剂。比较实施例1
制备如实施例1的形成粘合剂层的涂敷溶液，并将该涂敷溶液涂布到如实施例1的载体无纺布上，使干燥后的厚度为90微米，并干燥，得到结构为载体/粘合剂层的经皮吸收制剂。比较实施例2
将丙烯酸粘合剂(95份，丙烯酸(2-乙基己基)酯/丙烯酸共聚物，丙烯酸(2-乙基己基)酯/丙烯酸＝95/5(重量比))溶解在乙酸乙酯中，并加入自由形式的甲胺乙吡啶(5份)，得到形成粘合剂层的涂敷溶液。将该溶液涂布到如实施例1的载体无纺布上，使干燥后的厚度为90微米，并干燥，得到结构为载体/粘合剂层的经皮吸收制剂。比较实施例3
制备如实施例2的形成粘合剂层的涂敷溶液，并将该涂敷溶液涂布到如实施例2的载体无纺布上，使干燥后的厚度为50微米，并干燥，得到结构为载体/粘合剂层的经皮吸收制剂。比较实施例4
将一种聚异丁烯粘合剂(90份，为粘均分子量为1,400,000的聚异丁烯(100份)与粘均分子量为60,000的聚异丁烯(100份)的混合物)的混合物溶解在己烷中。加入自由形式的甲胺乙吡啶(10份)，得到形成粘合剂层的涂敷溶液。将该涂敷溶液涂布到载体无纺布上，使干燥后的厚度为50微米，并干燥，得到结构为载体/粘合剂层的经皮吸收制剂。
在实施例1～2和比较实施例1～4中得到的经皮吸收制剂进行如下试验。测试实施例1(释放性试验)
在上述各实施例和比较实施例中得到的经皮吸收制剂冲压成10cm2圆形物，并根据日本药典，扩散试验方法2(水坑方法)进行水下释放试验。结果示于图1。图1的结果清楚地表明，在粘合剂层中释放控制层的存在可得到所需的药物释放控制模式。测试实施例2(皮肤刺激性试验)
在上述各实施例和比较实施例中得到的经皮吸收制剂冲压成10cm2圆形物，并粘贴在Wistar大鼠(8周大)的背上，该鼠的皮肤表面已进行了剪毛，剃刮和清洁。在粘贴18h后剥离该制剂，按照Draize等的标准评价在粘合剂涂敷部位是否有由药物引起的刺激性的存在。结果列于表1。评价标准如下。<对皮肤的刺激性>
○：对皮肤无刺激
△：对皮肤有弱刺激
×：对皮肤有中等或中等以上的刺激测试实施例3(通过蛇皮的渗透性)
在上述各实施例和比较实施例中得到的经皮吸收制剂冲压成直径为6cm的圆形物，并粘贴在网状巨蟒皮的一面上。网状巨蟒皮的没有经皮吸收制剂的一面上，放置直径6mm的渗滤池，并测定渗透到渗滤池的药物的量，以评价渗透性。渗透的药物的量采用HPLC测定，并计算每单位面积的渗透量(24h累积)和每单位面积的最大药物渗透速率。结果列于表1。
【表1】
| 对皮肤的刺激性 | 渗透量(μg/cm2)(24h累积) | 最大渗透速率(μg/cm2/h) | |
| 实施例1 | ○ | 380 | 18.5 |
| 比较实施例1 | × | 410 | 63.0 |
| 比较实施例2 | ○ | 105 | 5.2 |
| 实施例2 | ○ | 200 | 15.0 |
| 比较实施例3 | × | 220 | 65.0 |
| 比较实施例4 | ○ | 100 | 7.5 |
如上表1所清楚表明的那样，实施例1-2的制剂几乎没有表现出药物对皮肤的刺激性，并且在药物渗透性方面没有实际问题。相反，比较实施例1-4的没有释放控制层的制剂，在药物对皮肤的刺激性和渗透性方面，实际上不能令人满意。比较实施例1和3的制剂含有有机液体组分，但是没有释放控制层。结果，所述药物显示最大的渗透速率，引起药物对皮肤的刺激。比较实施例2和4的制剂没有释放控制层，但是由于缺少有机液体组分，药物的渗透量很小。
上述说明清楚表明，本发明可以提供一种经皮吸收制剂，该制剂可以提供药物的持续经皮吸收，以在长时间内发挥需要的药效。另外，本发明的制剂具有经皮可吸收性和低的皮肤刺激性，其中抑制了药物对皮肤的刺激性。
本申请是基于在日本提交的专利申请No.2000-268899，其内容结合在此作为参考。
Claims (10)
1.一种经皮吸收制剂，包括载体和具有释放控制层的粘合剂层，该粘合剂层形成在载体的至少一面上，其中粘合剂层含有粘合剂和0.5～60wt％的除1，2-乙二醇衍生物外的药物。
2.权利要求1的经皮吸收制剂，其中所述的粘合剂选自下列粘合剂中至少之一：丙烯酸粘合剂，该粘合剂含有一种聚合物作为主要组分，该聚合物含有作为聚合组分的(甲基)丙烯酸C2-18烷基酯，其含量不低于40wt％；橡胶粘合剂，该粘合剂含有选自聚异丁烯，聚异戊二烯，和苯乙烯-二烯-苯乙烯共聚物中的至少一种作为主要组分；和硅氧烷粘合剂，该粘合剂包含含有二甲基硅氧烷单元的聚有机硅氧烷作为主要组分。
3.权利要求1的经皮吸收制剂，其中所述粘合剂层含有选自二元醇，脂肪和油，脂肪酸，醇和脂肪酸酯的至少一种有机液体组分。
4.权利要求1的经皮吸收制剂，其中所述粘合剂是橡胶粘合剂，包括聚异丁烯作为主要组分，并且所述粘合剂层还含有高级脂肪酸的低级烷基酯。
5.权利要求1的经皮吸收制剂，其中所述释放控制层是多孔塑料薄膜。
6.权利要求5的经皮吸收制剂，其中所述多孔塑料薄膜由高分子量聚乙烯制成。
7.权利要求5的经皮吸收制剂，其中所述多孔塑料薄膜的孔隙率为20～60％。
8.权利要求6的经皮吸收制剂，其中所述多孔塑料薄膜的孔隙率为20～60％。
