WO2010074239A1 - マイクロニードルデバイス - Google Patents
マイクロニードルデバイス Download PDFInfo
- Publication number
- WO2010074239A1 WO2010074239A1 PCT/JP2009/071621 JP2009071621W WO2010074239A1 WO 2010074239 A1 WO2010074239 A1 WO 2010074239A1 JP 2009071621 W JP2009071621 W JP 2009071621W WO 2010074239 A1 WO2010074239 A1 WO 2010074239A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microneedle
- coating
- active ingredient
- pth
- skin
- Prior art date
Links
- 239000011248 coating agent Substances 0.000 claims abstract description 93
- 238000000576 coating method Methods 0.000 claims abstract description 88
- 239000004480 active ingredient Substances 0.000 claims abstract description 32
- 239000000758 substrate Substances 0.000 claims abstract description 27
- 239000000463 material Substances 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 102000003982 Parathyroid hormone Human genes 0.000 claims description 42
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 42
- 239000000199 parathyroid hormone Substances 0.000 claims description 42
- 229960001319 parathyroid hormone Drugs 0.000 claims description 41
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 claims description 24
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 claims description 24
- 229940028334 follicle stimulating hormone Drugs 0.000 claims description 23
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 10
- 239000004626 polylactic acid Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 description 39
- 210000003491 skin Anatomy 0.000 description 28
- 239000004373 Pullulan Substances 0.000 description 24
- 229920001218 Pullulan Polymers 0.000 description 24
- 235000019423 pullulan Nutrition 0.000 description 24
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 16
- 229930006000 Sucrose Natural products 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 239000005720 sucrose Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 239000007788 liquid Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000012545 processing Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- -1 capronolactone Polymers 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- 229920002307 Dextran Polymers 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 229920001287 Chondroitin sulfate Polymers 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000978776 Senegalia senegal Species 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- 108010049264 Teriparatide Proteins 0.000 description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940059329 chondroitin sulfate Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 229940010747 sodium hyaluronate Drugs 0.000 description 3
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 101001135770 Homo sapiens Parathyroid hormone Proteins 0.000 description 2
- 101001135995 Homo sapiens Probable peptidyl-tRNA hydrolase Proteins 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 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 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960002086 dextran Drugs 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 102000058004 human PTH Human genes 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
- 239000000025 natural resin Substances 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000057 synthetic resin Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 1
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229940124841 Herpesvirus vaccine Drugs 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 229940124726 Japanese encephalitis vaccine Drugs 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 101001135767 Rattus norvegicus Parathyroid hormone Proteins 0.000 description 1
- 229940124859 Rotavirus vaccine Drugs 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005004 cholera vaccine Drugs 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 230000003635 deoxygenating effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960005097 diphtheria vaccines Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001312 dry etching Methods 0.000 description 1
- 238000004049 embossing Methods 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 108010081934 follitropin beta Proteins 0.000 description 1
- 229960002907 follitropin beta Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000002474 gonadorelin antagonist Substances 0.000 description 1
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 1
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 description 1
- 229940124736 hepatitis-B vaccine Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003230 hygroscopic agent Substances 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940061515 laureth-4 Drugs 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 229940042470 lyme disease vaccine Drugs 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940041323 measles vaccine Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 229940095293 mumps vaccine Drugs 0.000 description 1
- 239000002103 nanocoating Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940043138 pentosan polysulfate Drugs 0.000 description 1
- 229940066827 pertussis vaccine Drugs 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229940124733 pneumococcal vaccine Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229960003127 rabies vaccine Drugs 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960003131 rubella vaccine Drugs 0.000 description 1
- 108010068072 salmon calcitonin Proteins 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 229950006451 sorbitan laurate Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960002766 tetanus vaccines Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 230000005068 transpiration Effects 0.000 description 1
- 229960002109 tuberculosis vaccine Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000001039 wet etching Methods 0.000 description 1
- 229960001515 yellow fever vaccine Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
Definitions
- the present invention relates to a microneedle device provided with a plurality of microneedles capable of perforating the skin on a substrate for administering an active ingredient through the skin.
- a microneedle device is known as a device for improving transdermal absorption of a drug.
- the microneedles provided in the microneedle device are intended to puncture the stratum corneum, which is the outermost layer of the skin, and various sizes and shapes have been proposed, and are expected as noninvasive administration methods (Patent Documents) 1).
- Patent Document 2 describes that a drug is coated on the surface of a microneedle, a groove or a hollow part for allowing the drug or a biological component to pass through the microneedle, and a drug is mixed in the microneedle itself. Yes.
- the reservoir medium contains saccharide, and in particular, it may contain a stabilizing saccharide such as lactose, raffinose, trehalose or sucrose forming glass (amorphous solid substance).
- a stabilizing saccharide such as lactose, raffinose, trehalose or sucrose forming glass (amorphous solid substance).
- a microcarrier array coating carrier used for transdermal administration of vaccines and the like is human albumin, polyglutamic acid, polyaspartic acid, polyhistidine, pentosan polysulfate and polyamino acid, reducing sugar, non-reducing It is described that it consists of a biocompatible carrier consisting of sugars and polysaccharides.
- microprojections having a capillary action control feature preferred characteristics include a microprojection density in the range of 100 to 2000 per square centimeter and a microprojection length in the range of about 50 to 500 ⁇ m. Is preferably applied to the skin using an impact applicator.
- the present invention has been made to solve this problem, and an object thereof is to provide a microneedle device capable of efficiently and simply administering an active ingredient through the skin.
- the microneedle device of the present invention comprises a substrate and a microneedle provided on the substrate and capable of perforating the skin and having a height of 300 to 500 ⁇ m, and is provided on at least one of the surface of the microneedle and / or the substrate.
- the part is coated with a coating agent containing an active ingredient and a coating carrier, and the mixing ratio of the active ingredient and the coating carrier is 10: 0.1 to 1:10.
- the coating agent containing the active ingredient and the coating carrier is coated, the active ingredient can be reliably coated on the microneedle and can be efficiently and easily administered through the skin. .
- the usability of the microneedle can be greatly enhanced.
- the active ingredient may be follicle stimulating hormone or parathyroid hormone.
- follicle stimulating hormone or parathyroid hormone can be efficiently administered through the skin.
- the density of microneedles may be 400 to 850 per square centimeter.
- the skin can be efficiently perforated by giving the microneedle strength capable of perforating the skin.
- the material of the microneedle may be polylactic acid.
- the safety of the device can be improved and the unit price of the material can be suppressed.
- the coating agent containing the active ingredient and the coating carrier is coated, the active ingredient can be reliably coated on the microneedle and can be efficiently and easily administered through the skin. .
- FIG. 2 is a sectional view taken along line II-II in FIG. (A)-(c) is a figure which shows an example of the method of coating a microneedle.
