CN107929266B - 一种治疗慢性阻塞性肺疾病的贴剂 - Google Patents
一种治疗慢性阻塞性肺疾病的贴剂 Download PDFInfo
- Publication number
- CN107929266B CN107929266B CN201711192893.4A CN201711192893A CN107929266B CN 107929266 B CN107929266 B CN 107929266B CN 201711192893 A CN201711192893 A CN 201711192893A CN 107929266 B CN107929266 B CN 107929266B
- Authority
- CN
- China
- Prior art keywords
- patch
- layer
- pulmonary disease
- chronic obstructive
- obstructive pulmonary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 title claims abstract description 41
- 239000010410 layer Substances 0.000 claims abstract description 42
- 239000003814 drug Substances 0.000 claims abstract description 36
- 229940079593 drug Drugs 0.000 claims abstract description 22
- 239000011159 matrix material Substances 0.000 claims abstract description 19
- 239000012790 adhesive layer Substances 0.000 claims abstract description 15
- ZSBXGIUJOOQZMP-UHFFFAOYSA-N Isomatrine Natural products C1CCC2CN3C(=O)CCCC3C3C2N1CCC3 ZSBXGIUJOOQZMP-UHFFFAOYSA-N 0.000 claims abstract description 14
- ZSBXGIUJOOQZMP-JLNYLFASSA-N Matrine Chemical compound C1CC[C@H]2CN3C(=O)CCC[C@@H]3[C@@H]3[C@H]2N1CCC3 ZSBXGIUJOOQZMP-JLNYLFASSA-N 0.000 claims abstract description 14
- 229930014456 matrine Natural products 0.000 claims abstract description 14
- RSKPJCDZAFMWHH-UHFFFAOYSA-N 3-but-1-enyl-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(C=CCC)OC(=O)C2=C1 RSKPJCDZAFMWHH-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011241 protective layer Substances 0.000 claims abstract description 12
- -1 polypropylene Polymers 0.000 claims description 26
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 22
- 229920006267 polyester film Polymers 0.000 claims description 10
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 7
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 7
- 239000005642 Oleic acid Substances 0.000 claims description 7
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000004698 Polyethylene Substances 0.000 claims description 7
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 7
- 229920000573 polyethylene Polymers 0.000 claims description 7
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical group CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 6
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000004743 Polypropylene Substances 0.000 claims description 6
- IUKLSMSEHKDIIP-BZMYINFQSA-N Verticine Chemical compound C([C@@H]1[C@@H](O)C[C@H]2[C@@H]3CC[C@@H]4[C@]5(C)O)[C@@H](O)CC[C@]1(C)[C@H]2C[C@H]3[C@@H]4CN1[C@H]5CC[C@H](C)C1 IUKLSMSEHKDIIP-BZMYINFQSA-N 0.000 claims description 6
- 239000010642 eucalyptus oil Substances 0.000 claims description 6
- 229940044949 eucalyptus oil Drugs 0.000 claims description 6
- 229940041616 menthol Drugs 0.000 claims description 6
- IUKLSMSEHKDIIP-UHFFFAOYSA-N petine Natural products CC1(O)C2CCC3C4CC(O)C5CC(O)CCC5(C)C4CC3C2CN2C1CCC(C)C2 IUKLSMSEHKDIIP-UHFFFAOYSA-N 0.000 claims description 6
- 229920000139 polyethylene terephthalate Polymers 0.000 claims description 6
- 239000005020 polyethylene terephthalate Substances 0.000 claims description 6