9.权利要求1的经皮吸收制剂，其中所述含有释放控制层的粘合剂层具有一种层压结构，该层压结构从载体侧开始，由粘合剂层A/释放控制层/粘合剂层B构成。
10.权利要求9的经皮吸收制剂，其中所述粘合剂层B的药物含量不超过200μg/cm2。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000268899A JP4358978B2 (ja) | 2000-09-05 | 2000-09-05 | 経皮吸収製剤 |
| JP268899/2000 | 2000-09-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1349794A true CN1349794A (zh) | 2002-05-22 |
| CN100418579C CN100418579C (zh) | 2008-09-17 |
Family
ID=18755600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011312890A Expired - Fee Related CN100418579C (zh) | 2000-09-05 | 2001-09-05 | 经皮吸收制剂 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7029693B2 (zh) |
| EP (1) | EP1188436B1 (zh) |
| JP (1) | JP4358978B2 (zh) |
| CN (1) | CN100418579C (zh) |
| CA (1) | CA2356743C (zh) |
| DE (1) | DE60116202T2 (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669924B (zh) * | 2008-09-12 | 2013-05-29 | 日东电工株式会社 | 贴剂和贴剂制剂 |
| CN106214332A (zh) * | 2016-09-07 | 2016-12-14 | 芜湖德鑫汽车部件有限公司 | 焊接面罩 |
| CN106309010A (zh) * | 2016-09-07 | 2017-01-11 | 芜湖德鑫汽车部件有限公司 | 手持式焊接面罩 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100941909B1 (ko) | 2002-02-19 | 2010-02-16 | 히사미쓰 세이야꾸 가부시키가이샤 | 경피흡수형 부착제 |
| JP4323138B2 (ja) * | 2002-06-05 | 2009-09-02 | 日東電工株式会社 | 経皮吸収型製剤およびその製造方法 |
| AU2003272878A1 (en) * | 2002-09-13 | 2004-04-30 | Hisamitsu Pharmaceutical Co., Inc. | Adhesive patch |
| US9205062B2 (en) * | 2004-03-09 | 2015-12-08 | Mylan Pharmaceuticals, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| US20050202073A1 (en) * | 2004-03-09 | 2005-09-15 | Mylan Technologies, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| JP5058531B2 (ja) | 2005-09-09 | 2012-10-24 | 日東電工株式会社 | ビソプロロール含有貼付製剤 |
| ES2368652T3 (es) * | 2005-09-09 | 2011-11-21 | Nitto Denko Corporation | Preparación adhesiva que contiene bisoprolol. |
| JP4945228B2 (ja) | 2005-12-13 | 2012-06-06 | 日東電工株式会社 | ビソプロロール含有貼付製剤 |
| NZ579240A (en) | 2007-03-08 | 2011-03-31 | Nitto Denko Corp | Device for the transdermal administration of bisoprolol |
| JP5226230B2 (ja) * | 2007-03-08 | 2013-07-03 | 日東電工株式会社 | 貼付剤用粘着剤組成物及びその用途 |
| CA2738524C (en) | 2008-10-02 | 2013-11-26 | Mylan Inc. | Method for making a multilayer adhesive laminate |