- 3 is a graph showing the accumulated transmission amount in Example 1.
- 10 is a graph showing the accumulated transmission amount in Example 2.
- 6 is a graph showing plasma FSH in Example 3.
- 4 is a graph showing serum PTH in Example 4.
- FIG. 1 is a perspective view showing an example of a microneedle device according to an embodiment.
- 2 is a cross-sectional view taken along line II-II in FIG.
- the microneedle device 1 includes a microneedle substrate 2 and a plurality of microneedles 3 that are two-dimensionally arranged on the microneedle substrate 2 and can perforate the skin.
- the microneedle substrate 2 is a base for supporting the microneedles 3.
- a plurality of through holes 4 are formed in the microneedle substrate 2 in a two-dimensional manner.
- the microneedles 3 and the through holes 4 are alternately arranged in the diagonal direction of the microneedle substrate 2.
- the through-hole 4 it becomes possible to administer a physiologically active component from the back surface of the microneedle substrate 2. But you may use the board
- the area of the microneedle substrate 2 is 0.5 cm 2 to 10 cm 2 , preferably 1 cm 2 to 5 cm 2 , more preferably 1 cm 2 to 3 cm 2 .
- a plurality of microneedle substrates 2 may be connected to form a substrate having a desired size.
- the microneedle 3 has a fine structure, and its height (length) h is preferably 50 to 500 ⁇ m.
- the length of the microneedle 3 is 50 ⁇ m or more in order to ensure the transdermal administration of the active ingredient, and the length of 500 ⁇ m or less is to avoid the microneedle from contacting the nerve. This is to reduce the possibility of pain and to avoid the possibility of bleeding.
- the length of the microneedle 3 is 500 ⁇ m or less, an amount of the active ingredient that should enter the skin can be efficiently administered.
- the length of the microneedle 3 is preferably 300 to 500 ⁇ m, and particularly preferably 400 to 500 ⁇ m.
- the microneedle means a convex structure and a needle shape in a broad sense or a structure including a needle shape.
- the microneedle is not limited to a needle shape having a sharp tip, and includes a shape having no sharp tip.
- the diameter at the base is about 50 to 200 ⁇ m.
- the microneedle 3 has a conical shape, but a polygonal pyramidal microneedle such as a quadrangular pyramid may be used.
- the microneedles 3 are typically spaced to provide a density of about 1 to 10 per millimeter (mm) for a row of needles. In general, adjacent rows are separated from each other by a substantially equal distance with respect to the space of the needles in the row and have a needle density of 100 to 10,000 per cm 2 . When there is a needle density of 100 or more, the skin can be efficiently perforated. On the other hand, when the needle density exceeds 10,000, it is difficult to provide the microneedles 3 with a strength capable of perforating the skin.
- the density of the microneedles 3 is preferably 200 to 5000, more preferably 300 to 2000, and most preferably 400 to 850.
- Examples of the material of the microneedle substrate 2 or the microneedle 3 include silicon, silicon dioxide, ceramic, metal (stainless steel, titanium, nickel, molybdenum, chromium, cobalt, etc.) and synthetic or natural resin materials.
- biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, capronolactone, polyurethane, polyanhydride, polycarbonate which is a non-degradable polymer, Synthetic or natural resin materials such as polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, and polyoxymethylene are particularly preferred.
- polysaccharides such as hyaluronic acid, sodium hyaluronate, dextran, dextrin or chondroitin sulfate.
- the manufacturing method of the microneedle 3 includes wet etching processing or dry etching processing using a silicon substrate, precision machining using metal or resin (electric discharge processing, laser processing, dicing processing, hot embossing processing, injection molding processing, etc.), Examples include machine cutting.
- wet etching processing or dry etching processing using a silicon substrate precision machining using metal or resin (electric discharge processing, laser processing, dicing processing, hot embossing processing, injection molding processing, etc.), Examples include machine cutting.
- the needle portion and the support portion are integrally molded.
- Examples of the method for hollowing the needle part include a method of performing secondary processing by laser processing or the like after the needle part is manufactured.
- a coating 5 is applied with a coating agent containing an active ingredient and a coating carrier for holding the active ingredient.
- the coating 5 is obtained by fixing a coating liquid containing a coating carrier having compatibility with an active ingredient to a part or the entire surface of the microneedle 3 and / or the microneedle substrate 2. “Having compatibility” means that, within the range of visual evaluation, centrifugation is performed after the solution is prepared, phase separation does not occur, and generation of aggregates is not observed. “Fixed” refers to maintaining a state in which the coating liquid adheres almost uniformly to the object.
- the coating solution is fixed in a dry state by a known drying method such as air drying, vacuum drying, freeze drying, or a combination thereof, but after transdermal administration, the water content in equilibrium with the surrounding atmosphere or Since the organic solvent may be retained, it is not always fixed in a dry state.
- FIGS. 3A to 3C are diagrams showing an example of a method for coating the microneedles 3.
- the coating liquid 10 is swept on the mask plate 11 in the direction of arrow A by the spatula 12 to fill the opening 13 with the coating liquid 10.
- the microneedle 3 is inserted into the opening 13 of the mask plate 11.
- the microneedle 3 is pulled out from the opening 13 of the mask plate 11.
- the coating 5 of the coating liquid 10 is applied to the microneedle 3.
- the coating range H of the microneedle 3 is adjusted by a clearance (gap) C shown in FIG.
- This clearance C is defined by the distance from the base of the microneedle 3 to the lower surface of the mask plate 11 (the substrate thickness is not involved), and is set according to the tension of the mask plate 11 and the length of the microneedle 3.
- the distance range of the clearance C is preferably 0 to 500 ⁇ m. When the distance of the clearance C is 0, the entire microneedle 3 is coated.
- the coating range H varies depending on the height h of the microneedle 3, but can be 0 to 500 ⁇ m, usually 10 to 500 ⁇ m, and preferably about 30 to 300 ⁇ m.
- the thickness of the coating 5 of the microneedle 3 is less than 50 ⁇ m, preferably less than 25 ⁇ m, more preferably 1 to 10 ⁇ m. In general, the thickness of the coating is the average thickness measured over the surface of the microneedle 3 after drying.
- the thickness of the coating can generally be increased by applying multiple coatings of the coating carrier, i.e. by repeating the coating process after fixing the coating carrier.
- the temperature and humidity of the installation environment of the apparatus are preferably controlled to be constant in order to minimize the change in concentration and physical properties of the drug due to the solvent evaporation of the coating agent.
- the humidity at room temperature is 50 to 100% RH as relative humidity, and preferably 70.0 to 99.9% RH. If it is 50% RH or less, the solvent evaporates and the physical properties of the coating solution change.
- the humidification method is not particularly limited as long as the target humidity state can be secured.