- 229920001155 polypropylene Polymers 0.000 claims description 6
- 229920001296 polysiloxane Polymers 0.000 claims description 6
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 6
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 6
- 229920002367 Polyisobutene Polymers 0.000 claims description 5
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical group [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
- 239000000022 bacteriostatic agent Substances 0.000 claims description 4
- 239000002131 composite material Substances 0.000 claims description 4
- 239000011888 foil Substances 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000004302 potassium sorbate Substances 0.000 claims description 4
- 229940069338 potassium sorbate Drugs 0.000 claims description 4
- 235000010241 potassium sorbate Nutrition 0.000 claims description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 3
- 239000003623 enhancer Substances 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 239000005038 ethylene vinyl acetate Substances 0.000 claims description 3
- 229960002969 oleic acid Drugs 0.000 claims description 3
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- 241000416162 Astragalus gummifer Species 0.000 claims description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 2
- 241000628997 Flos Species 0.000 claims description 2
- 244000178870 Lavandula angustifolia Species 0.000 claims description 2
- 235000010663 Lavandula angustifolia Nutrition 0.000 claims description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 240000007164 Salvia officinalis Species 0.000 claims description 2
- 235000002912 Salvia officinalis Nutrition 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 229920001615 Tragacanth Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 229960003237 betaine Drugs 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- 239000012943 hotmelt Substances 0.000 claims description 2
- 239000001102 lavandula vera Substances 0.000 claims description 2
- 235000018219 lavender Nutrition 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 2
- 235000002020 sage Nutrition 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000196 tragacanth Substances 0.000 claims description 2
- 235000010487 tragacanth Nutrition 0.000 claims description 2
- 229940116362 tragacanth Drugs 0.000 claims description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 238000002360 preparation method Methods 0.000 abstract description 9
- 241000700199 Cavia porcellus Species 0.000 abstract description 7
- OVHUAFPHYGFWPY-UHFFFAOYSA-N Imperialin Natural products CC1CN2CC3C(CCC4C3CC5C4CC(=O)C6CC(O)CCC56C)CC2C(C)(O)C1 OVHUAFPHYGFWPY-UHFFFAOYSA-N 0.000 abstract description 7
- IQDIERHFZVCNRZ-YUYPDVIUSA-N Imperialine Chemical compound C([C@@H]1C(=O)C[C@H]2[C@@H]3CC[C@@H]4[C@]5(C)O)[C@@H](O)CC[C@]1(C)[C@H]2C[C@H]3[C@@H]4CN1[C@H]5CC[C@H](C)C1 IQDIERHFZVCNRZ-YUYPDVIUSA-N 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 210000004969 inflammatory cell Anatomy 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 210000000222 eosinocyte Anatomy 0.000 abstract description 4