| JP2010120912A (ja) * | 2008-11-21 | 2010-06-03 | Lead Chemical Co Ltd | ５−メチル−１−フェニル−２−（１ｈ）−ピリドン含有貼付剤 |
| US9072682B2 (en) | 2012-12-31 | 2015-07-07 | Mylan Inc. | Transdermal dosage form for low-melting point active agent |
| US11241174B2 (en) * | 2016-06-07 | 2022-02-08 | International Business Machines Corporation | Wearable device for monitoring bodily fluids |
| US11872320B2 (en) | 2021-02-25 | 2024-01-16 | Hisamitsu Pharmaceutical Co., Inc. | Method for treating osteoarthritis |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4615699A (en) * | 1985-05-03 | 1986-10-07 | Alza Corporation | Transdermal delivery system for delivering nitroglycerin at high transdermal fluxes |
| US4645502A (en) * | 1985-05-03 | 1987-02-24 | Alza Corporation | Transdermal delivery of highly ionized fat insoluble drugs |
| US5186939A (en) * | 1987-04-23 | 1993-02-16 | Cygnus Therapeutic Systems | Laminated composite for transdermal administration of fentanyl |
| JP2688062B2 (ja) * | 1988-06-20 | 1997-12-08 | 積水化学工業株式会社 | 医療用貼付部材 |
| US4855294A (en) * | 1988-09-06 | 1989-08-08 | Theratech, Inc. | Method for reducing skin irritation associated with drug/penetration enhancer compositions |
| US5124157A (en) * | 1989-08-18 | 1992-06-23 | Cygnus Therapeutic Systems | Method and device for administering dexmedetomidine transdermally |
| GB9021674D0 (en) * | 1990-10-05 | 1990-11-21 | Ethical Pharma Ltd | Transdermal device |
| JP3191219B2 (ja) * | 1990-12-28 | 2001-07-23 | 三笠製薬株式会社 | 全身性経皮投与製剤 |
| JP2556182Y2 (ja) * | 1991-05-30 | 1997-12-03 | 三笠製薬株式会社 | シート状経皮投与製剤 |
| JPH06199659A (ja) * | 1992-10-28 | 1994-07-19 | Hisamitsu Pharmaceut Co Inc | 経皮治療用装置 |
| US5494680A (en) * | 1993-12-08 | 1996-02-27 | Minnesota Mining And Manufacturing Company | Transdermal delivery device |
| EP0828783B1 (en) * | 1995-05-30 | 2002-08-21 | Landec Corporation | Gas-permeable membrane |
| US6183853B1 (en) * | 1999-04-30 | 2001-02-06 | 3M Innovative Properties Company | Porous materials containing melamine resin |
| JP2002029969A (ja) * | 2000-07-17 | 2002-01-29 | Nitto Denko Corp | 経皮吸収製剤 |
-
2000
- 2000-09-05 JP JP2000268899A patent/JP4358978B2/ja not_active Expired - Fee Related
-
2001