- the thickener to be mixed with the coating solution, it is preferable to select a pullulan having high wettability and high moisture retention that suppresses the volatility of the solvent as much as possible.
- the coating agent contains a physiologically active ingredient and purified water and / or a coating carrier.
- the coating carrier includes a low molecular coating carrier and a polymer coating carrier. Examples of the low molecular weight coating carrier include proline, trehalose, sucrose, lactose, fructose, galactose, mannose, maltose, glucose, mannitol, isopropanol, propanol, butanol, propylene glycol, glycerin and the like.
- polymer coating carrier examples include polyethylene oxide, polyhydroxymethyl cellulose, polyhydroxypropyl cellulose, polyhydroxypropyl methyl cellulose, polymethyl cellulose, dextran, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, pullulan, carmellose sodium, chondroitin sulfate, hyaluronic acid, Examples include sodium hyaluronate, dextrin, gum arabic and the like.
- saccharide coating carrier that is relatively compatible (properly intersects with) proteins or peptides among the active ingredients.
- polyvinylpyrrolidone polyvinyl alcohol
- carboxyvinyl polymer polyacrylic acid
- sodium polyacrylate polyethylene oxide
- polyethylene polyethylene
- the content of the coating carrier in the coating agent is 1 to 90% by weight, preferably 1 to 70% by weight, and particularly preferably 10 to 65% by weight.
- this coating carrier may require a certain degree of viscosity so as not to drip, and the viscosity is required to be about 100 to 100,000 cps. A more preferred viscosity is 500 to 50,000 cps.
- a desired amount of coating solution can be applied at a time without depending on the material of the microneedle 3. In general, the higher the viscosity, the greater the amount of coating solution.
- the liquid composition used to coat the microneedles 3 is obtained by mixing a biocompatible carrier, a beneficial active ingredient to be delivered, and possibly any coating aids with a volatile liquid.
- a volatile liquid can be water, dimethyl sulfoxide, dimethylformamide, ethanol, isopropyl alcohol and mixtures thereof. Of these, water is most preferred.
- the liquid coating solution or suspension can typically have a beneficial bioactive ingredient concentration of 0.1 to 65 wt%, preferably 1 to 40 wt%, more preferably 10 to 30 wt%. % Concentration.
- the coating is particularly preferably in a fixed state.
- Surfactants can be zwitterionic, zwitterionic, cationic, anionic, or nonionic.
- Tween 20 and Tween 80 other sorbitan derivatives such as sorbitan laurate, and alkoxylated alcohols such as laureth-4.
- it is also effective to add a surfactant to dissolve more polymeric active ingredients in the coating carrier or to coat the needle.
- formulation aids may be added to the coating as long as they do not adversely affect the required solubility and viscosity characteristics of the coating and the physical integrity of the dried coating.
- the active ingredient used in the present invention is not particularly limited, but a polymer compound such as a protein or peptide having a relatively large molecular weight or a derivative thereof is suitable.
- the high molecular weight is a molecular weight of 1000 or more as a guideline, and no upper limit is set for the molecular weight.
- ⁇ -interferon for multiple sclerosis, erythropoietin, follicle stimulating hormone (FSH), follitropin ⁇ , follitropin ⁇ , G-CSF, GM-CSF, human chorionic gonadotropin
- FSH follicle stimulating hormone
- follitropin ⁇ for multiple sclerosis
- G-CSF follitropin ⁇
- GM-CSF human chorionic gonadotropin
- Examples include luteinizing hormone, salmon calcitonin, glucagon, GNRH antagonist, insulin, human growth hormone, filgrastim, parathyroid hormone (PTH), somatropin and the like.
- vaccines include influenza vaccine, Japanese encephalitis vaccine, rotavirus vaccine, Alzheimer's disease vaccine, arteriosclerosis vaccine, cancer vaccine, nicotine vaccine, diphtheria vaccine, tetanus vaccine, pertussis vaccine, Lyme disease vaccine, rabies vaccine,
- examples include pneumococcal vaccine, yellow fever vaccine, cholera vaccine, vaginal vaccine, tuberculosis vaccine, rubella vaccine, measles vaccine, mumps vaccine, butulinus vaccine, herpesvirus vaccine, other DNA vaccines, hepatitis B vaccine and the like.
- FSH follicle stimulating hormone
- PTH parathyroid hormone
- these drugs may be used alone or in combination of two or more, and exist as a free form or a pharmaceutically acceptable salt.
- a pharmaceutically acceptable salt it naturally includes a drug in any form of an inorganic salt or an organic salt.
- the drug is basically included in the coating carrier, but the drug is not included in the coating carrier and may be supplied later through the through-hole 4 formed in the microneedle substrate 2. it can.
- the active ingredient and the coating carrier are generally blended at a ratio of 1:10 to 10: 0.1, preferably 1: 8 to 8: 1, more preferably 1: 3 to 8: 1. Blended.
- the compounding ratio of pullulan suitable as a coating carrier and follicle stimulating hormone as an active ingredient is 1: 2.
- the administration method using the microneedle device 1 may be direct administration by hand or may be a method of administration by hand after using a simple auxiliary device for fixing the microneedle device 1.
- the microneedle device 1 when it is in contact with the skin, it is administered with a force of 1.0 to 10 kg, preferably with a force of 1.0 to 7 kg, more preferably with a force of 1.0 to 4 kg.
- the administration time with that force is not so long, it may be from a few seconds to a few minutes, and in some cases there may be an instantaneous administration of less than 1 second.
- the microneedle device 1 can be administered using a device that generates collision energy.
- Example 1 In vitro test with microneedle (follicle stimulating hormone) ⁇ Human skin permeation test> Three types (h: 300 ⁇ m, 400 ⁇ m, 500 ⁇ m) of polylactic acid microneedles having different needle lengths were used. Each of these three types of microneedles was a quadrangular pyramid, and its density was 400 / cm 2 . The area of each microneedle device was 1 cm 2 .
- the coated microneedle device was punctured by finger pressing (2 kg / patch) on the human excised skin, then placed on an acrylic cell and sampled over time.
- a phosphate buffer solution (PBS) is used, and 1 mL of the receptor solution obtained every hour and acetonitrile are mixed at a ratio of 1: 1, stirred, centrifuged (15,000 rpm, 5 ° C., 5 min), The supernatant was collected and the FSH concentration was measured with a ⁇ -counter as described below.
- a result is as the graph shown in FIG.
- the coating amount was calculated by using a microneedle device in which 1 to 5 ⁇ L of [ 125 I] FSHaq concentrated 10-fold was dropped as a calibration curve using a ⁇ -counter and a NaI counter.
- the amount of FSH coating on the microneedles was about 30 ⁇ g.
