WO2006099818A1 - Light curable monomer compostion and use thereof - Google Patents
Light curable monomer compostion and use thereof Download PDFInfo
- Publication number
- WO2006099818A1 WO2006099818A1 PCT/CN2006/000509 CN2006000509W WO2006099818A1 WO 2006099818 A1 WO2006099818 A1 WO 2006099818A1 CN 2006000509 W CN2006000509 W CN 2006000509W WO 2006099818 A1 WO2006099818 A1 WO 2006099818A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- meth
- acrylate
- methyl
- weight
- ester
- Prior art date
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- 239000000178 monomer Substances 0.000 title claims abstract description 33
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 178
- -1 -C6H5 Chemical group 0.000 claims abstract description 119
- 239000000203 mixture Substances 0.000 claims abstract description 53
- 238000013270 controlled release Methods 0.000 claims abstract description 35
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000004185 ester group Chemical group 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 239000012965 benzophenone Substances 0.000 claims description 29
- OMNKZBIFPJNNIO-UHFFFAOYSA-N n-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical group CC(=O)CC(C)(C)NC(=O)C=C OMNKZBIFPJNNIO-UHFFFAOYSA-N 0.000 claims description 15
- PXKLMJQFEQBVLD-UHFFFAOYSA-N bisphenol F Chemical class C1=CC(O)=CC=C1CC1=CC=C(O)C=C1 PXKLMJQFEQBVLD-UHFFFAOYSA-N 0.000 claims description 10
- 238000013271 transdermal drug delivery Methods 0.000 claims description 9
- QWQFVUQPHUKAMY-UHFFFAOYSA-N 1,2-diphenyl-2-propoxyethanone Chemical compound C=1C=CC=CC=1C(OCCC)C(=O)C1=CC=CC=C1 QWQFVUQPHUKAMY-UHFFFAOYSA-N 0.000 claims description 8
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical class C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims description 8
- 239000012956 1-hydroxycyclohexylphenyl-ketone Substances 0.000 claims description 7
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 7
- MQDJYUACMFCOFT-UHFFFAOYSA-N bis[2-(1-hydroxycyclohexyl)phenyl]methanone Chemical compound C=1C=CC=C(C(=O)C=2C(=CC=CC=2)C2(O)CCCCC2)C=1C1(O)CCCCC1 MQDJYUACMFCOFT-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 claims description 6
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 6
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- FWLDHHJLVGRRHD-UHFFFAOYSA-N decyl prop-2-enoate Chemical compound CCCCCCCCCCOC(=O)C=C FWLDHHJLVGRRHD-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000004014 plasticizer Substances 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 4
- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 claims description 4
- TXBCBTDQIULDIA-UHFFFAOYSA-N 2-[[3-hydroxy-2,2-bis(hydroxymethyl)propoxy]methyl]-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC(CO)(CO)CO TXBCBTDQIULDIA-UHFFFAOYSA-N 0.000 claims description 4
- 239000004593 Epoxy Substances 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 4
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])* 0.000 claims description 4
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 claims description 4
- BPXVHIRIPLPOPT-UHFFFAOYSA-N 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinane-2,4,6-trione Chemical compound OCCN1C(=O)N(CCO)C(=O)N(CCO)C1=O BPXVHIRIPLPOPT-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 125000004079 stearyl 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])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])[H] 0.000 claims description 3
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 claims description 2
- ALVZNPYWJMLXKV-UHFFFAOYSA-N 1,9-Nonanediol Chemical compound OCCCCCCCCCO ALVZNPYWJMLXKV-UHFFFAOYSA-N 0.000 claims description 2
- LCZVSXRMYJUNFX-UHFFFAOYSA-N 2-[2-(2-hydroxypropoxy)propoxy]propan-1-ol Chemical compound CC(O)COC(C)COC(C)CO LCZVSXRMYJUNFX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- UZDMJPAQQFSMMV-UHFFFAOYSA-N 4-oxo-4-(2-prop-2-enoyloxyethoxy)butanoic acid Chemical compound OC(=O)CCC(=O)OCCOC(=O)C=C UZDMJPAQQFSMMV-UHFFFAOYSA-N 0.000 claims description 2
- IZSHZLKNFQAAKX-UHFFFAOYSA-N 5-cyclopenta-2,4-dien-1-ylcyclopenta-1,3-diene Chemical group C1=CC=CC1C1C=CC=C1 IZSHZLKNFQAAKX-UHFFFAOYSA-N 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229940116229 borneol Drugs 0.000 claims description 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 claims description 2
- 125000006226 butoxyethyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- QSAWQNUELGIYBC-UHFFFAOYSA-N cyclohexane-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCCC1C(O)=O QSAWQNUELGIYBC-UHFFFAOYSA-N 0.000 claims description 2
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 claims description 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 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 claims description 2
- LNMQRPPRQDGUDR-UHFFFAOYSA-N hexyl prop-2-enoate Chemical compound CCCCCCOC(=O)C=C LNMQRPPRQDGUDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- OTLDLKLSNZMTTA-UHFFFAOYSA-N octahydro-1h-4,7-methanoindene-1,5-diyldimethanol Chemical compound C1C2C3C(CO)CCC3C1C(CO)C2 OTLDLKLSNZMTTA-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 229940116351 sebacate Drugs 0.000 claims description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 claims description 2
- NJRHMGPRPPEGQL-UHFFFAOYSA-N 2-hydroxybutyl prop-2-enoate Chemical compound CCC(O)COC(=O)C=C NJRHMGPRPPEGQL-UHFFFAOYSA-N 0.000 claims 1
- ZYUVGYBAPZYKSA-UHFFFAOYSA-N 5-(3-hydroxybutan-2-yl)-4-methylbenzene-1,3-diol Chemical compound CC(O)C(C)C1=CC(O)=CC(O)=C1C ZYUVGYBAPZYKSA-UHFFFAOYSA-N 0.000 claims 1
- CAMQFJOZKDDIQE-UHFFFAOYSA-N C(O)C(C(O)(CO)CO)(O)CO.CCC Chemical compound C(O)C(C(O)(CO)CO)(O)CO.CCC CAMQFJOZKDDIQE-UHFFFAOYSA-N 0.000 claims 1
- GDFCSMCGLZFNFY-UHFFFAOYSA-N Dimethylaminopropyl Methacrylamide Chemical compound CN(C)CCCNC(=O)C(C)=C GDFCSMCGLZFNFY-UHFFFAOYSA-N 0.000 claims 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims 1
- 239000007983 Tris buffer Substances 0.000 claims 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims 1
- NHADDZMCASKINP-HTRCEHHLSA-N decarboxydihydrocitrinin Natural products C1=C(O)C(C)=C2[C@H](C)[C@@H](C)OCC2=C1O NHADDZMCASKINP-HTRCEHHLSA-N 0.000 claims 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 125000005395 methacrylic acid group Chemical group 0.000 claims 1
- HMZGPNHSPWNGEP-UHFFFAOYSA-N octadecyl 2-methylprop-2-enoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)C(C)=C HMZGPNHSPWNGEP-UHFFFAOYSA-N 0.000 claims 1
- 125000005498 phthalate group Chemical class 0.000 claims 1
- LYBIZMNPXTXVMV-UHFFFAOYSA-N propan-2-yl prop-2-enoate Chemical compound CC(C)OC(=O)C=C LYBIZMNPXTXVMV-UHFFFAOYSA-N 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 125000002948 undecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000012528 membrane Substances 0.000 abstract description 23
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 abstract 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 106
- 229960001047 methyl salicylate Drugs 0.000 description 56
- 239000003814 drug Substances 0.000 description 49
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- 241001465754 Metazoa Species 0.000 description 30
- 238000009792 diffusion process Methods 0.000 description 25
- 238000004128 high performance liquid chromatography Methods 0.000 description 25
- 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 24
- 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 24
- 229960002009 naproxen Drugs 0.000 description 24
- 238000000338 in vitro Methods 0.000 description 19
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- 239000011248 coating agent Substances 0.000 description 12
- 238000000576 coating method Methods 0.000 description 12
- SAPGBCWOQLHKKZ-UHFFFAOYSA-N 6-(2-methylprop-2-enoyloxy)hexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCOC(=O)C(C)=C SAPGBCWOQLHKKZ-UHFFFAOYSA-N 0.000 description 11
- 239000002504 physiological saline solution Substances 0.000 description 9
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- 239000010959 steel Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- QNODIIQQMGDSEF-UHFFFAOYSA-N (1-hydroxycyclohexyl)-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)C1(O)CCCCC1 QNODIIQQMGDSEF-UHFFFAOYSA-N 0.000 description 1
- CSCSROFYRUZJJH-UHFFFAOYSA-N 1-methoxyethane-1,2-diol Chemical compound COC(O)CO CSCSROFYRUZJJH-UHFFFAOYSA-N 0.000 description 1
- UECGJSXCVLTIMQ-UHFFFAOYSA-N 2-(2-prop-2-enoyloxyethoxycarbonyl)cyclohexane-1-carboxylic acid Chemical compound OC(=O)C1CCCCC1C(=O)OCCOC(=O)C=C UECGJSXCVLTIMQ-UHFFFAOYSA-N 0.000 description 1
- JEPGPKGGSYXGKV-UHFFFAOYSA-N 2-ethoxybutanoic acid Chemical compound CCOC(CC)C(O)=O JEPGPKGGSYXGKV-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical compound OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 description 1
- JHWGFJBTMHEZME-UHFFFAOYSA-N 4-prop-2-enoyloxybutyl prop-2-enoate Chemical compound C=CC(=O)OCCCCOC(=O)C=C JHWGFJBTMHEZME-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- QODGGXQLNZTIDG-UHFFFAOYSA-N OC(C(=O)O)CCC.OCC(C)(CO)C Chemical compound OC(C(=O)O)CCC.OCC(C)(CO)C QODGGXQLNZTIDG-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229940059312 androderm Drugs 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 125000005577 anthracene group Chemical group 0.000 description 1
- CLHAOIOLCMPIRX-UHFFFAOYSA-N benzoic acid diphenylmethanone Chemical compound OC(=O)C1=CC=CC=C1.C=1C=CC=CC=1C(=O)C1=CC=CC=C1 CLHAOIOLCMPIRX-UHFFFAOYSA-N 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
- 239000012267 brine Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- KBLWLMPSVYBVDK-UHFFFAOYSA-N cyclohexyl prop-2-enoate Chemical compound C=CC(=O)OC1CCCCC1 KBLWLMPSVYBVDK-UHFFFAOYSA-N 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
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940074117 estraderm Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- PQWVIUSCFLEBHJ-UHFFFAOYSA-N n-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NC(CO)(CO)CO PQWVIUSCFLEBHJ-UHFFFAOYSA-N 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- CIBMHJPPKCXONB-UHFFFAOYSA-N propane-2,2-diol Chemical compound CC(C)(O)O CIBMHJPPKCXONB-UHFFFAOYSA-N 0.000 description 1
- PNXMTCDJUBJHQJ-UHFFFAOYSA-N propyl prop-2-enoate Chemical compound CCCOC(=O)C=C PNXMTCDJUBJHQJ-UHFFFAOYSA-N 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- MUTNCGKQJGXKEM-UHFFFAOYSA-N tamibarotene Chemical compound C=1C=C2C(C)(C)CCC(C)(C)C2=CC=1NC(=O)C1=CC=C(C(O)=O)C=C1 MUTNCGKQJGXKEM-UHFFFAOYSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229940035321 transderm scop Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
- C08F2/50—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light with sensitising agents
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F220/56—Acrylamide; Methacrylamide
Definitions
- the present invention relates to a class of photocurable monomer compositions, and more particularly to a combination of photocurable monomers comprising acrylates and acrylamides having an alkyl group moiety, a hydroxyl group, an ester group, a carboxyl group or an alkoxy group.
- the invention also relates to the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal delivery system.
- a transdermal delivery system refers to a controlled release formulation in which the drug is released from a specially designed device and absorbed through the intact skin into the entire blood system.
- Transdermal drug delivery systems can be broadly divided into two broad categories, membrane controlled release and backbone diffusion.
- the membrane controlled release transdermal drug delivery system is a drug or percutaneous absorption enhancer controlled release film or other controlled release material wrapped into a depot, and the release rate of the drug is controlled by the properties of the controlled release membrane or the controlled release material.
- control membranes are microporous polypropylene membranes
- nitroglycerin trade name Transderm-Nitro
- fentai Nie trade name Dm'ogesic
- estradiol trade name Estraderm
- testosterone trade name Androderm
- controlled release membrane is polyethylene-vinyl acetate
- nicotine trade name NicoDerm CQ
- the control film is a polyethylene film.
- microporous membranes to control the rate of drug release is described in U.S. Patent No. 3,797,494.
- the pores of the membrane are from 0.1 to 0.85, the curvature of the membrane is from 1 to 10, and the thickness of the membrane is from 10 to 100 ⁇ m.
- Examples of membranes are polypropylene, polytetrafluoroethylene, polycarbonate, polyvinyl chloride, cellulose acetate, nitric acid. Cellulose, polyacrylonitrile, etc.
- Their disadvantage is that there are few types of microporous membranes available, and no more pharmaceuticals can be prepared for transdermal administration.
- Disadvantages are the residual problem of the organic solvent in the ethylene-vinyl acetate copolymer, and the need to constantly adjust the content of vinyl acetate to adjust the permeability of the drug.
- One object of the present invention is to provide a monomer composition having excellent curing properties and capable of producing a polymer which can be used in a controlled release film in a transdermal drug delivery system, in view of the deficiencies of the prior art.
- Another object of the present invention is to provide the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal drug delivery system.
- a photocurable monomer composition comprising:
- the content of the component (A) is 0% by weight/weight
- the content of the component (B) is 0.1 to 99.9% by weight/weight
- the content of the component (B) is 0% by weight
- the component (A) is contained in an amount of from 0.1 to 99.9% by weight/weight.
- the component (A) is contained in an amount of 20 to 80% by weight; the component (B) is contained in an amount of 12 to 78% by weight; and the component (C) The content is from 2 to 8% by weight/weight.
- the acrylate monomer which is an alkane group in the component (A) can be exemplified by, but not limited to, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, ( Methyl) isopropyl acrylate, butyl (meth)acrylate, amyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, isoamyl (meth)acrylate , (meth) hexyl acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, (methyl) Ethyl acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, (Methy
- cyclohexyl acrylate (Methyl) phenoxyethyl acrylate, methoxyethylene glycol (meth) acrylate, ethoxyethyl (meth) acrylate, dicyclopentadienyl (meth) acrylate, (methyl) Dicyclopentyl acrylate, dicyclopentenyloxyethyl (meth)acrylate, tricyclodecyl (meth)acrylate, isobornyl (meth)acrylate, borneol (meth)acrylate, ( Methyl) dimethylaminoethyl acrylate, diethylaminoethyl (meth)acrylate, 7-amino-3,7-dimethyloctyl (meth)acrylate, (meth)acryloylmorpholine , 2-(meth)acryloyloxyethyl phthalate, 2 - (A Acryloxyethylhexahydrophthalate, 2-
- the acrylate monomer wherein R 4 is a hydroxyl group in the component (A) may be exemplified by, but not limited to, 4-methylhydroxybutyl (meth)acrylate, 2-hydroxy-3-phenoxy (methyl) ) propyl acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 1, 4-butanediol- Methyl) acrylate, (meth)acryloyl phosphate mono-2-hydroxydecyl ester (in which alkyl group such as methyl, ethyl, propyl), (meth)acrylic acid 4-tetrahydroxycyclohexyl ester, 1, 6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate; wherein, 4-tetrahydroxybutyl
- Component (A), 1? 4 is an ester group of acrylate monomers may be exemplified by, but not limited to, ethylene glycol di (meth) acrylate, 1, 4-butanediol di (meth Acrylate, 1,6-hexanediol di(meth)acrylate, propylene glycol di(meth)acrylate, 1,9-nonanediol di(meth)acrylate, diglyceride di(methyl) Acrylate, triglyceride di(meth) acrylate, tetraglycol di(meth) acrylate, dipropylene glycol di(meth) acrylate, tripropylene glycol di(meth) acrylate, neopentyl glycol Di(meth) acrylate, hydroxyvaleric acid neopentyl glycol di(meth) acrylate, trimethyl glycerol propane tri(meth) acrylate, pentaerythritol
- the acrylate monomer which is a carboxyl group may, for example, be, but not limited to, 2-methylcarboxyl (meth)acrylate, 3-carboxypropyl (meth)acrylate, or (meth)acrylic acid-2 —Carboxypropyl ester, 4-methylcarboxy n-butyl (meth)acrylate, 3-carboxy-n-butyl (meth)acrylate, 2-carboxy-n-butyl (meth)acrylate, (meth)acrylic acid 2-carboxyisobutyl ester, (meth)acrylic acid-6-carboxy-n-hexyl ester, (meth)acrylic acid 5-carboxy-n-hexyl ester, (meth)acrylic acid 4-tetracarboxy-n-hexyl ester, (meth)acrylic acid-3 —Carboxy n-hexyl ester, (meth)acrylic acid 2-carboxy-n-hexyl ester
- the acrylate monomer wherein R 4 is an alkoxy group in the component (A) may be exemplified by, but not limited to, 2-methethoxyethyl (meth)acrylate and 2-methyl methacrylate.