- 230000002829 reductive effect Effects 0.000 abstract description 3
- 238000010171 animal model Methods 0.000 abstract description 2
- 239000000427 antigen Substances 0.000 abstract description 2
- 102000036639 antigens Human genes 0.000 abstract description 2
- 108091007433 antigens Proteins 0.000 abstract description 2
- 231100000673 dose–response relationship Toxicity 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 230000004044 response Effects 0.000 abstract description 2
- 238000011156 evaluation Methods 0.000 abstract 1
- 210000004072 lung Anatomy 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000011248 coating agent Substances 0.000 description 10
- 238000000576 coating method Methods 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- 241000700198 Cavia Species 0.000 description 8
- 235000019504 cigarettes Nutrition 0.000 description 7
- 239000000779 smoke Substances 0.000 description 7
- 238000000643 oven drying Methods 0.000 description 6
- 238000013329 compounding Methods 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 210000003979 eosinophil Anatomy 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920002379 silicone rubber Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 241000935235 Fritillaria meleagris Species 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WMBOCUXXNSOQHM-FLIBITNWSA-N (Z)-3-butylidenephthalide Chemical compound C1=CC=C2C(=C/CCC)/OC(=O)C2=C1 WMBOCUXXNSOQHM-FLIBITNWSA-N 0.000 description 1
- KSDSYIXRWHRPMN-UHFFFAOYSA-N 4'-O-beta-D-Galactopyranoside-6''-p-Coumaroylprunin-4',5,7-Trihydroxyflavanone Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C2OC3=CC(O)=CC(O)=C3C(=O)C2)C=C1 KSDSYIXRWHRPMN-UHFFFAOYSA-N 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 241000213006 Angelica dahurica Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- DEMKZLAVQYISIA-ONJCETCRSA-N Liquiritin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)c1ccc([C@@H]2Oc3c(C(=O)C2)ccc(O)c3)cc1 DEMKZLAVQYISIA-ONJCETCRSA-N 0.000 description 1
- DEMKZLAVQYISIA-UHFFFAOYSA-N Liquirtin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C2OC3=CC(O)=CC=C3C(=O)C2)C=C1 DEMKZLAVQYISIA-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029888 Obliterative bronchiolitis Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 201000003848 bronchiolitis obliterans Diseases 0.000 description 1
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- DEMKZLAVQYISIA-ZRWXNEIDSA-N liquiritin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C([C@H]2OC3=CC(O)=CC=C3C(=O)C2)C=C1 DEMKZLAVQYISIA-ZRWXNEIDSA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- WMBOCUXXNSOQHM-UHFFFAOYSA-N n-butylidenephthalide Natural products C1=CC=C2C(=CCCC)OC(=O)C2=C1 WMBOCUXXNSOQHM-UHFFFAOYSA-N 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- GSZUGBAEBARHAW-UHFFFAOYSA-N sophoraflavone B Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(C=2OC3=CC(O)=CC=C3C(=O)C=2)C=C1 GSZUGBAEBARHAW-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7092—Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明提供了一种治疗慢性阻塞性肺疾病的贴剂，由包括背衬层、含药骨架层、粘合剂层和保护层组成，含药骨架层由有效成分丁烯基苯酞、苦参碱、贝母甲素以及药学上可接受的基质构成。本发明还提供了该贴剂的制剂处方及工艺方法。本发明的在一个目的是提供所述贴剂在制备治疗慢性阻塞性肺疾病药物中的应用。本发明贴剂为储库型贴剂，能够直接作用于患处，起效快，疗效好，通过COPD动物模型评价，证实其能呈剂量依赖抑制致敏豚鼠抗原攻击后BALF中嗜酸粒细胞升高，同时高剂量贴剂组嗜酸性粒细胞的比例也有显著下降，提示贴剂有抑制COPD炎症细胞渗出的作用，具有潜在的抗COPD的作用，具有临床应用价值，可用于治疗慢性阻塞性肺疾病。