- Example 2 In vitro human skin permeation test using a microneedle (parathyroid hormone) ⁇ Human skin permeation test> Two types (h: 300 ⁇ m, 500 ⁇ m) of polylactic acid microneedles having different needle lengths were used. Each of these two types of microneedles was a quadrangular pyramid, and its density was 400 / cm 2 . The area of each microneedle device was 1 cm 2 .
- a coating solution (30% human parathyroid hormone hPTH (1-34) (Unibiochem), 7.5% pullulan, 0.1% Tween 20) prepared by the method described below was applied to the microneedle device in the same manner as in Example 1. After coating, the microneedle device was punctured by finger pressing (2 kg / patch) on the human excised skin, placed on an acrylic cell, and sampled over time. A physiological saline solution containing 0.01% benzalkonium chloride was used for the receptor layer, and 1 mL of the receptor solution obtained every time was measured with a gamma counter, and the PTH concentration was calculated. In addition, the sticking time of the microneedle device was 6 hours. The sampling result is as shown in the graph of FIG.
- Preparation of coating solution and measuring method of coating amount (1) Add to the solution containing 125 I-PTH so that hPTH (1-34) is 30%, pullulan is 7.5%, and Tween is 0.1%. And then dissolved by centrifugation after stirring. (2) After coating the microneedles using the coating solution prepared in (1), the radioactivity of each preparation was counted using a NaI counter, and the content of PTH coated on the needles was estimated. The microneedle coating amount was set to 40 ⁇ g as the hPTH content.
- Example 3 In vivo absorption test with microneedle (follicle stimulating hormone) ⁇ Hairless rat in vivo administration test> Polylactic acid microneedles with a density of 841 / cm 2 and a needle length of 300 ⁇ m, and three types with a density of 400 needles / cm 2 but different needle lengths (h: 300 ⁇ m, 400 ⁇ m) The hairless rat in vivo absorption test was performed using a total of four types of polylactic acid microneedles (500 ⁇ m). Each of these four types of microneedles was a quadrangular pyramid, and the area of each microneedle device was 1 cm 2 .
- a microneedle device in which the tip of the needle was coated with the same coating liquid (30% FSH, 15% pullulan) as in Example 1 in the same manner as in Example 1 was manually punctured into the abdomen of a hairless rat. .
- plasma was collected over time (amount of collected blood: 300 ⁇ L / time), and the FSH concentration was measured with a SPAC-S FSH kit (manufactured by TEFB Co., Ltd.).
- 300 ⁇ L of 1 IU / mL FSH (saline solution) was subcutaneously administered to the back of the hairless rat, and the FSH concentration was measured in the same manner.
- the sticking time of the microneedle device was 2 hours.
- Example 4 In vivo absorption test using microneedle (parathyroid hormone) ⁇ Hairless rat in vivo administration test> Two types (h: 300 ⁇ m, 500 ⁇ m) of polylactic acid microneedles having different needle lengths were used. Each of these two types of microneedles was a quadrangular pyramid, and its density was 400 / cm 2 . The area of each microneedle device was 1 cm 2 .
- Example 2 the same coating solution (30% human parathyroid hormone hPTH (1-34) (Unibiochem), 7.5% pullulan, 0.1% Tween 20) as in Example 2 was applied to the tip of the needle.
- the microneedle device coated in the same manner as described above was punctured into the abdomen of the hairless rat by finger pressing, and the microneedle device was covered with foam tape (manufactured by 3M) and applied for 6 hours.
- blood was collected over time (blood collection amount 200 ⁇ L / times), and the hPTH concentration in the serum was measured with a Rat PTH IRMA kit (manufactured by Immutopics International).
- 0.2 mg / mL hPTH physiological saline
- 40 ⁇ L was subcutaneously administered to the back of the hairless rat, and the PTH concentration was measured in the same manner.
- Example 5 Skin primary irritation test using rabbits Three types (h: 300 ⁇ m, 400 ⁇ m, 500 ⁇ m) of polylactic acid microneedles having different needle lengths were prepared. All of these three types of microneedles had a quadrangular pyramid shape, a density of 400 needles / cm 2 , and an area of 1 cm 2 . Using these microneedles, skin reaction was evaluated according to the method of Draize. That is, the test substance was pressed against the skin for 5 seconds with a force of 3 kg / patch on the shaved back of an 18-week-old female white rabbit (KBl: JW) and applied for 2 hours (with cover material) did.
- KBl 18-week-old female white rabbit
- test substance was peeled off 2 hours after administration, and erythema / crust and edema formation were observed macroscopically at 0.5, 2, 24, 48 and 72 hours after peeling, and evaluated by Draize (Table 1) and others. Scoring based on criteria.
- Skin primary irritation was determined by calculating a primary irritation index (PI) and using the following Draize evaluation criteria (Table 2).
- PI primary irritation index
- Table 2 Draize evaluation criteria
- the primary irritation index (PI) of three types of microneedles (300 ⁇ m, 400 ⁇ m, and 500 ⁇ m) having different needle heights is 0.3, 0.5, and 0.5, respectively. Although judged, the skin irritation tended to increase according to the needle height.
- Example 6 Preservation method of parathyroid hormone (PTH) PTH was prepared to 40 mg / mL with water for injection and dispensed into a drug solution, and further diluted to 20 mg / mL with water for injection before the experiment. was dropped on a microneedle substrate (400 ⁇ g / patch) to form a drug part.
- PTH parathyroid hormone
- Extract 0.01% benzalkonium chloride solution or 2% TMTDAB, 1% sodium chloride, 10 mM acetate buffer
- Detector Ultraviolet absorptiometer (measurement wavelength: 220 nm)
- Example 7 Examination of sucrose addition amount with respect to parathyroid hormone (PTH) Sucrose was dissolved in water for injection, sucrose (1 mg) 10% solution, sucrose (0.5 mg) 5% solution, sucrose (0.1 mg) Each 1% solution was prepared and mixed with a 40 mg / mL PTH solution in a ratio of 1: 1 to obtain a chemical solution. Other than that, it carried out similarly to the previous Example.
- PTH parathyroid hormone
- sucrose additive for parathyroid hormone (PTH) Sucrose was dissolved in water for injection to prepare a 10% solution of sucrose (1 mg), and 1: 1 with 40 mg / mL PTH solution. A chemical solution was prepared by mixing, and a chemical solution part was prepared using this, and the storage stability under various drying times was examined under a nitrogen stream.
- Example 9 In order to optimize the ratio of PTH (1-34) (manufactured by Unibiochem) and the coating carrier that is a water-soluble polymer, examination was performed using PTH and the coating carrier (pullulan). As shown in Table 6, the solution was adjusted so that the concentration of PTH was 0-40% (w / w). The concentration of pullulan was adjusted based on the viscosity of the solution at the time of dissolution, and the concentration range of pullulan was set to 0-30% (w / w). In addition, the pullulan used the Japanese Pharmacopoeia pullulan (made by Hayashibara Biochemical Research Institute). In addition, in order to improve the adhesion to the needle, the case where a surfactant (Tween 20, 0.1%) was added as shown in Table 7 was also examined.