- the acrylamide monomer of the present invention may be exemplified by, but not limited to, N-(1,1-dimethyl-3-oxobutyl)-acrylamide, (meth)acrylamide, N ,N-Dimethyl(meth)acrylamide, N-isopropyl(meth)acrylamide, N-(butoxymethyl)(meth)acrylamide, N-(hydroxymethyl) (A Acrylamide, N-[(trimethylol)methyl](methyl)acrylamide, N-[3-(dimethylamino)propyl](meth)acrylamide; wherein, N- ( 1,1-Dimethyl-3-oxobutyl) Monoacrylamide is an example of the most preferred monomer.
- the photoinitiator (C) used in the present invention includes a photoinitiator which is sensitive to ultraviolet light and which can initiate a curing reaction of a monomer, such as, but not limited to, benzophenone peroxide, 1-hydroxycyclohexyl phenyl ketone. , benzoin propyl ether.
- composition of the present invention may further comprise a plasticizer, such as, but not limited to Then, citrate, phthalate or sebacate to further improve the physical properties of the polymer film.
- a plasticizer such as, but not limited to Then, citrate, phthalate or sebacate to further improve the physical properties of the polymer film.
- component (b) When component (A) is in a solid form, the components (A), (B) and (C) are mixed and dissolved in an organic solvent (preferably ethanol) to obtain a desired composition. Solution. If the composition of the present invention further contains a plasticizer, the method further comprises the step (c); adding a plasticizer to the resulting composition solution.
- an organic solvent preferably ethanol
- Another aspect of the invention relates to the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal delivery system; in particular, a polymeric film prepared from the composition can be used as Controlled-release membranes in transdermal drug delivery systems (TDDs), by adjusting the type and amount of monomers (A) and (B) in the composition, can fine-tune the physicochemical properties of the film, and rapidly prepare transdermal drug for different drugs. Controlled release membrane in the system.
- TDDs transdermal drug delivery systems
- the present inventors conducted a drug permeability test on a part of the polymer film prepared from the photocurable composition of the present invention, and compared it with the drug permeability test of the animal skin, from the comparison results, The results of the drug permeability test of some polymer films are higher than those of animal skin, and the drug permeability test results of another part of the polymer film are lower than that of animal skin, and the results can be seen in the preparation of the present invention.
- the polymer film is free to control the permeability of the drug, which is significant for controlled release of the drug in the transdermal drug delivery system.
- the present invention also broadens the types of materials for the preparation of controlled release membranes in transdermal drug delivery systems, and expands the range of material selection.
- Example 1 is a graph comparing the permeability test of a cured film obtained by curing the composition obtained in Example 1 with an in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative drug flux Qt (g/cni 2 ).
- Example 2 is a graph comparing the permeability test of the cured film obtained by the curing of the composition obtained in Example 2 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
- 3 and 4 are graphs comparing the permeability test of methyl salicylate and naproxen to the in vitro transdermal test of animal skin by the cured film obtained by ultraviolet light curing of the composition obtained in Example 7.
- the horizontal axis represents time T (h)
- the vertical axis represents cumulative drug penetration Qt (g/cm 2 ).
- 5 and 6 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 8 against methyl salicylate and naproxen, wherein the horizontal axis represents time T (h). ), the vertical axis represents The cumulative amount of drug permeation Qt ( ⁇ 8 / ⁇ 2 ).
- FIG. 7 and 8 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 9 against methyl salicylate and naproxen, wherein the horizontal axis represents time T (h). ), the vertical axis represents the cumulative drug penetration Qt ( ⁇ ⁇ / ⁇ 2 ).
- Figure 9 is a graph comparing the permeability test of the cured film obtained by the curing of the composition obtained in Example 10 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
- Figure 10 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 16 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
- Figure 11 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 17 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
- Figure 12 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 18 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt H/cm 2 .
- Figure 13 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 24, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt ( ⁇ ⁇ / ⁇ 2 ).
- Figure 14 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 29, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt ( ⁇ ⁇ / ⁇ 2 ).
- Figure 15 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 30, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt ( ⁇ ⁇ / ⁇ ! 2 ).
- Figure 16 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 31, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt (g). /cm 2 ).
- 17 and 18 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 34 against methyl salicylate and naproxen, respectively, wherein the horizontal axis represents time T (h). ), the vertical axis represents the cumulative drug throughput Qt ( ⁇ ⁇ / ⁇ 2 ).
- 19 and 20 are graphs comparing the permeability test of methyl salicylate and naproxen to the in vitro transdermal test of animal skin by the cured film obtained by ultraviolet light curing of the composition obtained in Example 35, respectively. , where the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt ( g/cffl 2 ).
- 21 and 22 are graphs showing the permeability test of the cured film obtained by ultraviolet light curing of the composition obtained in Example 36 against methyl salicylate and naproxen, respectively, wherein the horizontal axis represents time T (h). ), vertical axis generation Table drug cumulative permeability Qt (g/cni 2 ).
- N-decyl acrylate 200mg
- 4-tetrahydroxybutyl acrylate 800mg
- benzophenone peroxide 50mg
- dissolved, filtered, 30ul mixed solution placed on a stainless steel circular carrier substrate Upper ( ⁇ 30 ⁇ )
- coated and flattened placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the obtained cured film was placed in a Valia-Chien diffusion cell, which was a lmg/ml solution of clonidine hydrochloride in the supply tank, and the receiving tank was physiological saline.
- the release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
- N-dodecyl acrylate 200mg
- 2-hydroxy-3-phenoxy propyl acrylate SOOrag
- benzophenone peroxide 50mg
- dissolved, filtered, mixed solution 30ul placed in stainless steel round
- the substrate of the carrier ⁇ 30 ⁇
- it is coated and flattened, and it is completely cured in an ultraviolet curing instrument (3kw power, Beijing Esper Machinery Electronic Equipment Center).
- the resulting cured film was placed in a Valia-Chien diffusion cell in which the methyl salicylate solution was present and the receiving tank was physiological saline.
- the release rate of methyl salicylate was analyzed by high performance liquid chromatography.
- N-dodecyl acrylate 200mg
- 1,6-hexanediol dimethacrylate by mass 800nig
- benzophenone peroxide 15mg
- dissolved, filtered, mixed solution 30ul placed in stainless steel
- a circular carrier substrate ⁇ 30 capsule
- coated and flattened placed in a UV curing instrument (3kw power, Beijing Esbow Machinery) In the electronic equipment center
- N-dodecyl acrylate 500 mg
- ethyl 2-carboxycarboxylate 500 mg
- 1-hydroxycyclohexyl phenyl ketone 80 mg
- 30 ul of a mixed solution placed on a circular carrier substrate of stainless steel ( ⁇ 30 ⁇ )
- the coating is flattened and placed in a UV curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
- N-dodecyl acrylate 600 mg
- ethyl 2-butoxyacrylate 400 mg
- benzophenone peroxide 50 mg
- 30 ul of a mixed solution placed on a stainless steel circular carrier substrate (() 30mm)
- coated and flattened placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- N-dodecyl acrylate 800 mg
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 200 mg
- benzoin propyl ether 1 mg
- 30 ul of a mixed solution Placed on a stainless steel circular carrier substrate (()) 30 ⁇ , coated and flattened, and placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the phosphate buffer of pH 7.4 is received in the cell.
- the solution is placed in a modified Franz diffusion cell.
- the solution is a lmg/ml naproxen methyl salicylate solution.
- the release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography.
- the fresh Kunming mice's abdominal skin was placed in a modified Franz diffusion cell.
- the supply pool was a lmg/ml naproxen methyl salicylate solution, and the receiving cell was pH 7. Phosphate buffer. .
- the release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography.
- Example 8 4-tetrahydroxybutyl acrylate (200 m g), 2-hydroxy-3-phenoxy propyl acrylate (SOOmg), benzophenone peroxide (80 mg), dissolved, 30 ul of mixed solution, not tempted
- the steel is placed on a circular carrier substrate ((j>30mm), coated and flattened, and placed in a UV curing unit (3kw power, Beijing Esper Machinery Electronic Equipment Center) for complete curing.
- the phosphate buffer solution of the pH 7.4 is received in the pool.
- the obtained solution is placed in a modified Franz diffusion cell in a supply tank of 1 mg/ml of a naproxen methyl salicylate solution.
- the phosphate buffer solution of the pH 7.4 is received in the pool.
- the obtained solution is placed in a modified Franz diffusion cell in a supply tank of 1 mg/ml of a naproxen methyl salicylate solution.
- the phosphate buffer of pH 7.4 is received in the cell.
- the solution is placed in a modified Franz diffusion cell in a 3 m g / ral aqueous solution of clonidine hydrochloride.
- the release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
- Ethylene glycol dimethacrylate 100 mg
- benzophenone peroxide 1 mg
- 50 ul of a mixed solution placed on a stainless steel circular carrier substrate ((j) 30 inra)
- coated and laid placed
- the curing is complete in the UV curing instrument (3kw power, Beijing Esbo Mechanical and Electronic Equipment Center).
- the resulting cured film was placed in a Valia-Chien diffusion cell in which the methyl salicylate solution was present and the receiving tank was physiological saline.
- the release rate of methyl salicylate was analyzed by high performance liquid chromatography.
- the resulting cured film was placed in a Valia-Chien diffusion cell in a 90% (v/v) solution of methyl salicylate in an isopropanol solution, and the receiving tank was physiological saline.
- the release rate of methyl salicylate was analyzed by high performance liquid chromatography.
- 1,6-hexanediol dimethacrylate 100 mg
- benzophenone peroxide 150 mg
- 30 ⁇ l of a mixed solution placed on a stainless steel circular carrier substrate ( ⁇ ) 30 mm), coated Flat, placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) solidified completely.
- the obtained cured film was placed in a Valia-Chien diffusion cell, and the supply tank was a 10 m g /ml solution of salicylic acid in isopropanol, and the receiving tank was physiological saline.
- the release rate of methyl salicylate was analyzed by high performance liquid chromatography.
- Ethylene glycol dimethacrylate (900mg), 2-hydroxy-3-phenoxy propyl acrylate (100mg), benzophenone peroxide (50rag), 30ul of mixed solution, placed in stainless steel circular carrier On the substrate ( ⁇ 30 ⁇ , ⁇ ), the coating was flattened and placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- 1,6-hexanediol dimethacrylate 800 mg
- 2-carboxyethyl acrylate 200 mg
- 1 monohydroxycyclohexyl phenyl ketone 50 mg
- a mixed solution of 30 ul placed in a stainless steel circular carrier
- the coating is flattened, and it is completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
- 1,6-hexanediol dimethacrylate 600 mg
- ethyl 2-butoxyacrylate 400 mg
- benzophenone peroxide 50 mg
- 30 ul of a mixed solution placed in a circular carrier of stainless steel
- the coating is flattened, and it is completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
- 1,6-hexanediol dimethacrylate 700 mg
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 300 mg
- benzoin propyl ether 50 mg
- Placed on a stainless steel circular carrier substrate ⁇ 30 ⁇
- coated and flattened and placed in a UV curing apparatus (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the phosphate buffer of pH 7.4 is received in the pool.
- the solution is placed in a modified Franz diffusion cell.
- 2-carboxyethyl acrylate 200mg
- 4-hydroxybutyrate SOOnig
- benzophenone peroxide 50mg
- dissolved, filtered, 30ul of mixed solution placed on a stainless steel circular carrier substrate ( ⁇ 30 let), coated and flattened, placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- Ethyl 2-carboxycarboxylate 700 mg
- ethyl 2-butoxyacrylate 300 mg
- 1-hydroxycyclohexyl phenyl ketone 1 mg
- 30 ul of a mixed solution placed on a circular carrier substrate of stainless steel ((
- 2-carboxyethyl acrylate 100 mg
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 900 mg
- benzoin propyl ether 150 mg
- the mixed solution was 30 ul, placed on a stainless steel circular carrier substrate ((j) 30 mm), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
- 2-butoxyethyl acrylate 200m g
- n-dodecyl acrylate 800mg
- benzophenone peroxide 50mg
- dissolved, filtered, mixed solution 30ul placed on a stainless steel circular carrier substrate On ( ⁇ 30 let), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) solidified completely.
- the phosphate buffer solution of the pH 7.4 is received in the pool.
- the solution is placed in a modified Franz diffusion cell.
- 2-butoxyethyl acrylate 200m g
- 4-tetrahydroxybutyl acrylate 800mg
- benzophenone peroxide 50mg
- dissolved, filtered, mixed solution 30ul placed in stainless steel circular carrier
- the coating is flattened and placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the obtained cured film was placed in a modified Franz diffusion cell, and the supply cell was 1 mg/ml of clonidine hydrochloride.
- the phosphate buffer solution was pH 7.4 in the receiving solution.
- the release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
- 2-butoxyethyl acrylate 200 mg
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 800 mg
- benzophenone peroxide 50 mg
- dissolved, filtered Placed on a stainless steel circular carrier substrate ( ⁇ 30 ⁇ ), coated and flattened, and placed in a UV curing apparatus (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the phosphate buffer solution of the pH 7.4 is received in the pool.
- the solution is placed in a modified Franz diffusion cell.
- 2-butoxyethyl acrylate 700 mg
- 2-carboxyethyl acrylate 300 ni g
- 1-hydroxycyclohexyl phenyl ketone 1 mg
- 30 ul of a mixed solution placed on a circular carrier substrate of stainless steel ( ⁇ 30 ⁇ ), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- N- ( 1 , 1 - dimethyl 3- oxobutyl ) monoacrylamide 500 rag ) , 1 ml of absolute ethanol , benzophenone peroxide ( 25 mg ) , 30 ul of mixed solution, placed in a round stainless steel On the base of the carrier ( ⁇ 30 ⁇ ), it is coated and flattened, and it is completely cured in an ultraviolet curing instrument (3k W power, Beijing Esper Mechanical and Electronic Equipment Center).
- the resulting cured film was placed in a modified Franz diffusion cell, which was 1 mg/ml of naproxen water in the supply cell.
- the phosphate buffer solution was pH 7. 4 in the receiving tank.
- the solution was 30 ul, placed on a stainless steel circular carrier substrate ( ⁇ 30 let), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
- the phosphate buffer solution of pH 7.4 is received in the cell.
- the solution is placed in a modified Franz diffusion cell.
- the solution is a lmg/ml naproxen methyl salicylate solution in the supply cell.
- the release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography.
- the phosphate skin buffer of the pH is 7.4, and the pool is a solution of the methyl sulphate solution of the naproxen in the supply tank. liquid.
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 200 mg
- 4-tetrahydroxybutyl acrylate 800 mg
- benzophenone peroxide 50 mg
- mixed solution 30 ul Placed on a stainless steel circular carrier substrate ( ⁇ 30 let), coated and flattened, and placed in a UV curing device (3 power, Beijing Esbo Machinery and Electronics Center) to cure completely.
- the phosphate buffer of pH 7.4 is received in the cell.
- the solution is placed in a modified Franz diffusion cell.
- the solution is a lmg/ml naproxen methyl salicylate solution.
- N-( 1,1 - dimethyl 3-oxobutyl) monoacrylamide 500 mg
- 1,6-hexanediol dimethacrylate 50 mg
- benzophenone peroxide 150 mg
- take 30ul of mixed solution put it in no
- the rusted steel is placed on a circular carrier substrate ( ⁇ 30 ⁇ ), coated and flattened, and placed in a UV curing apparatus (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) for complete curing.
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide (700 mg), n-decyl acrylate (300 mg), 1-hydroxycyclohexyl phenyl ketone (80 mg), dissolved, filtered 30 ul of the mixed solution was placed on a circular carrier substrate of stainless steel ( ⁇ 30 brain), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide (600 mg), ethyl 2-carboxycarboxylate OOmg), benzophenone peroxide (50 mg), 30 ul of mixed solution, put On a stainless steel circular carrier substrate ( ⁇ 30 surface), the coating was flattened and placed in a UV curing apparatus (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
- N-(1,1-dimethyl-3-oxobutyl)-acrylamide 800 mg
- ethyl 2-butoxyacrylate 200 mg
- benzoin propyl ether 1 mg
- mixed solution 30 ul placed on a stainless steel circular carrier substrate ( ⁇ 30 awake), coated and flattened, and placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
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Abstract
The invention relates to a light curable monomer composition including (A) from 0 to 99.9 weight percent of one or two or more than two acrylate monomers represented by the formula CR2R1=CR3COOR4 based on total weight of the composition, wherein said R1, R2 and R3 is independently each other selected from -H, -CH3, -C6H5, -CH=CH2, -COOH, -OCH3, -NH2 or -N(CH3)Cl; said R4 is selected from hydrocarbyl, hydroxy, ester group, carboxyl or alkoxy, said groups contain from 1 to 20 carbon atoms; (B) from 0 to 99.9 weight percent of one or two or more than two acrylamide monomers represented by the formula CR2R1=CR3CONR4 based on total weight of the composition, wherein R1 to R4 are defined as before; and (C) from 0.1 to 15 weight percent photoinitiator based on total weight of the composition. The invention also relates to the use of said light curable monomer composition in preparing controlled release membrane for transdermal administration system.