Description
技术领域
本发明属医药技术领域，具体涉及治疗慢性阻塞性肺疾病的贴剂药物，是一种以丁烯基苯酞、苦参碱、贝母甲素为原料制备的具有治疗COPD药效的贴剂药物。
背景技术
慢性阻塞性肺病(Chronic Obstructive Pulmonary Disease，COPD)是以不完全可逆的气流受限为特征的疾病，是小气道病变(闭塞性细支气管炎)和肺实质破坏(肺气肿)共同作用的结果。COPD是世界范围内严重危害公众健康的主要病种之一，据世卫组织预测，到2030年慢性阻塞性肺病将成为仅次于心脑血管疾病和肿瘤的全世界第三大死因。2007年我国对7个地区20245成年人群进行的调查显示，COPD患病率在40岁以上人群中高达8.2％。COPD不仅仅患病率高，而且病程呈进行性发展，可引起劳动力丧失、生活质量减退，最终导致的致残、致死率也很高。
迄今为止COPD的发病机制尚未完全明了，而普遍认为COPD的发病机制主要包括气道、肺实质和肺血管的慢性炎症、氧化应激、肺部的蛋白酶/抗蛋白酶失衡、慢性黏液高分泌以及自主神经系统功能紊乱(如胆碱能神经受体分布异常)等。根据COPD的主要特征，改善气流受限和控制炎症反应是目前临床上的主要治疗措施。
前期研究中我们以《金匮要略》所载经方“当归贝母苦参丸”复方为基础，通过超临界流体萃取和大孔树脂技术分别精制得到当归挥发油和贝母苦参总生物碱有效部位，从而研发出对COPD具有明确治疗作用的有效组分中药(ZL 200810061131.5)。
我们进一步研究发现，该组方中起主要作用的分别为三种类型的有效成分，通过其有效成分组方，可以发挥更好的药效，通过制剂处方筛选和工艺优化制备贴剂，能够使得药物经皮吸收，发挥良好的药效，同时避免了中药成分复杂带来的临床风险。
发明内容
本发明的目的是提供一种治疗慢性阻塞性肺疾病的贴剂，具有抗慢性阻塞性肺病(COPD)的活性，所述的贴剂由背衬层、含药骨架层、粘合剂层和保护层组成，含药骨架层由有效成分及药学上可接受的基质构成，其中有效成分是由丁烯基苯酞、苦参碱、贝母甲素三种化合物按照质量比丁烯基苯酞10～30％，苦参碱50～70％，贝母甲素10～20％的比例组成。
三种有效成分的结构式如下：
所述含药骨架层中的基质选自乙烯-醋酸乙烯共聚物丙烯酸(EVA)、甲基纤维素(MC-Na)、乙基纤维素(EC)、羧甲基纤维素钠(CMC-Na)、聚乙烯醇(PVA)、聚乙烯吡咯烷酮(PVP)、羟丙基甲基纤维素(HPMC)、聚丙烯(PP)、聚乙烯(PE)、聚对苯二甲酸乙二酯(PET)、聚乙二醇、丙烯酸树脂、西黄蓍胶、明胶中的一种或两种以上的混合物。
所述的粘合剂层选自聚异丁烯类压敏胶、丙烯酸类压敏胶、硅橡胶压敏胶、聚硅氧烷压敏胶、热熔压敏胶、聚丙烯(PP)、聚乙烯(PE)、聚对苯二甲酸乙二酯(PET)中的一种或两种以上混合物，不含药物或含部分药物作为负荷剂量。
所述的粘合剂层中含有天然透皮促进剂，选自薄荷醇、油酸、桉叶油等，用量为0-10％。所述的粘合剂层中含有保湿剂，选自甘油、丙二醇、山梨醇等，用量为0-10％。
所述的含药骨架层中含有天然透皮促进剂、表面活性剂、抑菌剂，天然透皮促进剂选自薄荷醇、油酸、桉叶油等，用量为0-10％。表面活性剂选自硬脂酸，十二烷基苯磺酸钠，季铵化物，卵磷脂，氨基酸型，甜菜碱型，脂肪酸甘油酯，脂肪酸山梨坦(司盘)，聚山梨酯(吐温)等，用量为0-10％。抑菌剂选自山梨酸钾、丁香、薰衣草、迷迭香、鼠尾草等，用量为0-10％。
背衬层选自聚四氟乙烯膜、聚酯膜、复合铝箔、聚酯膜等。
本发明的另一个目的是提供所述的贴剂的制备方法，通过以下步骤实现：
(1)先配制空白基质，然后将化合物丁烯基苯酞、苦参碱、贝母甲素加入95％乙醇溶液溶解，加入透皮促进剂、表面活性剂、抑菌剂，搅拌均匀，与空白基质混和均匀得含药骨架层，涂布在背衬层上，烘干；
(2)另取不含药的粘合剂，加入透皮促进剂、保湿剂，混合均匀涂布在保护层上，烘干；
(3)将背衬层上涂有含药骨架层一面与粘合剂层复合；
(4)剪裁成1-100cm2的形状，总厚度≤50mm，得成品。
本发明的再一个目的是提供所述贴剂在制备治疗慢性阻塞性肺疾病药物中的应用。本发明所述的治疗COPD的贴剂的释药面积为1-100cm2，总厚度≤50mm，持续释药时间为1-7天。
本发明贴剂为储库型贴剂，能够直接作用于患处，起效快，疗效好，经Hartley品系豚鼠COPD模型动物实验证明其能呈剂量依赖抑制致敏豚鼠抗原攻击后BALF中嗜酸粒细胞升高，同时高剂量贴剂组嗜酸性粒细胞的比例也有显著下降，提示贴剂有抑制COPD炎症细胞渗出的作用，具有潜在的抗COPD的作用，具有临床应用价值，可用于治疗慢性阻塞性肺疾病。
附图说明
图1是贴剂药物对不同组别豚鼠肺组织炎症的影响(HE染色法×400)。
图2是凝胶贴膏对肺泡灌洗液中白细胞总数及嗜酸性粒细胞比例的影响。
具体实施方式
本发明结合附图和具体实施例作进一步说明。
实施例1
本发明贴剂由背衬层、含药骨架层、粘合剂层和保护层组成，具体各层所用材料如下：
背衬层：聚四氟乙烯膜，
粘合剂层：空白聚异丁烯类压敏胶，
保护层：防粘纸，
含药骨架层有效成分组成如下(100贴)：
丁烯基苯酞：苦参碱：贝母甲素按照1:0.5:0.1摩尔比混合，共8g，
明胶 1g
油酸 0.5g
山梨酸钾 0.1g
制备工艺：(1)先将明胶加入水中得空白基质，然后将丁烯基苯酞、苦参碱、贝母甲素加入95％乙醇溶解，加入油酸、山梨酸钾，与空白基质混和均匀得含药骨架层，涂布在聚四氟乙烯膜上，烘干；
(2)取空白聚异丁烯类压敏胶涂布在防粘纸上，烘干；
(3)将步骤(1)涂有有效成分的一面与步骤(2)中涂有聚异丁烯类压敏胶的一面复合；
(4)剪裁成1-100cm2的形状，得成品。
实施例2
本发明贴剂由背衬层、含药骨架层、粘合剂层和保护层组成，具体各层所用材料如下：
背衬层：聚酯膜
粘合剂层：空白丙烯酸类压敏胶
保护层：金属塑料
含药骨架层有效成分组成如下(100贴)：
丁烯基苯酞：苦参碱：贝母甲素按照1:0.2:0.5摩尔比混合 共4g
CMC-Na 1.5g
薄荷醇 0.8g
制备工艺：
(1)先将CMC-Na加入水中得空白基质，然后将丁烯基苯酞、苦参碱、贝母甲素加入95％乙醇溶解，，加入0.4g薄荷醇，与空白基质混和均匀得含药骨架层，涂布在聚酯膜上，烘干；
(2)取空白丙烯酸类压敏胶，加入0.4g薄荷醇，搅拌均匀，涂布在金属塑料上，烘干；
(3)将步骤(1)中涂有有效成分的一面与步骤(2)中涂有丙烯酸类压敏胶的一面复合；
(4)剪裁成1-100cm2的形状，得成品。
实施例3.