- a surfactant Tween 20, 0.15%
- the coating method was carried out according to the method described above, and coating was performed only on the tip of the needle using a metal mask (only the needle part was coated using a metal mask having an opening diameter of 220 ⁇ m and a thickness of 100 ⁇ m).
- the ratio of PTH to pullulan is preferably 1: 3 to 8: 1, and the concentration of PTH during coating solution adjustment is preferably 10% or more.
- the active ingredient can be uniformly coated on the microneedles. Moreover, since the solution is uniform, highly accurate coating control can be performed on the microneedles. Furthermore, since the active ingredient can be efficiently administered from the skin by the microneedle device and its utility can be remarkably enhanced, it has industrial applicability.
- Microneedle device 1 ... Microneedle device, 2 ... Microneedle substrate, 3 ... Microneedle, 4 ... Through hole, 5 ... Coating.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Medical Informatics (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
<ヒト皮膚透過試験>
針部の長さが異なる3タイプ(h:300μm、400μm、500μm)のポリ乳酸製マイクロニードルを使用した。これら3種類のマイクロニードルの形状はいずれも四角錐であり、その密度は400本/cm2であった。また、マイクロニードルデバイスの面積はいずれも1cm2であった。
<ヒト皮膚透過試験>
針部の長さが異なる2タイプ(h:300μm、500μm)のポリ乳酸製マイクロニードルを使用した。これら2種類のマイクロニードルの形状はいずれも四角錐であり、その密度は400本/cm2であった。また、マイクロニードルデバイスの面積はいずれも1cm2であった。
(1)125I-PTHを含む溶液に、hPTH(1-34)を30%、プルランを7.5%、Tweenを0.1%となるように添加し、攪拌後遠心分離法にて溶解させた。
(2)(1)で調製したコーティング溶液を用いてマイクロニードルにコーティングを施した後、NaIカウンターを用いて各製剤の放射能をカウントし、針部にコーティングされたPTHの含量を見積もった。なお、マイクロニードルのコーティング量は、hPTH含量として40μgになるように設定した。
<ヘアレスラットin vivo投与試験>
密度が841本/cm2で針部の長さが300μmのポリ乳酸製マイクロニードルと、密度はいずれも400本/cm2であるが針部の長さが異なる3タイプ(h:300μm、400μm、500μm)のポリ乳酸製マイクロニードルの計4タイプを使用してヘアレスラットin vivo吸収試験を実施した。これら4種類のマイクロニードルの形状はいずれも四角錐であり、各マイクロニードルデバイスの面積は1cm2であった。
<ヘアレスラットin vivo投与試験>
針部の長さが異なる2タイプ(h:300μm、500μm)のポリ乳酸製マイクロニードルを使用した。これら2種類のマイクロニードルの形状はいずれも四角錐であり、その密度は400本/cm2であった。また、マイクロニードルデバイスの面積はいずれも1cm2であった。
針部の長さが異なる3タイプ(h:300μm、400μm、500μm)のポリ乳酸製マイクロニードルを用意した。これら3種類のマイクロニードルの形状はいずれも四角錐であり、その密度はいずれも400本/cm2であり、その面積はいずれも1cm2であった。これらのマイクロニードルを使用し、Draizeの方法に準じて皮膚反応の評価を実施した。すなわち、18週齢の雌性白色種ウサギ(KBl:JW)の毛を剃った背中の部分に披験物質を3kg/patchの力で5秒間皮膚に押し付けた後に、2時間貼付(カバー材有り)した。そして、投与2時間後に被験物質を剥離し、剥離後0.5,2,24,48及び72時間目に紅斑・痂皮及び浮腫形成について肉眼的に観察し、Draize(表1)らの評価基準に基づいて採点した。
PTHを注射用水で40mg/mLに調製後分注して薬液とし、実験前に更に注射用水で20mg/mLに希釈して薬液とし、これをマイクロニードル基板上に20μL滴下(400μg/patch)し、薬物部とした。
抽出液:0.01%塩化ベンザルコニウム溶液または2%TMTDAB、1%塩化ナトリウム、10mM酢酸緩衝液
検出器:紫外吸光光度計(測定波長:220nm)
カラム:YMC-PackODS-AM(YMC社)
カラム温度:25℃
スクロースを注射用水に溶解して、スクロース(1mg)10%溶液、スクロース(0.5mg)5%溶液、スクロース(0.1mg)1%溶液をそれぞれ調製し、40mg/mLのPTH溶液と1:1に混合して薬液とした。それ以外は、先の実施例と同様に行った。
スクロースを注射用水に溶解してスクロース(1mg)10%溶液を調製し、40mg/mLのPTH溶液と1:1に混合して薬液とし、これを用いて薬液部を作製し、窒素気流下で各種乾燥時間による保存性を調べた。
PTH(1-34)(Unibiochem社製)と水溶性高分子ポリマーであるコーティング担体との比率を最適化するために、PTHとコーティング担体(プルラン)とを用いて検討を行った。表6に示すように、PTHの濃度が0-40%(w/w)になるように溶液を調整した。プルランの濃度は溶解時の溶液の粘度を基準として調整し、プルランの濃度範囲は0-30%(w/w)に設定した。なお、プルランは日本薬局方プルラン(林原生物化学研究所製)を使用した。また、針への付着性を向上させるために、表7に示すように界面活性剤(Tween20、0.1%)を添加した場合についても検討を実施した。
Claims (4)
- 基板と、
前記基板に設けられた、皮膚を穿孔可能で高さが300~500μmであるマイクロニードルと、
を備え、
前記マイクロニードルの表面上および/または前記基板上の少なくとも一部には、活性成分とコーティング担体とを含むコーティング剤がコーティングされており、
前記活性成分と前記コーティング担体との配合比が10:0.1~1:10である、
マイクロニードルデバイス。 - 前記活性成分が卵胞刺激ホルモンまたは副甲状腺ホルモンである、請求項1に記載のマイクロニードルデバイス。
- 前記マイクロニードルの密度が1平方センチメートル当たり400~850本である、請求項1又は2に記載のマイクロニードルデバイス。
- 前記マイクロニードルの材質がポリ乳酸である、請求項1~3のいずれか一項に記載のマイクロニードルデバイス。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010544160A JP5902390B2 (ja) | 2008-12-26 | 2009-12-25 | マイクロニードルデバイス |
US13/140,891 US20110288485A1 (en) | 2008-12-26 | 2009-12-25 | Microneedle device |
CN200980152286.2A CN102264429B (zh) | 2008-12-26 | 2009-12-25 | 微针装置 |
EP09835035A EP2383013A4 (en) | 2008-12-26 | 2009-12-25 | MICRO NEEDLE DEVICE |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008-334545 | 2008-12-26 | ||
JP2008334545 | 2008-12-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010074239A1 true WO2010074239A1 (ja) | 2010-07-01 |
Family
ID=42287843
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2009/071621 WO2010074239A1 (ja) | 2008-12-26 | 2009-12-25 | マイクロニードルデバイス |
Country Status (6)
Country | Link |
---|---|
US (1) | US20110288485A1 (ja) |
EP (1) | EP2383013A4 (ja) |
JP (1) | JP5902390B2 (ja) |
KR (1) | KR101634836B1 (ja) |
CN (1) | CN102264429B (ja) |
WO (1) | WO2010074239A1 (ja) |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012235977A (ja) * | 2011-05-13 | 2012-12-06 | Bioserentack Co Ltd | 溶解性マイクロニードルの強度増強 |
JP2013052202A (ja) * | 2011-09-01 | 2013-03-21 | Kosumedei Seiyaku Kk | Dnaワクチンマイクロニードル |