Description
可光固化的单体组合物及其用途 Photocurable monomer composition and use thereof
技术领域 Technical field
本发明涉及一类可光固化单体组合物， 特别是涉及一类包含酯基部分带烷径 基、 羟基、 酯基、 羧基或烷氧基的丙烯酸酯和丙烯酰胺的可光固化单体组合物； 本发明也涉及所述可光固化单体组合物在制备经皮给药系统中控释膜的用途。 The present invention relates to a class of photocurable monomer compositions, and more particularly to a combination of photocurable monomers comprising acrylates and acrylamides having an alkyl group moiety, a hydroxyl group, an ester group, a carboxyl group or an alkoxy group. The invention also relates to the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal delivery system.
背景技术 Background technique
经皮给药系统是指药物从特殊设计的装置释放， 通过完整的皮肤吸收， 进入全 身血液系统的控释给药剂型。 经皮给药系统基本上可以分成两大类， 即膜控释型 与骨架扩散型。 膜控释型经皮给药系统是药物或经皮吸收促进剂被控释膜或其他 控释材料包裹成贮库， 由控释膜或控释材料的性质控制药物的释放速率。 目前市 售的贴剂中东莨菪碱 （商品名 Transderm-Scop) 、 可乐定 （商品名 Catapres TTS ) 是膜控型， 控制膜是微孔聚丙烯膜； 硝酸甘油 （商品名 Transderm-Nitro) 、 芬太 尼（商品名 Dm'ogesic) 、 雌二醇（商品名 Estraderm) 、 睾酮（商品名 Androderm ) 是膜控型， 控释膜是聚乙烯一醋酸乙烯； 尼古丁 （商品名 NicoDerm CQ) 是膜控 型， 控制膜是聚乙烯膜。 A transdermal delivery system refers to a controlled release formulation in which the drug is released from a specially designed device and absorbed through the intact skin into the entire blood system. Transdermal drug delivery systems can be broadly divided into two broad categories, membrane controlled release and backbone diffusion. The membrane controlled release transdermal drug delivery system is a drug or percutaneous absorption enhancer controlled release film or other controlled release material wrapped into a depot, and the release rate of the drug is controlled by the properties of the controlled release membrane or the controlled release material. Currently commercially available patches of Middle East (trade name Transderm-Scop), clonidine (trade name Catapres TTS) are membrane-controlled, control membranes are microporous polypropylene membranes; nitroglycerin (trade name Transderm-Nitro), fentai Nie (trade name Dm'ogesic), estradiol (trade name Estraderm), testosterone (trade name Androderm) is membrane-controlled, controlled release membrane is polyethylene-vinyl acetate; nicotine (trade name NicoDerm CQ) is membrane-controlled The control film is a polyethylene film.
在欧洲专利 No. 46069， 美国专利 No. 3,797,494中描述到利用微孔膜控制释药 速率。 膜的孔隙从 0.1至 0.85， 膜的曲率从 1至 10， 膜厚度从 10至 100微米， 举 例用的膜有聚丙烯， 聚四氟乙烯， 聚碳酸酯， 聚氯乙烯， 醋酸纤维素， 硝酸纤维 素， 聚丙烯腈等。 它们的缺点是可供选用的微孔膜的种类少， 满足不了更多的药 物制成经皮给药的剂型。 The use of microporous membranes to control the rate of drug release is described in U.S. Patent No. 3,797,494. The pores of the membrane are from 0.1 to 0.85, the curvature of the membrane is from 1 to 10, and the thickness of the membrane is from 10 to 100 μm. Examples of membranes are polypropylene, polytetrafluoroethylene, polycarbonate, polyvinyl chloride, cellulose acetate, nitric acid. Cellulose, polyacrylonitrile, etc. Their disadvantage is that there are few types of microporous membranes available, and no more pharmaceuticals can be prepared for transdermal administration.
在美国专利 No. 6,537,571B1中描述到的东莨菪碱贴剂，美国专利 No. 4,681,584 中描述到的硝酸甘油贴剂， 所用的控释膜都是乙烯一醋酸乙烯的共聚物。 缺点是 乙烯一醋酸乙烯共聚物中有机溶剂的残留问题， 以及需要不断调节醋酸乙烯的含 量以调节药物的通透性。 A nitroglycerin patch as described in U.S. Patent No. 6,537,571 B1, the nitroglycerin patch described in U.S. Patent No. 4,681,584, which is a copolymer of ethylene-vinyl acetate. Disadvantages are the residual problem of the organic solvent in the ethylene-vinyl acetate copolymer, and the need to constantly adjust the content of vinyl acetate to adjust the permeability of the drug.
在欧洲专利 No. 1103260A2,美国专利 No. 2004/0028726A1中描述到的可乐定 贴剂中， 利用丙烯酸- ( 2-乙基） 己酯， 甲基丙烯酸甲酯， 丙烯酸与醋酸乙烯酯， 发生自由基聚合反应， 得到的共聚物用作贴剂中的压敏胶层和贮库层， 同时能够 控制药物的释放。 缺点是自由基聚合反应受很多因素影响， 有反应时间、 反应温 度、 原料起始浓度、 溶剂等因素， 贴剂也存在有机溶剂的残留问题。 In the clonidine patch described in the European Patent No. 1103260A2, U.S. Patent No. 2004/0028726 A1, the use of acrylic acid - (2-ethyl) hexyl ester, methyl methacrylate, acrylic acid and vinyl acetate occurs freely. The base polymerization reaction, the obtained copolymer is used as a pressure-sensitive adhesive layer and a reservoir layer in the patch, and at the same time, the release of the drug can be controlled. The disadvantage is that the free radical polymerization reaction is affected by many factors, such as reaction time, reaction temperature, starting concentration of raw materials, solvent, etc., and the residual solvent of the organic solvent remains in the patch.
在经皮给药系统中用到的薄膜， 总的来说控释膜种类缺乏， 可选择性小， 这为
经皮给药制剂的开发带来很大阻碍。 In the film used in the transdermal drug delivery system, the type of controlled release membrane is generally lacking, and the selectivity is small, which is The development of transdermal formulations has been a major obstacle.
发明内容 Summary of the invention
本发明的一个目的在于针对现有技术的不足，提供一种具有优异固化性能， 能 生产出可用于经皮给药系统中的控释膜的聚合物的单体组合物。 SUMMARY OF THE INVENTION One object of the present invention is to provide a monomer composition having excellent curing properties and capable of producing a polymer which can be used in a controlled release film in a transdermal drug delivery system, in view of the deficiencies of the prior art.
本发明的另一个目的是提供所述可光固化单体组合物在制备经皮给药系统中 控释膜的用途。 Another object of the present invention is to provide the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal drug delivery system.
本发明的上述目的是通过下列构思实现的：一种可光固化的单体组合物，包括： The above object of the present invention is achieved by the following concept: a photocurable monomer composition comprising:
(A)占组合物总重量的 0%- 99.9%重量的一种或两种或两种以上的由通式 CR2Rl=GR3C )R4¾示的丙烯酸酯单体， 其中 所述的 、 R2和 R3各自独立地选自- H、 - CH3、 - C6H5、 - CH = C¾、 - 0H、 -C00H、(A) from 0% to 99.9% by weight of the total weight of the composition of one or two or more acrylate monomers represented by the formula CR2R1 = GR3 C) R43⁄4 , wherein said R 2 and R 3 is each independently selected from - H, - CH 3 , - C 6 H 5 , - CH = C3⁄4, - 0H, -C00H,
- 0CH3、 - S03H、 -蘭 2或- N(CH3)3C1; - 0CH 3 , - S0 3 H, - Lan 2 or - N(CH 3 ) 3 C1;
所述的 选自烷烃基、 羟基、 酯基、 羧基或烷氧基， 所述基团中的碳原子数 为 1— 20; The selected from the group consisting of an alkane group, a hydroxyl group, an ester group, a carboxyl group or an alkoxy group, wherein the number of carbon atoms in the group is from 1 to 20;
(B) 占组合物总重量的 0— 99.9%重量的一种或两种或两种以上的由通式 CR2Ri=CR3CQNR4代表的丙烯酰胺单体， 其中 Rl— R4的定义同上； 和 (B) from 0 to 99.9% by weight, based on the total weight of the composition, of one or two or more acrylamide monomers represented by the formula CR 2Ri = CR 3 CQNR 4 wherein R1 - R 4 are as defined above ; with
(0 占组合物总重量的 0.1- 15%重量的光引发剂。 (0) 0.1 to 15% by weight of the photoinitiator based on the total weight of the composition.
当所述组分（A)的含量为 0%重量 /重量时，所述组分（B)的含量为 0.1-99.9 %重量 /重量； 当所述组分 （B) 的含量为 0%重量 /重量时， 所述组分 （A) 的含 量为 0.1-99.9%重量 /重量。 When the content of the component (A) is 0% by weight/weight, the content of the component (B) is 0.1 to 99.9% by weight/weight; when the content of the component (B) is 0% by weight The component (A) is contained in an amount of from 0.1 to 99.9% by weight/weight.
在优选的技术方案中， 所述组分 （A) 的含量为 20— 80%重量 /重量； 所述组 分（B)的含量为 12— 78%重量 /重量； 所述组分（C)的含量为 2— 8%重量 /重量。 In a preferred embodiment, the component (A) is contained in an amount of 20 to 80% by weight; the component (B) is contained in an amount of 12 to 78% by weight; and the component (C) The content is from 2 to 8% by weight/weight.
在一个技术方案中， 是选自 - (CH2)3CH3、 -（CH2)UCH3或- C¾CH = CH2的垸烃基； 或是选 自 （CH2)2CH20H、 -（CH2)3CH20H 或 -（CH2)4C 0H 的羟基； 或是选 自In one embodiment, it is an anthracene hydrocarbon group selected from -(CH 2 ) 3 CH 3 , -(CH 2 ) U CH 3 or - C3⁄4CH = CH 2 ; or is selected from (CH 2 ) 2 CH 2 0H, - a hydroxyl group of (CH 2 ) 3 CH 2 0H or -(CH 2 ) 4 C 0H; or
- (CH2) 200CCH二 C 、 - (CH2) 400CCH=C¾ 或 - (CH2) 600CCH=CH2 的酯基； 或是选自 - (C )2C00H、 - (CH2) 4COOH 或-（C¾)6C00H 的羧基; 或是选自-（CH2)20(C )2C¾、- (CH 2 ) 2 00CCH di C, - (CH 2 ) 4 00CCH=C3⁄4 or - (CH 2 ) 6 00CCH=CH 2 ester group; or selected from - (C) 2 C00H, - (CH 2 ) 4COOH or -(C3⁄4) 6 C00H carboxyl group; or selected from -(CH 2 ) 2 0(C ) 2 C3⁄4,
- (CH2) 30 (CH2) 2CH3或- (CH2) 20 (CH2) 4CH3的垸氧基。 - (CH 2 ) 3 0 (CH 2 ) 2 CH 3 or a decyloxy group of -(CH 2 ) 2 0 (CH 2 ) 4 CH 3 .
组分（A) 中 为烷烃基的丙烯酸酯单体可例举的是， 但并非局限于， （甲基) 丙烯酸甲酯、 （甲基） 丙烯酸乙酯、 （甲基） 丙烯酸丙酯、 （甲基） 丙烯酸异丙 酯、 （甲基） 丙烯酸丁酯、 （甲基） 丙烯酸戊酯、 （甲基） 丙烯酸异丁酯、 （甲 基） 丙烯酸叔丁酯、 （甲基） 丙烯酸异戊酯、 （甲基） 丙烯酸己酯、 （甲基） 丙 烯酸庚酯、 （甲基） 丙烯酸辛酯、 （甲基） 丙烯酸异辛酯、 （甲基） 丙烯酸 2— 乙基己酯、 （甲基） 丙烯酸壬酯、 （甲基） 丙烯酸癸酯、 （甲基） 丙烯酸异癸酯、
(甲基） 丙烯酸十一烷酯、 （甲基） 丙烯酸十二垸酯、 （甲基） 丙烯酸月桂酯、 (甲基） 丙烯酸十八烷酯、 （甲基） 丙烯酸硬脂基酯、 （甲基） 丙烯酸四氢糠酯、 (甲基） 丙烯酸丁氧基乙酯、 （甲基） 丙烯酸乙氧基二甘醇酯、 （甲基） 丙烯酸 苄酯、 （甲基） .丙烯酸环己酯、 （甲基） 丙烯酸苯氧基乙酯、 甲氧基乙二醇 （甲 基）丙烯酸酯、 （甲基）丙烯酸乙氧基乙酯、 （甲基）丙烯酸二环戊二烯酯、 （甲 基） 丙烯酸二环戊烯酯、 （甲基） 丙烯酸二环戊烯氧基乙酯、 （甲基） 丙烯酸三 环癸酯、 （甲基） 丙烯酸异冰片酯、 （甲基） 丙烯酸冰片酯、 （甲基） 丙烯酸二 甲基氨基乙酯、 （甲基） 丙烯酸二乙基氨基乙酯、 （甲基） 丙烯酸 7—氨基一 3， 7—二甲基辛酯、 （甲基） 丙烯酰吗啉、 2— (甲基） 丙烯酰氧乙基邻苯二甲酸酯、 2 - (甲基） 丙烯酰氧乙基六氢邻苯二甲酸酯、 2— （甲基） 丙烯酰氧丙基邻苯二 甲酸酯、 2— （甲基） 丙烯酰氧丙基四氢邻苯二甲酸酯、 2— （甲基） 丙烯酰氧丙 基六氢邻苯二甲酸酯、 2— （甲基） 丙烯酰氧乙基琥珀酸酯、 丙烯酰吗啉； 其中， 丙烯酸正十二烷酯是最佳的单体示例。 The acrylate monomer which is an alkane group in the component (A) can be exemplified by, but not limited to, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, ( Methyl) isopropyl acrylate, butyl (meth)acrylate, amyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, isoamyl (meth)acrylate , (meth) hexyl acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, (methyl) Ethyl acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, (Methyl) undecyl acrylate, dodecyl (meth)acrylate, lauryl (meth)acrylate, octadecyl (meth)acrylate, stearyl (meth)acrylate, (A) Base) tetrahydrofurfuryl acrylate, butoxyethyl (meth)acrylate, ethoxydiglycol (meth)acrylate, benzyl (meth)acrylate, (methyl). cyclohexyl acrylate, (Methyl) phenoxyethyl acrylate, methoxyethylene glycol (meth) acrylate, ethoxyethyl (meth) acrylate, dicyclopentadienyl (meth) acrylate, (methyl) Dicyclopentyl acrylate, dicyclopentenyloxyethyl (meth)acrylate, tricyclodecyl (meth)acrylate, isobornyl (meth)acrylate, borneol (meth)acrylate, ( Methyl) dimethylaminoethyl acrylate, diethylaminoethyl (meth)acrylate, 7-amino-3,7-dimethyloctyl (meth)acrylate, (meth)acryloylmorpholine , 2-(meth)acryloyloxyethyl phthalate, 2 - (A Acryloxyethylhexahydrophthalate, 2-(meth)acryloyloxypropyl phthalate, 2-(meth)acryloyloxypropyltetrahydroortylene Formate, 2-(meth)acryloyloxypropyl hexahydrophthalate, 2-(meth)acryloyloxyethyl succinate, acryloylmorpholine; Alkyl esters are an example of the best monomers.
组分 （A) 中 R4为羟基的丙烯酸酯单体可例举的是， 但并非局限于， （甲基） 丙烯酸一 4一羟基丁酯、 2—羟基一 3—苯氧基 （甲基） 丙烯酸丙酯、 （甲基） 丙烯 酸一 2—羟基乙酯、 （甲基） 丙烯酸一 2—羟基丙酯、 （甲基） 丙烯酸一2—羟基丁 酯、 1， 4一丁二醇一（甲基）丙烯酸酯、 （甲基）丙烯酰磷酸一 2—羟基垸基酯（其 中烷基例如甲基、 乙基、 丙基） 、 （甲基） 丙烯酸一 4一羟基环己酯、 1， 6—己二 醇一 （甲基） 丙烯酸酯、 新戊四醇三 （甲基） 丙烯酸酯、 二季戊四醇五 （甲基） 丙烯酸酯； 其中， 丙烯酸一 4一羟基丁酯和 2—羟基一 3—苯氧基丙烯酸丙酯是最 佳的单体示例。 The acrylate monomer wherein R 4 is a hydroxyl group in the component (A) may be exemplified by, but not limited to, 4-methylhydroxybutyl (meth)acrylate, 2-hydroxy-3-phenoxy (methyl) ) propyl acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 1, 4-butanediol- Methyl) acrylate, (meth)acryloyl phosphate mono-2-hydroxydecyl ester (in which alkyl group such as methyl, ethyl, propyl), (meth)acrylic acid 4-tetrahydroxycyclohexyl ester, 1, 6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate; wherein, 4-tetrahydroxybutyl acrylate and 2-hydroxy-3 - Propyl phenoxy acrylate is an example of the best monomer.
