JP2017524662A - 滞留構造体および関連方法 - Google Patents
滞留構造体および関連方法 Download PDFInfo
- Publication number
- JP2017524662A JP2017524662A JP2016572445A JP2016572445A JP2017524662A JP 2017524662 A JP2017524662 A JP 2017524662A JP 2016572445 A JP2016572445 A JP 2016572445A JP 2016572445 A JP2016572445 A JP 2016572445A JP 2017524662 A JP2017524662 A JP 2017524662A
- Authority
- JP
- Japan
- Prior art keywords
- polymer element
- polymer
- fillable
- linker
- retention
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 56
- 230000014759 maintenance of location Effects 0.000 claims abstract description 145
- 239000013543 active substance Substances 0.000 claims abstract description 104
- 239000003814 drug Substances 0.000 claims abstract description 104
- 239000000463 material Substances 0.000 claims abstract description 96
- 230000002496 gastric effect Effects 0.000 claims abstract description 78
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 39
- 239000000126 substance Substances 0.000 claims abstract description 17
- 230000037406 food intake Effects 0.000 claims abstract description 10
- 229920000642 polymer Polymers 0.000 claims description 515
- 239000000178 monomer Substances 0.000 claims description 95
- 239000004632 polycaprolactone Substances 0.000 claims description 82
- 229920001610 polycaprolactone Polymers 0.000 claims description 82
- 239000002775 capsule Substances 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 49
- 210000002784 stomach Anatomy 0.000 claims description 41
- -1 polysiloxanes Polymers 0.000 claims description 28
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 claims description 27
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 claims description 27
- 229960002418 ivermectin Drugs 0.000 claims description 27
- 235000013305 food Nutrition 0.000 claims description 26
- 238000001727 in vivo Methods 0.000 claims description 24
- 230000004962 physiological condition Effects 0.000 claims description 24
- FMPGQHYZYWZIKL-UHFFFAOYSA-N 6-amino-2-prop-2-enoylhexanoic acid Chemical compound NCCCCC(C(O)=O)C(=O)C=C FMPGQHYZYWZIKL-UHFFFAOYSA-N 0.000 claims description 21
- 239000000032 diagnostic agent Substances 0.000 claims description 21
- 229940039227 diagnostic agent Drugs 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000012530 fluid Substances 0.000 claims description 17
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 12
- 238000005452 bending Methods 0.000 claims description 12
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 230000000717 retained effect Effects 0.000 claims description 12
- 239000000853 adhesive Substances 0.000 claims description 10
- 230000001070 adhesive effect Effects 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 229920002959 polymer blend Polymers 0.000 claims description 8
- 229920002635 polyurethane Polymers 0.000 claims description 8
- 239000004814 polyurethane Substances 0.000 claims description 8
- 239000003430 antimalarial agent Substances 0.000 claims description 7
- 238000010494 dissociation reaction Methods 0.000 claims description 7
- 230000005593 dissociations Effects 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- 230000002441 reversible effect Effects 0.000 claims description 7
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 6
- 229960001948 caffeine Drugs 0.000 claims description 6
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920001451 polypropylene glycol Polymers 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 claims description 5
- 239000000164 antipsychotic agent Substances 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 210000004051 gastric juice Anatomy 0.000 claims description 5
- 229920000728 polyester Polymers 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
- 229940005529 antipsychotics Drugs 0.000 claims description 4
- 239000013060 biological fluid Substances 0.000 claims description 4
- 229920006037 cross link polymer Polymers 0.000 claims description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 4
- 239000005556 hormone Substances 0.000 claims description 4
- 229950008325 levothyroxine Drugs 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 claims description 4
- OGQLPJUHBHRUCA-UHFFFAOYSA-N 10-amino-2-(2-methylprop-2-enoyl)decanoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCCCCCCN OGQLPJUHBHRUCA-UHFFFAOYSA-N 0.000 claims description 3
- XPHNFTKWPVRJCM-UHFFFAOYSA-N 10-amino-2-prop-2-enoyldecanoic acid Chemical compound C(C=C)(=O)C(C(=O)O)CCCCCCCCN XPHNFTKWPVRJCM-UHFFFAOYSA-N 0.000 claims description 3
- BDQHVMXNDQTYGS-UHFFFAOYSA-N 11-amino-2-(2-methylprop-2-enoyl)undecanoic acid Chemical compound CC(=C)C(=O)C(C(O)=O)CCCCCCCCCN BDQHVMXNDQTYGS-UHFFFAOYSA-N 0.000 claims description 3
- XRZYQFQUJPVYQT-UHFFFAOYSA-N 11-amino-2-prop-2-enoylundecanoic acid Chemical compound NCCCCCCCCCC(C(O)=O)C(=O)C=C XRZYQFQUJPVYQT-UHFFFAOYSA-N 0.000 claims description 3
- MEVOABYJKISPQF-UHFFFAOYSA-N 12-amino-2-(2-methylprop-2-enoyl)dodecanoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCCCCCCCCN MEVOABYJKISPQF-UHFFFAOYSA-N 0.000 claims description 3
- OFFOKEDYYQHCFA-UHFFFAOYSA-N 12-amino-2-prop-2-enoyldodecanoic acid Chemical compound C(C=C)(=O)C(C(=O)O)CCCCCCCCCCN OFFOKEDYYQHCFA-UHFFFAOYSA-N 0.000 claims description 3
- CJPFRWHJXVQURI-UHFFFAOYSA-N 2-(3-aminopropyl)-3-oxopent-4-enoic acid Chemical group C(C=C)(=O)C(C(=O)O)CCCN CJPFRWHJXVQURI-UHFFFAOYSA-N 0.000 claims description 3
- DRSZVBVGXNKYMO-UHFFFAOYSA-N 2-(3-aminopropyl)-4-methyl-3-oxopent-4-enoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCN DRSZVBVGXNKYMO-UHFFFAOYSA-N 0.000 claims description 3
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 claims description 3
- IQIAWUAJTBXDMZ-UHFFFAOYSA-N 6-amino-2-(2-methylprop-2-enoyl)hexanoic acid Chemical compound CC(=C)C(=O)C(C(O)=O)CCCCN IQIAWUAJTBXDMZ-UHFFFAOYSA-N 0.000 claims description 3
- WZCJCIWACGBZQR-UHFFFAOYSA-N 7-amino-2-(2-methylprop-2-enoyl)heptanoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCCCN WZCJCIWACGBZQR-UHFFFAOYSA-N 0.000 claims description 3