EP2578264A1 (en) * | 2010-05-28 | 2013-04-10 | Hisamitsu Pharmaceutical Co., Inc. | Device having array provided with fine protrusions |
JP2013162861A (ja) * | 2012-02-10 | 2013-08-22 | Bioserentack Co Ltd | 細胞間液モニター用マイクロニードル |
WO2014034882A1 (ja) | 2012-08-30 | 2014-03-06 | 帝人株式会社 | 薬剤組成物が塗布されたマイクロニードルアレイ |
US8747362B2 (en) | 2009-06-10 | 2014-06-10 | Hisamitsu Pharmaceutical Co., Inc | Microneedle device |
CN104434561A (zh) * | 2014-11-10 | 2015-03-25 | 广州市博卡利生物科技有限公司 | 一种微针面膜 |
EP2769749A4 (en) * | 2011-10-20 | 2015-05-06 | Cosmed Pharmaceutical Co Ltd | MICRO NEEDLE CAPTURE TECHNOLOGY |
WO2016067956A1 (ja) * | 2014-10-27 | 2016-05-06 | 久光製薬株式会社 | 遺伝子組換型卵胞刺激ホルモンを含有するマイクロニードルデバイス |
JP2017164308A (ja) * | 2016-03-16 | 2017-09-21 | 凸版印刷株式会社 | 穿刺デバイス及びその製造方法 |
US9918932B2 (en) | 2016-02-19 | 2018-03-20 | Zosano Pharma Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines |
CN108096699A (zh) * | 2017-12-28 | 2018-06-01 | 浙江大学台州研究院 | 用于药物传输和体液采集的空心微针阵列及其制备方法 |
JP2019511480A (ja) * | 2016-03-01 | 2019-04-25 | ジョージア テック リサーチ コーポレイション | マイクロニードル粒子、組成物、治療方法、及び目的の物質の送達方法 |
WO2019225650A1 (ja) * | 2018-05-23 | 2019-11-28 | 富士フイルム株式会社 | 日本脳炎ワクチン含有マイクロニードルアレイ |
US10537723B2 (en) | 2014-09-11 | 2020-01-21 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle device |
JP2021088600A (ja) * | 2013-03-15 | 2021-06-10 | コリウム, インコーポレイテッド | ポリマーを含まない微細構造物を含むマイクロアレイ、製造方法および使用方法 |
JPWO2022014695A1 (ja) * | 2020-07-17 | 2022-01-20 | ||
US11660265B2 (en) | 2018-06-28 | 2023-05-30 | Emergex USA Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines and cluster headaches |
US11660264B2 (en) | 2017-08-23 | 2023-05-30 | Emergex USA Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines and cluster headaches |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008130587A2 (en) | 2007-04-16 | 2008-10-30 | Corium International, Inc. | Solvent-cast microneedle arrays containing active |
JP5820805B2 (ja) * | 2009-04-24 | 2015-11-24 | コリウム インターナショナル, インコーポレイテッド | マイクロプロジェクションのアレイの製造のためのプロセス |
US9687641B2 (en) | 2010-05-04 | 2017-06-27 | Corium International, Inc. | Method and device for transdermal delivery of parathyroid hormone using a microprojection array |
EP2568806B1 (en) | 2010-05-12 | 2016-05-11 | Radius Health, Inc. | Therapeutic regimens |
JP5797644B2 (ja) * | 2010-05-28 | 2015-10-21 | 久光製薬株式会社 | 微小突起付きアレイ |
AU2011312490B2 (en) | 2010-09-28 | 2015-06-25 | Radius Pharmaceuticals, Inc. | Selective androgen receptor modulators |
US9623087B2 (en) | 2011-11-30 | 2017-04-18 | 3M Innovative Properties Company | Microneedle device including a peptide therapeutic agent and an amino acid and methods of making and using the same |
US10548854B2 (en) | 2012-10-01 | 2020-02-04 | The Hong Kong University Of Science And Technology | Manufacture of nonelectronic, active-infusion patch and device for transdermal delivery across skin |
MX2015008157A (es) | 2012-12-21 | 2016-02-22 | Corium Int Inc | Microarreglo para la entrega de agente terapeutico y metodos de uso. |
BR112015022253B1 (pt) | 2013-03-12 | 2022-03-15 | Corium, Inc | Aplicador de microprojeções |
CA2903459C (en) | 2013-03-15 | 2024-02-20 | Corium International, Inc. | Multiple impact microprojection applicators and methods of use |
BR112015022625B1 (pt) | 2013-03-15 | 2023-01-31 | Corium, Inc | Aparelho de microestrutura para entrega de agente terapêutico |
BR112015031162A2 (pt) * | 2013-06-13 | 2017-07-25 | Microdermics Inc | microagulhas metálicas |
WO2015073919A1 (en) * | 2013-11-14 | 2015-05-21 | University Medical Pharmaceuticals Corporation | Microneedles for therapeutic agent delivery with improved mechanical properties |
CN104970804B (zh) * | 2014-04-01 | 2018-05-04 | 微凸科技股份有限公司 | 连续经皮微针监测*** |
WO2016036866A1 (en) | 2014-09-04 | 2016-03-10 | Corium International, Inc. | Microstructure array, methods of making, and methods of use |
MA41818A (fr) * | 2015-03-27 | 2018-01-30 | Leo Pharma As | Timbre à micro-aiguilles pour administration d'un principe actif à la peau |
IL255148B2 (en) | 2015-04-29 | 2023-04-01 | Radius Pharmaceuticals Inc | 1901 rad for use in a method to inhibit a cancerous growth or induce tumor regression in a patient who is resistant to the drug and/or has cancer positive for an estrogen receptor alpha mutation |
CN104888343A (zh) * | 2015-05-07 | 2015-09-09 | 北京化工大学 | 一种高分子实心微针及其批量制备方法 |
US10857093B2 (en) | 2015-06-29 | 2020-12-08 | Corium, Inc. | Microarray for delivery of therapeutic agent, methods of use, and methods of making |
EP3474841B1 (en) | 2016-06-22 | 2022-03-16 | Ellipses Pharma Ltd | Ar+ breast cancer treatment methods |
WO2018056584A1 (ko) | 2016-09-21 | 2018-03-29 | 삼성전자 주식회사 | 피부 상태 측정 방법 및 이를 위한 전자 장치 |
CN117417263A (zh) | 2017-01-05 | 2024-01-19 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
KR102343698B1 (ko) * | 2017-02-24 | 2021-12-24 | 히사미쓰 세이야꾸 가부시키가이샤 | 마이크로니들 디바이스 |
KR102033686B1 (ko) * | 2017-05-19 | 2019-10-18 | 보령제약 주식회사 | 도네페질을 함유하는 마이크로니들 경피 패치 |
EP3815737B1 (en) * | 2018-06-26 | 2023-10-04 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle device and method for manufacturing same |
CN112423844A (zh) | 2018-07-04 | 2021-02-26 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
CN109010036A (zh) * | 2018-08-23 | 2018-12-18 | 周宇 | 一种药物针灸针 |
JP2020099513A (ja) * | 2018-12-21 | 2020-07-02 | ロレアル | マイクロニードルシートを使用するキット及び美容方法 |
CN113841365B (zh) * | 2019-05-23 | 2023-11-24 | 三菱电机株式会社 | 接收电路 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001506904A (ja) | 1996-12-20 | 2001-05-29 | アルザ・コーポレーション | 経皮作用剤流量を強化するための組成物と方法 |
JP2004504120A (ja) | 2000-07-21 | 2004-02-12 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
JP2004528900A (ja) | 2001-04-20 | 2004-09-24 | アルザ・コーポレーシヨン | 有益な作用物質を含有するコーティングを有する微小突起アレイ |
JP2007501070A (ja) | 2003-08-04 | 2007-01-25 | アルザ・コーポレーシヨン | 経皮作用剤流率を向上させる方法および装置 |
JP2008534151A (ja) | 2005-03-28 | 2008-08-28 | アルザ コーポレイション | 毛管作用制御特徴部を有するマイクロプロジェクション及び方法 |
WO2008139648A1 (ja) * | 2007-05-15 | 2008-11-20 | Hisamitsu Pharmaceutical Co., Inc. | マイクロニードルのコーティング方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100993477B1 (ko) * | 2002-06-25 | 2010-11-11 | 권성윤 | 약물 송달 및 다른 용도를 위한 신속 용해형마이크로-퍼포레이터 |
AR040819A1 (es) * | 2002-08-08 | 2005-04-20 | Alza Corp | Dispositivo de administracion transdermica de vacuna que tiene microproyecciones revestidas |
AU2004253571A1 (en) * | 2003-07-02 | 2005-01-13 | Alza Corporation | Microprojection array immunization patch and method |
CN1541724A (zh) * | 2003-11-04 | 2004-11-03 | 浙江大学 | 一种用于药物控释的微针阵列 |
CN2654137Y (zh) * | 2003-11-04 | 2004-11-10 | 浙江大学 | 一种基于微加工技术的无痛微针阵列 |
EP1744683B1 (en) * | 2004-05-13 | 2016-03-16 | Alza Corporation | Apparatus and method for transdermal delivery of parathyroid hormone agents |
EP1827564B1 (en) * | 2004-11-18 | 2015-07-29 | 3M Innovative Properties Company | Masking method for coating a microneedle array |
CA2612005C (en) * | 2005-06-17 | 2013-10-29 | Georgia Tech Research Corporation | Coated microstructures and method of manufacture thereof |
ATE532553T1 (de) * | 2006-02-10 | 2011-11-15 | Hisamitsu Pharmaceutical Co | Transdermales arzneiverabreichungsgerät mit mikronadeln |
US20090099502A1 (en) * | 2006-04-07 | 2009-04-16 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle Device And Transdermal Administration Device Provided With Microneedles |
US20100030100A1 (en) * | 2007-02-06 | 2010-02-04 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle Device For Diagnosis Of Allergy |
-
2009
- 2009-12-25 KR KR1020117015427A patent/KR101634836B1/ko active IP Right Grant
- 2009-12-25 EP EP09835035A patent/EP2383013A4/en not_active Ceased
- 2009-12-25 WO PCT/JP2009/071621 patent/WO2010074239A1/ja active Application Filing
- 2009-12-25 CN CN200980152286.2A patent/CN102264429B/zh active Active
- 2009-12-25 US US13/140,891 patent/US20110288485A1/en not_active Abandoned
- 2009-12-25 JP JP2010544160A patent/JP5902390B2/ja active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001506904A (ja) | 1996-12-20 | 2001-05-29 | アルザ・コーポレーション | 経皮作用剤流量を強化するための組成物と方法 |
JP2004504120A (ja) | 2000-07-21 | 2004-02-12 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
JP2004528900A (ja) | 2001-04-20 | 2004-09-24 | アルザ・コーポレーシヨン | 有益な作用物質を含有するコーティングを有する微小突起アレイ |
JP2007501070A (ja) | 2003-08-04 | 2007-01-25 | アルザ・コーポレーシヨン | 経皮作用剤流率を向上させる方法および装置 |
JP2008534151A (ja) | 2005-03-28 | 2008-08-28 | アルザ コーポレイション | 毛管作用制御特徴部を有するマイクロプロジェクション及び方法 |
WO2008139648A1 (ja) * | 2007-05-15 | 2008-11-20 | Hisamitsu Pharmaceutical Co., Inc. | マイクロニードルのコーティング方法 |
Non-Patent Citations (1)
Title |
---|
See also references of EP2383013A4 * |
Cited By (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8747362B2 (en) | 2009-06-10 | 2014-06-10 | Hisamitsu Pharmaceutical Co., Inc | Microneedle device |
EP2578264A1 (en) * | 2010-05-28 | 2013-04-10 | Hisamitsu Pharmaceutical Co., Inc. | Device having array provided with fine protrusions |
EP2578264A4 (en) * | 2010-05-28 | 2014-01-15 | Hisamitsu Pharmaceutical Co | DEVICE COMPRISING A MATRIX PROVIDED WITH FINE PROJECTS |
JP2012235977A (ja) * | 2011-05-13 | 2012-12-06 | Bioserentack Co Ltd | 溶解性マイクロニードルの強度増強 |
JP2013052202A (ja) * | 2011-09-01 | 2013-03-21 | Kosumedei Seiyaku Kk | Dnaワクチンマイクロニードル |