组分 （A) 中 1?4为酯基的丙烯酸酯单体可例举的是， 但并非局限于， 乙二醇二 (甲基）丙烯酸酯、 1， 4一丁二醇二 （甲基） 丙烯酸酯、 1， 6—己二醇二（甲基）丙 烯酸酯、 丙二醇二 （甲基） 丙烯酸酯、 1， 9一壬二醇二 （甲基） 丙烯酸酯、 二甘 酯二 （甲基） 丙烯酸酯、 三甘酯二 （甲基） 丙烯酸酯、 四甘酯二 （甲基） 丙烯酸 酯、 二丙二醇二 （甲基） 丙烯酸酯、 三丙二醇二 （甲基） 丙烯酸酯、 新戊二醇二 (甲基） 丙烯酸酯、 羟基戊酸新戊二醇二 （甲基） 丙烯酸酯、 三羟甲甘油丙烷三 (甲基） 丙烯酸酯、 季戊四醇 （甲基） 丙烯酸酯、 季戊四醇四 （甲基） 丙烯酸酯、 二 （三羟甲基丙垸） 四 （甲基） 丙烯酸酯、 二季戊四醇六 （甲基） 丙烯酸酯、 三 羟甲基丙垸三氧乙基 （甲基） 丙烯酸酯、 二羟甲基丙烷三氧丙基 （甲基） 丙烯酸 酯、 三 （2—羟基乙基） 异氰脲酸酯三 （甲基） 丙烯酸酯、 三 （2—羟基乙基） 异 氰脲酸酯二 （甲基） 丙烯酸酯、 乙氧基化双酚 A二 （甲基） 丙烯酸酯、 乙氧基化
双酚 F二 （甲基） 丙烯酸酯、 丙氧基化双酚 A二 （甲基） 丙烯酸酯、 丙氧基化双 酚 F二 （甲基） 丙烯酸酯、 三环癸烷二甲醇二 （甲基） 丙烯酸酯、 双酚 A环氧基 二 （甲基） 丙烯酸酯、 双酚 F环氧基二 （甲基） 丙烯酸酯； 其中， 乙二醇二甲基 丙烯酸酯、 1， 4一丁二醇二丙烯酸酯和 1， 6—己二醇二甲基丙烯酸酯是最佳的单 体示例。 Component (A), 1? 4 is an ester group of acrylate monomers may be exemplified by, but not limited to, ethylene glycol di (meth) acrylate, 1, 4-butanediol di (meth Acrylate, 1,6-hexanediol di(meth)acrylate, propylene glycol di(meth)acrylate, 1,9-nonanediol di(meth)acrylate, diglyceride di(methyl) Acrylate, triglyceride di(meth) acrylate, tetraglycol di(meth) acrylate, dipropylene glycol di(meth) acrylate, tripropylene glycol di(meth) acrylate, neopentyl glycol Di(meth) acrylate, hydroxyvaleric acid neopentyl glycol di(meth) acrylate, trimethyl glycerol propane tri(meth) acrylate, pentaerythritol (meth) acrylate, pentaerythritol tetra (methyl) Acrylate, bis(trishydroxymethylpropionamidine) tetra(meth) acrylate, dipentaerythritol hexa(meth) acrylate, trishydroxymethylpropionate trioxyethyl (meth) acrylate, dihydroxyl Propane trioxypropyl (meth) acrylate, three (2 - Ethyl ethyl) isocyanurate tri(meth) acrylate, tris(2-hydroxyethyl) isocyanurate di(meth) acrylate, ethoxylated bisphenol A di(methyl) Acrylate, ethoxylated Bisphenol F di(meth) acrylate, propoxylated bisphenol A di(meth) acrylate, propoxylated bisphenol F di(meth) acrylate, tricyclodecane dimethanol di(a) Acrylate, bisphenol A epoxy di(meth) acrylate, bisphenol F epoxy di(meth) acrylate; wherein, ethylene glycol dimethacrylate, 1, 4 - butyl Alcohol diacrylate and 1,6-hexanediol dimethacrylate are examples of the best monomers.
组分 （A) 中！^为羧基的丙烯酸酯单体可例举的是， 但并非局限于， （甲基） 丙烯酸一 2—羧基乙酯、 （甲基）丙烯酸一 3—羧基丙酯、 （甲基） 丙烯酸一2—羧 基丙酯、 （甲基） 丙烯酸一 4一羧基正丁酯、 （甲基） 丙烯酸一 3—羧基正丁酯、 (甲基） 丙烯酸一 2—羧基正丁酯、 （甲基） 丙烯酸一 2—羧基异丁酯、 （甲基） 丙烯酸一 6—羧基正己酯、 （甲基） 丙烯酸一 5—羧基正己酯、 （甲基） 丙烯酸一4 一羧基正己酯、 （甲基） 丙烯酸一 3—羧基正己酯、 （甲基） 丙烯酸一2—羧基正 己酯； 其中， 2—羧基丙烯酸乙酯是最佳的单体示例。 In component (A)! The acrylate monomer which is a carboxyl group may, for example, be, but not limited to, 2-methylcarboxyl (meth)acrylate, 3-carboxypropyl (meth)acrylate, or (meth)acrylic acid-2 —Carboxypropyl ester, 4-methylcarboxy n-butyl (meth)acrylate, 3-carboxy-n-butyl (meth)acrylate, 2-carboxy-n-butyl (meth)acrylate, (meth)acrylic acid 2-carboxyisobutyl ester, (meth)acrylic acid-6-carboxy-n-hexyl ester, (meth)acrylic acid 5-carboxy-n-hexyl ester, (meth)acrylic acid 4-tetracarboxy-n-hexyl ester, (meth)acrylic acid-3 —Carboxy n-hexyl ester, (meth)acrylic acid 2-carboxy-n-hexyl ester; wherein 2-carboxyethyl acrylate is an example of an optimum monomer.
组分（A) 中 R4为烷氧基的丙烯酸酯单体可例举的是， 但并非局限于， （甲基） 丙烯酸一 2—甲氧基乙酯、 （甲基） 丙烯酸一 2—乙氧基乙酯、 （甲基）丙烯酸一2 一丙氧基乙酯、 （甲基） 丙烯酸一 2—丁氧基乙酯、 （甲基） 丙烯酸一 3—甲氧基 丙酯、 （甲基）丙烯酸一 3—乙氧基丙酯、 （甲基）丙烯酸一 3—丙氧基丙酯、 （甲 基） 丙烯酸一 3—丁氧基丙酯、 （甲基） 丙烯酸一 2—甲氧基丙酯、 （甲基） 丙烯 酸一 2—乙氧基丙酯、 （甲基） 丙烯酸一 2—丙氧基丙酯、 （甲基） 丙烯酸一 2—丁 氧基丙酯、 （甲基）丙烯酸一 2—苯氧基乙酯、 （甲基） 丙烯酸一 2—苯氧基丙酯、 (甲基） 丙烯酸一 3—苯氧基丙酯、 （甲基） 丙烯酸一 2—苯氧基丁酯、 （甲基） 丙烯酸一 3—苯氧基丁酯、 （甲基）丙烯酸一 4一苯氧基丁酯； 其中， 2—丁氧基丙 烯酸乙酯是最佳的单体示例。 The acrylate monomer wherein R 4 is an alkoxy group in the component (A) may be exemplified by, but not limited to, 2-methethoxyethyl (meth)acrylate and 2-methyl methacrylate. Ethoxyethyl ester, 2-propoxyethyl (meth)acrylate, 2-butoxyethyl (meth)acrylate, 3-methoxypropyl (meth)acrylate, (A) 3-(3-propyl) propyl acrylate, 3-propoxypropyl (meth) acrylate, 3-butoxypropyl (meth) acrylate, 2-methoxy methacrylate Propyl propyl ester, 2-ethoxypropyl (meth)acrylate, 2-propoxypropyl (meth)acrylate, 2-butoxypropyl (meth)acrylate, (methyl) 2-Phenoxyethyl acrylate, 2-phenoxypropyl (meth)acrylate, 3-phenoxypropyl (meth)acrylate, 2-phenoxy butyl (meth)acrylate Ester, 3-phenoxybutyl (meth)acrylate, 1,4-phenoxybutyl (meth)acrylate; wherein 2-ethyloxybutyrate is the best Single example.
本发明所述的丙烯酰胺单体可例举的是， 但并非局限于， N— （1， 1一二甲基 一 3—氧代丁基） 一丙烯酰胺、 （甲基） 丙烯酰胺、 N，N—二甲基 （甲基） 丙烯酰 胺、 N—异丙基（甲基）丙烯酰胺、 N— (丁氧基甲基） （甲基）丙烯酰胺、 N—（羟 甲基） （甲基） 丙烯酰胺、 N—[ (三羟甲基） 甲基] (甲基） 丙烯酰胺、 N— [3— (二甲基氨基） 丙基] (甲基） 丙烯酰胺； 其中， N— （1， 1一二甲基一 3—氧代丁 基） 一丙烯酰胺是最佳单体的示例。 The acrylamide monomer of the present invention may be exemplified by, but not limited to, N-(1,1-dimethyl-3-oxobutyl)-acrylamide, (meth)acrylamide, N ,N-Dimethyl(meth)acrylamide, N-isopropyl(meth)acrylamide, N-(butoxymethyl)(meth)acrylamide, N-(hydroxymethyl) (A Acrylamide, N-[(trimethylol)methyl](methyl)acrylamide, N-[3-(dimethylamino)propyl](meth)acrylamide; wherein, N- ( 1,1-Dimethyl-3-oxobutyl) Monoacrylamide is an example of the most preferred monomer.
本发明中使用的光引发剂 （C) 包括对于紫外光敏感， 能引发单体进行固化反 应的光引发剂， 例如， 但不限于， 过氧化二苯甲酮、 1一羟基环己基苯基酮、 苯偶 姻丙基醚。 The photoinitiator (C) used in the present invention includes a photoinitiator which is sensitive to ultraviolet light and which can initiate a curing reaction of a monomer, such as, but not limited to, benzophenone peroxide, 1-hydroxycyclohexyl phenyl ketone. , benzoin propyl ether.
在另一个实施方案中， 本发明的组合物还可进一步包含增塑剂， 例如， 但不限
于， 柠檬酸盐、 邻苯二甲酸盐或癸二酸盐， 以进一步改善聚合物薄膜的物理性能。 本发明的可光固化的单体组合物通过下列方法制备得到： In another embodiment, the composition of the present invention may further comprise a plasticizer, such as, but not limited to Then, citrate, phthalate or sebacate to further improve the physical properties of the polymer film. The photocurable monomer composition of the present invention is prepared by the following method:
( a) 当所述的组分 （A) 是液体形式时， 将所述的组分 （B) 或 （C) 溶于 组分 （A) ， 得到所需的组合物溶液； (a) when the component (A) is in a liquid form, the component (B) or (C) is dissolved in the component (A) to obtain a desired composition solution;
( b) 当组分 （A) 是固体形式时， 将所述的组分 （A) 、 ( B) 和 （C ) 混 合后溶于有机溶剂 （优选的是乙醇） ， 得到所需的组合物溶液。 若本发明组合物中还含有增塑剂， 则所述的方法还包括步骤 （c ) ； 向所得的 组合物溶液中加入增塑剂。 (b) When component (A) is in a solid form, the components (A), (B) and (C) are mixed and dissolved in an organic solvent (preferably ethanol) to obtain a desired composition. Solution. If the composition of the present invention further contains a plasticizer, the method further comprises the step (c); adding a plasticizer to the resulting composition solution.
本发明另一方面涉及所述的可光固化的单体组合物在制备经皮给药系统中控 释膜的用途； 具体来说， 从所述的组合物制备得到的聚合物薄膜可用作经皮给药 系统 （TDDs) 中的控释膜， 通过调节组合物中单体 （A) 和 （B) 的种类和含量， 可以微调薄膜物化性能， 快速制备适用于不同药物的经皮给药系统中的控释膜。 Another aspect of the invention relates to the use of the photocurable monomer composition for the preparation of a controlled release film in a transdermal delivery system; in particular, a polymeric film prepared from the composition can be used as Controlled-release membranes in transdermal drug delivery systems (TDDs), by adjusting the type and amount of monomers (A) and (B) in the composition, can fine-tune the physicochemical properties of the film, and rapidly prepare transdermal drug for different drugs. Controlled release membrane in the system.
本发明人对从本发明可光固化的组合物制备的部分聚合物薄膜进行了药物的 通透性实验， 并与动物离体皮肤的药物通透性实验进行了比较， 从比较的结果发 现有部分的聚合物薄膜的药物通透性实验结果是高于动物皮肤的， 也有另一部分 的聚合物薄膜的药物通透性实验结果是低于动物皮肤的， 由此结果可以看出本发 明中制备的聚合物薄膜可以自由的控制药物的通透性能， 这对于经皮给药系统中 药物的控制释放是很有意义的。 The present inventors conducted a drug permeability test on a part of the polymer film prepared from the photocurable composition of the present invention, and compared it with the drug permeability test of the animal skin, from the comparison results, The results of the drug permeability test of some polymer films are higher than those of animal skin, and the drug permeability test results of another part of the polymer film are lower than that of animal skin, and the results can be seen in the preparation of the present invention. The polymer film is free to control the permeability of the drug, which is significant for controlled release of the drug in the transdermal drug delivery system.
进一步的是， 本发明还拓宽了制备经皮给药系统中的控释膜的材料种类，扩大 了材料选择范围。 Further, the present invention also broadens the types of materials for the preparation of controlled release membranes in transdermal drug delivery systems, and expands the range of material selection.
附图说明 DRAWINGS
图 1是实施例 1得到的组合物经紫外光固化后得到的固化膜的通透性实验与动 物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T ( h) ， 纵轴代 表药物累计通透量 Qt ( g/cni2) 。 1 is a graph comparing the permeability test of a cured film obtained by curing the composition obtained in Example 1 with an in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative drug flux Qt (g/cni 2 ).
图 2是实施例 2得到的组合物经紫外光固化后得到的固化膜的通透性实验与动 物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T ( h) ， 纵轴代 表药物累计通透量 Qt ( g/cm2) 。 2 is a graph comparing the permeability test of the cured film obtained by the curing of the composition obtained in Example 2 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
图 3、 4是实施例 7得到的组合物经紫外光固化后得到的固化膜分别针对水杨 酸甲酯和萘普生的通透性实验与动物皮肤的体外透皮实验进行比较的曲线图， 其 中， 横轴代表时间 T ( h) ， 纵轴代表药物累计通透量 Qt ( g/cm2) 。 3 and 4 are graphs comparing the permeability test of methyl salicylate and naproxen to the in vitro transdermal test of animal skin by the cured film obtained by ultraviolet light curing of the composition obtained in Example 7. Wherein, the horizontal axis represents time T (h), and the vertical axis represents cumulative drug penetration Qt (g/cm 2 ).
图 5、 6是实施例 8得到的组合物经紫外光固化后得到的固化膜分别针对水杨 酸甲酯和萘普生的通透性实验的曲线图， 其中， 横轴代表时间 T ( h) ， 纵轴代表
药物累计通透量 Qt (μ8/οηι2) 。 5 and 6 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 8 against methyl salicylate and naproxen, wherein the horizontal axis represents time T (h). ), the vertical axis represents The cumulative amount of drug permeation Qt (μ 8 /οηι 2 ).
图 7、 8是实施例 9得到的组合物经紫外光固化后得到的固化膜分别针对水杨 酸甲酯和萘普生的通透性实验的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代表 药物累计通透量 Qt (μ§/οιιι2) 。 7 and 8 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 9 against methyl salicylate and naproxen, wherein the horizontal axis represents time T (h). ), the vertical axis represents the cumulative drug penetration Qt (μ § / οιιι 2 ).
图 9是实施例 10得到的组合物经紫外光固化后得到的固化膜的通透性实验与 动物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴 代表药物累计通透量 Qt ( g/cm2) 。 Figure 9 is a graph comparing the permeability test of the cured film obtained by the curing of the composition obtained in Example 10 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
图 10是实施例 16得到的组合物经紫外光固化后得到的固化膜的通透性实验与 动物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴 代表药物累计通透量 Qt ( g/cm2) 。 Figure 10 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 16 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
图 11是实施例 17得到的组合物经紫外光固化后得到的固化膜的通透性实验与 动物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴 代表药物累计通透量 Qt ( g/cm2) 。 Figure 11 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 17 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt (g/cm 2 ).