本发明贴剂由背衬层、含药骨架层、粘合剂层和保护层组成，具体各层所用材料如下：
背衬层：复合铝箔
粘合剂层：空白聚硅氧烷压敏胶
保护层：聚酯膜
含药骨架层有效成分组成如下(100贴)：
丁烯基苯酞：苦参碱：贝母甲素按照1:1:0.8摩尔比混合 共10g
聚乙烯醇 1.5g
吐温 0.1g
桉叶油 0.2g
制备工艺：
(1)先将聚乙烯醇加入水中得空白基质，然后将丁烯基苯酞、苦参碱、贝母甲素加入95％乙醇溶解，加入吐温、桉叶油，与空白基质混和均匀得含药骨架层，涂布在复合铝箔上，烘干；
(2)取空白聚硅氧烷压敏胶涂布在聚酯膜上，烘干；
(3)将步骤(1)中涂有有效成分的一面与步骤(2)中涂有聚硅氧烷压敏胶的一面复合；
(4)剪裁成1-100cm2的形状，得成品。
实施例4中试制备
本发明贴剂由背衬层、含药骨架层、粘合剂层和保护层组成，具体各层所用材料如下：
背衬层：聚酯膜
粘合剂层：空白硅橡胶压敏胶
保护层：聚乙烯薄膜
含药骨架层有效成分组成如下(10000贴)：
丁烯基苯酞：苦参碱：贝母甲素按照1:1:0.5摩尔比混合 共1000g
羟丙甲基纤维素 160g 甘油 适量
油酸 9g
桉叶油 9g
制备工艺：
(1)先将羟丙甲基纤维素加入水中得空白基质，然后将丁烯基苯酞、苦参碱、贝母甲素加入95％乙醇溶解，加入油酸、桉叶油，与空白基质混和均匀得含药骨架层，涂布在聚酯膜上，烘干；
(2)取空白硅橡胶压敏胶，加适量甘油，混合均匀涂布在聚乙烯薄膜上，烘干；
(3)将步骤(1)中涂有有效成分的一面与步骤(2)中涂有硅橡胶压敏胶的一面复合；
(4)剪裁成1-100cm2的形状，得成品。
实施例5 贴剂药物对COPD模型豚鼠的影响
(1)豚鼠急性吸烟早期COPD模型：依据文献(GUAN Y,LI F F,HONG L.Protectiveeffects of liquiritin apioside on cigarette smoke-induced lung epithelialcell injury[J].Fundam Clin Pharmacol,2012,26(4):473-483.)中的方法为基础，豚鼠在熏烟装置中使用香烟连续吸烟4天，装置内温度维持在25℃左右。第l天，上下午各使用两包万宝路香烟，进行烟雾暴露；第2天，上下午各使用3包香烟进行烟雾暴露；第3天和第4天，上下午各使用5包香烟进行烟雾暴露。每天暴露两次。每包香烟烟雾暴露持续20分钟，在烟雾暴露同时进行通风。最后一次香烟烟雾攻击15h后对实验动物进行处理。空白组使用空气进行暴露。
(2)实验分组：Hartley品系豚鼠，雌雄兼用，体重250-300g，浙江大学实验动物中心提供，合格证号：医动字第20020016号。每一批动物数量和分组情况具体如下：豚鼠分为6组，每组8-12只，雌雄各半：正常对照组，COPD模型组(COPD模型豚鼠)，阳性对照组(1mg/kg地塞米松)，10mg/kg、20mg/kg、30mg/kg剂量贴剂治疗组(即低、中、高剂量组)。
(3)取气管左主支气管作横切面，肺取左叶，均经4％甲醛固定、漂洗、脱水、透明和石蜡包埋，制备石蜡切片，HE染色观察肺组织炎症细胞浸润及结构变化。
(4)BALF中白细胞计数和分类的测定：
COPD豚鼠末次攻击后股动脉放血处死豚鼠，右肺结扎，用生理盐水1.5ml进行左侧肺支气管肺泡灌洗，分3次，所得灌洗液放置冰上。将肺泡灌洗液振荡摇匀，取50ul，用炎症细胞计数液稀释10倍，用细胞计数板在显微镜下进行计数。余肺泡灌洗液2000rpm离心,取取右肺-80℃保存备用。
以1：3比例加入白细胞计数液，用细胞计数板计数白细胞总数，再以2000rpm离心l0min，取细胞沉淀涂片，凉干后行Wright染色，做细胞分类计数，计算嗜酸性粒细胞绝对数
(5)结果表明与正常豚鼠比较，COPD豚鼠具有非常明显的过敏性炎症反应，白细胞总数、嗜酸粒细胞、中性粒细胞和淋巴细胞明显增多(附图1)。药物贴剂呈剂量依赖抑制COPD豚鼠BALF中嗜酸粒细胞升高，同时高剂量贴剂组嗜酸性粒细胞的比例也有显著下降，提示贴剂具有一定的抑制COPD炎症细胞渗出的作用(附图2)。