EP2769749A4 (en) * | 2011-10-20 | 2015-05-06 | Cosmed Pharmaceutical Co Ltd | MICRO NEEDLE CAPTURE TECHNOLOGY |
US9993423B2 (en) | 2011-10-20 | 2018-06-12 | Cosmed Pharmaceutical Co., Ltd. | Microneedle deposition method |
JP2013162861A (ja) * | 2012-02-10 | 2013-08-22 | Bioserentack Co Ltd | 細胞間液モニター用マイクロニードル |
US10556098B2 (en) | 2012-08-30 | 2020-02-11 | Medrx Co., Ltd. | Microneedle array coated with drug composition |
WO2014034882A1 (ja) | 2012-08-30 | 2014-03-06 | 帝人株式会社 | 薬剤組成物が塗布されたマイクロニードルアレイ |
JP2021088600A (ja) * | 2013-03-15 | 2021-06-10 | コリウム, インコーポレイテッド | ポリマーを含まない微細構造物を含むマイクロアレイ、製造方法および使用方法 |
US10537723B2 (en) | 2014-09-11 | 2020-01-21 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle device |
US10632065B2 (en) | 2014-10-27 | 2020-04-28 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle device containing recombinant follicle stimulating hormone |
WO2016067956A1 (ja) * | 2014-10-27 | 2016-05-06 | 久光製薬株式会社 | 遺伝子組換型卵胞刺激ホルモンを含有するマイクロニードルデバイス |
JPWO2016067956A1 (ja) * | 2014-10-27 | 2017-08-10 | 久光製薬株式会社 | 遺伝子組換型卵胞刺激ホルモンを含有するマイクロニードルデバイス |
CN104434561A (zh) * | 2014-11-10 | 2015-03-25 | 广州市博卡利生物科技有限公司 | 一种微针面膜 |
US11058630B2 (en) | 2016-02-19 | 2021-07-13 | Zosano Pharma Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines |
US9918932B2 (en) | 2016-02-19 | 2018-03-20 | Zosano Pharma Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines |
US11839683B2 (en) | 2016-02-19 | 2023-12-12 | Emergex USA Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines |
JP2019511480A (ja) * | 2016-03-01 | 2019-04-25 | ジョージア テック リサーチ コーポレイション | マイクロニードル粒子、組成物、治療方法、及び目的の物質の送達方法 |
JP2022071012A (ja) * | 2016-03-01 | 2022-05-13 | ジョージア テック リサーチ コーポレイション | マイクロニードル粒子、組成物、治療方法、及び目的の物質の送達方法 |
JP7350113B2 (ja) | 2016-03-01 | 2023-09-25 | ジョージア テック リサーチ コーポレイション | マイクロニードル粒子、組成物、治療方法、及び目的の物質の送達方法 |
JP7101121B2 (ja) | 2016-03-01 | 2022-07-14 | ジョージア テック リサーチ コーポレイション | マイクロニードル粒子、組成物、治療方法、及び目的の物質の送達方法 |
JP2017164308A (ja) * | 2016-03-16 | 2017-09-21 | 凸版印刷株式会社 | 穿刺デバイス及びその製造方法 |
US11660264B2 (en) | 2017-08-23 | 2023-05-30 | Emergex USA Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines and cluster headaches |
CN108096699B (zh) * | 2017-12-28 | 2020-12-01 | 浙江大学台州研究院 | 用于药物传输和体液采集的空心微针阵列及其制备方法 |
CN108096699A (zh) * | 2017-12-28 | 2018-06-01 | 浙江大学台州研究院 | 用于药物传输和体液采集的空心微针阵列及其制备方法 |
WO2019225650A1 (ja) * | 2018-05-23 | 2019-11-28 | 富士フイルム株式会社 | 日本脳炎ワクチン含有マイクロニードルアレイ |
JP6997866B2 (ja) | 2018-05-23 | 2022-01-18 | 富士フイルム株式会社 | 日本脳炎ワクチン含有マイクロニードルアレイ |
JPWO2019225650A1 (ja) * | 2018-05-23 | 2021-07-08 | 富士フイルム株式会社 | 日本脳炎ワクチン含有マイクロニードルアレイ |
US11660265B2 (en) | 2018-06-28 | 2023-05-30 | Emergex USA Corporation | Method of rapidly achieving therapeutic concentrations of triptans for treatment of migraines and cluster headaches |
WO2022014695A1 (ja) * | 2020-07-17 | 2022-01-20 | 富士フイルム株式会社 | 日本脳炎予防剤及び日本脳炎ワクチン剤 |
JPWO2022014695A1 (ja) * | 2020-07-17 | 2022-01-20 |
Also Published As
Publication number | Publication date |
---|---|
KR101634836B1 (ko) | 2016-06-29 |
CN102264429B (zh) | 2014-01-08 |
CN102264429A (zh) | 2011-11-30 |
EP2383013A1 (en) | 2011-11-02 |
KR20110107333A (ko) | 2011-09-30 |
JP5902390B2 (ja) | 2016-04-13 |
EP2383013A4 (en) | 2012-11-28 |
US20110288485A1 (en) | 2011-11-24 |
JPWO2010074239A1 (ja) | 2012-06-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5902390B2 (ja) | マイクロニードルデバイス | |
KR101728194B1 (ko) | 마이크로 니들 디바이스 및 그 제조 방법 | |
JP5419702B2 (ja) | マイクロニードルデバイス | |
JP5709530B2 (ja) | マイクロニードルデバイス | |
EP1517722B1 (en) | Method of coating transdermal drug delivery devices having coated microprotrusions | |
KR101866005B1 (ko) | 마이크로 니들 코팅용 조성물 및 마이크로 니들 디바이스 | |
US20050226922A1 (en) | Apparatus and method for transdermal delivery of fentanyl-based agents | |
JP5695731B2 (ja) | マイクロニードルデバイス用生理活性非水組成物及びマイクロニードル上に付着している生理活性非水組成物 | |
US20060034903A1 (en) | Apparatus and method for transdermal delivery of natriuretic peptides | |
KR20170105105A (ko) | 마이크로니들 백신 패치를 위한 명반-함유 코팅 제형 | |
US20060182789A1 (en) | Apparatus and method for transdermal delivery of epoetin-based agents | |
EP3251722B1 (en) | Microprojection array having a beneficial agent containing coating and method of forming the coating thereon | |
TWI631965B (zh) | 微針裝置及其製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200980152286.2 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 09835035 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2010544160 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20117015427 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2009835035 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13140891 Country of ref document: US |