图 12是实施例 18得到的组合物经紫外光固化后得到的固化膜的通透性实验与 动物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴 代表药物累计通透量 Qt H/cm2 。 Figure 12 is a graph comparing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 18 with the in vitro transdermal test of animal skin, wherein the horizontal axis represents time T (h), longitudinal The axis represents the cumulative amount of drug permeation Qt H/cm 2 .
图 13是实施例 24得到的组合物经紫外光固化后得到的固化膜的通透性实验的 曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代表药物累计通透量 Qt (μ§/οηι2) 。 Figure 13 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 24, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt (μ § /οηι 2 ).
图 14是实施例 29得到的组合物经紫外光固化后得到的固化膜的通透性实验的 曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代表药物累计通透量 Qt (μ§/οπι2) 。 Figure 14 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 29, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt (μ § /οπι 2 ).
图 15是实施例 30得到的组合物经紫外光固化后得到的固化膜的通透性实验的 曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代表药物累计通透量 Qt (μ§/οη!2) 。 Figure 15 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 30, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt (μ § /οη! 2 ).
图 16是实施例 31得到的组合物经紫外光固化后得到的固化膜的通透性实验的 曲线图， 其中， 横轴代表时间 T (h) , 纵轴代表药物累计通透量 Qt ( g/cm2) 。 Figure 16 is a graph showing the permeability test of the cured film obtained by curing the composition obtained in Example 31, wherein the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt (g). /cm 2 ).
图 17、 18是实施例 34得到的组合物经紫外光固化后得到的固化膜分别针对水 杨酸甲酯和萘普生的通透性实验的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代 表药物累计通透量 Qt (μ§/οπι2) 。 17 and 18 are graphs showing the permeability test of the cured film obtained by the ultraviolet light curing of the composition obtained in Example 34 against methyl salicylate and naproxen, respectively, wherein the horizontal axis represents time T (h). ), the vertical axis represents the cumulative drug throughput Qt (μ § /οπι 2 ).
图 19、20是实施例 35得到的组合物经紫外光固化后得到的固化膜分别针对水 杨酸甲酯和萘普生的通透性实验与动物皮肤的体外透皮实验进行比较的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代表药物累计通透量 Qt ( g/cffl2) 。 19 and 20 are graphs comparing the permeability test of methyl salicylate and naproxen to the in vitro transdermal test of animal skin by the cured film obtained by ultraviolet light curing of the composition obtained in Example 35, respectively. , where the horizontal axis represents time T (h) and the vertical axis represents cumulative drug throughput Qt ( g/cffl 2 ).
图 21、22是实施例 36得到的组合物经紫外光固化后得到的固化膜分别针对水 杨酸甲酯和萘普生的通透性实验的曲线图， 其中， 横轴代表时间 T (h) ， 纵轴代
表药物累计通透量 Qt ( g/cni2) 。 21 and 22 are graphs showing the permeability test of the cured film obtained by ultraviolet light curing of the composition obtained in Example 36 against methyl salicylate and naproxen, respectively, wherein the horizontal axis represents time T (h). ), vertical axis generation Table drug cumulative permeability Qt (g/cni 2 ).
具体实施方式 detailed description
现通过下列实施例对本发明作进一步示例性的阐述， 应当明白， 这些实施例仅 供阐述用， 并非用来构成对本发明的限制。 The invention is further illustrated by the following examples, which are not to be construed as limiting.
实施例 1 Example 1
丙烯酸正十二垸酯 （200mg) ， 丙烯酸一 4一羟基丁酯 （800mg) ， 再加入过氧 化二苯甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基 底上 （φ30πιηι) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子 设备中心） 中固化完全。 N-decyl acrylate (200mg), 4-tetrahydroxybutyl acrylate (800mg), then benzophenone peroxide (50mg), dissolved, filtered, 30ul mixed solution, placed on a stainless steel circular carrier substrate Upper (φ30πιηι), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
得到的固化膜置于 Valia- Chien扩散池， 供给池中是 lmg/ml的盐酸可乐定水 溶液， 接受池中是生理盐水。 利用高效液相色谱分析盐酸可乐定的释放速率。 The obtained cured film was placed in a Valia-Chien diffusion cell, which was a lmg/ml solution of clonidine hydrochloride in the supply tank, and the receiving tank was physiological saline. The release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于 Valia- Chien扩散池， 供 给池中是 lmg/ml的盐酸可乐定水溶液， 接受池中是生理盐水。利用髙效液相色谱 分析盐酸可乐定的释放速率。 见图 1 : 曲线 1是盐酸可乐定对固化膜的体外透皮 实验 （数据点： ； 相关系数 r=0. 9938) ， 曲线 2是盐酸可乐定对动物皮肤的通透 性实验， 从图中可看出固化膜对药物有线性控释作用。 For animal skin comparison, the fresh Kunming mice's abdominal skin was placed in a Valia-Chien diffusion cell. The supply pool was a lmg/ml aqueous solution of clonidine hydrochloride, and the receiving pool was physiological saline. The release rate of clonidine hydrochloride was analyzed by HPLC. See Figure 1: Curve 1 is an in vitro transdermal test of clonidine hydrochloride on the cured film (data point: ; correlation coefficient r = 0.9938), curve 2 is the permeability test of clonidine hydrochloride on animal skin, from the figure It can be seen that the cured film has a linear controlled release effect on the drug.
实施例 2 Example 2
丙烯酸正十二烷酯 （200mg) ， 2—羟基一 3—苯氧基丙烯酸丙酯 （SOOrag) ， 过 氧化二苯甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体 基底上 （φ30ιηπι) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电 子设备中心） 中固化完全。 N-dodecyl acrylate (200mg), 2-hydroxy-3-phenoxy propyl acrylate (SOOrag), benzophenone peroxide (50mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel round On the substrate of the carrier (φ30ιηπι), it is coated and flattened, and it is completely cured in an ultraviolet curing instrument (3kw power, Beijing Esper Machinery Electronic Equipment Center).
得到的固化膜置于 Valia- Chien扩散池， 供给池中是水杨酸甲酯溶液， 接受池 中是生理盐水。 利用高效液相色谱分析水杨酸甲酯的释放速率。 The resulting cured film was placed in a Valia-Chien diffusion cell in which the methyl salicylate solution was present and the receiving tank was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于 Valia- Chien扩散池， 供 给池中是水杨酸甲酯溶液， 接受池中是生理盐水。 利用高效液相色谱分析水杨酸 甲酯的释放速率。 见图 2: 曲线 1 是水杨酸甲酯对固化膜的体外透皮实验 （相关 系数 r=0. 9873 ) ， 曲线 2是水杨酸甲酯对动物皮肤的通透性实验， 从图中可看出 固化膜对药物有线性控释作用。 For comparison of animal skin, the fresh Kunming mice's abdominal skin was placed in a Valia-Chien diffusion cell. The supply pool was a methyl salicylate solution, and the receiving pool was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 2: Curve 1 is the in vitro transdermal test of methyl salicylate on the cured film (correlation coefficient r = 0.9873), curve 2 is the permeability test of methyl salicylate on animal skin, from the figure It can be seen that the cured film has a linear controlled release effect on the drug.
实施例 3 Example 3
丙烯酸正十二烷酯（200mg )， 1， 6—己二醇二甲基丙烯酸酯按质量（800nig)， 过氧化二苯甲酮 （15mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载 体基底上 （Φ30囊） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械
电子设备中心） 中固化完全。 N-dodecyl acrylate (200mg), 1,6-hexanediol dimethacrylate by mass (800nig), benzophenone peroxide (15mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel On a circular carrier substrate (Φ30 capsule), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbow Machinery) In the electronic equipment center) the curing is complete.
实施例 4 Example 4
丙烯酸正十二烷酯 （500mg) ， 2—羧基丙烯酸乙酯 （500mg) ， 1一羟基环己基 苯基酮 （80mg) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 （φ30ππη) ， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 N-dodecyl acrylate (500 mg), ethyl 2-carboxycarboxylate (500 mg), 1-hydroxycyclohexyl phenyl ketone (80 mg), 30 ul of a mixed solution, placed on a circular carrier substrate of stainless steel (φ30ππη), The coating is flattened and placed in a UV curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
实施例 5 Example 5
丙烯酸正十二烷酯 （600mg) , 2—丁氧基丙烯酸乙酯 （400mg) ， 过氧化二苯 甲酮 （50mg) , 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 （(()30mm) ， 涂 布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固化 完全。 N-dodecyl acrylate (600 mg), ethyl 2-butoxyacrylate (400 mg), benzophenone peroxide (50 mg), 30 ul of a mixed solution, placed on a stainless steel circular carrier substrate (() 30mm), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 6 Example 6
丙烯酸正十二烷酯 （800mg) , N- ( 1， 1一二甲基一 3—氧代丁基） 一丙烯酰 胺 （200mg) ， 苯偶姻丙基醚 （lmg) ， 取混合溶液 30ul， 放在不锈钢的圆形载体 基底上 （())30ηιπ ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电 子设备中心） 中固化完全。 N-dodecyl acrylate (800 mg), N-(1,1-dimethyl-3-oxobutyl)-acrylamide (200 mg), benzoin propyl ether (1 mg), 30 ul of a mixed solution, Placed on a stainless steel circular carrier substrate (()) 30ηιπ, coated and flattened, and placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 7 Example 7
丙烯酸一 4一羟基丁酯 （800mg) ， 2—羟基一 3—苯氧基丙烯酸丙酯 （200mg) , 过氧化二苯甲酮 （lmg) , 溶解， 取混合溶液 30ul， 放在不锈钢的圆形载体基底 上 （<|)30腿） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设 备中心） 中固化完全。 4-Hydroxybutyl acrylate (800 mg), 2-hydroxy-3-phenoxy propyl acrylate (200 mg ), benzophenone peroxide (1 mg ), dissolved, 30 ul of mixed solution, placed in a round stainless steel On the base of the carrier (<|) 30 legs, it was coated and flattened, and it was completely cured in an ultraviolet curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center).
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是 lmg/ml的萘普生的水 杨酸甲酯溶液， 接受池中是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 The phosphate buffer of pH 7.4 is received in the cell. The solution is placed in a modified Franz diffusion cell. The solution is a lmg/ml naproxen methyl salicylate solution. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于改良的 Franz扩散池， 供 给池中是 lmg/ml的萘普生的水杨酸甲酯溶液， 接受池是 pH7. 的磷酸盐缓冲液。 利用高效液相色谱分析水杨酸甲酯和萘普生的释放速率。 见图 3: 曲线 1是水杨 酸甲酯对动物皮肤的体外透皮实验， 曲线 2是水杨酸甲酯对固化膜的通透性实验 (相关系数 r=0. 9977 ) ； 图 4: 曲线 1是萘普生对动物皮肤的体外透皮实验， 曲 线 2是萘普生对固化膜的通透性实验 （相关系数 r=0. 9977 ) ， 从图中可看出固化 膜对药物有线性控释作用。 For comparison of animal skin, the fresh Kunming mice's abdominal skin was placed in a modified Franz diffusion cell. The supply pool was a lmg/ml naproxen methyl salicylate solution, and the receiving cell was pH 7. Phosphate buffer. . The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 3: Curve 1 is an in vitro transdermal experiment of methyl salicylate on animal skin, and curve 2 is a permeability test of methyl salicylate on the cured film (correlation coefficient r = 0.9977); Figure 4: Curve 1 is an in vitro transdermal test of naproxen on animal skin, and curve 2 is a permeability test of naproxen on the cured film (correlation coefficient r=0. 9977). It can be seen from the figure that the cured film has a drug for the drug. Linear controlled release.
实施例 8
丙烯酸一 4一羟基丁酯 （200mg)， 2—羟基一 3—苯氧基丙烯酸丙酯 （SOOmg) ， 过氧化二苯甲酮 （80mg) ， 溶解， 取混合溶液 30ul， 放在不诱钢的圆形载体基底 上 （(j>30mm) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设 备中心） 中固化完全。 Example 8 4-tetrahydroxybutyl acrylate (200 m g), 2-hydroxy-3-phenoxy propyl acrylate (SOOmg), benzophenone peroxide (80 mg), dissolved, 30 ul of mixed solution, not tempted The steel is placed on a circular carrier substrate ((j>30mm), coated and flattened, and placed in a UV curing unit (3kw power, Beijing Esper Machinery Electronic Equipment Center) for complete curing.
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是 lmg/ml的萘普生的水 杨酸甲酯溶液， 接受池中是 PH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 见图 5: 水杨酸甲酯对固化膜的通透性实验 （相关 系数 r=0. 9974) ； 图 6 : 萘普生对固化膜的通透性实验 （相关系数 r=0. 9677 ) ， 从图中可看出固化膜对药物有线性控释作用。 The phosphate buffer solution of the pH 7.4 is received in the pool. The obtained solution is placed in a modified Franz diffusion cell in a supply tank of 1 mg/ml of a naproxen methyl salicylate solution. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 5: Permeability test of methyl salicylate on cured film (correlation coefficient r=0. 9974); Figure 6: Permeability test of naproxen on cured film (correlation coefficient r=0. 9677) It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 9 Example 9
丙烯酸一 4一羟基丁酯 （200mg ) , 2—羟基一 3—苯氧基丙烯酸丙酯 （800mg) ， 过氧化二苯甲酮 a50ing) ， 溶解， 取混合溶液 20ul， 放在不锈钢的圆形载体基 底上 （φ30ιηπι) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子 设备中心） 中固化完全。 4-tert-hydroxybutyl acrylate (200mg), 2-hydroxy-3-phenoxy propyl acrylate (800mg), benzophenone benzoate a50ing), dissolved, take 20ul of mixed solution, placed in stainless steel circular carrier On the substrate (φ30ιηπι), the coating was flattened, and it was completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是 lmg/ml的萘普生的水 杨酸甲酯溶液， 接受池中是 PH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 见图 7: 水杨酸甲酯对固化膜的通透性实验 （相关 系数 r=0. 9989 ) ； 图 8: 萘普生对固化膜的通透性实验 （相关系数 r=0. 9677 ) ， 从图中可看出固化膜对药物有线性控释作用。 The phosphate buffer solution of the pH 7.4 is received in the pool. The obtained solution is placed in a modified Franz diffusion cell in a supply tank of 1 mg/ml of a naproxen methyl salicylate solution. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 7: Permeability test of methyl salicylate on cured film (correlation coefficient r=0. 9989); Figure 8: Permeability test of naproxen on cured film (correlation coefficient r=0. 9677) It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 10 Example 10
丙烯酸一 4一羟基丁酯 （500mg)， 2—羟基一 3—苯氧基丙烯酸丙酯 （500mg) ， 过氧化二苯甲酮 （50mg) ， 溶解， 取混合溶液 30ul， 放在不锈钢的圆形载体基底 上 （φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设 备中心） 中固化完全。 4-Hydroxybutyl acrylate (500mg), 2-hydroxy-3-phenoxy propyl acrylate (500mg), benzophenone peroxide (50mg), dissolved, take 30ul of mixed solution, placed in stainless steel round On the carrier substrate (φ30 let), the coating was flattened and placed in a UV curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是 3mg/ral的盐酸可乐定 水溶液， 接受池中是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析盐酸可乐定 的释放速率。 The phosphate buffer of pH 7.4 is received in the cell. The solution is placed in a modified Franz diffusion cell in a 3 m g / ral aqueous solution of clonidine hydrochloride. The release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于改良的 Franz扩散池， 供 给池中是 3mg/ml的盐酸可乐定水溶液， 接受池是 pH7. 4的磷酸盐缓冲液。利用高 效液相色谱分析盐酸可乐定的释放速率。 见图 9: 曲线 1是盐酸可乐定对动物皮 肤的体外透皮实验 （相关系数 r=0. 9945 ) ， 曲线 2是盐酸可乐定对固化膜的通透 性实验 （相关系数 r=0. 9942 ) ， 从图中可看出固化膜对药物有线性控释作用。
丙烯酸一 4一羟基丁酯 （700mg) ， 丙烯酸正十二垸酯 （300mg) ， 过氧化二苯 甲酮（50mg)， 溶解， 取混合溶液 30ul , 放在不锈钢的圆形载体基底上（(|)30醒） ， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 The phosphate skin buffer of the pH 7.4 was taken in the supply tank. The aqueous solution of the fresh Kunming mouse was placed in a modified Franz diffusion cell in a 3 mm/ml aqueous solution of clonidine hydrochloride. The release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography. See Figure 9: Curve 1 is an in vitro transdermal test of clonidine hydrochloride on animal skin (correlation coefficient r = 0.9945), and curve 2 is a permeability test of clonidine hydrochloride on cured film (correlation coefficient r = 0.9942) ), it can be seen from the figure that the cured film has a linear controlled release effect on the drug. 4-tetrahydroxybutyl acrylate (700 mg), n-decyl acrylate (300 mg), benzophenone peroxide (50 mg ), dissolved, 30 ul of a mixed solution, placed on a circular carrier substrate of stainless steel (( |) 30 awake), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 12 Example 12
2—羟基一 3—苯氧基丙烯酸丙酯 （SOOnig ) ， 1， 6—己二醇二甲基丙烯酸酯 ( 200rag) ， 1一羟基环己基苯基酮 （50mg) ， 取混合溶液 30ul， 放在不锈钢的圆 形载体基底上 （φ30腿） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博 机械电子设备中心） 中固化完全。 2-hydroxy-3-phenoxy propyl acrylate (SOOnig), 1,6-hexanediol dimethacrylate (200rag), 1-hydroxycyclohexyl phenyl ketone (50mg), take 30ul of mixed solution, put On a stainless steel circular carrier substrate (φ30 legs), the coating was flattened and placed in a UV curing apparatus (3kw power, Beijing Esper Machinery Electronic Equipment Center) to cure completely.