Claims (5)
1.一种治疗慢性阻塞性肺疾病的贴剂，所述的贴剂药物由背衬层、含药骨架层、粘合剂层和保护层组成，其特征在于，含药骨架层由有效成分及药学上可接受的基质构成，其中有效成分是由丁烯基苯酞、苦参碱、贝母甲素三种化合物按照质量比丁烯基苯酞10~30%，苦参碱50~70%，贝母甲素10~20%的比例组成，所述的含药骨架层中含有天然透皮促进剂、表面活性剂和抑菌剂，天然透皮促进剂用量选自薄荷醇、油酸、桉叶油，用量为1.5-5.2%，表面活性剂选自硬脂酸，十二烷基苯磺酸钠，季铵化物，卵磷脂，氨基酸型，甜菜碱型，脂肪酸甘油酯，脂肪酸山梨坦，聚山梨酯，用量为0.85%，抑菌剂选自山梨酸钾、丁香、薰衣草、迷迭香、鼠尾草，用量为1.0%。
2.根据权利要求1所述的一种治疗慢性阻塞性肺疾病的贴剂，其特征在于，所述基质选用乙烯-醋酸乙烯共聚物丙烯酸、甲基纤维素、乙基纤维素、羧甲基纤维素钠、聚乙烯醇、聚乙烯吡咯烷酮、羟丙基甲基纤维素、聚丙烯、聚乙烯、聚对苯二甲酸乙二酯、聚乙二醇、丙烯酸树脂、西黄蓍胶、明胶中的一种或两种以上的混合物。
3.根据权利要求1所述的一种治疗慢性阻塞性肺疾病的贴剂，其特征在于，所述粘合剂层选用聚异丁烯类压敏胶、丙烯酸类压敏胶、硅橡胶压敏胶、聚硅氧烷压敏胶、热熔压敏胶、聚丙烯、聚乙烯、聚对苯二甲酸乙二酯中的一种或两种以上混合物，不含药物或含部分药物作为负荷剂量。
4.根据权利要求1所述的一种治疗慢性阻塞性肺疾病的贴剂，其特征在于，背衬层选自聚四氟乙烯膜、聚酯膜、复合铝箔、聚酯膜。
5.根据权利要求1所述的贴剂在制备治疗慢性阻塞性肺疾病药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711192893.4A CN107929266B (zh) | 2017-11-24 | 2017-11-24 | 一种治疗慢性阻塞性肺疾病的贴剂 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711192893.4A CN107929266B (zh) | 2017-11-24 | 2017-11-24 | 一种治疗慢性阻塞性肺疾病的贴剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107929266A CN107929266A (zh) | 2018-04-20 |
| CN107929266B true CN107929266B (zh) | 2020-07-03 |
Family
ID=61948705
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711192893.4A Active CN107929266B (zh) | 2017-11-24 | 2017-11-24 | 一种治疗慢性阻塞性肺疾病的贴剂 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107929266B (zh) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1041725C (zh) * | 1992-11-12 | 1999-01-20 | 兰州大学 | 一种合成3－丁烯基苯酞的方法 |
| CN101234168B (zh) * | 2008-03-11 | 2010-09-29 | 浙江大学 | 一种复方当归制剂及制备方法和用途 |
| CN101822652B (zh) * | 2009-03-03 | 2013-10-16 | 杭州民生药业有限公司 | 长春西汀透皮贴剂及其制备方法 |
| CN101838253A (zh) * | 2009-03-20 | 2010-09-22 | 马良伟 | 一种藁本内酯及丁烯基苯酞的制备方法 |