- 2001-09-05 CA CA002356743A patent/CA2356743C/en not_active Expired - Fee Related
- 2001-09-05 US US09/946,889 patent/US7029693B2/en not_active Expired - Fee Related
- 2001-09-05 DE DE60116202T patent/DE60116202T2/de not_active Expired - Lifetime
- 2001-09-05 EP EP01121228A patent/EP1188436B1/en not_active Expired - Lifetime
- 2001-09-05 CN CNB011312890A patent/CN100418579C/zh not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669924B (zh) * | 2008-09-12 | 2013-05-29 | 日东电工株式会社 | 贴剂和贴剂制剂 |
| CN106214332A (zh) * | 2016-09-07 | 2016-12-14 | 芜湖德鑫汽车部件有限公司 | 焊接面罩 |
| CN106309010A (zh) * | 2016-09-07 | 2017-01-11 | 芜湖德鑫汽车部件有限公司 | 手持式焊接面罩 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2356743A1 (en) | 2002-03-05 |
| EP1188436B1 (en) | 2005-12-28 |
| DE60116202D1 (de) | 2006-02-02 |
| CN100418579C (zh) | 2008-09-17 |
| EP1188436A2 (en) | 2002-03-20 |
| US20020106401A1 (en) | 2002-08-08 |
| US7029693B2 (en) | 2006-04-18 |
| CA2356743C (en) | 2009-04-21 |
| JP4358978B2 (ja) | 2009-11-04 |
| DE60116202T2 (de) | 2006-08-24 |
| JP2002080349A (ja) | 2002-03-19 |
| EP1188436A3 (en) | 2003-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5581368B2 (ja) | 経皮吸収製剤 | |
| CN1349794A (zh) | 经皮吸收制剂 | |
| JP5068003B2 (ja) | 室温で液体である低分子量薬を含む経皮組成物 | |
| JP5702434B2 (ja) | 経皮薬物送達システムにおいて有用な非反応型接着剤 | |
| JP5130203B2 (ja) | 非水系粘着剤組成物、貼付剤および貼付剤の製造方法 | |
| JP4999366B2 (ja) | 経皮吸収製剤 | |
| TWI462755B (zh) | Stickers | |
| CN1466452A (zh) | 用于经皮传递芬太尼的组合物 | |
| JP2010521525A (ja) | 非晶質薬物の経皮系、製造方法、および安定化 | |
| WO2009145269A1 (ja) | 経皮吸収製剤 | |
| JP4478757B2 (ja) | ビソプロロール含有貼付剤 | |
| JP2000044904A (ja) | アクリル系粘着テープおよび経皮吸収製剤 | |
| JP5185509B2 (ja) | 貼付剤 | |
| TWI280126B (en) | Tulobuterol adhesive patch | |
| JP2013060393A (ja) | 経皮吸収促進用組成物および貼付製剤 | |
| CN1219874A (zh) | 透皮给药用制剂 | |
| EP3744321B1 (en) | Patch | |
| JP2003300868A (ja) | 貼付剤およびその製造方法 | |
| JPH11209271A (ja) | 経皮吸収製剤 | |
| JPH0798744B2 (ja) | 貼付剤 | |
| JPH11209270A (ja) | 経皮吸収製剤 | |
| JP5281973B2 (ja) | ビソプロロール含有貼付剤 | |
| TW201114865A (en) | Transdermal preparation | |
| KR20220143074A (ko) | 패치 제제 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080917 Termination date: 20150905 |
|
| EXPY | Termination of patent right or utility model |