实施例 13 Example 13
2—羟基一 3—苯氧基丙烯酸丙酯 （600mg) ， 2—羧基丙烯酸乙酯 （400mg) ， 过氧化二苯甲酮 （50mg ) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( (j)30mm) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 2-Hydroxy-3-phenoxypropyl acrylate (600mg), 2-carboxyethyl acrylate (400mg), benzophenone peroxide (50mg), 30ul of mixed solution, placed on a stainless steel circular carrier substrate ((j) 30mm), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 14 Example 14
丙烯酸一 4—羟基丁酯 （800mg) ， 2—丁氧基丙烯酸乙酯 （200mg) ， 过氧化二 苯甲酮 （50mg) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 （φ30ηπη) ， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 4- 4-hydroxybutyl acrylate (800 mg), ethyl 2-butoxyacrylate (200 mg), benzophenone peroxide (50 mg), 30 ul of mixed solution, placed on a circular carrier substrate of stainless steel (φ30ηπη) , coating and flattening, placed in a UV curing instrument (3kw power, Beijing Esbo Mechanical and Electronic Equipment Center) solidified completely.
实施例 15 Example 15
丙烯酸一 4—羟基丁酯 （500mg) ， N- ( 1， 1一二甲基— 3—氧代丁基） 一丙烯 酰胺 （500mg) ， 苯偶姻丙基醚 （50mg ) ， 取混合溶液 30ul， 放在不锈钢的圆形 载体基底上 （φ30薩） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机 械电子设备中心） 中固化完全。 4- 4-hydroxybutyl acrylate (500mg), N-( 1,1 - dimethyl-3-oxobutyl) monoacrylamide (500mg), benzoin propyl ether (50mg), mixed solution 30ul , placed on a stainless steel circular carrier substrate (φ30 Sa), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Mechanical and Electronic Equipment Center) solidified completely.
实施例 16 Example 16
乙二醇二甲基丙烯酸酯（lOOOmg)，过氧化二苯甲酮（lmg )，取混合溶液 50ul， 放在不锈钢的圆形载体基底上 （(j)30inra) ， 涂布铺平， 置于紫外光固化仪 （3kw功 率， 北京埃士博机械电子设备中心） 中固化完全。 Ethylene glycol dimethacrylate (100 mg), benzophenone peroxide (1 mg), 50 ul of a mixed solution, placed on a stainless steel circular carrier substrate ((j) 30 inra), coated and laid, placed The curing is complete in the UV curing instrument (3kw power, Beijing Esbo Mechanical and Electronic Equipment Center).
得到的固化膜置于 Valia- Chien扩散池， 供给池中是水杨酸甲酯溶液， 接受池 中是生理盐水。 利用高效液相色谱分析水杨酸甲酯的释放速率。 The resulting cured film was placed in a Valia-Chien diffusion cell in which the methyl salicylate solution was present and the receiving tank was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于 Valia- Chien扩散池， 供
给池中是水杨酸甲酯溶液， 接受池中是生理盐水。 利用高效液相色谱分析水杨酸 甲酯的释放速率。 见图 10: 曲线 1是水杨酸甲酯对固化膜动物皮肤的体外透皮实 验 （相关系数 r=0. 9104) ， 曲线 2是水杨酸甲酯对动物皮肤的通透性实验， 从图 中可看出固化膜对药物有线性控释作用。 Animal skin comparison, take the fresh Kunming mice white skin into the Valia-Chien diffusion pool, for In the pool, the solution is methyl salicylate, and the receiving tank is physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 10: Curve 1 is an in vitro transdermal test of methyl salicylate on cured membrane animal skin (correlation coefficient r = 0.9104), and curve 2 is a permeability test of methyl salicylate on animal skin. It can be seen that the cured film has a linear controlled release effect on the drug.
实施例 17 Example 17
1， 4一丁二醇二丙烯酸酯 （lOOOmg) ， 过氧化二苯甲酮 （80mg) ， 取混合溶液 30ul，放在不锈钢的圆形载体基底上（Φ30画） ，涂布铺平，置于紫外光固化仪（3kw 功率， 北京埃士博机械电子设备中心） 中固化完全。 1, 4-butanediol diacrylate (100 mg), benzophenone peroxide (80 mg), 30 ul of a mixed solution, placed on a stainless steel circular carrier substrate (Φ30), coated and laid, placed The curing is complete in the UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center).
得到的固化膜， 置于 Valia- Chien扩散池， 供给池中是 90% (v/v)的水杨酸甲 酯溶液的异丙醇溶液， 接受池中是生理盐水。 利用高效液相色谱分析水杨酸甲酯 的释放速率。 The resulting cured film was placed in a Valia-Chien diffusion cell in a 90% (v/v) solution of methyl salicylate in an isopropanol solution, and the receiving tank was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于 Valia- Chien扩散池， 供 给池中是 90% (v/v)的水杨酸甲酯溶液的异丙醇溶液， 接受池中是生理盐水。 利用 高效液相色谱分析水杨酸甲酯的释放速率。 见图 11 : 曲线 1是水杨酸甲酯对固化 膜的通透性实验 （相关系数 r=0. 9507 ) ， 曲线 2是水杨酸甲酯对动物皮肤的体外 透皮实验， 从图中可看出固化膜对药物有线性控释作用。 Animal skin comparison, take the fresh Kunming mice white skin into the Valia-Chien diffusion cell, the supply pool is 90% (v / v) of methyl salicylate solution in isopropanol, the receiving pool is physiological brine. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 11: Curve 1 is the permeability test of methyl salicylate on the cured film (correlation coefficient r=0. 9507), curve 2 is the in vitro transdermal experiment of methyl salicylate on animal skin, from the figure It can be seen that the cured film has a linear controlled release effect on the drug.
实施例 18 Example 18
1， 6—己二醇二甲基丙烯酸酯 （lOOOmg) ， 过氧化二苯甲酮 （150mg) ， 取混 合溶液 30ul , 放在不锈钢的圆形载体基底上 （<))30mm) ， 涂布铺平， 置于紫外光 固化仪 （3kw功率， 北京埃士博机械电子设备中心） 中固化完全。 1,6-hexanediol dimethacrylate (100 mg), benzophenone peroxide (150 mg), 30 μl of a mixed solution, placed on a stainless steel circular carrier substrate (<) 30 mm), coated Flat, placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) solidified completely.
得到的固化膜， 置于 Valia-Chien扩散池， 供给池中是 10mg/ml的水杨酸的异 丙醇溶液， 接受池中是生理盐水。利用高效液相色谱分析水杨酸甲酯的释放速率。 The obtained cured film was placed in a Valia-Chien diffusion cell, and the supply tank was a 10 m g /ml solution of salicylic acid in isopropanol, and the receiving tank was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于 Val ia- Chien扩散池， 供 给池中是 10mg/ml的水杨酸的异丙醇溶液， 接受池中是生理盐水。 利用高效液相 色谱分析水杨酸甲酯的释放速率。 见图 12: 曲线 1是水杨酸甲酯对固化膜动物皮 肤的体外透皮实验 （相关系数 r=0. 9460) ， 曲线 2是水杨酸甲酯对动物皮肤的通 透性实验， 从图中可看出固化膜对药物有线性控释作用。 For comparison of animal skin, the fresh Kunming mice's abdominal skin was placed in a Val ia-Chien diffusion cell, and the supply pool was a 10 mg/ml solution of salicylic acid in isopropanol. The receiving pool was physiological saline. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 12: Curve 1 is an in vitro transdermal test of methyl salicylate on cured membrane animal skin (correlation coefficient r = 0.946), and curve 2 is a permeability test of methyl salicylate on animal skin. It can be seen that the cured film has a linear controlled release effect on the drug.
实施例 19 Example 19
1， 6—己二醇二甲基丙烯酸酯 （500mg) ， 丙烯酸正十二烷酯 （500mg ) ， 过氧 化二苯甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基 底上 （φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子 设备中心） 中固化完全。
实施例 20 1,6-hexanediol dimethacrylate (500mg), n-dodecyl acrylate (500mg), benzophenone peroxide (50mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel round On the base of the carrier (φ30 let), it is coated and flattened, and it is completely cured in an ultraviolet curing instrument (3kw power, Beijing Esper Mechanical and Electronic Equipment Center). Example 20
乙二醇二甲基丙烯酸酯（900mg) ， 2—羟基一 3—苯氧基丙烯酸丙酯（lOOmg) ， 过氧化二苯甲酮 （50rag ) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( φ30π,ιη) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 Ethylene glycol dimethacrylate (900mg), 2-hydroxy-3-phenoxy propyl acrylate (100mg), benzophenone peroxide (50rag), 30ul of mixed solution, placed in stainless steel circular carrier On the substrate (φ30π, ιη), the coating was flattened and placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 21 Example 21
1， 6—己二醇二甲基丙烯酸酯 （800mg) ， 2—羧基丙烯酸乙酯 （200mg) ， 1 一羟基环己基苯基酮 （50mg) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 1,6-hexanediol dimethacrylate (800 mg), 2-carboxyethyl acrylate (200 mg), 1 monohydroxycyclohexyl phenyl ketone (50 mg), a mixed solution of 30 ul, placed in a stainless steel circular carrier On the substrate (φ30 let), the coating is flattened, and it is completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
实施例 22 Example 22
1， 6—己二醇二甲基丙烯酸酯 （600mg) ， 2—丁氧基丙烯酸乙酯 （400mg) ， 过氧化二苯甲酮 （50mg ) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( Omm) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 1,6-hexanediol dimethacrylate (600 mg), ethyl 2-butoxyacrylate (400 mg), benzophenone peroxide (50 mg), 30 ul of a mixed solution, placed in a circular carrier of stainless steel On the substrate (Omm), the coating is flattened, and it is completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
实施例 23 Example 23
1 , 6—己二醇二甲基丙烯酸酯（700mg) ， N- ( 1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （300mg ) ， 苯偶姻丙基醚 （50mg ) ， 放在不锈钢的圆形载体基底上 ( φ30πιηι) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 1,6-hexanediol dimethacrylate (700 mg), N-(1,1-dimethyl-3-oxobutyl)-acrylamide (300 mg), benzoin propyl ether (50 mg) Placed on a stainless steel circular carrier substrate (φ30πιηι), coated and flattened, and placed in a UV curing apparatus (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 24 Example 24
2—羧基丙烯酸乙酯 （500mg) ， 丙烯酸正十二垸酯 （500mg) ， 过氧化二苯甲 酮（50mg)，溶解，过滤，取混合溶液 30ul，放在不锈钢的圆形载体基底上（φ30讓）， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 2-carboxyethyl acrylate (500mg), n-decyl acrylate (500mg), benzophenone peroxide (50mg), dissolved, filtered, 30ul mixed solution, placed on a stainless steel circular carrier substrate (φ30 Let), coating and flattening, and curing in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center).
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是水杨酸甲酯溶液， 接 受池中是 pH7. 4的磷酸盐缓冲液。利用高效液相色谱分析水杨酸甲酯的释放速率。 见图 13: 水杨酸甲酯对固化膜的通透性实验 （相关系数 r=0. 9874) ， 从图中可看 出固化膜对药物有线性控释作用。 The phosphate buffer of pH 7.4 is received in the pool. The solution is placed in a modified Franz diffusion cell. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 13: Permeability test of methyl salicylate on cured film (correlation coefficient r = 0.9874). It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 25 Example 25
2—羧基丙烯酸乙酯 （200rag) ， 1， 6—己二醇二甲基丙烯酸酯 （800mg) ， 过 氧化二苯甲酮 （80mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体
基底上 （φ30匪） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电 子设备中心） 中固化完全。 2-carboxyethyl acrylate (200rag), 1,6-hexanediol dimethacrylate (800mg), benzophenone peroxide (80mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel round Shape carrier On the substrate (φ30匪), the coating was flattened, and it was completely cured in an ultraviolet curing instrument (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
实施例 26 Example 26
2—羧基丙烯酸乙酯） （200mg ) ， 丙烯酸一 4一羟基丁酯 （SOOnig) ， 过氧化 二苯甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基底 上 （φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设 备中心） 中固化完全。 2-carboxyethyl acrylate (200mg), 4-hydroxybutyrate (SOOnig), benzophenone peroxide (50mg), dissolved, filtered, 30ul of mixed solution, placed on a stainless steel circular carrier substrate (φ30 let), coated and flattened, placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 27 Example 27
2—羧基丙烯酸乙酯 （700mg) ， 2—丁氧基丙烯酸乙酯 （300mg )， 1一羟基环 己基苯基酮 （lmg) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上（(|)30mm) ， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 Ethyl 2-carboxycarboxylate (700 mg), ethyl 2-butoxyacrylate (300 mg), 1-hydroxycyclohexyl phenyl ketone (1 mg), 30 ul of a mixed solution, placed on a circular carrier substrate of stainless steel (( |) 30mm), coated and flattened, placed in a UV curing unit (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 28 Example 28
2—羧基丙烯酸乙酯 （lOOmg ) ， N— （1， 1一二甲基一 3—氧代丁基） 一丙烯 酰胺 （900mg) ， 苯偶姻丙基醚 （150mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在 不锈钢的圆形载体基底上 （(j)30mm) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备中心） 中固化完全。 2-carboxyethyl acrylate (100 mg), N-(1,1-dimethyl-3-oxobutyl)-acrylamide (900 mg), benzoin propyl ether (150 mg), dissolved, filtered, taken The mixed solution was 30 ul, placed on a stainless steel circular carrier substrate ((j) 30 mm), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
实施例 29 Example 29
2—丁氧基丙烯酸乙酯 （200mg) ， 丙烯酸正十二烷酯 （800mg) ， 过氧化二苯 甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( ψ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设备 中心） 中固化完全。 2-butoxyethyl acrylate (200m g ), n-dodecyl acrylate (800mg), benzophenone peroxide (50mg), dissolved, filtered, mixed solution 30ul, placed on a stainless steel circular carrier substrate On (ψ30 let), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) solidified completely.
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是水杨酸甲酯溶液， 接 受池中是 PH7. 4的磷酸盐缓冲液。利用高效液相色谱分析水杨酸甲酯的释放速率。 见图 14: 水杨酸甲酯对固化膜的通透性实验 （相关系数 r=0. 9873 ) ， 从图中可看 出固化膜对药物有线性控释作用。 The phosphate buffer solution of the pH 7.4 is received in the pool. The solution is placed in a modified Franz diffusion cell. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 14: Permeability test of methyl salicylate on cured film (correlation coefficient r = 0.9873). It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 30 Example 30
2—丁氧基丙烯酸乙酯 （200mg) ， 丙烯酸一4一羟基丁酯 （800mg) ， 过氧化 二苯甲酮 （50mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基底 上 （<j)30mm) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械电子设 备中心） 中固化完全。 2-butoxyethyl acrylate (200m g ), 4-tetrahydroxybutyl acrylate (800mg), benzophenone peroxide (50mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel circular carrier On the substrate (<j) 30mm), the coating is flattened and placed in a UV curing device (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
得到的固化膜，置于改良的 Franz扩散池，供给池中是 lmg/ml的盐酸可乐定
水溶液， 接受池中是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析盐酸可乐定 的释放速率。 The obtained cured film was placed in a modified Franz diffusion cell, and the supply cell was 1 mg/ml of clonidine hydrochloride. The phosphate buffer solution was pH 7.4 in the receiving solution. The release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于改良的 Franz扩散池， 供给池中是 lmg/ml的盐酸可乐定水溶液， 接受池是 pH7. 4的磷酸盐缓冲液。利用 高效液相色谱分析盐酸可乐定的释放速率。 见图 15 : 曲线 1是盐酸可乐定对动物 皮肤的体外透皮实验， 曲线 2 是盐酸可乐定对固化膜的通透性实验 （相关系数 r=0. 9901 ) ， 从图中可看出固化膜对药物有线性控释作用。 The skin of the fresh Kunming mice was placed in a modified Franz diffusion cell. The supply pool was a lmg/ml aqueous solution of clonidine hydrochloride, and the receiving cell was a pH 7.4 phosphate buffer. The release rate of clonidine hydrochloride was analyzed by high performance liquid chromatography. See Figure 15: Curve 1 is an in vitro transdermal test of clonidine hydrochloride on animal skin, curve 2 is a permeability test of clonidine hydrochloride on cured film (correlation coefficient r = 0.9901), as can be seen from the figure The membrane has a linear controlled release effect on the drug.