| CN104940260A (zh) * | 2014-03-31 | 2015-09-30 | 江苏省中医药研究院 | 一种快速干燥新鲜当归整根的加工方法 |
-
2017
- 2017-11-24 CN CN201711192893.4A patent/CN107929266B/zh active Active
Non-Patent Citations (1)
| Title |
|---|
| "高异黄酮及当归贝母苦参方的有效部位研究";陈金杰;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20150115;第40-42页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107929266A (zh) | 2018-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101371845B (zh) | 一种用于治疗口腔溃疡药物组合物 | |
| CN106581401B (zh) | 一种中药复方凝胶贴膏膏剂及其制备方法和用途 | |
| WO2017063448A1 (zh) | 治疗银屑病的中药组合物 | |
| CN101417013A (zh) | 一种用于风湿骨痛的中药巴布剂及其制备方法 | |
| CN102380015B (zh) | 治疗类风湿性关节炎的药物组合物及其制备方法和用途 | |
| WO2016119220A1 (zh) | 杜仲叶提取物及其制备方法和用途 | |
| CN103520129B (zh) | 一种孟鲁斯特钠脉冲释放制剂 | |
| CN104546928B (zh) | 一种治疗小儿尿布疹的中药组合物及其制备方法 | |
| CN107929266B (zh) | 一种治疗慢性阻塞性肺疾病的贴剂 | |
| CN101095800A (zh) | 一种用于治疗口腔溃疡的贴片的研制 | |
| CN101278948A (zh) | 一种生物型药膜及其制备方法 | |
| CN1814025A (zh) | 解毒止痒中药组合物及其制备方法 | |
| CN100525797C (zh) | 一种阴道外用药物组合物及其制备方法和用途 | |
| WO2007144081A2 (de) | Raucherentwöhnungs-kombinationswafer | |
| CN113995821B (zh) | 一种治疗新型冠状病毒及其它病毒肺炎的中药组合物、制剂及制备方法 | |
| CN114796183B (zh) | 益母草碱在制备用于预防或治疗呼吸系统疾病的药物中的应用 | |
| WO2009062374A1 (fr) | Utilisation pharmaceutique de liquiritigénine pour préparer un médicament destiné au traitement de maladies neurodégénératives | |
| CN110859914B (zh) | 一种治疗口腔溃疡的中药贴膜 | |
| CN101337026A (zh) | 一种治疗痛风的外用药物组合物 | |
| CN108159114B (zh) | 独一味总环烯醚萜苷提取物、提取方法及其应用 | |
| CN110833621A (zh) | 多巴胺受体1拮抗剂在制备治疗对氯胺酮致小鼠类精神分裂症药物上的应用 | |
| CN114748527B (zh) | 一种治疗婴幼儿湿疹、皮炎的复方龙胆凝胶 | |
| CN110755508B (zh) | 一种消肿止痒中药组合物及其制备方法 | |
| CN113876844B (zh) | 一种用于治疗慢性气管炎的纯中药藏药及其制备方法和应用 | |
| CN100431590C (zh) | 治疗咳喘的中药组合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |