CN102772417B - Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof - Google Patents
Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof Download PDFInfo
- Publication number
- CN102772417B CN102772417B CN201210258378.2A CN201210258378A CN102772417B CN 102772417 B CN102772417 B CN 102772417B CN 201210258378 A CN201210258378 A CN 201210258378A CN 102772417 B CN102772417 B CN 102772417B
- Authority
- CN
- China
- Prior art keywords
- stickiness
- elastomeric matrices
- testosterone
- patch
- layer
- 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
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims abstract description 112
- 229960003604 testosterone Drugs 0.000 title claims abstract description 56
- 239000000758 substrate Substances 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 230000000694 effects Effects 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 71
- 238000002844 melting Methods 0.000 claims abstract description 8
- 230000008018 melting Effects 0.000 claims abstract description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 229920005989 resin Polymers 0.000 claims description 36
- 239000011347 resin Substances 0.000 claims description 36
- VSKJLJHPAFKHBX-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 VSKJLJHPAFKHBX-UHFFFAOYSA-N 0.000 claims description 25
- 239000004014 plasticizer Substances 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 239000002202 Polyethylene glycol Substances 0.000 claims description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims description 16
- 229940057995 liquid paraffin Drugs 0.000 claims description 15
- 239000003208 petroleum Substances 0.000 claims description 14
- 229920002725 thermoplastic elastomer Polymers 0.000 claims description 14
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 13
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 13
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 12
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical group O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 11
- 229920001083 polybutene Polymers 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 239000003921 oil Substances 0.000 claims description 10
- 235000019198 oils Nutrition 0.000 claims description 10
- 229920000428 triblock copolymer Polymers 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 9
- 235000010603 pastilles Nutrition 0.000 claims description 9
- -1 alkane ketone Chemical class 0.000 claims description 8
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 8
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
- 239000000463 material Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 6
- 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 4
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 4
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 claims description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 4
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 claims description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 4
- 230000033444 hydroxylation Effects 0.000 claims description 4
- 238000005805 hydroxylation reaction Methods 0.000 claims description 4
- 239000000787 lecithin Substances 0.000 claims description 4
- 235000010445 lecithin Nutrition 0.000 claims description 4
- 229940067606 lecithin Drugs 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229920005996 polystyrene-poly(ethylene-butylene)-polystyrene Polymers 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- ONKUXPIBXRRIDU-UHFFFAOYSA-N Diethyl decanedioate Chemical compound CCOC(=O)CCCCCCCCC(=O)OCC ONKUXPIBXRRIDU-UHFFFAOYSA-N 0.000 claims description 2
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 claims description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000005639 Lauric acid Substances 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920002367 Polyisobutene Polymers 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 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
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- BXOUVIIITJXIKB-UHFFFAOYSA-N ethene;styrene Chemical group C=C.C=CC1=CC=CC=C1 BXOUVIIITJXIKB-UHFFFAOYSA-N 0.000 claims description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 2
- 229940093471 ethyl oleate Drugs 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 235000000396 iron Nutrition 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- 229940041616 menthol Drugs 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
- 239000002480 mineral oil Substances 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound 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
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 239000004006 olive oil Substances 0.000 claims description 2
- 235000008390 olive oil Nutrition 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- 229920001568 phenolic resin Polymers 0.000 claims description 2
- 239000005011 phenolic resin Substances 0.000 claims description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 229920002545 silicone oil Polymers 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 229940032094 squalane Drugs 0.000 claims description 2
- 229940031439 squalene Drugs 0.000 claims description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 150000003505 terpenes Chemical class 0.000 claims description 2
- 235000007586 terpenes Nutrition 0.000 claims description 2
- 229940099259 vaseline Drugs 0.000 claims description 2
- 229940117958 vinyl acetate Drugs 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 abstract description 10
- 238000000576 coating method Methods 0.000 abstract description 10
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 230000035699 permeability Effects 0.000 abstract description 4
- 238000011068 loading method Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract 2
- 230000000149 penetrating effect Effects 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 42
- 238000012360 testing method Methods 0.000 description 29
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 28
- 229940079593 drug Drugs 0.000 description 24
- 239000000203 mixture Substances 0.000 description 16
- 239000011787 zinc oxide Substances 0.000 description 14
- 239000000523 sample Substances 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 206010040880 Skin irritation Diseases 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 230000005540 biological transmission Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- 231100000475 skin irritation Toxicity 0.000 description 6
- 230000036556 skin irritation Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000004606 Fillers/Extenders Substances 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 206010040844 Skin exfoliation Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 206010002198 Anaphylactic reaction Diseases 0.000 description 3
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000004026 adhesive bonding Methods 0.000 description 3
- 230000036783 anaphylactic response Effects 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 235000008429 bread Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000011505 plaster Substances 0.000 description 3
- 230000008313 sensitization Effects 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000035617 depilation Effects 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 231100000021 irritant Toxicity 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229920006268 silicone film Polymers 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 241000521257 Hydrops Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 241000276489 Merlangius merlangus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 239000005030 aluminium foil Substances 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003640 drug residue Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 201000003585 eunuchism Diseases 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229920003049 isoprene rubber Polymers 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical class OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 208000037106 male hypogonadism Diseases 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical group O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920006264 polyurethane film Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000009864 tensile test Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical class OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a period effect percutaneous patch of a self viscosity elastic body substrate covering and bearing testosterone and a preparation method thereof. The period effect percutaneous patch comprises a support layer, a medicine taking self viscosity elastic body substrate layer and a separation layer. The support layer is covered on one side of the medicine taking self viscosity elastic body substrate layer, and the separation layer is covered on the other side of the medicine taking self viscosity elastic body substrate layer. The period effect percutaneous patch adopts the lipotropy elastic body substrate with the low melting point to contain the testosterone, and a stable and effective testosterone blood concentration is maintained in 7 days. The patch is excellent in medicine skin penetrating performance, good in adhering performance, high in medicine loading rate, good in air permeability and free of residue when being stripped from the skin. A preparation process of the period effect percutaneous patch of the testosterone uses no machine solvent and is environment-friendly, coating is carried out in a melting state, and the preparation process has the advantages of being high in coating speed, high in production efficiency and low in cost.
Description
Technical field
The present invention relates to a kind of bag and carry testosterone from week effect percutaneous patch and the preparation method of stickiness elastomeric matrices.
Background technology
Testosterone belongs to androgen, is mainly used in treating the very few and complication such as the male hypogonadism that causes and the manlike obstacle of secondary sex characteristics of androgen secretion.Due to the existence of liver first-pass effect, testosterone is oral invalid, and bioavailability is extremely low; Though drug administration by injection has been avoided first pass effect, can cause that in body, peak valley effect appears in testosterone concentration.
Therefore, seeking a kind of preparation that is suitable for testosterone, is the problem that people are extremely concerned about.
Testosterone (testosterone) transdermal patch of U.S. FDA approval Waston drugmaker exploitation (trade name:
) listing,
for reservoir devices transdermal patch, compare matrix type patch (Drug-in-adhesive, DIA) and there is the slow feature of drug absorption, there is the problem of intravenous extravasation, in bank solution, contain ethanol, agents area is produced to strong impulse.
Therefore the transdermal administration that, trial is used for testosterone with matrix type patch is to solving the problem of above-mentioned existence.The medicine-releasing performance of acrylate pressure sensitive adhesive is limited, must just can reach the ideal concentration of drug release by increasing the content of principal agent.And the increase of drug content tends to cause other problems, as medicine crystallization between the storage life, drug loading causes greatly crude drug waste, and cost increases, and patch is used the problems such as rear drug residue.
The transdermal testosterone drug-supplying system product having gone on the market at present mainly contains testosterone patch, testosterone gel and testosterone spray, is 1 administration on the one, patient's medication inconvenience, poor compliance.
Summary of the invention
The object of this invention is to provide a kind of bag and carry testosterone from week effect percutaneous patch and the method for making of stickiness elastomeric matrices, the defect existing to overcome prior art.
Another object of the present invention is to provide a kind of bag and carries testosterone from stickiness elastomeric matrices.
Bag of the present invention carries testosterone from stickiness elastomeric matrices
From stickiness elastomeric matrices layer, the component by following percentage by weight forms described medicine carrying:
There is the lipotropy elastomeric matrices 90～99% from stickiness matter
Preferably, from stickiness elastomeric matrices layer, the component by following percentage by weight forms described medicine carrying:
There is the lipotropy elastomeric matrices 94～98% from stickiness matter
The described lipotropy elastomeric matrices having from stickiness matter, is comprised of the component of following parts by weight:
Preferably, described in there is the lipotropy elastomeric matrices from stickiness matter, by the component of following parts by weight, formed:
The described fusing point having from the lipotropy elastomeric matrices of stickiness matter is 60 ℃～100 ℃, under room temperature, is solid, is liquid under high temperature;
Described thermoplastic elastomer (TPE) is selected from one or more in the thermoplastic elastomer (TPE)s such as styrene-isoprene-phenylethene (SIS) triblock copolymer, s-B-S (SBS) triblock copolymer, hydroxylation styrene-ethylene/butylene-styrene (SEBS) triblock copolymer, hydroxylation styrene-ethylene/propylene-styrene (SEPS) triblock copolymer;
Styrene-isoprene-phenylethene (SIS) triblock copolymer modulus is low, there is good cohesiveness and stick performance, flexibility is good, melting viscosity is little, easily coating, there is the good compatibility with other components such as tackifiers, so optimization styrene-isoprene-styrene (SIS) triblock copolymer;
Tackifier is to affect the just key component of viscous force and pressure-sensitive of substrate, and the adhesion to skin is provided, and reduces the melting viscosity of pressure sensitive adhesive and is beneficial to coating.Can increase the cohesive strength of substrate with the good tackifier of the polyglass phase compatibility, can significantly reduce elastic modelling quantity and the cohesive strength of substrate with the good tackifier of the isoprene rubber phase compatibility, reduce the softening point of substrate, give just viscous force, pressure-sensitive and peel strength;
Described tackifier is selected from one or more in terpene resin, phenolic resins, indene resin, C5 hydrogenated petroleum resin, C9 hydrogenated petroleum resin, Petropols, abietic resin or Foral resin etc.Compare abietic resin, it is low that Foral resin has acid number, the advantage that skin irritation is little; Petropols have the advantages such as acid number is low, of light color, adhesion is good, softening point is low, antioxidant effect is good, good with the compatibility of thermoplastic elastomer (TPE), when being provided, reduces adhesive force the softening point of pressure sensitive adhesive, therefore, preferably Foral resin and Petropols are combined use as tackifier, and preferred weight ratio is: Foral portions of resin Petropols=1:1～1:3;
80～160 parts of the consumptions of tackifier, preferably 120～140 parts, if consumption is very few, substrate stickiness is not enough, and the transdermal patch of preparation can not stick with skin during medication; If consumption is too much, substrate stickiness is excessively strong, causes pain during from skin peeling, produces zest;
During plasticizer room temperature, be the liquid of low-viscosity, can reduce the cohesive strength of thermoplastic elastomer (TPE), improve flexibility and the original viscosity of substrate, increase the adaptability with skin, reduce the melting viscosity of substrate and be beneficial to coating.Available main plasticizer comprises liquid paraffin, silicone oil, naphthenic oil, mineral oil, Oleum Ricini, olive oil, vaseline, squalane, Squalene, polybutene or polyisobutylene etc.Liquid paraffin and polybutene are with low cost, little to skin irritation, so preferred liquid paraffin and polybutene combine and be used as main plasticizer, and preferred weight ratio is: liquid paraffin: polybutene=1:0.5～1:1.The consumption of main plasticizer is 40～100 parts, and preferably 60～100 parts, if the consumption of main plasticizer is very few, the bad adaptability of patch to skin, easily from skin peeling; If the consumption of main plasticizer is too much, the cohesiveness of hypothallus significantly declines, and when patch is peeled off, easily at skin, forms residue.
Co-plasticizer has the effect that promotes Drug Percutaneous Absorption when improving substrate cohesiveness.Available co-plasticizer comprises fatty acid ester (isopropyl myristate, adipic acid diisopropyl ester, ethyl sebacate etc., LA, triacetyl glycerine, ethyl oleate etc.), phthalate (dibutyl phthalate, diethyl phthalate etc.), polyhydric alcohol (Polyethylene Glycol, propylene glycol, glycerol, menthol etc.), organic acid (oleic acid, Palmic acid, stearic acid, salicylic acid, sad, capric acid, lauric acid etc.), phospholipid (lecithin, fabaceous lecithin, phosphatidyl glycerol, PHOSPHATIDYL ETHANOLAMINE etc.), N-methyl pyrrole irons alkane ketone, azone etc.Isopropyl myristate and Polyethylene Glycol are little to the destruction of substrate, transdermal amount that can significantly increasing medicament, cutaneous safety is good, therefore preferably isopropyl myristate and Polyethylene Glycol are combined and are used as extender plasticizer, and preferred weight ratio is: isopropyl myristate: Polyethylene Glycol=1: 0.5～1:1; The consumption of co-plasticizer is 20～50 parts, preferably 30～40 parts, if extender plasticizer consumption is very few, can not fully guarantee medicine transit dose for a long time, and blood drug level does not reach treatment concentration; If co-plasticizer consumption is too much, the increase of skin permeability reaches extreme value, and skin irritation is increased, and destroys the cohesive strength of hypothallus, easily causes that skin is residual while peeling off.
Primary plasticizer and extender plasticizer should have certain ratio, with 2:1～3:1, are advisable, and further preferably the consumption of main plasticizer is 60～100 parts, and the consumption of extender plasticizer is 30～40 parts;
Excipient can improve the dissolubility of substrate Chinese medicine, medicine is steady statue dispersed, avoid the formation of drug crystallization, guarantee the skin permeability of medicine, soft and the high resilience from stickiness lipotropy substrate forming, the adhesion and the stability that regulate substrate, made patch compliance is good, a little less than skin irritation.Available excipient comprises polyvinylpyrrolidone, cellulose derivative (methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose etc.), poloxamer, polyvinyl alcohol, vinylacetate, acrylic acid-2-ethyl caproite, methyl methacrylate, butyl methacrylate, dimethylaminoethyl methacrylate etc., preferably polyethylene ketopyrrolidine and acrylic acid-2-ethyl caproite are combined and are used as excipient, and preferred weight ratio is: polyvinylpyrrolidone: acrylic acid-2-ethyl caproite=1: 1～1:2; Consumption is 10～40 parts, preferably 10～20 parts.
Filler is mainly common inorganic salt and metal-oxide, can improve substrate performance, increases cohesive strength, improves the thermostability of substrate, reduces substrate cost.The granularity of filler should be as far as possible little, guarantees to be uniformly dispersed in substrate, and chemical inertness, does not react with other components of substrate.Available filler comprises calcium carbonate, magnesium carbonate, silicate, Pulvis Talci, aluminium hydroxide, zinc oxide, titanium oxide, calcium sulfate, barium sulfate etc.Zinc oxide particles is little, has slight antiseptic property, can in and some acidic components in tackifier, so preferential oxidation zinc, 10～40 parts of consumptions, preferably 10～20 parts.
Antioxidant can avoid the unsaturated molecule segment in the centre of thermoplastic elastomer (TPE) in preparation process owing to being heated or oxidation that high-speed stirred occurs and aging.Available antioxidant comprises dibenzylatiooluene (BHT) and esters derivative, tocopherol and esters derivative thereof, ascorbic acid and esters derivative thereof, butylated hydroxyarisol, propyl gallate, 2-mercaptobenzimidazole etc.Preferred dibenzylatiooluene, 2～10 parts of consumptions, preferably 2～5 parts.
Described have a preparation method from the lipotropy substrate of stickiness matter, comprises the steps:
(1) thermoplastic elastomer (TPE), antioxidant, primary plasticizer and extender plasticizer are heated under nitrogen protection to 160 ℃～180 ℃, until each component is in molten condition;
(2) temperature is adjusted to 100 ℃～120 ℃, add tackifier, excipient and filler, under nitrogen protection, continuing to be heated to each component stirs, cooling, obtain the lipotropy substrate from stickiness matter that has of clear, colorless, this substrate has lower softening point and coating temperature, sticks functional;
Provided by the invention have in the lipotropy substrate preparation method of stickiness matter, with an organic solvent do not avoid producing environmental pollution, has the feature of energy-conserving and environment-protective.In preparation process, by isolated air and high-speed stirred, reduce the heated time in matrix composition process, avoid occurring aging and oxidation.
Described bag carries testosterone from the week of stickiness elastomeric matrices effect percutaneous patch, comprises that shelf layer, medicine carrying are from stickiness elastomeric matrices layer and release layer;
Described shelf layer covers described medicine carrying from a side of stickiness elastomeric matrices layer, and described release layer covers described medicine carrying from the opposite side of stickiness elastomeric matrices layer;
Described shelf layer is for covering and support medicine carrying from stickiness elastomeric matrices layer, preferably good, the impervious material of pliability.The elasticity of shelf layer and draftability guarantee that patch is to the adaptability of skin and docile property, greatly the Transdermal absorption of the assurance medicine of degree.Optional shelf layer material comprises micro-porous permeable based polyurethane thin film or silicone film, its pore size 20～50 μ m, and porosity is 20%～50%, thickness is 30～50 μ m.The ideal thickness of shelf layer is 10～100 μ m, if thickness is excessive, the elasticity of shelf layer and draftability reduce, and makes can not fit the completely variation of skin of patch, and Drug Percutaneous Absorption declines; The present invention simultaneously requires to maintain the effect of 7 days, so the permeability of shelf layer is extremely important, and need to select air penetrability is 50g/cm
2/ hr～200g/cm
2good polyurethane film or the silicone film material of transparent performance of/hr, and assistant micropore design on material, its pore size 20～50 μ m, porosity is 20%～50%, more can guarantee to stick for a long time eupnea and the comfort level of skin.
Described release layer is the polyethylene film of fluorination treatment, and thickness is 60～80 μ m.Release layer material is release protecting film, for covering and protection hypothallus, removes before use.
Bag of the present invention carries the preparation method of imitating transdermal composition week of testosterone, comprises the steps:
(1) the lipotropy elastomeric matrices having from stickiness matter is heated to melting (70 ℃～90 ℃) under nitrogen protection, adds testosterone, mix homogeneously, makes the substrate of pastille;
(2) while hot the substrate of pastille is coated to shelf layer, release layer in cooling rear covering, die-cut by required size, obtain bag and carry testosterone from the week of stickiness elastomeric matrices effect percutaneous patch.
In the present invention, to the thickness of hypothallus is strict, do not limit especially.But if coating thickness is excessively thin, adhesion declines, and can not maintain medicine Stable Release; If coating thickness is blocked up, the medicine of hypothallus can not thoroughly discharge, and cost increases, and easily comes off during with the contact friction such as medicated clothing.Therefore, preferred coating thickness 20～100 μ m.
When the week effect transdermal composition that contains testosterone in the present invention is used, can be attached on patient's intact skin, dosage is one week 1 time, each 1 subsides, and area is with 30～60cm
2for suitable;
Because testosterone is fat-soluble strong compound, molecular weight, therefore, the present invention is prepared into Percutaneously administrable preparation, makes medicine see through skin and slowly discharges into blood and play whole body administration effect, maintains blood drug level stable, and safety is good.
This patch can be used the stable release that extends principal agent testosterone in 7 days continuously, has the stability of long term storage, good cutaneous safety and the suitable performance of sticking.
The present invention adopts the novel low melting point that has to hold and carry testosterone from the lipotropy substrate of stickiness matter, maintains one and stablize and effective testosterone blood drug level in 7 days.Patch drug transdermal performance of the present invention is excellent, stick functional, drug loading is high, good permeability, skin irritation are little, extended storage stability is good, from skin peeling noresidue, patient's medication is convenient, flexible, compliance is good.In the present invention, in the preparation process of the weekly-acting percutaneous patch of testosterone, do not use machine solvent, environmental friendliness is coated with under molten condition, has the advantages that coating speed is fast, production efficiency is high, with low cost.
Accompanying drawing explanation
Fig. 1 is the structural representation of the weekly-acting percutaneous transdermal composition that contains testosterone.
Fig. 2 is the release in vitro curve chart of imitating transdermal composition week that contains testosterone in embodiment 3～6.
Fig. 3 is the transdermal test in vitro accumulation transit dose curve chart of imitating transdermal composition week that contains testosterone in embodiment 3～6.
The specific embodiment
Referring to Fig. 1, the week effect transdermal composition that contains testosterone of the present invention, comprises shelf layer 1, medicine carrying controlled release matrix layer 2 and release layer 3; Described shelf layer 1 covers a side of described medicine carrying controlled release matrix layer 2, and described release layer 3 covers the opposite side of described medicine carrying controlled release matrix layer 2.
Below in conjunction with specific embodiment, further set forth the present invention.
These embodiment are only not used in and limit the scope of the invention for the present invention is described.Term " part " represents " weight portion " in an embodiment, unless otherwise defined.
There is the preparation from the lipotropy elastomeric matrices of stickiness matter:
Get 100g SIS (SIS), hydrogenated petroleum resin 140g, naphthenic oil 80g, isopropyl myristate 10g, Polyethylene Glycol 5g, N-Methyl pyrrolidone 15g, polyvinylpyrrolidone 10g, zinc oxide 10g, dibenzylatiooluene 2g.SIS, naphthenic oil, isopropyl myristate, Polyethylene Glycol, N-Methyl pyrrolidone and dibenzylatiooluene are heated to 160 ℃ under nitrogen protection; after each component melts, adjust the temperature to 100 ℃～120 ℃; add hydrogenated petroleum resin, polyvinylpyrrolidone and zinc oxide; continue heated and stirred 20min to the colloid that forms transparent and homogeneous; pour out while hot, cooling and get final product.
After measured, the fusing point having from the lipotropy elastomeric matrices of stickiness matter making is 87 ℃.
There is the preparation from the lipotropy elastomeric matrices of stickiness matter:
Get SIS (SIS) 100g, hydrogenated petroleum resin and each 60g of Foral resin, each 50g of liquid paraffin and polybutene, diethyl phthalate 20g, Polyethylene Glycol 10g, LA 10g, acrylic acid-2-ethyl caproite 20g, zinc oxide 10g, dibenzylatiooluene 5g.SIS, liquid paraffin, polybutene, diethyl phthalate, Polyethylene Glycol, LA and dibenzylatiooluene are heated to 180 ℃ under nitrogen protection; after each component melts, adjust the temperature to 100 ℃～120 ℃; add hydrogenated petroleum resin, Foral resin, acrylic acid-2-ethyl caproite and zinc oxide; continue heated and stirred 20min to the colloid that forms transparent and homogeneous; pour out while hot, cooling and get final product.
After measured, the fusing point having from the lipotropy elastomeric matrices of stickiness matter making is 72 ℃.
Containing the week of testosterone, imitate the preparation of transdermal composition:
[prescription] (in 1000)
Get SIS (SIS) 100g, hydrogenated petroleum resin 80g, Foral resin 40g, liquid paraffin 60g, naphthenic oil 40g, isopropyl myristate 10g, Polyethylene Glycol 10g, N-Methyl pyrrolidone 10g, methyl methacrylate 10g, polyvinylpyrrolidone 5g, zinc oxide 5g, dibenzylatiooluene 2g.
SIS, liquid paraffin, naphthenic oil, isopropyl myristate, Polyethylene Glycol, N-Methyl pyrrolidone and dibenzylatiooluene are heated under nitrogen protection to 160 ℃～180 ℃, after each component melts, adjust the temperature to 100 ℃～120 ℃, add hydrogenated petroleum resin, Foral resin, polyvinylpyrrolidone, methyl methacrylate and zinc oxide, under nitrogen protection, continue to be heated to each component and stir; Temperature is adjusted to 70 ℃～90 ℃, adds testosterone 22g, under nitrogen protection, continue to be heated to each component mix homogeneously; The substrate of pastille is coated in shelf layer while hot, release layer in cooling rear covering, die-cut by required size, make the weekly-acting percutaneous patch that contains testosterone.
Embodiment 4
Containing the week of testosterone, imitate the preparation of transdermal composition:
[prescription] (in 1000)
Get SIS (SIS) 100g, hydrogenated petroleum resin 90g, Foral resin 30g, naphthenic oil 60g, liquid paraffin 20g, polybutene 20g, azone 10g, Polyethylene Glycol 10g, N-Methyl pyrrolidone 10g, acrylic acid-2-ethyl caproite 10g, zinc oxide 10g, dibenzylatiooluene 5g.SIS, naphthenic oil, liquid paraffin, polybutene, azone, Polyethylene Glycol, N-Methyl pyrrolidone and dibenzylatiooluene are heated under nitrogen protection to 160 ℃～180 ℃, after each component melts, adjust the temperature to 100 ℃～120 ℃, add hydrogenated petroleum resin, Foral resin, acrylic acid-2-ethyl caproite and zinc oxide, under nitrogen protection, continue to be heated to each component and stir; Temperature is adjusted to 70 ℃～90 ℃, adds testosterone 7.5g, under nitrogen protection, continue to be heated to each component mix homogeneously; The substrate of pastille is coated in shelf layer while hot, release layer in cooling rear covering, die-cut by required size, make the weekly-acting percutaneous patch that contains testosterone.
Containing the week of testosterone, imitate the preparation of transdermal composition:
[prescription] (in 1000)
Get SIS (SIS) 100g, hydrogenated petroleum resin 120g, liquid paraffin 100g, azone 20g, N-Methyl pyrrolidone 10g, polyvinylpyrrolidone 15g, zinc oxide 10g, dibenzylatiooluene 2g.SIS, liquid paraffin, azone N-Methyl pyrrolidone and dibenzylatiooluene are heated to 160 ℃～180 ℃ under nitrogen protection, after each component melts, adjust the temperature to 100 ℃～120 ℃, add hydrogenated petroleum resin, polyvinylpyrrolidone and zinc oxide, under nitrogen protection, continue to be heated to each component and stir; Temperature is adjusted to 70 ℃～90 ℃, adds testosterone 18g, under nitrogen protection, continue to be heated to each component mix homogeneously; The substrate of pastille is coated in shelf layer while hot, release layer in cooling rear covering, die-cut by required size, make the weekly-acting percutaneous patch that contains testosterone.
Embodiment 6
Containing the week of testosterone, imitate the preparation of transdermal composition:
[prescription] (in 1000)
Get SIS (SIS) 100g, Foral resin 140g, naphthenic oil 100g, LA 20g, Polyethylene Glycol 10g, polyvinylpyrrolidone 10g, acrylic acid-2-ethyl caproite 10g, zinc oxide 10g, dibenzylatiooluene 5g.SIS, naphthenic oil, LA and dibenzylatiooluene are heated under nitrogen protection to 160 ℃～180 ℃, after each component melts, adjust the temperature to 100 ℃～120 ℃, add Foral resin, polyvinylpyrrolidone, acrylic acid-2-ethyl caproite and zinc oxide, under nitrogen protection, continue to be heated to each component and stir; Temperature is adjusted to 70 ℃～90 ℃, adds testosterone 15g, under nitrogen protection, continue to be heated to each component mix homogeneously; The substrate of pastille is coated in shelf layer while hot, release layer in cooling rear covering, die-cut by required size, make the weekly-acting percutaneous patch that contains testosterone.
Embodiment 7
The mensuration of sticking performance
1. the mensuration of viscous force at the beginning of
Use tensile testing machine to measure the first viscous force of patch.Test sample patch is cut out as throwing off release layer after 4cm * 4cm size, sticked in clean bread board, with 200g counterweight and dynamometer probe, push down sample 10s, dynamometer moves down moment and records the pulling force of sample to probe.METHOD FOR CONTINUOUS DETERMINATION 6 times, averages.The results are shown in Table 1.
2. hold the mensuration of viscous force
Patch is sticked in the bread board of vertical placement, with holding viscous force analyzer, measure.Test sample patch is cut out as throwing off release layer after 5cm * 4cm size, be parallel to the longitudinal of plate, paste at the clean rustless steel bread board being close to and rustless steel load plate middle part, with pressure roller on patch with the speed of (300 ± 10) mm/min back and forth roll extrusion once, guarantee that gluing place exists without bubble.Room temperature is vertically fixed on it on test stand after placing 20min, hangs the counterweight of certain mass along the length direction of patch, records the time that patch comes off.METHOD FOR CONTINUOUS DETERMINATION 6 times, averages.The results are shown in Table 1.
3. the mensuration of peel strength
Adopt 180 ° of disbonded tests to measure the peel strength of patch.Test sample patch is cut out as throwing off release layer after 10cm * 2cm size, be affixed on clean corrosion resistant plate, end is by the adhesive layer of patch and clean mylar gluing, with pressure roller on patch with the speed of (300 ± 10) mm/min back and forth roll extrusion once, guarantee that gluing place exists without bubble.Room temperature is placed 20～40min, and by thin film and corrosion resistant plate upper and lower being held on electronic stripping tester respectively, with (300 ± 10), mm/min peels off continuously, records the peel strength of patch.METHOD FOR CONTINUOUS DETERMINATION 6 times, averages.The results are shown in Table 1.
Embodiment 8
The mensuration of moisture-vapor transmission
The moisture-vapor transmission of transdermal patch is the important indicator of investigating its comfort level, and moisture-vapor transmission is higher, and breathability is better, is difficult for causing the stimulation anaphylaxis of skin, and skin is not prone to hydrops or whiting.Adopt weight reduction to measure the moisture-vapor transmission of patch.Getting nonhygroscopic floor space is circular test board and the patch to be measured of A, puts into (32 ± 2) ℃, and bottom covers in the thermostatic drier of anhydrous calcium chloride, after balance 6h, takes out.To the KNO that adds approximately 2/3rds in test board
3saturated solution, relative humidity (90 ± 5) %, throws off the release layer of test sample patch, faces down and covers on test board, after sealing and suitably cuts out test sample patch to edge, precise weighing (W containing glue
1).Test board is put into exsiccator, after 24h, take out and put to room temperature, (W weighs
2).By the moisture-vapor transmission of formula calculating below.METHOD FOR CONTINUOUS DETERMINATION 6 times, averages.The results are shown in Table 1.
Water vapour permeability=(W1-W2)/A
Table 1 has from the lipotropy substrate adhesion energy of stickiness matter and the result of the test of moisture-vapor transmission
Embodiment 9
The mensuration of patch vitro release
With percutaneous dispersion test instrument, investigate the release of medicine.The patch preparing is thrown off to release layer, and shelf layer upward, pastille object plane is fixed on the reception tank of Franz diffusion cell down, covers first pond and clamp with iron clamp.In acceptance pool, add release medium 60% alcoholic solution of ultrasonic degas.Diffusion area is 3.14cm
2, accepting volume is 7ml, and mixing speed is 250r/min, and the temperature of acceptable solution is controlled at (32 ± 0.5) ℃.1,2,4,6,8,10,12,14,24,48,72,96,120,144 and 168h after starting respectively at experiment takes out release medium 5ml(and supplements the fresh release medium of equality of temperature equivalent simultaneously), direct injected is measured.Test parallel 3 times for every group.Unit of account area drug accumulation burst size and drug accumulation release rate Q%(are drug per unit area cumulative release amount and the ratio of unit are patch Chinese medicine content).Result drug accumulation release rate Q% is in Table 2, and drug release curve is shown in Fig. 2 (a) and (b).
Permeation test in vitro
1. the processing of isolated skin
Nude mice is put to death rear bark fetching skin, carefully removes subcutaneous fat, with normal saline, cleans up, and is laid on aluminium-foil paper, and-30 ℃ of Refrigerator store 24h are standby.Bark fetching skin is placed 20min in room temperature before use, with normal saline, cleans, and non-woven fabrics blots the water of skin keratin aspect, is cut to suitable big or small skin.
2. transdermal test
Adopt vertical type diffusion cell to carry out permeation test in vitro.Keratodermatitis is upwards fixed on the reception tank of the Franz diffusion cell that magnetic stir bar is housed, and is affixed on skin surface after the patch preparing is thrown off to release layer, gets rid of the bubble between patch and skin, covers first pond and clamps with iron clamp.The accepting medium 40%PEG200 solution that adds preheating and ultrasonic degas in acceptance pool.The diffusion area of diffusion cell is 3.14cm
2, accepting volume is 7ml, magnetic agitation speed is 250rmin
-1, the temperature of acceptable solution is controlled at (32 scholar 0.5) ℃.1,2,4,6,8,10,12,14 and 24h after starting respectively at experiment takes out 0.5ml acceptable solution and supplements the fresh accepting medium of equal-volume, equitemperature.The acceptable solution taking out is in 12000rmin
-1after getting supernatant after centrifugal 5min, use its concentration of high-performance liquid chromatogram determination.Chromatographic condition is as follows: chromatographic column is Shim-packVP-ODS C
18post (4.6mm * 250mm, 5 μ m); Mobile phase is methanol-water (66:34); Flow velocity: 1.0mlmin
-1; Detect wavelength: 241nm; Column temperature: 40 ℃; Sampling volume: 20 μ l, external standard method is quantitative.Test parallel five times, average for every group.According to following formula unit of account area accumulation transit dose Q
n.The results are shown in Table 2, accumulation transdermal test in vitro curve is shown in Fig. 3.
The result of the weekly-acting percutaneous patch release in vitro of table 2 testosterone and permeation test in vitro
Embodiment 11
Stability test
1. test method: the weekly-acting percutaneous patch of testosterone in embodiment 3～6 was at room temperature stored after 3 months, and whether visual observations outward appearance has crystallization.
2. the patch of result of the test: embodiment 3～6, through observing, forms without crystallization, illustrates that this patch has good stability.
Embodiment 12
Irritation test
1. test method: get 6 of 2.8～3.0kg healthy rabbits, be equally divided into intact skin group and damaged skin group, 24h loses hair or feathers back part of animal before administration.Respectively by tested medicine (patch of embodiment 3～6,10cm
2) and control drug (patch of embodiment 1～2,10cm
2) each 5 tested medicament region and control drug district (50cm2) that are affixed on respectively back part of animal, apply ointment or plaster every day 1 time, continuous 7 days.After last administration, 24h removes residue with warm water and normal saline, observe and remove tested medicine 1,24,48 and the erythema of 72h application site and recovery situation and the time of edema situation and above-mentioned variation, every animal test results is carried out to irritant reaction scoring and stimulus intensity evaluation.
2. the patch of result of the test: embodiment 1～6 is through rabbit skin irritation test, completes skin group and the administration of damaged skin group is showed no irritant reaction.
Embodiment 13
Skin anaphylactic test
1. test method: get 30 of 250g～300g healthy guinea pigs, be equally divided into three groups, 10 every group, male and female half and half.Before administration, 24h takes off guinea pig back left side (sensitization) or right side (exciting) hair, and the every side of unhairing scope is 4 * 4cm approximately.The 1st group is pasted tested medicine (patch of embodiment 3～6,10cm
2), the 2nd group is pasted control drug (patch of embodiment 1～2,10cm
2), the 3rd group of every side pasted positive sensitizer, 1% alcoholic solution 0.2ml of 2,4-dinitrochlorobenzene.
Sensitization: get tested medicine (patch of embodiment 3～6,10cm
2) be affixed on depilation district, animal left side skin, with rubber plaster, fix, continue to remove tested medicine after 6h.The 7th day and the 14th day in kind respectively repeats once.Negative control group and positive controls method are all with tested medicine group.
Excite: after last sensitization 14 days, tested medicine is affixed on to depilation district, animal right side outer, with rubber plaster, fix, continue to remove tested medicine after 6h, at once observe, then in 24,48,72h observes skin allergy situation again.Negative control group and positive controls method are all with tested medicine group.
Every animal test results is carried out to anaphylaxis scoring and irritated intensity evaluation.
2. the patch of result of the test: embodiment 1～6, through allergic reaction on guinea pigs, has no anaphylaxis.
Claims (7)
1. medicine carrying, from stickiness elastomeric matrices, is characterized in that, the component of following percentage by weight, consists of:
Testosterone 1～10%
There is the lipotropy elastomeric matrices 90～99% from stickiness matter;
The described lipotropy elastomeric matrices having from stickiness matter, is comprised of the component of following parts by weight:
Described thermoplastic elastomer (TPE) is selected from one or more in styrene-isoprene-phenylethene (SIS) triblock copolymer, s-B-S (SBS) triblock copolymer, hydroxylation styrene-ethylene/butylene-styrene (SEBS) triblock copolymer, hydroxylation styrene-ethylene/propylene-styrene (SEPS) triblock copolymer;
Described tackifier is selected from one or more in terpene resin, phenolic resins, indene resin, C5 hydrogenated petroleum resin, C9 hydrogenated petroleum resin, Petropols, abietic resin or Foral resin;
Described primary plasticizer is selected from liquid paraffin, silicone oil, naphthenic oil, mineral oil, Oleum Ricini, olive oil, vaseline, squalane, Squalene, polybutene or polyisobutylene;
Described co-plasticizer is selected from isopropyl myristate, adipic acid diisopropyl ester, ethyl sebacate, LA, triacetyl glycerine, ethyl oleate, dibutyl phthalate, diethyl phthalate, Polyethylene Glycol, propylene glycol, glycerol, menthol, oleic acid, Palmic acid, stearic acid, salicylic acid, sad, capric acid, lauric acid, lecithin, fabaceous lecithin, phosphatidyl glycerol, PHOSPHATIDYL ETHANOLAMINE, N-methyl pyrrole irons alkane ketone or azone;
Described excipient is selected from polyvinylpyrrolidone, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, poloxamer, polyvinyl alcohol, vinylacetate, acrylic acid-2-ethyl caproite, methyl methacrylate, butyl methacrylate or dimethylaminoethyl methacrylate.
2. medicine carrying according to claim 1, from stickiness elastomeric matrices, is characterized in that, described in there is the lipotropy elastomeric matrices from stickiness matter, by the component of following parts by weight, formed:
3. medicine carrying according to claim 1, from stickiness elastomeric matrices, is characterized in that, the described fusing point having from the lipotropy elastomeric matrices of stickiness matter is 60 ℃～100 ℃, under room temperature, is solid, is liquid under high temperature.
4. medicine carrying according to claim 1, from stickiness elastomeric matrices, is characterized in that, described tackifier is Foral resin and Petropols, and weight ratio is: Foral portions of resin Petropols=11～1: 3;
Described primary plasticizer is liquid paraffin and polybutene, and weight ratio is: liquid paraffin: polybutene=1: 0.5～1: 1;
Described co-plasticizer is isopropyl myristate and Polyethylene Glycol, and weight ratio is: isopropyl myristate: Polyethylene Glycol=1: 0.5～1: 1;
Excipient is polyvinylpyrrolidone and acrylic acid-2-ethyl caproite, and weight ratio is: polyvinylpyrrolidone: acrylic acid-2-ethyl caproite=1: 1～1: 2.
5. medicine carrying according to claim 4, from stickiness elastomeric matrices, is characterized in that, the mass ratio of primary plasticizer and co-plasticizer is 2:1～3:1.
6. bag carries testosterone from the week of a stickiness elastomeric matrices effect percutaneous patch, it is characterized in that, comprises that shelf layer, medicine carrying are from stickiness elastomeric matrices layer and release layer;
Described shelf layer covers described medicine carrying from a side of stickiness elastomeric matrices layer, and described release layer covers described medicine carrying from the opposite side of stickiness elastomeric matrices layer;
Described medicine carrying is that medicine carrying described in claim 1～5 any one is from stickiness elastomeric matrices from the material of stickiness elastomeric matrices layer.
7. preparation bag claimed in claim 6 carries testosterone from the method for the week of stickiness elastomeric matrices effect percutaneous patch, it is characterized in that, comprises the steps:
(1) the lipotropy elastomeric matrices having from stickiness matter is heated to melting under nitrogen protection, adds testosterone, mix, make the substrate of pastille;
(2) while hot the substrate of pastille is coated to shelf layer, release layer in cooling rear covering, die-cut by required size, obtain bag and carry testosterone from the week of stickiness elastomeric matrices effect percutaneous patch.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210258378.2A CN102772417B (en) | 2012-07-24 | 2012-07-24 | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210258378.2A CN102772417B (en) | 2012-07-24 | 2012-07-24 | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102772417A CN102772417A (en) | 2012-11-14 |
| CN102772417B true CN102772417B (en) | 2014-01-29 |
Family
ID=47117674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210258378.2A Active CN102772417B (en) | 2012-07-24 | 2012-07-24 | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102772417B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103961805B (en) * | 2014-04-04 | 2017-06-20 | 李宏博 | Tissue equivalent filler for cancer radiotherapy |
| CN107754009A (en) * | 2016-08-18 | 2018-03-06 | 浙江海创医疗器械有限公司 | The preparation method and application method of a kind of low high viscosity water colloid of anaphylaxis |
| CN110693935A (en) * | 2019-10-30 | 2020-01-17 | 黑龙江中医药大学 | Garcinia entrapped transdermal patch containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and self-adhesive matrix and preparation method thereof |
| WO2024119303A1 (en) * | 2022-12-05 | 2024-06-13 | Henkel Ag & Co. Kgaa | Modified hot-melt pressure sensitive adhesive for chinese herbal medicine patches, and patches made thereby |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1131907A (en) * | 1993-08-03 | 1996-09-25 | 瑟拉技术有限公司 | Skin patches and methods for providing testosterone |
| US6010715A (en) * | 1992-04-01 | 2000-01-04 | Bertek, Inc. | Transdermal patch incorporating a polymer film incorporated with an active agent |
| CN1409628A (en) * | 1999-12-15 | 2003-04-09 | 久光制药株式会社 | Adhesive preparations |
| CN101966339A (en) * | 2009-12-22 | 2011-02-09 | 侯玉庆 | Thermoplastic elastomer styrene-isoprene-styrene (SIS) framework material extruded and coated by extruder |
-
2012
- 2012-07-24 CN CN201210258378.2A patent/CN102772417B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6010715A (en) * | 1992-04-01 | 2000-01-04 | Bertek, Inc. | Transdermal patch incorporating a polymer film incorporated with an active agent |
| CN1131907A (en) * | 1993-08-03 | 1996-09-25 | 瑟拉技术有限公司 | Skin patches and methods for providing testosterone |
| CN1409628A (en) * | 1999-12-15 | 2003-04-09 | 久光制药株式会社 | Adhesive preparations |
| CN101966339A (en) * | 2009-12-22 | 2011-02-09 | 侯玉庆 | Thermoplastic elastomer styrene-isoprene-styrene (SIS) framework material extruded and coated by extruder |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102772417A (en) | 2012-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7415306B2 (en) | Transdermal delivery system for anti-emetic medication | |
| JP5020061B2 (en) | Transdermal preparation | |
| CN102946873B (en) | Transdermal absorption preparation | |
| ES2848395T3 (en) | Fentanyl transdermal patch | |
| CN106074453B (en) | Lappaconitine Gel emplastrum and preparation method thereof | |
| PT1814531E (en) | Transdermal delivery systems | |
| TWI542368B (en) | Patch containing serotonin receptor antagonist | |
| CN104379139A (en) | Skin patch | |
| CN102772417B (en) | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof | |
| CN104188939B (en) | A kind of local topical paster agent containing lidocaine or its pharmaceutical salts | |
| NO338478B1 (en) | Outer plastics containing etofenamate | |
| ES2786504T3 (en) | Transdermal absorption preparation containing oxybutynin | |
| CN102379862B (en) | Spirosal-containing hydrophilic cataplasm | |
| EP2650019B1 (en) | Noradrenergic and specific serotonergic antidepressant-containing transdermal patch | |
| JPWO2017164084A1 (en) | Patch preparation with anti-misuse properties | |
| CN103301093B (en) | Testoderm | |
| CN107028916B (en) | Skin external preparation containing bupivacaine or its medicinal salt | |
| CN110115710B (en) | A transdermal preparation for the treatment of asthma | |
| CN110573160B (en) | Adhesive patch | |
| KR101353478B1 (en) | Transdermal patch for administering fentanyl | |
| KR100192149B1 (en) | Transdermal administration preparation of a 9-aminocyclopenta (b) quinoline | |
| WO2011140236A2 (en) | Triamcinolone acetonide formulations for treating dermatitis and psoriasis | |
| JP4981402B2 (en) | Nicotine transdermal absorption preparation and method for producing the same | |
| JP2017190309A (en) | Rivastigmine percutaneously absorbable preparation | |
| TW202114649A (en) | A pharmaceutical composition of a skin absorbed amide containing local anesthetic and a preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 201203 Shanghai City Harley Road, Zhangjiang High Tech Park of Pudong New Area No. 1111 Patentee after: Shanghai Modern National Pharmaceutical Engineering Research Center Co., Ltd. Patentee after: CHINA?RESOURCES?ZIZHU?PHARMACEUTICAL?CO., LTD. Address before: 201203 Shanghai City Harley Road, Zhangjiang High Tech Park of Pudong New Area No. 1111 Patentee before: Shanghai Modern National Pharmaceutical Engineering Research Center Co., Ltd. Patentee before: Zizhu Pharmaceutical Co., Ltd., Beijing |