实施例 31 Example 31
2—丁氧基丙烯酸乙酯 （200mg) ， N— （1， 1一二甲基一 3—氧代丁基） 一丙 烯酰胺 （800mg ) ， 过氧化二苯甲酮 （50mg) ， 溶解， 过滤， 放在不锈钢的圆形载 体基底上 （φ30ιηπι) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械 电子设备中心） 中固化完全。 2-butoxyethyl acrylate (200 mg), N-(1,1-dimethyl-3-oxobutyl)-acrylamide (800 mg), benzophenone peroxide (50 mg), dissolved, filtered Placed on a stainless steel circular carrier substrate (φ30ιηπι), coated and flattened, and placed in a UV curing apparatus (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是水杨酸甲酯溶液， 接 受池中是 PH7. 4的磷酸盐缓冲液。利用高效液相色谱分析水杨酸甲酯的释放速率。 见图 16: 水杨酸甲酯对固化膜的通透性实验 （相关系数 r=0. 9973 ) ， 从图中可看 出固化膜对药物有线性控释作用。 The phosphate buffer solution of the pH 7.4 is received in the pool. The solution is placed in a modified Franz diffusion cell. The release rate of methyl salicylate was analyzed by high performance liquid chromatography. See Figure 16: Permeability test of methyl salicylate on cured film (correlation coefficient r = 0.9973). It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 32 Example 32
2—丁氧基丙烯酸乙酯 （400mg ) ， 1， 6—己二醇二甲基丙烯酸酯 （600mg ) , 苯偶姻丙基醚 （150mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载 体基底上 （φ30匪） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机械 电子设备中心） 中固化完全。 2-butoxyethyl acrylate (400mg), 1,6-hexanediol dimethacrylate (600mg), benzoin propyl ether (150mg), dissolved, filtered, mixed solution 30ul, placed in stainless steel The circular carrier substrate (φ30匪) was coated and flattened, and it was completely cured in an ultraviolet curing device (3kw power, Beijing Esper Mechanical and Electronic Equipment Center).
实施例 33 Example 33
2—丁氧基丙烯酸乙酯 （700mg ) ， 2—羧基丙烯酸乙酯 （300nig)， 1一羟基环 己基苯基酮 （lmg ) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 （φ30ππη )， 涂布铺平， 置于紫外光固化仪 （3kw 功率， 北京埃士博机械电子设备中心） 中固 化完全。 2-butoxyethyl acrylate (700 mg), 2-carboxyethyl acrylate (300 ni g ), 1-hydroxycyclohexyl phenyl ketone (1 mg), 30 ul of a mixed solution, placed on a circular carrier substrate of stainless steel ( Φ30ππη ), coated and flattened, placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
实施例 34 Example 34
N- ( 1 , 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （500rag) ， 无水乙醇 lml， 过氧化二苯甲酮 （25mg ) ， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 ( φ30ππη) ， 涂布铺平， 置于紫外光固化仪 （3kW功率， 北京埃士博机械电子设备 中心） 中固化完全。 N- ( 1 , 1 - dimethyl 3- oxobutyl ) monoacrylamide (500 rag ) , 1 ml of absolute ethanol , benzophenone peroxide ( 25 mg ) , 30 ul of mixed solution, placed in a round stainless steel On the base of the carrier (φ30ππη), it is coated and flattened, and it is completely cured in an ultraviolet curing instrument (3k W power, Beijing Esper Mechanical and Electronic Equipment Center).
得到的固化膜，置于改良的 Franz扩散池，供给池中是 lmg/ml的萘普生的水
杨酸甲酯溶液， 接受池中是 PH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 见图 17: 水杨酸甲酯对固化膜的通透性实验 （相关 系数 r=0. 9739 ) ； 图 18: 萘普生对固化膜的通透性实验 （相关系数 r=0. 9993 ) ， 从图中可看出固化膜对药物有线性控释作用。 The resulting cured film was placed in a modified Franz diffusion cell, which was 1 mg/ml of naproxen water in the supply cell. The phosphate buffer solution was pH 7. 4 in the receiving tank. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 17: Permeability test of methyl salicylate on cured film (correlation coefficient r = 0.9739); Figure 18: Permeability test of naproxen on cured film (correlation coefficient r = 0.9993) It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 35 Example 35
N- ( 1， 1—二甲基一 3—氧代丁基） 一丙烯酰胺 （500mg ) ， 丙烯酸一4—羟 基丁酯 （500mg) ， 过氧化二苯甲酮 （50fflg) ， 取混合溶液 30ul， 放在不锈钢的 圆形载体基底上 （φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士 博机械电子设备中心） 中固化完全。 N-( 1,1-dimethyl-3-oxobutyl)-acrylamide (500mg), 4-hydroxybutyl acrylate (500mg), benzophenone peroxide (50 ffl g), mixed The solution was 30 ul, placed on a stainless steel circular carrier substrate (φ30 let), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
得到的固化膜，置于改良的 Franz扩散池，供给池中是 lmg/ml的萘普生的水 杨酸甲酯溶液， 接受池中是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 The phosphate buffer solution of pH 7.4 is received in the cell. The solution is placed in a modified Franz diffusion cell. The solution is a lmg/ml naproxen methyl salicylate solution in the supply cell. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography.
动物皮肤比较， 取新鲜的昆明种小白鼠腹部皮肤置于改良的 Franz扩散池， 供给池中是 lmg/ml的萘普生的水杨酸甲酯溶液，接受池是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨酸甲酯和萘普生的释放速率。 见图 19: 曲线 1是水杨 酸甲酯对动物皮肤的体外透皮实验， 曲线 2是水杨酸甲酯对固化膜的通透性实验 (相关系数 r=0. 9933 ) ; 图 20: 曲线 1是萘普生对固化膜的通透性实验 （相关系 数 r=0. 9973 ) , 曲线 2是萘普生对动物皮肤的体外透皮实验， 从图中可看出固化 膜对药物有线性控释作用。 The phosphate skin buffer of the pH is 7.4, and the pool is a solution of the methyl sulphate solution of the naproxen in the supply tank. liquid. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 19: Curve 1 is an in vitro transdermal test of methyl salicylate on animal skin, and curve 2 is a permeability test of methyl salicylate on the cured film (correlation coefficient r = 0.9933) ; Figure 20: Curve 1 is the permeability test of naproxen on the cured film (correlation coefficient r=0. 9973), and curve 2 is the in vitro transdermal experiment of naproxen on animal skin. It can be seen from the figure that the cured film has a drug for the drug. Linear controlled release.
实施例 36 Example 36
N— （1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （200mg ) ， 丙烯酸一4一羟 基丁酯 （800mg) , 过氧化二苯甲酮 （50mg ) ， 取混合溶液 30ul， 放在不锈钢的 圆形载体基底上 （φ30讓） ， 涂布铺平， 置于紫外光固化仪 （3 功率， 北京埃士 博机械电子设备中心） 中固化完全。 N-(1,1-dimethyl-3-oxobutyl)-acrylamide (200 mg), 4-tetrahydroxybutyl acrylate (800 mg), benzophenone peroxide (50 mg), mixed solution 30 ul Placed on a stainless steel circular carrier substrate (φ30 let), coated and flattened, and placed in a UV curing device (3 power, Beijing Esbo Machinery and Electronics Center) to cure completely.
得到的固化膜， 置于改良的 Franz扩散池， 供给池中是 lmg/ml的萘普生的水 杨酸甲酯溶液， 接受池中是 pH7. 4的磷酸盐缓冲液。 利用高效液相色谱分析水杨 酸甲酯和萘普生的释放速率。 见图 21 : 水杨酸甲酯对固化膜的通透性实验 （相关 系数 r=0. 9828 ) ； 图 22: 萘普生对固化膜的通透性实验 （相关系数 r=0. 9877 ) ， 从图中可看出固化膜对药物有线性控释作用。 The phosphate buffer of pH 7.4 is received in the cell. The solution is placed in a modified Franz diffusion cell. The solution is a lmg/ml naproxen methyl salicylate solution. The release rate of methyl salicylate and naproxen was analyzed by high performance liquid chromatography. See Figure 21: Permeability test of methyl salicylate on cured film (correlation coefficient r=0.9828); Figure 22: Permeability test of naproxen on cured film (correlation coefficient r=0. 9877) It can be seen from the figure that the cured film has a linear controlled release effect on the drug.
实施例 37 Example 37
N- ( 1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （500mg ) ， 1， 6—己二醇二 甲基丙烯酸酯 （50mg) ， 过氧化二苯甲酮 （150mg ) ， 取混合溶液 30ul， 放在不
锈钢的圆形载体基底上 （φ30ιπιη) ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北 京埃士博机械电子设备中心） 中固化完全。 N-( 1,1 - dimethyl 3-oxobutyl) monoacrylamide (500 mg), 1,6-hexanediol dimethacrylate (50 mg), benzophenone peroxide (150 mg) , take 30ul of mixed solution, put it in no The rusted steel is placed on a circular carrier substrate (φ30ιπιη), coated and flattened, and placed in a UV curing apparatus (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) for complete curing.
实施例 38 Example 38
N- (1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （700mg) , 丙烯酸正十二垸 酯 （300mg) ， 1一羟基环己基苯基酮 （80mg) ， 溶解， 过滤， 取混合溶液 30ul， 放在不锈钢的圆形载体基底上 （φ30腦） ， 涂布铺平， 置于紫外光固化仪 （3kw功 率， 北京埃士博机械电子设备中心） 中固化完全。 N-(1,1-dimethyl-3-oxobutyl)-acrylamide (700 mg), n-decyl acrylate (300 mg), 1-hydroxycyclohexyl phenyl ketone (80 mg), dissolved, filtered 30 ul of the mixed solution was placed on a circular carrier substrate of stainless steel (φ30 brain), coated and flattened, and placed in a UV curing apparatus (3 kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
实施例 39 Example 39
N— (1, 1—二甲基一 3—氧代丁基） —丙烯酰胺 （600mg) ， 2—羧基丙烯酸 乙酯 OOmg) ， 过氧化二苯甲酮 （50mg) ， 取混合溶液 30ul， 放在不锈钢的圆 形载体基底上 （φ30麵） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博 机械电子设备中心） 中固化完全。 N-(1,1-dimethyl-3-oxobutyl)-acrylamide (600 mg), ethyl 2-carboxycarboxylate OOmg), benzophenone peroxide (50 mg), 30 ul of mixed solution, put On a stainless steel circular carrier substrate (φ30 surface), the coating was flattened and placed in a UV curing apparatus (3kw power, Beijing Esper Mechanical and Electronic Equipment Center) to cure completely.
实施例 40 Example 40
N— (1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺 （800mg) ， 2—丁氧基丙烯 酸乙酯 （200mg) ， 苯偶姻丙基醚 （lmg) ， 取混合溶液 30ul, 放在不锈钢的圆形 载体基底上 （φ30醒） ， 涂布铺平， 置于紫外光固化仪 （3kw功率， 北京埃士博机 械电子设备中心） 中固化完全。
N-(1,1-dimethyl-3-oxobutyl)-acrylamide (800 mg), ethyl 2-butoxyacrylate (200 mg), benzoin propyl ether (1 mg), mixed solution 30 ul, placed on a stainless steel circular carrier substrate (φ30 awake), coated and flattened, and placed in a UV curing instrument (3kw power, Beijing Esbo Machinery and Electronics Center) to cure completely.
Claims
1. —种可光固化的单体组合物， 包括： （A)占组合物总重量的 0%- 99.9%重量 的一种或两种或两种以上的由通式 CR2R1==CR3COOR4表示的丙烯酸酯单体， 其中 所述的！^、 R2和 R3各自独立地选自- H、 - CH3、 - CSH5、 - CH=C¾、 -OH, - C00H、1. A photocurable monomer composition comprising: (A) from 0% to 99.9% by weight of the total weight of the composition of one or two or more of the formula CR 2 R 1 == The acrylate monomer represented by CR 3COOR 4 , which is described! ^, R 2 and R 3 are each independently selected from - H, -CH 3 , - C S H 5 , - CH=C3⁄4, -OH, - C00H,
-0C 、 - S03H、 -顧 2或- N(C )3C1; -0C, - S0 3 H, - Gu 2 or - N(C ) 3 C1;
所述的 选自烷烃基、 羟基、 酯基、 羧基或烷氧基， 所述基团中的碳原子数 为 1一 20; The selected one is selected from the group consisting of an alkane group, a hydroxyl group, an ester group, a carboxyl group or an alkoxy group, and the number of carbon atoms in the group is 1-20;
(B) 占组合物总重量的 0— 99.9%重量的一种或两种或两种以上的由通式 CR2Rl=CR3CONR4代表的丙烯酰胺单体， 其中 — 的定义同上； 和 (B) from 0 to 99.9% by weight, based on the total weight of the composition, of one or two or more acrylamide monomers represented by the formula CR2R1=CR 3CONR 4 wherein - is as defined above;
(0 占组合物总重量的 0.1- 15%重量的光引发剂； (0) from 0.1 to 15% by weight of the total weight of the composition of the photoinitiator;
当所述组分（A)的含量为 0%重量 /重量时，所述组分（B)的含量为 0.1-99.9 %重量 /重量； 当所述组分 （B) 的含量为 0%重量 /重量时， 所述组分 （A) 的含 量为 0.1— 99.9%重量 /重量。 When the content of the component (A) is 0% by weight/weight, the content of the component (B) is 0.1 to 99.9% by weight/weight; when the content of the component (B) is 0% by weight The component (A) is contained in an amount of from 0.1 to 99.9% by weight/weight.
2. 根据权利要求 1所述的组合物， 其中所述组分 （A) 的优选含量为 20— 80 2. The composition according to claim 1, wherein the component (A) is preferably present in an amount of from 20 to 80.
%重量 /重量； 所述组分 （B) 的优选含量为 12— 78%重量 /重量； 所述组分 （C) 的优选含量为 2— 8%重量 /重量。 % by weight / weight; the preferred content of the component (B) is from 12 to 78% by weight / weight; and the preferred content of the component (C) is from 2 to 8% by weight / weight.
3. 根据权利要求 1或 2所述的组合物， 其中， R4是选自 - (C )nCH3 或- CH2CH = CH2的烷烃基； 或是选自（CH2)2CH20H、 -（CH2) 3C 0H或 -（C ) 4C¾0H的羟 基； 或是选自-（C¾)200CCH=C¾、 -（CH2)400CCH=C¾或-（C )600CCH=C¾的酯基； 或 是 选 自 -（C¾)2C00H、 -(C¾)4C00H 或 _(C¾)6C00H 的 羧 基 ； 或是 选 自 - (C¾) 20 (C¾) 2C¾、 - (C¾) 30 (CH2) 2CH3或- (CH2) 20 (CH2) 4CH3的烷氧基。 The composition according to claim 1 or 2, wherein R 4 is an alkane group selected from - (C ) nCH 3 or - CH 2 CH = CH 2 ; or is selected from (CH 2 ) 2 CH 2 0H, -(CH 2 ) 3 C 0H or -(C ) 4 C3⁄40H hydroxy; or selected from -(C3⁄4) 2 00CCH=C3⁄4, -(CH 2 ) 4 00CCH=C3⁄4 or -(C ) 6 00CCH= An ester group of C3⁄4; or a carboxyl group selected from -(C3⁄4) 2 C00H, -(C3⁄4) 4 C00H or _(C3⁄4) 6 C00H; or selected from -(C3⁄4) 2 0 (C3⁄4) 2 C3⁄4, - ( C3⁄4) 3 0 (CH 2 ) 2 CH 3 or alkoxy group of -(CH 2 ) 2 0 (CH 2 ) 4 CH 3 .
4. 根据权利要求 1或 2所述的组合物， 其中所述的组分 （A) 选自 （甲基） 丙 烯酸甲酯、 （甲基） 丙烯酸乙酯、 （甲基） 丙烯酸丙酯、 （甲基） 丙烯酸异丙酯、 (甲基） 丙烯酸丁酯、 （甲基） 丙烯酸戊酯、 （甲基） 丙烯酸异丁酯、 （甲基） 丙烯酸叔丁酯、 （甲基） 丙烯酸异戊酯、 （甲基） 丙烯酸己酯、 （甲基） 丙烯酸 庚酯、 （甲基） 丙烯酸辛酯、 （甲基） 丙烯酸异辛酯、 （甲基） 丙烯酸 2—乙基 己酯、 （甲基）丙烯酸壬酯、 （申基）丙烯酸癸酯、 （甲基）丙烯酸异癸酯、 （甲 基） 丙烯酸十一烷酯、 （甲基） 丙烯酸十二烷酯、 （甲基） 丙烯酸月桂酯、 （甲 基）丙烯酸十八垸酯、 （甲基）丙烯酸硬脂基酯、 （甲基）丙烯酸四氢糠酯、 （甲 基） 丙烯酸丁氧基乙酯、 （甲基） 丙烯酸乙氧基二甘醇酯、 （甲基） 丙烯酸苄酯、 (甲基） 丙烯酸环己酯、 （甲基） 丙烯酸苯氧基乙酯、 甲氧基乙二醇 （甲基） 丙
烯酸酯、 （甲基） 丙烯酸乙氧基乙酯、 （甲基） 丙烯酸二环戊二烯酯、 （甲基） 丙烯酸二环戊烯酯、 （甲基） 丙烯酸二环戊烯氧基乙酯、 （甲基） 丙烯酸三环癸 酯、 （甲基） 丙烯酸异冰片酯、 （甲基） 丙烯酸冰片酯、 （甲基） 丙烯酸二甲基 氨基乙酯、 （甲基） 丙烯酸二乙基氨基乙酯、 （甲基） 丙烯酸 7—氨基一3， 7- 二甲基辛酯、 （甲基） 丙烯酰吗啉、 2— （甲基） 丙烯酰氧乙基邻苯二甲酸酯、 2 一 （甲基） 丙烯酰氧乙基六氢邻苯二甲酸酯、 2— （甲基） 丙烯酰氧丙基邻苯二甲 酸酯、 2— （甲基） 丙烯酰氧丙基四氢邻苯二甲酸酯、 2— (甲基） 丙烯酰氧丙基 六氢邻苯二甲酸酯、 2— （甲基） 丙烯酰氧乙基琥珀酸酯、 丙烯酰吗啉； （甲基） 丙烯酸一 4一羟基丁酯、 （甲基）丙烯酸一 2—羟基乙酯、 （甲基）丙烯酸一 2—羟 基丙酯、 （甲基） 丙烯酸一 2—羟基丁酯、 （甲基） 丙烯酸一 2—羟基一 3—苯氧基 丙酯、 1， 4一丁二醇一 （甲基） 丙烯酸酯、 （甲基） 丙烯酰磷酸一 2—羟基垸基酯 (其中烷基例如甲基、 乙基、 丙基） 、 （甲基） 丙烯酸一 4一羟基环己酯、 1， 6 一己二醇一 （甲基）丙烯酸酯、 新戊四醇三 （甲基）丙烯酸酯、 二季戊四醇五（甲 基） 丙烯酸酯； 乙二醇二 （甲基） 丙烯酸酯、 1， 4一丁二醇二 （甲基） 丙烯酸酯、 1， 6—己二醇二 （甲基） 丙烯酸酯、 丙二醇二 （甲基） 丙烯酸酯、 1， 9一壬二醇 二 （甲基） 丙烯酸酯、 二甘酯二 （甲基） 丙烯酸酯、 三甘酯二 （甲基） 丙烯酸酯、 四甘酯二 （甲基） 丙烯酸酯、 二丙二醇二 （甲基） 丙烯酸酯、 三丙二醇二 （甲基） 丙烯酸酯、 新戊二醇二 （甲基） 丙烯酸酯、 羟基戊酸新戊二醇二丙烯酸酯、 三羟 甲甘油丙烷三 （甲基） 丙烯酸酯、 季戊四醇 （甲基） 丙烯酸酯、 季戊四醇四 （甲 基） 丙烯酸酯、 二 （三羟甲基丙垸） 四 （甲基） 丙烯酸酯、 二季戊四醇六 （甲基） 丙烯酸酯、三羟甲基丙烷三氧乙基（甲基）丙烯酸酯、 二羟甲基丙烷三氧丙基（甲 基） 丙烯酸酯、 三 （2—羟基乙基） 异氰脲酸酯三 （甲基） 丙烯酸酯、 三 （2—羟 基乙基） 异氰脲酸酯二 （甲基） 丙烯酸酯、 乙氧基化双酚 A二 （甲基） 丙烯酸酯、 乙氧基化双酚 F二 （甲基） 丙烯酸酯、 丙氧基化双酚 A二 （甲基） 丙烯酸酯、 丙 氧基化双酚 F二 （甲基） 丙烯酸酯、 三环癸烷二甲醇二 （甲基） 丙烯酸酯、 双酚 A环氧基二 （甲基） 丙烯酸酯、 双酚 F环氧基二 （甲基） 丙烯酸酯； （甲基） 丙 烯酸— 2—羧基乙酯、 （甲基）丙烯酸一 3—羧基丙酯、 （甲基） 丙烯酸一 2—羧基 丙酯、 （甲基）丙烯酸一 4一羧基正丁酯、 （甲基）丙烯酸—3—羧基正丁酯、 （甲 基） 丙烯酸一 2—羧基正丁酯、 （甲基） 丙烯酸一 2—羧基异丁酯、 （甲基 丙烯 酸一 6—羧基正己酯、 （甲基） 丙烯酸一5—羧基正己酯、 （甲基）丙烯酸一 4—羧 基正己酯、 （甲基） 丙烯酸—3—羧基正己酯、 （甲基）丙烯酸—2—羧基正己酯； (甲基） 丙烯酸一2—甲氧基乙酯、 （甲基） 丙烯酸一 2—乙氧基乙酯、 （甲基）
丙烯酸一 2—丙氧基乙酯、 （甲基）丙烯酸一3—甲氧基丙酯、 （甲基） 丙烯酸一 3 一乙氧基丙酯、 （甲基） 丙烯酸一 3—丙氧基丙酯、 （甲基） 丙烯酸一 3—丁氧基 丙酯、 （甲基）丙烯酸一2—甲氧基丙酯、 （甲基）丙烯酸一 2—乙氧基丙酯、 （甲 基） 丙烯酸一 2—丙氧基丙酯、 （甲基） 丙烯酸一 2—丁氧基乙酯、 （甲基） 丙烯 酸一 2—丁氧基丙酯、 （甲基）丙烯酸一 2—苯氧基乙酯、 （甲基）丙烯酸一 2—苯 氧基丙酯、 （甲基） 丙烯酸一 3—苯氧基丙酯、 （甲基） 丙烯酸一 2—苯氧基丁酯、 (甲基） 丙烯酸一 3—苯氧基丁酯或 （甲基） 丙烯酸一 4一苯氧基丁酯； The composition according to claim 1 or 2, wherein the component (A) is selected from the group consisting of methyl (meth)acrylate, ethyl (meth)acrylate, and propyl (meth)acrylate, Methyl) isopropyl acrylate, butyl (meth)acrylate, amyl (meth)acrylate, isobutyl (meth)acrylate, tert-butyl (meth)acrylate, isoamyl (meth)acrylate , (meth) hexyl acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, (methyl) Ethyl acrylate, decyl acrylate, isodecyl (meth) acrylate, undecyl (meth) acrylate, lauryl (meth) acrylate, lauryl (meth) acrylate, ( Octadecyl methacrylate, stearyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, butoxyethyl (meth) acrylate, ethoxylated bis(methyl) acrylate Alcohol ester, benzyl (meth) acrylate, (methyl) Cyclohexyl acrylate, phenoxyethyl (meth)acrylate, methoxyethylene glycol (methyl) propyl Ethyl ester, ethoxyethyl (meth)acrylate, dicyclopentadienyl (meth)acrylate, dicyclopentenyl (meth)acrylate, dicyclopenteneoxy (meth)acrylate Ester, tricyclodecyl (meth)acrylate, isobornyl (meth)acrylate, borneol (meth)acrylate, dimethylaminoethyl (meth)acrylate, diethylamino (meth)acrylate Ethyl ester, 7-amino-3,7-dimethyloctyl (meth)acrylate, (meth)acryloylmorpholine, 2-(meth)acryloyloxyethyl phthalate, 2 Mono(methyl)acryloyloxyethylhexahydrophthalate, 2-(meth)acryloyloxypropyl phthalate, 2-(meth)acryloyloxypropyltetrahydrogen Phthalates, 2-(meth)acryloyloxypropyl hexahydrophthalate, 2-(meth)acryloyloxyethyl succinate, acryloylmorpholine; ) 4-tetrahydroxybutyl acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, Methyl) 2-hydroxybutyl acrylate, 2-hydroxy-3-phenoxypropyl (meth)acrylate, 1, 4-butanediol mono(meth) acrylate, (meth) acryloyl 2-hydroxyhydrinyl phosphate (in which alkyl group such as methyl, ethyl, propyl), (meth)acrylic acid 4-tetrahydroxycyclohexyl ester, 1,6-hexanediol mono(meth)acrylate, Pentaerythritol tri(meth) acrylate, dipentaerythritol penta (meth) acrylate; ethylene glycol di(meth) acrylate, 1, 4-butanediol di(meth) acrylate, 1, 6-hexanediol di(meth) acrylate, propylene glycol di(meth) acrylate, 1,9-nonanediol di(meth) acrylate, diglyceride di(meth) acrylate, tripartine Ester di(meth) acrylate, tetraglycol di(meth) acrylate, dipropylene glycol di(meth) acrylate, tripropylene glycol di(meth) acrylate, neopentyl glycol di(meth) acrylate Ester, hydroxyvalerate neopentyl glycol diacrylate, trimethylolglycerol propane (meth) acrylate, pentaerythritol (meth) acrylate, pentaerythritol tetra(meth) acrylate, bis(trimethylol propyl) tetra(meth) acrylate, dipentaerythritol hexa(meth) acrylate , trimethylolpropane trioxyethyl (meth) acrylate, dimethylolpropane trioxypropyl (meth) acrylate, tris(2-hydroxyethyl) isocyanurate tris(methyl) Acrylate, tris(2-hydroxyethyl) isocyanurate di(meth) acrylate, ethoxylated bisphenol A di(meth) acrylate, ethoxylated bisphenol F II Acrylate, propoxylated bisphenol A di(meth) acrylate, propoxylated bisphenol F di(meth) acrylate, tricyclodecane dimethanol di(meth) acrylate, double Phenol A epoxy di(meth) acrylate, bisphenol F epoxy di(meth) acrylate; (methyl) acrylate 2-carboxyethyl ester, 3-methyl carboxypropyl (meth) acrylate , (meth)acrylic acid 2-carboxypropyl ester, (meth)acrylic acid 4-41 N-butyl acrylate, 3-carboxy n-butyl (meth) acrylate, 2-carboxy-n-butyl (meth) acrylate, 2-carboxy-isobutyl (meth) acrylate, (methacrylic acid-1) —Carboxy n-hexyl ester, 5-methyl-n-hexyl (meth)acrylate, 4-carboxy-n-hexyl (meth)acrylate, 3-carboxy-n-hexyl (meth)acrylate, 2-carboxyl (meth)acrylate n-Hexyl ester; (meth)acrylic acid 2-methoxyethyl, (meth)acrylic acid 2-ethoxyethyl ester, (methyl) 2-Ethyloxyethyl acrylate, 3-methoxypropyl (meth)acrylate, 3-methoxypropyl (meth)acrylate, 3-methoxypropoxy (meth)acrylate Ester, 3-butoxypropyl (meth)acrylate, 2-methoxypropyl (meth)acrylate, 2-ethoxypropyl (meth)acrylate, (meth)acrylic acid 2-propoxypropyl ester, 2-methyloxyethyl (meth)acrylate, 2-butoxypropyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, 2-Benzyloxypropyl (meth)acrylate, 3-phenoxypropyl (meth)acrylate, 2-phenoxybutyl (meth)acrylate, (meth)acrylic acid 3- 3 Phenoxybutyl ester or 1,4-phenoxybutyl (meth)acrylate;
所述的丙烯酰胺单体选自 N— （1， 1一二甲基一 3—氧代丁基） 一丙烯酰胺、 (甲基） 丙烯酰胺、 N，N—二甲基 （甲基） 丙烯酰胺、 N—异丙基 （甲基） 丙烯酰 胺、 N— (丁氧基甲基） （甲基） 丙烯酰胺、 N— (羟甲基） （甲基） 丙烯酰胺、 N - [ (三羟甲基） 甲基] (甲基） 丙烯酰胺、 N— [3— （二甲基氨基） 丙基] (甲基） 丙烯酰胺； The acrylamide monomer is selected from the group consisting of N-(1,1-dimethyl-3-oxobutyl)-acrylamide, (meth)acrylamide, N,N-dimethyl(methyl)propylene Amide, N-isopropyl (meth)acrylamide, N-(butoxymethyl) (meth)acrylamide, N-(hydroxymethyl)(meth)acrylamide, N-[(trihydroxyl) Methyl)methyl](meth)acrylamide, N-[3-(dimethylamino)propyl](methyl)acrylamide;
所述的光引发剂 （C ) 包括对于紫外光敏感， 能引发单体进行固化反应的光引 发剂。 The photoinitiator (C) includes a photoinitiator which is sensitive to ultraviolet light and which is capable of initiating a curing reaction of the monomer.
5. 根据权利要求 1或 2所述的组合物， 其中所述的光引发剂（C )选自但不限 于过氧化二苯甲酮、 1一羟基环己基苯基酮或苯偶姻丙基醚。 The composition according to claim 1 or 2, wherein the photoinitiator (C) is selected from, but not limited to, benzophenone peroxide, 1-hydroxycyclohexyl phenyl ketone or benzoin propyl ether.
6. 根据权利要求 1或 2所述的组合物， 它还可以进一步包含增塑剂。 6. The composition of claim 1 or 2, which may further comprise a plasticizer.
7. 根据权利要求 6所述的组合物， 其中所述的增塑剂选自但不限于柠檬酸盐、 邻苯二甲酸盐或癸二酸盐。 7. The composition of claim 6 wherein the plasticizer is selected from the group consisting of, but not limited to, citrate, phthalate or sebacate.
8.如权利要求 1一 7任一所述的可光固化的单体组合物在制备经皮给药系统中 控释膜的用途。
8. Use of a photocurable monomer composition according to any one of claims 1 to 7 for the preparation of a controlled release film in a transdermal drug delivery system.
Applications Claiming Priority (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510024589XA CN1320005C (en) | 2005-03-24 | 2005-03-24 | Combination of acrylic ester containing ester group including paraffin base |
| CN200510024589.X | 2005-03-24 | ||
| CN200510024590.2 | 2005-03-24 | ||
| CNB2005100245902A CN1326894C (en) | 2005-03-24 | 2005-03-24 | Combination of acrylic ester containing ester group including partial alkoxyl |
| CN200510024587.0 | 2005-03-24 | ||
| CN200510024591.7 | 2005-03-24 | ||
| CNB2005100245866A CN1320012C (en) | 2005-03-24 | 2005-03-24 | Combination containing acrylamide |
| CNB2005100245917A CN1320006C (en) | 2005-03-24 | 2005-03-24 | Combination of acrylic ester containing ester group including partial radical of ester group |
| CN200510024586.6 | 2005-03-24 | ||
| CN200510024588.5 | 2005-03-24 | ||
| CNB2005100245870A CN1320009C (en) | 2005-03-24 | 2005-03-24 | Combination of acrylic ester containing ester group including partial radical of hydroxy group |
| CNB2005100245885A CN1320008C (en) | 2005-03-24 | 2005-03-24 | Combination of acrylic ester containing ester group including partial radical of carboxyl group |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2006099818A1 true WO2006099818A1 (en) | 2006-09-28 |
Family
ID=37023378
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2006/000509 WO2006099818A1 (en) | 2005-03-24 | 2006-03-24 | Light curable monomer compostion and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2006099818A1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5614586A (en) * | 1994-04-06 | 1997-03-25 | Graphic Controls Corporation | Polyacrylate and Polymethacrylate ester based hydrogel adhesives |
| US5674275A (en) * | 1994-04-06 | 1997-10-07 | Graphic Controls Corporation | Polyacrylate and polymethacrylate ester based hydrogel adhesives |
| CN1248267A (en) * | 1997-02-19 | 2000-03-22 | 西巴特殊化学品控股有限公司 | (Co) polymers by photopolymerization |
| US6833176B2 (en) * | 2003-01-06 | 2004-12-21 | General Electric Company | Radiation curable microstructure-bearing articles |
-
2006
- 2006-03-24 WO PCT/CN2006/000509 patent/WO2006099818A1/en not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5614586A (en) * | 1994-04-06 | 1997-03-25 | Graphic Controls Corporation | Polyacrylate and Polymethacrylate ester based hydrogel adhesives |
| US5674275A (en) * | 1994-04-06 | 1997-10-07 | Graphic Controls Corporation | Polyacrylate and polymethacrylate ester based hydrogel adhesives |
| CN1248267A (en) * | 1997-02-19 | 2000-03-22 | 西巴特殊化学品控股有限公司 | (Co) polymers by photopolymerization |
| US6833176B2 (en) * | 2003-01-06 | 2004-12-21 | General Electric Company | Radiation curable microstructure-bearing articles |
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