- YVYYDNBMGRPXHU-UHFFFAOYSA-N 7-amino-2-prop-2-enoylheptanoic acid Chemical compound C(C=C)(=O)C(C(=O)O)CCCCCN YVYYDNBMGRPXHU-UHFFFAOYSA-N 0.000 claims description 3
- HBZLHFQMFLJELN-UHFFFAOYSA-N 8-amino-2-(2-methylprop-2-enoyl)octanoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCCCCN HBZLHFQMFLJELN-UHFFFAOYSA-N 0.000 claims description 3
- UMTNFXRTMOOJGZ-UHFFFAOYSA-N 8-amino-2-prop-2-enoyloctanoic acid Chemical compound NCCCCCCC(C(O)=O)C(=O)C=C UMTNFXRTMOOJGZ-UHFFFAOYSA-N 0.000 claims description 3
- NUXBFODAZOPYJU-UHFFFAOYSA-N 9-amino-2-(2-methylprop-2-enoyl)nonanoic acid Chemical compound C(C(=C)C)(=O)C(C(=O)O)CCCCCCCN NUXBFODAZOPYJU-UHFFFAOYSA-N 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 3
- 229920002292 Nylon 6 Polymers 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 229920001054 Poly(ethylene‐co‐vinyl acetate) Polymers 0.000 claims description 3
- 239000004952 Polyamide Substances 0.000 claims description 3
- 229920002732 Polyanhydride Polymers 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 3
- 229940124339 anthelmintic agent Drugs 0.000 claims description 3
- 239000000921 anthelmintic agent Substances 0.000 claims description 3
- 229940033495 antimalarials Drugs 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229960005069 calcium Drugs 0.000 claims description 3
- 235000001465 calcium Nutrition 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 3
- LKFHUFAEFBRVQX-UHFFFAOYSA-N decanedioic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)CCCCCCCCC(O)=O LKFHUFAEFBRVQX-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 3
- 229940065514 poly(lactide) Drugs 0.000 claims description 3
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 3
- 229920000058 polyacrylate Polymers 0.000 claims description 3
- 229920002647 polyamide Polymers 0.000 claims description 3
- 229920001896 polybutyrate Polymers 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- 229920001299 polypropylene fumarate Polymers 0.000 claims description 3
- 229920001296 polysiloxane Polymers 0.000 claims description 3
- XZTOZSFQTFZRGX-UHFFFAOYSA-N 9-amino-2-prop-2-enoylnonanoic acid Chemical compound C(C=C)(=O)C(C(=O)O)CCCCCCCN XZTOZSFQTFZRGX-UHFFFAOYSA-N 0.000 claims description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 2
- 229930003268 Vitamin C Natural products 0.000 claims description 2
- 229930003316 Vitamin D Natural products 0.000 claims description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- 210000000941 bile Anatomy 0.000 claims description 2
- BFMKFCLXZSUVPI-UHFFFAOYSA-N ethyl but-3-enoate Chemical compound CCOC(=O)CC=C BFMKFCLXZSUVPI-UHFFFAOYSA-N 0.000 claims description 2
- 229960000304 folic acid Drugs 0.000 claims description 2
- 235000019152 folic acid Nutrition 0.000 claims description 2
- 239000011724 folic acid Substances 0.000 claims description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
- 229960003943 hypromellose Drugs 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229960003284 iron Drugs 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 238000005728 strengthening Methods 0.000 claims description 2
- 235000019157 thiamine Nutrition 0.000 claims description 2
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 2
- 229960003495 thiamine Drugs 0.000 claims description 2
- 239000011721 thiamine Substances 0.000 claims description 2
- 235000019154 vitamin C Nutrition 0.000 claims description 2
- 239000011718 vitamin C Substances 0.000 claims description 2
- 235000019166 vitamin D Nutrition 0.000 claims description 2
- 239000011710 vitamin D Substances 0.000 claims description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 2
- 229940046008 vitamin d Drugs 0.000 claims description 2
- 235000016804 zinc Nutrition 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 230000000507 anthelmentic effect Effects 0.000 claims 1
- 229940124522 antiretrovirals Drugs 0.000 claims 1
- 239000003903 antiretrovirus agent Substances 0.000 claims 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 abstract description 35
- 238000006731 degradation reaction Methods 0.000 abstract description 35
- 238000004090 dissolution Methods 0.000 abstract description 27
- 230000002378 acidificating effect Effects 0.000 abstract description 17
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 16
- 238000011068 loading method Methods 0.000 abstract description 8
- 230000000968 intestinal effect Effects 0.000 abstract description 4
- 230000004044 response Effects 0.000 abstract description 3
- 125000005647 linker group Chemical group 0.000 description 184
- 229920001971 elastomer Polymers 0.000 description 87
- 239000000806 elastomer Substances 0.000 description 87
- 229940079593 drug Drugs 0.000 description 56
- 125000000524 functional group Chemical group 0.000 description 46
- 239000003054 catalyst Substances 0.000 description 30
- 238000013461 design Methods 0.000 description 27
- 239000011159 matrix material Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 238000012360 testing method Methods 0.000 description 22
- 125000000217 alkyl group Chemical group 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 21
- 210000001187 pylorus Anatomy 0.000 description 21
- 229960003722 doxycycline Drugs 0.000 description 17
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 17
- 238000010586 diagram Methods 0.000 description 16
- 239000003623 enhancer Substances 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 241000282887 Suidae Species 0.000 description 12
- 238000012512 characterization method Methods 0.000 description 12
- 230000006835 compression Effects 0.000 description 12
- 238000007906 compression Methods 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- 230000002209 hydrophobic effect Effects 0.000 description 11
- 230000000269 nucleophilic effect Effects 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000001647 drug administration Methods 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 229920001983 poloxamer Polymers 0.000 description 9
- 239000002861 polymer material Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 238000006073 displacement reaction Methods 0.000 description 8
- 238000012377 drug delivery Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 210000000936 intestine Anatomy 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229920003135 Eudragit® L 100-55 Polymers 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 239000007903 gelatin capsule Substances 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 230000000670 limiting effect Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000012856 packing Methods 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- 239000012038 nucleophile Substances 0.000 description 6
- 150000002894 organic compounds Chemical class 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 239000011593 sulfur Substances 0.000 description 6
- 230000008961 swelling Effects 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 229920003134 Eudragit® polymer Polymers 0.000 description 5
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 description 5
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229920003169 water-soluble polymer Polymers 0.000 description 5
- AZSNMRSAGSSBNP-XPNPUAGNSA-N 22,23-dihydroavermectin B1a Chemical compound C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 AZSNMRSAGSSBNP-XPNPUAGNSA-N 0.000 description 4
- 229920003083 Kollidon® VA64 Polymers 0.000 description 4
- 206010029957 Obstruction gastric Diseases 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- 201000000660 Pyloric Stenosis Diseases 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 4
- 230000003187 abdominal effect Effects 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 239000012670 alkaline solution Substances 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 4
- 208000008386 gastric outlet obstruction Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 4
- 229960004618 prednisone Drugs 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000012744 reinforcing agent Substances 0.000 description 4
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 4
- 229960001534 risperidone Drugs 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000004154 testing of material Methods 0.000 description 4
- 230000036962 time dependent Effects 0.000 description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 3
- 238000006845 Michael addition reaction Methods 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 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
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 3
- 229960003009 clopidogrel Drugs 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000012039 electrophile Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 229960000980 entecavir Drugs 0.000 description 3
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 3
- 210000003238 esophagus Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 229920001519 homopolymer Polymers 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 208000003243 intestinal obstruction Diseases 0.000 description 3
- 150000003951 lactams Chemical class 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 3
- 229960000381 omeprazole Drugs 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 3
- 229960000672 rosuvastatin Drugs 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 150000007970 thio esters Chemical group 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- GHBSPIPJMLAMEP-UHFFFAOYSA-N 6-pentyloxan-2-one Chemical compound CCCCCC1CCCC(=O)O1 GHBSPIPJMLAMEP-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 239000005465 B01AC22 - Prasugrel Substances 0.000 description 2
- 206010004542 Bezoar Diseases 0.000 description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 2
- 229920001651 Cyanoacrylate Polymers 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010061974 Gastrointestinal obstruction Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 229920000331 Polyhydroxybutyrate Polymers 0.000 description 2
- 229920001710 Polyorthoester Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 2
- YUWBVKYVJWNVLE-UHFFFAOYSA-N [N].[P] Chemical compound [N].[P] YUWBVKYVJWNVLE-UHFFFAOYSA-N 0.000 description 2
- RMFNOBSFEXIOFQ-UHFFFAOYSA-M [Na+].C(C=C)(=O)C(C(=O)[O-])CCCCN Chemical compound [Na+].C(C=C)(=O)C(C(=O)[O-])CCCCN RMFNOBSFEXIOFQ-UHFFFAOYSA-M 0.000 description 2
- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 description 2
- XAQHXGSHRMHVMU-UHFFFAOYSA-N [S].[S] Chemical compound [S].[S] XAQHXGSHRMHVMU-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229960004191 artemisinin Drugs 0.000 description 2
- 229930101531 artemisinin Natural products 0.000 description 2
- FIHJKUPKCHIPAT-AHIGJZGOSA-N artesunate Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@@H](OC(=O)CCC(O)=O)[C@@H]4C FIHJKUPKCHIPAT-AHIGJZGOSA-N 0.000 description 2
- 229960004991 artesunate Drugs 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
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 238000006065 biodegradation reaction Methods 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- NLCKLZIHJQEMCU-UHFFFAOYSA-N cyano prop-2-enoate Chemical class C=CC(=O)OC#N NLCKLZIHJQEMCU-UHFFFAOYSA-N 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229920006237 degradable polymer Polymers 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 230000005489 elastic deformation Effects 0.000 description 2
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- IFYYFLINQYPWGJ-UHFFFAOYSA-N gamma-decalactone Chemical compound CCCCCCC1CCC(=O)O1 IFYYFLINQYPWGJ-UHFFFAOYSA-N 0.000 description 2
- 230000030136 gastric emptying Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000021472 generally recognized as safe Nutrition 0.000 description 2
- 239000001087 glyceryl triacetate Substances 0.000 description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 206010022694 intestinal perforation Diseases 0.000 description 2
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 150000002924 oxiranes Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 238000002464 physical blending Methods 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 2
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 description 2
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 229920000903 polyhydroxyalkanoate Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 2
- 229960004197 prasugrel Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000021 stimulant Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 150000003512 tertiary amines Chemical group 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 229920001187 thermosetting polymer Polymers 0.000 description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
- 239000012745 toughening agent Substances 0.000 description 2
- 229960002622 triacetin Drugs 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 1
- MXDOOIVQXATHKU-RYVPXURESA-N (8s,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-17-hydroxy-11-methylidene-2,6,7,8,9,10,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 MXDOOIVQXATHKU-RYVPXURESA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- QXRRAZIZHCWBQY-UHFFFAOYSA-N 1,1-bis(isocyanatomethyl)cyclohexane Chemical compound O=C=NCC1(CN=C=O)CCCCC1 QXRRAZIZHCWBQY-UHFFFAOYSA-N 0.000 description 1
- XZQKBOCJARZTRF-UHFFFAOYSA-N 12-aminododec-1-en-3-one Chemical compound C(C=C)(=O)CCCCCCCCCN XZQKBOCJARZTRF-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- OROGUZVNAFJPHA-UHFFFAOYSA-N 3-hydroxy-2,4-dimethyl-2H-thiophen-5-one Chemical group CC1SC(=O)C(C)=C1O OROGUZVNAFJPHA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- GJOHLWZHWQUKAU-UHFFFAOYSA-N 5-azaniumylpentan-2-yl-(6-methoxyquinolin-8-yl)azanium;dihydrogen phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 GJOHLWZHWQUKAU-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 238000006596 Alder-ene reaction Methods 0.000 description 1
- OVCDSSHSILBFBN-UHFFFAOYSA-N Amodiaquine Chemical compound C1=C(O)C(CN(CC)CC)=CC(NC=2C3=CC=C(Cl)C=C3N=CC=2)=C1 OVCDSSHSILBFBN-UHFFFAOYSA-N 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 208000034048 Asymptomatic disease Diseases 0.000 description 1
- 208000023514 Barrett esophagus Diseases 0.000 description 1
- 208000023665 Barrett oesophagus Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- FKUPPRZPSYCDRS-UHFFFAOYSA-N Cyclopentadecanolide Chemical compound O=C1CCCCCCCCCCCCCCO1 FKUPPRZPSYCDRS-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229920003160 Eudragit® RS PO Polymers 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000999322 Homo sapiens Putative insulin-like growth factor 2 antisense gene protein Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000005646 Pneumoperitoneum Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100036485 Putative insulin-like growth factor 2 antisense gene protein Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- PJSFRIWCGOHTNF-UHFFFAOYSA-N Sulphormetoxin Chemical compound COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC PJSFRIWCGOHTNF-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 125000005354 acylalkyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000004171 alkoxy aryl group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 229960001444 amodiaquine Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 230000001022 anti-muscarinic effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- BJDCWCLMFKKGEE-ISOSDAIHSA-N artenimol Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-ISOSDAIHSA-N 0.000 description 1
- 229960002521 artenimol Drugs 0.000 description 1
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 1
- 229960003159 atovaquone Drugs 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000013590 bulk material Substances 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 1
- 229960002227 clindamycin Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 238000012669 compression test Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000009223 counseling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 229930016266 dihydroartemisinin Natural products 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000011977 dual antiplatelet therapy Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229940037395 electrolytes Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
- 229960004341 escitalopram Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- GCKFUYQCUCGESZ-BPIQYHPVSA-N etonogestrel Chemical compound O=C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 GCKFUYQCUCGESZ-BPIQYHPVSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- IFYYFLINQYPWGJ-VIFPVBQESA-N gamma-Decalactone Natural products CCCCCC[C@H]1CCC(=O)O1 IFYYFLINQYPWGJ-VIFPVBQESA-N 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 229940127227 gastrointestinal drug Drugs 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 210000003767 ileocecal valve Anatomy 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 125000005945 imidazopyridyl group Chemical group 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 229940044513 implanon Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- DYLGFOYVTXJFJP-MYYYXRDXSA-N lumefantrine Chemical compound C12=CC(Cl)=CC=C2C=2C(C(O)CN(CCCC)CCCC)=CC(Cl)=CC=2\C1=C/C1=CC=C(Cl)C=C1 DYLGFOYVTXJFJP-MYYYXRDXSA-N 0.000 description 1
- 229960004985 lumefantrine Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960001962 mefloquine Drugs 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940029985 mineral supplement Drugs 0.000 description 1
- 235000020786 mineral supplement Nutrition 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical class 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000002417 nutraceutical Substances 0.000 description 1
- 235000021436 nutraceutical agent Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940115044 nuvaring Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- GLZWNFNQMJAZGY-UHFFFAOYSA-N octaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCO GLZWNFNQMJAZGY-UHFFFAOYSA-N 0.000 description 1
- LOKPJYNMYCVCRM-UHFFFAOYSA-N omega-pentadecalactone Natural products O=C1CCCCCCCCCCCCCCCO1 LOKPJYNMYCVCRM-UHFFFAOYSA-N 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000000734 parasympathomimetic agent Substances 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 229940005542 parasympathomimetics Drugs 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical class 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000003375 plant hormone Substances 0.000 description 1
- 238000013001 point bending Methods 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001855 polyketal Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 239000002685 polymerization catalyst Substances 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960005179 primaquine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229960005385 proguanil Drugs 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
- 229960000611 pyrimethamine Drugs 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical group 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000008684 selective degradation Effects 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910001285 shape-memory alloy Inorganic materials 0.000 description 1
- 229920000431 shape-memory polymer Polymers 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 150000003384 small molecules Chemical group 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000008143 steroidal glycosides Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960004673 sulfadoxine Drugs 0.000 description 1
- VLYWMPOKSSWJAL-UHFFFAOYSA-N sulfamethoxypyridazine Chemical compound N1=NC(OC)=CC=C1NS(=O)(=O)C1=CC=C(N)C=C1 VLYWMPOKSSWJAL-UHFFFAOYSA-N 0.000 description 1
- 229960004936 sulfamethoxypyridazine Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940099268 synthroid Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960002613 tamsulosin Drugs 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000009864 tensile test Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005888 tetrahydroindolyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000012749 thinning agent Substances 0.000 description 1
- NJRXVEJTAYWCQJ-UHFFFAOYSA-N thiomalic acid Chemical compound OC(=O)CC(S)C(O)=O NJRXVEJTAYWCQJ-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- UONOETXJSWQNOL-UHFFFAOYSA-N tungsten carbide Chemical compound [W+]#[C-] UONOETXJSWQNOL-UHFFFAOYSA-N 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
- 229960004751 varenicline Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical group [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- 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
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
- C08G18/4269—Lactones
- C08G18/4277—Caprolactone and/or substituted caprolactone
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/73—Polyisocyanates or polyisothiocyanates acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/002—Dendritic macromolecules
- C08G83/005—Hyperbranched macromolecules
- C08G83/006—After treatment of hyperbranched macromolecules
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/02—Homopolymers or copolymers of acids; Metal or ammonium salts thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/04—Homopolymers or copolymers of esters
- C08L33/06—Homopolymers or copolymers of esters of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical
- C08L33/08—Homopolymers or copolymers of acrylic acid esters
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L33/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- C08L33/04—Homopolymers or copolymers of esters
- C08L33/14—Homopolymers or copolymers of esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2230/00—Compositions for preparing biodegradable polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2203/00—Applications
- C08L2203/02—Applications for biomedical use
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Virology (AREA)
- Anesthesiology (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biomedical Technology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Prostheses (AREA)
Abstract
Description
この出願は、米国特許法§119(e)の下、2014年6月11日に出願された同時係属中の米国仮出願第62/010,992号(この内容は、全ての目的のためにその全体が参考として本明細書に援用される)に対する優先権を主張する。
この発明は、National Institutes of Healthによって付与された助成金番号5T32HL007604−28の下、政府の支援を受けてなされた。政府は、本発明に一定の権利を有する。
Q1−L−Q2 (II)
におけるような構造を有し、式中、Q1およびQ2は同じまたは異なる反応性官能基であり、Lは、式(III):
別に定める場合を除き、構造体の充填可能ポリマー要素として、ポリカプロラクトン(PCL)を、その機械的なおよび物理化学的性質の理由で選択した。PCLは約60℃の低い融点を有する分解可能ポリエステルであり、複数の処理技術を可能にする。PCLは、生理的条件下で、そのエステル結合の加水分解によりゆっくり分解し、長期インビボ滞留構造体の特定の実施形態の調製にとって、PCLを適切な材料にしている。PCLは、種々の薬物の制御放出および標的化送達のために使用されてきた。
機械的安定性を提供する薬物マトリックスとしての比較的剛性の要素(充填可能ポリマー要素)と、可撓性跳ね返り要素(弾性ポリマー要素)との組み合わせを使うことにより、設計の制約に対処した。図4A〜5Bに示すように、それ自体の上に折り畳まれる交互になった剛性要素および可撓性要素の「多角形」ファミリー、ならびに剛性要素が中心可撓性要素から突き出た「星形」ファミリーの、剛性要素および可撓性要素の2種の幾何学的ファミリーを更に詳細に調査した。標準的サイズ000ゼラチンカプセル中に効率的にカプセル化され得る設計を、Inventor CADソフトウエア、3Dプリンターで生成し、これを陽性型(positive)として使用してPDMS陰性型(negative mold)を作製した。より大きな獣医学カプセル、ならびにより容易なヒト消費用の00−EL、0−ELを含むより小さいカプセルなどの、その他のサイズのカプセル用に最適化したバージョンも同様に開発した。
図5Aでは、六角形構造体を有する実施形態が000サイズカプセルの隣に示されている。六角形の頂点は、弾性ポリマー要素を含み、六角形の辺は、剛性充填可能ポリマー要素を含む。カプセル化されていない最終の形態がカプセル長さのほぼ2倍に等しい外接直径を有するように、それぞれの辺は、カプセルの長さよりわずかに短い長さを有する。図5Bでは、内側セクター角度が約360°/Nに等しいセクター形状を有する放射状突起を備えた種々の構造体が示されている。正方形、六角形、八面体、および十二面体の構造体の4つの実施形態がそれぞれ、カプセル化されていない形態で示されている。形状は、圧縮に対する抵抗を高め、胃中滞留期間を延長するために、高弾性係数を有する少なくとも1つの材料から形成される。
図6は、大型動物モデルで、それぞれ摂取の3分、5分、および12分後に得られた一連の胸/腹部X線画像であり、約12分間にわたるカプセルからの多腕構造体の展開および元々のコンフォメーションの構造体によるインビボ受け入れ(adoption)を示している。
図8は、いくつかの実施形態による、腸溶性エラストマーおよび腸溶性エラストマー調製方法の模式図である。図8Aでは、ポリマーゲルネットワークが図示されており、第1のセットの線は、合成されたポリ(アクリロイル−6−アミノカプロン酸)を表し、第2のセットの線は、線形ポリ(メタクリル酸−co−アクリル酸エチル)(例えば、Evonik Industries AG(Essen,Germany)から入手可能なオイドラギット(登録商標)L100−55)を表し、複数の箱は、ポリマー鎖間の水素結合を表し、スポットは水分子を表す。図8Bでは、製造プロセスフローが示されている。図8Bの左から、ポリ(アクリロイル−6−アミノカプロン酸)ナトリウム塩水溶液およびポリ(メタクリル酸−co−アクリル酸エチル)ナトリウム塩水溶液を、種々の比率(限定されないが、1:0、1:1、および1:2など)の1つで混合し、均一ポリマーナトリウム塩水溶液にした。その後、2種のポリマーをHCl溶液の添加により共沈させた。ポリマー複合体の沈殿物を腸溶性、弾性ポリマーゲルへと変換し、遠心管の底部で回収した。形成された腸溶性エラストマーは、構造体の構築、機械的な特徴付け、などのために、各種形状に切断および/または加圧成形することが可能である。
腸溶性リンカー要素を圧縮成形により形成した。一実施形態では、pH依存性溶解プロファイルを有することが当技術分野で知られている腸溶性材料である、オイドラギットL100−55(Evonik)を可塑剤(トリアセチン)と、60:40〜80:20の間の比率でブレンドした。3gの得られた混合物を2枚の6x6インチテフロン(登録商標)シートの間に置き、110〜120℃のホットプレス上に置き、5000psiで20分間圧縮した。テフロン(登録商標)シートをプレスから取り出し、室温の水道水中で10秒間短時間急冷し、その後、オイドラギットフィルムを取り出した。
引張、圧縮、およびクリープ荷重を使って、PCLエラストマーを機械的に特徴付けた。機械的な特徴付けは、ASTM規格D638(引張)、D575(圧縮)、およびD2990(クリープ)に従って行った。
PCLエラストマーを2mm厚さのポリマーシートに硬化した。シートを冷却し、標準ダンベルダイ(ASTM D−638)を使ってシートから試験片を切り出した。試験片をインストロン材料試験機のグリップに装着し、ゲージ長をデジタルマイクロメーターを使って測定した。試料が断裂するまで、10mm/分の速度で試験片に変位を加えた。力を垂直応力(F/A)に変換し、変位を歪み(ΔL/L)に変換して、図11Aにプロットする。
PCLエラストマーを13mm厚さのスラブに硬化した。スラブを冷却し、回転中空ドリルビットを使って、スラブから28mm直径の試験片を切り出した。試験片を拘束荷重圧縮ジグ中に配置し、12mm/minでの変位に供した。30%圧縮歪みに到達するまで試験片を試験した。力を圧力(F/A)に変換し、変位を体積比(ΔV/V)に変換して、図11Bにプロットする。
PCLエラストマー、ポリジメチルシロキサン(シリコーン)、およびポリエチレン酢酸ビニル(PEVA)を2mm厚さのポリマーシートに硬化した。シートを冷却し、標準ダンベルダイ(ASTM D−638)を使ってシートから試験片を切り出した。試験片をインストロン材料試験機のグリップに装着し、ゲージ長をデジタルマイクロメーターを使って測定した。各材料の極限引張強さの30%に相当する一定の応力を、60分間にわたり試験片に加えた。力と変位を試験全体を通して計算し、垂直応力(F/A)および歪み(ΔL/L)に変換して、図11Cにプロットする。
有限要素法を使って、SIMULIA Abaqus FEAソフトウエアにおいて構造体の応力および歪みプロファイルを解析した。構造体の幾何をAutoDesk InventorからAbaqusにインポートした。PCLエラストマーの材料特性を、前述の引張および圧縮試験由来のMooney−Rivlin超弾性モデルを使って定義した。線形PCL腕を、線形弾性であると仮定し、弾性率は上記曲げ試験から導かれた。モデルをC3D4要素を使ってメッシュ処理(mesh)し、PCLエラストマーと線形PCLを界面で結合させた。1mm直径のプレートをPCLエラストマーの底部に導入し、変形全体を通して構造体を所定位置に保持した。力をそれぞれの腕の頂部に垂直に適用し、構造体のカプセル中への折り畳みをシミュレーションした。計算後、フォン・ミーゼス(von Misses)応力、最大主応力、長手方向応力および横方向(laterial)応力を解析した。有限要素モデル化の結果を図12に示す。
幽門を通る保持構造体の通過をよりよく理解するために、カスタム実験設定を開発した。実験設定の概略を図13Aに示す。20cmの上部直径と2cmの下部直径のポリプロピレン漏斗を使って、幽門括約筋をシミュレーションした。上述の星形状を有する構造体を漏斗内に配置し、カスタム設計プランジャを使って、2cmの注ぎ口を通って構造体を押し込んだ。プランジャをインストロン材料試験機の引張クロスヘッドに取り付け、漏斗をクランプに取り付けた。構造体を漏斗を通って10mm/分の速度で押し込み、試験全体を通して、力と変位を取得し、図13Bに示す。
胃中保持を達成する能力のために開発された特定の配合物を評価するために、上述の構造体(例えば、六角形および星形)を大型動物モデル、35〜50kgのヨークシャーブタに投与した。このモデルは、ヒトに類似する胃の解剖学的構造を有していることが既知であり、胃腸管空間中の構造体を評価するのに広く使用されているという理由で選択された。ブタにおける食物ボーラス通過の延長は通常、時間単位で測定され、従って、日数のオーダーの保持の評価に対しては、これは、小さな誤差を生ずるに過ぎないはずであり、胃の解剖学的構造および胃排出の良好なモデルを提供する。
HPLCおよびLC−MS/MS分析を使って胃中環境における薬物の安定性を評価した。親水性薬物を遠心管中の模擬胃液(SGF、0.2%(w/v)NaCl、0.83%(v/v)HCl、pH=1)中に溶解した。疎水性薬物を、IAW(イソプロパノール70%、アセトニトリル20%、水10%)に溶解し、HClを使ってpHを1に調節した。対照として、薬物を同一溶媒に溶解し、pHを6.0に調節した(1M NaOHを使用)。1分間のボルテックスおよび10分間の超音波処理後、チューブを振盪インキュベーター(150rpm、37℃)中に置いた。試料を2週間まで所定時点で収集し、HPLCおよびLC−MS/MSで分析して薬物の安定性を定量化した。
HPLCによって分析された2週間にわたるSGF(pH=1、37℃)中でのドキシサイクリンの安定性を図14に示す。オートサンプラーおよびC8逆相カラム(4.6×150mm、i.d.、5um粒径)を備えたAgilent 1260 infinity model HPLCシステムを使用した。移動相は、ACN/水+0.1%ギ酸、pH3.5(60/40)とした。20μlの試料を、1mL/分の移動相流量でカラムに注入し、350nmのUV吸収を10分間にわたり記録した。
HPLCによって分析された2週間にわたるIAW(pH=1、37℃)中でのアーテメータの安定性を図15に示す。薬物に関連する曲線下面積(AUC)を安定性パーセンテージの定量化に使用した。
遊離イベルメクチンは酸性条件(IAW、pH=1、37℃)では不安定であることを、図16Aに示す。PCL構造体は酸性分解に対しイベルメクチンを保護した。図16Bに示すイベルメクチン(IVM)充填構造体を、SGF+RH溶液(pH=1、37℃)中に72時間置いた。構造体をイソプロパノール中で10分間超音波処理することにより、薬物を抽出した。抽出したIVMのHPLCクロマトグラムは、イソプロパノールに溶解した新しいIVMのものに類似し、PCL構造体が酸性環境下でIVMを保護したことを示している。
種々の組成物を含む薬物充填経口送達構造体を、実施例16および17に記載のように調製した。親水性薬物を充填した構造体を、100mLのSGFを含む密閉カップ中に入れた。疎水性薬物については、Kolliphor(登録商標)RH40(非イオン性水中油型可溶化剤)をSGFに加え(0.25%(w/v))、放出される薬物の溶解度を高めた。カップを振盪インキュベーター(150rpm、37℃)中に置いた。試料を2週間まで規定の時点で収集し、HPLCおよびLC−MS/MSで分析して放出された薬物の量を定量化した。
図17Aは、SGF(pH=1、37℃)中のドキシサイクリン充填PCL星形構造体のインビトロ放出を示す:プルロニックP407(親水性界面活性剤)をPCLマトリックスに加え、ポリマーマトリックス中の薬物懸濁を容易にし、放出動力学を調整した。放出媒体中の薬物濃度をHPLCにより測定した。PCL:PLu:Doxの比を図の凡例中に重量%で表した。
図17Bは、SGF+RH40(pH=1、37℃)中の異なる配合物を含むイベルメクチン(IVM)充填星形構造体のインビトロ放出を示す。異なる賦形剤、すなわち、RH40、プルロニックP407、およびSoluplus、を加えて、表4に示すように、放出動力学を調整した。放出媒体中の薬物濃度をHPLCにより測定した。
ASTM規格D790にしたがい、そして図18に示されるように、屈曲における線形PCLを機械的に特徴付けた。線形PCL、賦形剤含有PCL、および賦形剤と薬物を含有するPCLのシートを、2mm厚さのシートに硬化させた。シートを冷却した後、シートから80mm長さ×8mm幅の長方形を切り出し、試料を作製した。試験の前に、デジタルマイクロメーターを使って、試験片の幅と厚さを測定した。3点曲げ固定治具を備えたインストロン材料試験機を使って試験片を試験した。0.85mm/分の速度で試験を行い、32mmのスパンを全ての試験片に使用した。試験片が破断するかまたは20%の曲げ歪み(flexural stain)に達した場合に、試験を停止した。力を曲げ応力に変換し、変位を曲げ歪みに変換した。
図19〜21は、3種の異なる構成の胃中滞留システムの指定時点での胃中保持確率のヒストグラムを示す。胃中滞留システムは、腕の重合中に、ポリマー薬物送達「腕」中に配置されたステンレス鋼の1mm基準を含んで形成された。胃中滞留システムは、ヨークシャーブタ(35〜50kg)に、鎮静下、胃腔中に内視鏡オーバーチューブを介して投与された。胸、腹部、および骨盤の複数の位置(前後方向、左側方向、右側方向)の連続X線像を取得した。送達後、15分までX線像を取得し、外側カプセルおよび/または拘束システムからの展開を確認した。その後、次の4日間毎日、および最初の5日間の後に毎週3回、X線像を取得した。胃腔中の滞留システムの位置を複数のX線検査視野から確認した。(図19、H1−EE1)ポリカプロラクトン「腕」および腸溶性エラストマーから作製された頂点での弾性要素を有する六角形滞留システム。(図20、H1−F1−F1−X1)イソシアネート架橋ポリカプロラクトンから作製された腕およびイソシアネート架橋ポリカプロラクトンから作製された弾性要素を備え、さらにオイドラギットL100−55フィルムから作製された溶解性リンカーを備えた六角形滞留システム。(図21、H1−F1−R1−X2)ポリカプロラクトンから作製された腕およびイソシアネート架橋ポリカプロラクトンから作製された弾性要素、ならびに90%オイドラギットL100−55および10%ポリ(アクリル酸)のブレンドから作製された溶解性リンカーを備えた六角形滞留システム。
肥満症の処置のための胃内バルーン(内視鏡下で展開される胃中滞留システム)は、部分的な胃排出口の閉塞と一致する言及される症状、特に18〜90%の範囲の患者における悪心を有する。本明細書で記載の滞留構造体による胃排出口の閉塞の可能性をモニターするために、これらの構造体を大型動物モデルで評価した。特に、非分解性弾性ポリマー要素から主に構築される構造体を、星形構成に調製し、潜在的な排出口閉塞を観察した。これを約50kgのブタの胃中で展開し、1日2回、腹部膨満、嘔吐および糞便生成の減少を含む胃腸管閉塞の証拠について臨床的にモニターした。さらに、連続X線を週3回実施して、胃膨満を含む閉塞の証拠について評価した。さらに、35日目に、内視鏡手順の前に、動物に液体食を24時間与えて、動物の胃内容物排出能力を評価し、さらに胃を内視鏡下で評価した。内視鏡画像処理時に、構造体は、幽門を覆う(overly)ことが確認され、また、胃腔は食材がなかった。このことは、構造体が胃から食物の通過を許容し、かつその上で胃空洞中に滞留したままであり、さらに幽門を覆う能力を支持するものである。
ドキシサイクリンハイクラート(doxycycline hyclate)100mgの市販錠剤を獣医学供給源(Patterson Veterinary)より購入した。3匹のブタに各1錠を0日目に投与し、選択した時点で、静脈カニューレ挿入により血清を収集した。別のブタに、およそ5日間にわたり1日2回の100mgと同じ投与量を与えることを意図した、合計約1000mgのドキシサイクリンの6腕星形配合物を投与した。ドキシサイクリンの25w/w%充填45,000MWポリカプロラクトンを、4w/w%のプルロニックP407親水性の賦形剤と共に配合した。ブレンドを、75℃で融解および混合し、PDMS型に注型した。冷却後に中心部分を星形から取り出し、弾性PCLプレポリマー溶液を中心空隙中に注ぎ込み、約75℃で48時間硬化させた。以前記載したように、得られた形状をカプセル化し、ヨークシャーブタに投与した。LC/LC−MSを使って、図24に示すように薬物レベルを定量化した。
イベルメクチンをEtOHと水の50:50溶液に溶解し、0.2mg/kgを10mlの溶液中の経口胃管栄養として、それぞれ40〜50kgのブタに投与した。投与の前後の指定時間に、末梢静脈カニューレ挿入により血液検体を血清分離器チューブに収集し、遠心分離にかけた。血清を、後のバッチ分析のためにアリコートで凍結した。イベルメクチンの血清レベルを、Waters LC−MSで、図25Aに示すように、標準的方法を使って測定した。
Claims (79)
- 滞留構造体であって、
充填可能ポリマー要素と、
前記充填可能ポリマー要素を第2のポリマー要素に結合する第1のリンカーと、
前記充填可能ポリマー要素および/または弾性ポリマー要素の少なくとも一部を含む、あるいは前記充填可能ポリマー要素および/または前記弾性ポリマー要素に結合した第2のリンカーとを含み、
前記充填可能ポリマー要素、前記第2のポリマー要素、および前記第1のリンカー、および前記第2のリンカーの内の少なくとも1つは、弾性ポリマー要素を含み、
前記充填可能ポリマー要素は、合計構造体重量の少なくとも約60重量%を構成し、
前記滞留構造体は、少なくとも約0.2Nの折り畳み力により特徴付けられ、
前記第1のリンカーは第1のセットの生理的条件下で分解可能であり、
前記第2のリンカーは、前記第1のセットの条件とは異なる第2のセットの生理的条件下で分解可能であり、前記第1のセットの条件下では実質的に分解可能ではない、滞留構造体。 - 前記第1のリンカーが弾性ポリマー要素を含む、請求項1に記載の滞留構造体。
- 前記第2のリンカーが弾性ポリマー要素を含む、請求項1に記載の滞留構造体。
- 滞留構造体であって、
充填可能ポリマー要素と、
少なくとも1つの分解可能リンカーを介して前記充填可能ポリマー要素に結合した第2のポリマー要素とを含み、
ここで、前記分解可能リンカーは、前記充填可能ポリマー要素および/または前記第2のポリマー要素の少なくとも一部を含み、または前記充填可能ポリマー要素および/または前記第2のポリマー要素に結合し、
前記充填可能ポリマー要素、前記第2のポリマー要素、および前記分解可能リンカーの内の少なくとも1つは、弾性ポリマー要素を含み、
前記充填可能ポリマー要素は合計構造体重量の少なくとも約60重量%を構成し、
少なくとも約0.2Nの折り畳み力を有し、
少なくとも約2cmの非圧縮断面寸法を有する、滞留構造体。 - 滞留構造体であって、
充填可能ポリマー要素および前記充填可能ポリマー要素に結合した第2のポリマー要素と、
前記充填可能ポリマー要素および/または前記第2のポリマー要素の少なくとも一部を含む、または前記充填可能ポリマー要素および/または前記第2のポリマー要素に結合した少なくとも1つの分解可能リンカーとを含み、
被験体の内部の位置に少なくとも約24時間保持されるように構成される、滞留構造体。 - 前記充填可能ポリマー要素、前記第2のポリマー要素、および前記分解可能リンカーの内の少なくとも1つが弾性ポリマー要素を含む、請求項5に記載の滞留構造体。
- 滞留構造体であって、
充填可能ポリマー要素および前記充填可能ポリマー要素に結合した第2のポリマー要素と、
前記充填可能ポリマー要素および/または前記第2のポリマー要素の少なくとも一部を含む、または前記充填可能ポリマー要素および/または前記第2のポリマー要素に結合した少なくとも1つの分解可能リンカーとを含み、
前記充填可能ポリマー要素は活性物質を含み、
前記活性物質が最初の24時間にわたる放出から測定される特定の初期平均速度で前記充填可能ポリマー材料から放出されるように、前記滞留構造体が構成され、
前記活性物質は、前記最初の24時間の放出後の24時間の期間にわたり、前記初期平均速度の、少なくとも約1%の平均速度で放出される、滞留構造体。 - 前記充填可能ポリマー要素、前記第2のポリマー要素、および前記分解可能リンカーの内の少なくとも1つが弾性ポリマー要素を含む、請求項7に記載の滞留構造体。
- 前記第2のポリマー要素が前記弾性ポリマー要素を含む、請求項4〜8のいずれか1項に記載の滞留構造体。
- 前記分解可能リンカーが弾性ポリマー要素を含む、請求項4〜9のいずれか1項に記載の滞留構造体。
- 追加の弾性ポリマー要素をさらに含む、請求項4〜10のいずれか1項に記載の滞留構造体。
- 前記分解可能リンカーが、前記充填可能ポリマー要素および/または前記第2のポリマー要素の少なくとも一部を含む、または前記充填可能ポリマー要素および/または前記第2のポリマー要素に結合している、請求項4〜11のいずれか1項に記載の滞留構造体。
- 活性物質を含む、請求項1〜5のいずれか1項に記載の滞留構造体。
- 前記活性物質が治療薬である、請求項7または13に記載の滞留構造体。
- 内部開口部に対しインビボの位置を維持するように構成された第1の構成を有する、前記請求項のいずれかに記載の滞留構造体。
- 前記第1の構成が多角形の形状を有する、前記請求項のいずれかに記載の滞留構造体。
- 前記第1の構成が多腕星形の形状を有する、請求項1〜15のいずれか1項に記載の滞留構造体。
- 3〜8腕を有する、請求項17に記載の滞留構造体。
- 接着剤を介して、化学結合により、および/または相互貫入ポリマー鎖により、前記充填可能ポリマー要素が前記第2のポリマー要素と結合する、前記請求項のいずれかに記載の滞留構造体。
- 前記第2のポリマー要素が、少なくとも約45度、少なくとも約60度、少なくとも約90度、少なくとも約120度、少なくとも約150度、または少なくとも約180度の機械的曲げ変形を、壊れずに受けるように構成される、前記請求項のいずれかに記載の滞留構造体。
- 前記第2のポリマー要素が、少なくとも約24時間、少なくとも約1週間、少なくとも約1ヶ月間、少なくとも約1年間、または少なくとも約2年間の期間にわたり、変形された構成で残存するように構成され、および前記期間後に実質的にその変形前の構成に戻るように構成される、前記請求項のいずれかに記載の滞留構造体。
- 前記第2のポリマー要素の弾性係数が、約0.1MPa〜約30MPaの範囲である、前記請求項のいずれかに記載の滞留構造体。
- 前記第2のポリマー要素が、血液、水、胆汁、胃液などの生体液の存在下で実質的に膨潤しない、前記請求項のいずれかに記載の滞留構造体。
- 胃液の存在下で実質的に膨潤しない、請求項23に記載の滞留構造体。
- デバイスが、生理的な温度の非撹拌胃液または模擬胃液中で、乾燥状態の前記第1のポリマー要素の体積に比べて、約10体積%未満、約5体積%未満、約2体積%未満、または約1体積%未満だけ膨潤する、前記請求項のいずれかに記載の滞留構造体。
- 前記生体液が胃液である、請求項25に記載の滞留構造体。
- 前記第2のポリマー要素の少なくとも一部が、ポリカプロラクトン、ポリ(フマル酸プロピレン)、ポリ(セバシン酸グリセロール)、ポリ(ラクチド)、ポリ(グリコール酸)、ポリ(乳酸−グリコール酸)、ポリブチレート、およびポリヒドロキシアルカノエートなどのポリエステル;ポリ(エチレンオキシド)およびポリ(プロピレンオキシド)などのポリエーテル;ポリ(ジメチルシロキサン)などのポリシロキサン;ポリ(カプロラクタム)などのポリアミド;ポリ(メタクリル酸メチル)およびポリ(エチルビニルアセテート)などのポリアクリレート/メタクリレート;ポリ無水物;ならびにポリウレタンを含む、前記請求項のいずれかに記載の滞留構造体。
- 前記第2のポリマー要素の少なくとも一部が、マルチブロックポリマーを含む、前記請求項のいずれかに記載の滞留構造体。
- 前記充填可能ポリマー要素が、ポリカプロラクトン(PCL)、ポリ(エチレン−co−酢酸ビニル)、および/またはポリエチレングリコール(PEG)を含む、前記請求項のいずれかに記載の滞留構造体。
- 前記充填可能ポリマー要素を、合計構造体重量に対して、少なくとも約70重量%、少なくとも約80重量%、少なくとも約90重量%、または少なくとも約93重量%の量で含む、前記請求項のいずれかに記載の滞留構造体。
- 前記活性物質が、前記充填可能ポリマー要素中に、合計充填可能ポリマー要素の重量に対して約0.01重量%〜約50重量%の範囲の量で存在する、請求項13または14のいずれか1項に記載の滞留構造体。
- 前記少なくとも1つの分解可能リンカーが、滞留期間にわたり、少なくとも部分的に解離するように構成される、請求項4〜33のいずれか1項に記載の滞留構造体。
- 前記滞留期間が24時間〜2年間の範囲である、請求項32に記載の滞留構造体。
- 少なくとも1つの分解可能リンカーが、生理的環境中で、少なくとも約24時間、少なくとも約48時間、少なくとも約1週間、少なくとも約1ヶ月、または少なくとも約1年間の一定時間にわたり安定である、請求項4〜33のいずれか1項に記載の滞留構造体。
- 前記生理的環境が胃中環境である、請求項34に記載の滞留構造体。
- 前記胃中環境が胃腔を含む、請求項35に記載の滞留構造体。
- 少なくとも1つの分解可能リンカーが、腸溶性ポリマーを含む、請求項4〜36のいずれか1項に記載の滞留構造体。
- 前記腸溶性ポリマーが、酢酸フタル酸セルロース、ヒプロメロース、ヒドロキシプロピルメチルセルロース、および/またはポリ(メタクリル酸−co−アクリル酸エチル)を含む、請求項37に記載の滞留構造体。
- 前記腸溶性ポリマーが、ポリ(アクリロイル−6−アミノカプロン酸)およびポリ(メタクリル酸−co−アクリル酸エチル)を含む、請求項37に記載の滞留構造体。
- 前記腸溶性ポリマーが含水率40体積%以下のポリマーゲルである、請求項37〜39のいずれか1項に記載の滞留構造体。
- 前記腸溶性ポリマーが、アクリロイルアミノアルキレン酸モノマーのポリマー、またはその塩を含む、請求項37〜40のいずれか1項に記載の滞留構造体。
- 前記アクリロイルアミノアルキレン酸モノマーが、アクリロイル−5−アミノペンタン酸、アクリロイル−6−アミノカプロン酸、アクリロイル−7−アミノヘプタン酸、アクリロイル−8−アミノオクタン酸、アクリロイル−9−アミノノナン酸、アクリロイル−10−アミノデカン酸、アクリロイル−11−アミノウンデカン酸、アクリロイル−12−アミノドデカン酸、メタクリロイル−5−アミノペンタン酸、メタクリロイル−6−アミノカプロン酸、メタクリロイル−7−アミノヘプタン酸、メタクリロイル−8−アミノオクタン酸、メタクリロイル−9−アミノノナン酸、メタクリロイル−10−アミノデカン酸、メタクリロイル−11−アミノウンデカン酸、メタクリロイル−12−アミノドデカン酸、これらの塩、およびこれらの組み合わせからなる群より選択される、請求項41に記載の滞留構造体。
- 少なくとも1つのリンカーが、少なくとも2種の腸溶性ポリマーの腸溶性ポリマーブレンドを含み、前記ブレンドが、請求項D25に記載の第1の腸溶性ポリマーおよびポリ(メタクリル酸−co−アルキルアクリレート)、またはその塩を含む第2の腸溶性ポリマーを含む、請求項37〜42のいずれか1項に記載の滞留構造体。
- 少なくとも1つのリンカーが、約40重量%未満の含水率を有する、請求項37〜43のいずれか1項に記載の滞留構造体。
- 前記腸溶性ポリマーが、その初期長さの50%から1500%まで伸長させると、可逆的伸びを示すように構成される、請求項37〜44のいずれか1項に記載の滞留構造体。
- 少なくとも1つのリンカーが、室温で測定して、約6.0を超えるpHで水溶液中に溶解することができ、かつ約3.0未満のpHで4〜40日間の期間にわたり水溶液中に実質的に不溶性である、請求項37〜45のいずれか1項に記載の滞留構造体。
- 前記腸溶性ポリマーが、0.1MPa〜100MPaの弾性係数を有する、請求項37〜46のいずれか1項に記載の滞留構造体。
- 前記活性物質が、スタチン、抗マラリア剤、ホルモン、レボチロキシン、イベルメクチン、抗レトロウイルス剤、駆虫剤、抗精神病薬、抗うつ剤、およびカフェインの内の少なくとも1種を含む、請求項13または14のいずれか1項に記載の滞留構造体。
- 前記活性物質が、タンパク質、葉酸、カルシウム、ヨウ素、鉄、亜鉛、チアミン、ナイアシン、ビタミンC、およびビタミンDの内の少なくとも1種を含む、請求項13または14のいずれか1項に記載の滞留構造体。
- 1つまたはそれを超える要素および/または1つまたはそれを超えるリンカーが、食品等級架橋ポリマーを含む、前記請求項のいずれかに記載の滞留構造体。
- 前記構造体が開窓部を有する形状である、請求項1〜15のいずれか1項に記載の滞留構造体。
- 前記構造体が、前記構造体の凸包体積の約10体積%〜約90体積%を占める、前記請求項のいずれかに記載の滞留構造体。
- 滞留構造体を送達するためのシステムであって、
収容構造体と、
前記収容構造体内に収容された滞留構造体とを含み、
前記滞留構造体は、前記収容構造体から放出後に、第1の構成を有するように構築および配置され、
前記滞留構造体は、前記収容構造体内に収容される場合に、第2の構成を有するように構築および配置され、
前記第1の構成は少なくとも約2cmの非圧縮断面寸法を有し、
前記第2の構成は前記第1の構成の凸包より少なくとも約10%小さい凸包を有し、および/または前記第2の構成は前記第1の構成の最大断面寸法より少なくとも約10%小さい最大断面寸法を有し、
デバイスの第1の部分は第1のセットの生理的条件下で分解可能であるが、前記デバイスの第2の部分は前記第1のセットの生理的条件下では実質的に分解可能ではない、システム。 - 前記滞留構造体が、充填可能ポリマー要素および前記充填可能ポリマー要素に結合した少なくとも1つの分解可能リンカーを含む、請求項53に記載のシステム。
- 前記デバイスの第2の部分が、第2のセットの生理的条件下で分解可能である、請求項53または54に記載のシステム。
- 前記デバイスの少なくとも一部が、屈曲可能および/または可撓性である、請求項53〜55のいずれか1項に記載のシステム。
- 前記収容構造体が、摂取、自己投与、および経口投与の内の少なくとも1種を行われるように構成される、請求項53〜56のいずれか1項に記載のシステム。
- 前記収容構造体が、000カプセル、00カプセル、0カプセル、1カプセル、2カプセル、3カプセル、4カプセル、および5カプセルの内の少なくとも1つを含む、請求項53〜57のいずれか1項に記載のシステム。
- 前記第2の構成が、前記収容構造体により画定される空洞の60%より大きい体積を前記滞留構造体が占めるように構成される、請求項53〜58のいずれか1項に記載のシステム。
- 前記滞留構造体が、前記収容構造体からの放出の際に、前記第1の構成をとるように構成される、請求項53〜59のいずれか1項に記載のシステム。
- 前記滞留構造体が弾性ポリマー要素を含む、請求項53〜60のいずれか1項に記載のシステム。
- 前記弾性ポリマー要素が、機械的変形の解放後、前記弾性ポリマー要素を、約30分未満で、および約10分未満、約5分未満、または約1分未満で、その変形前の形状に実質的に戻すのに十分な跳ね返り強度を有する、請求項61に記載のシステム。
- 前記収容構造体からの放出の前に、前記滞留構造体が、72時間、1週間、2週間、4週間、1年間および5年間のうちの少なくとも1つより長くにわたり、前記収容構造体中で前記第2の構成で保存される、請求項53〜62のいずれか1項に記載のシステム。
- 前記第1の構成の最大断面寸法が、前記第2の構成の最大断面寸法より、少なくとも約10%小さい、少なくとも約20%小さい、少なくとも約40%小さい、少なくとも約60%小さい、または少なくとも約80%小さい寸法である、請求項53〜63のいずれか1項に記載のシステム。
- 前記第1の構成の凸包体積が、前記第2の構成の凸包体積より、少なくとも約10%小さい、少なくとも約20%小さい、少なくとも約40%小さい、少なくとも約60%小さい、または少なくとも約80%小さい体積である、請求項53〜64のいずれか1項に記載のシステム。
- 滞留構造体を送達するための方法であって、
滞留構造体を含む収容構造体を被験体に投与するステップであって、それにより前記被験体内の位置で前記収容構造体が滞留構造体を放出する、ステップを含み、
前記滞留構造体は、前記収容構造体内で第2の構成を有し、
前記滞留構造体が前記収容構造体から放出された後に、前記滞留構造体は、前記被験体内の位置にまたはその近傍に少なくとも約24時間保持されるように第1の構成を取得する、方法。 - 前記被験体内の位置が開口部または空洞である、請求項66に記載の方法。
- 滞留構造体を送達するための方法であって、
滞留構造体を含む収容構造体を被験体に投与するステップであって、それにより前記被験体内の位置で前記収容構造体が滞留構造体を放出する、ステップを含み、
前記滞留構造体は、前記収容構造体内で第2の構成を有し、
滞留デバイスは、活性物質を含む充填可能ポリマー要素を含み、
前記滞留構造体は、前記活性物質が最初の24時間の放出にわたり初期平均速度で前記滞留構造体から放出されるように構成され、
前記活性物質は、前記最初の24時間の放出後の24時間の期間にわたり、前記初期平均速度の、少なくとも約1%の平均速度で放出される、方法。 - 前記滞留構造体が、弾性ポリマー要素および前記弾性ポリマー要素に機械的に結合された充填可能ポリマー要素を含み、
前記充填可能ポリマー要素が合計構造体重量の少なくとも約60重量%を構成し、
前記滞留構造体が少なくとも約0.2Nの折り畳み力を有する、請求項66または68に記載の方法。 - 前記第2の構成が前記第1の構成の凸包より少なくとも約10%小さい凸包を有し、および/または前記第2の構成が前記第1の構成の最大断面寸法より少なくとも約10%小さい最大断面寸法を有する、請求項66または68に記載の方法。
- 前記滞留構造体が、請求項A−D35のいずれか1項に記載の滞留構造体である、請求項66〜70のいずれか1項に記載の方法。
- 前記滞留構造体が、前記滞留構造体を前記被験体に投与する前に、治療薬、診断薬、および強化剤の内の少なくとも1種で充填される、請求項66〜71のいずれか1項に記載の方法。
- 0.05重量%〜99重量%の前記活性物質が、前記投与ステップ後の24時間〜1年間の間に放出される、請求項68に記載の方法。
- 前記被験体の内部の位置が内部空洞であり、前記滞留構造体が内部開口部により前記空洞内に保持される、請求項66〜73のいずれか1項に記載の方法。
- 前記滞留構造体が、前記滞留構造体が前記空洞内に保持されている期間中に前記内部開口部を通る液体の流れを実質的に制限しない、請求項74に記載の方法。
- 前記内部開口部が胃幽門口である、請求項75に記載の方法。
- 前記滞留構造体が、前記充填可能ポリマー要素に結合した少なくとも1つの分解可能リンカーを含む、請求項66〜76のいずれか1項に記載の方法。
- 前記少なくとも1つのリンカーの解離が、滞留期間を終わらせ、前記滞留構造体の前記内部開口部の通過を可能とする、請求項77に記載の方法。
- 前記滞留構造体が前記収容構造体から放出された後に、前記滞留構造体が、放出直後に始まる初期24時間の期間にわたり測定される初期平均放出速度の約1%〜約99%である、前記初期放出後の48時間〜約1年間の時間中の少なくとも1つの時点で測定される連続的な24時間にわたる平均速度で前記活性物質を放出する、請求項66〜78のいずれか1項に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462010992P | 2014-06-11 | 2014-06-11 | |
US62/010,992 | 2014-06-11 | ||
PCT/US2015/035423 WO2015191920A1 (en) | 2014-06-11 | 2015-06-11 | Residence structures and related methods |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020028439A Division JP2020097623A (ja) | 2014-06-11 | 2020-02-21 | 滞留構造体および関連方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017524662A true JP2017524662A (ja) | 2017-08-31 |
JP2017524662A5 JP2017524662A5 (ja) | 2019-02-07 |
JP6666858B2 JP6666858B2 (ja) | 2020-03-18 |
Family
ID=54834353
Family Applications (8)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016572445A Active JP6666858B2 (ja) | 2014-06-11 | 2015-06-11 | 滞留構造体および関連方法 |
JP2016572439A Pending JP2017519003A (ja) | 2014-06-11 | 2015-06-11 | 自己集合滞留デバイスおよび関連方法 |
JP2017517216A Active JP6681390B2 (ja) | 2014-06-11 | 2015-06-11 | 腸溶性エラストマー |
JP2020000278A Pending JP2020056042A (ja) | 2014-06-11 | 2020-01-06 | 腸溶性エラストマー |
JP2020028439A Withdrawn JP2020097623A (ja) | 2014-06-11 | 2020-02-21 | 滞留構造体および関連方法 |
JP2020074561A Active JP7337746B2 (ja) | 2014-06-11 | 2020-04-20 | 自己集合滞留デバイスおよび関連方法 |
JP2021202475A Active JP7405820B2 (ja) | 2014-06-11 | 2021-12-14 | 自己集合滞留デバイスおよび関連方法 |
JP2022197093A Pending JP2023022316A (ja) | 2014-06-11 | 2022-12-09 | 滞留構造体および関連方法 |
Family Applications After (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016572439A Pending JP2017519003A (ja) | 2014-06-11 | 2015-06-11 | 自己集合滞留デバイスおよび関連方法 |
JP2017517216A Active JP6681390B2 (ja) | 2014-06-11 | 2015-06-11 | 腸溶性エラストマー |
JP2020000278A Pending JP2020056042A (ja) | 2014-06-11 | 2020-01-06 | 腸溶性エラストマー |
JP2020028439A Withdrawn JP2020097623A (ja) | 2014-06-11 | 2020-02-21 | 滞留構造体および関連方法 |
JP2020074561A Active JP7337746B2 (ja) | 2014-06-11 | 2020-04-20 | 自己集合滞留デバイスおよび関連方法 |
JP2021202475A Active JP7405820B2 (ja) | 2014-06-11 | 2021-12-14 | 自己集合滞留デバイスおよび関連方法 |
JP2022197093A Pending JP2023022316A (ja) | 2014-06-11 | 2022-12-09 | 滞留構造体および関連方法 |
Country Status (17)
Country | Link |
---|---|
US (16) | US10849853B2 (ja) |
EP (4) | EP3155024B1 (ja) |
JP (8) | JP6666858B2 (ja) |
KR (2) | KR20220162852A (ja) |
CN (4) | CN116370644A (ja) |
AU (6) | AU2015274456B2 (ja) |
BR (2) | BR112016028957B1 (ja) |
CA (3) | CA2951909C (ja) |
DK (1) | DK3155024T3 (ja) |
ES (1) | ES2832334T3 (ja) |
IL (1) | IL249435B (ja) |
MX (2) | MX2016016406A (ja) |
NZ (1) | NZ727659A (ja) |
RU (1) | RU2766335C2 (ja) |
SG (2) | SG11201610246PA (ja) |
WO (3) | WO2015191925A1 (ja) |
ZA (1) | ZA201608889B (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018515476A (ja) * | 2015-05-01 | 2018-06-14 | マサチューセッツ インスティテュート オブ テクノロジー | 誘発性形状記憶誘導デバイス |
JP2019503347A (ja) * | 2015-12-08 | 2019-02-07 | リンドラ,インコーポレイティド | 胃滞留システムのための幾何学的構成 |
JP2020097623A (ja) * | 2014-06-11 | 2020-06-25 | マサチューセッツ インスティテュート オブ テクノロジー | 滞留構造体および関連方法 |
JP2021535090A (ja) * | 2018-08-15 | 2021-12-16 | リンドラ セラピューティクス, インコーポレイティド | 治療薬物の腸内送達のためのシステム |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103948557A (zh) | 2014-04-08 | 2014-07-30 | 闻晓光 | 一种新型控释片 |
US10485758B2 (en) | 2014-06-02 | 2019-11-26 | Clexio Biosciences Ltd. | Expandable gastroretentive dosage form |
US20170266112A1 (en) | 2014-06-11 | 2017-09-21 | Massachusetts Institute Of Technology | Residence structures and related methods |
US10939865B2 (en) * | 2015-10-06 | 2021-03-09 | Ligalli B.V. | Vaginal drug delivery device and vaginal diagnostic device |
AU2016342374B2 (en) * | 2015-10-23 | 2022-08-04 | Lyndra Therapeutics, Inc. | Gastric residence systems for sustained release of therapeutic agents and methods of use thereof |
WO2017096054A1 (en) * | 2015-12-01 | 2017-06-08 | Teva Pharmaceutical Industries, Ltd. | Gastric retentive devices |
WO2017185003A1 (en) * | 2016-04-21 | 2017-10-26 | Massachusetts Institute Of Technology | Origami robots and systems |
CA3025650A1 (en) * | 2016-05-27 | 2017-11-30 | Lyndra, Inc. | Materials architecture for gastric residence systems |
EP3509469A1 (en) | 2016-09-09 | 2019-07-17 | Progenity, Inc. | Electromechanical ingestible device for delivery of a dispensable substance |
CN110022861B (zh) * | 2016-09-30 | 2024-06-28 | 林德拉治疗公司 | 用于金刚烷类药物缓释的胃驻留系统 |
EP3320898A1 (en) | 2016-11-11 | 2018-05-16 | ratiopharm GmbH | Dosage form comprising a carrier structure and method for manufacturing the dosage form |
US10737079B2 (en) * | 2016-12-02 | 2020-08-11 | Clexio Biosciences Ltd. | Gastric residence system |
US20180206726A1 (en) | 2016-12-07 | 2018-07-26 | Progenity Inc. | Gastrointestinal tract detection methods, devices and systems |
JP7049315B2 (ja) * | 2017-03-16 | 2022-04-06 | テルモ株式会社 | カテーテル組立体 |
JP7071995B2 (ja) | 2017-03-31 | 2022-05-19 | プロジェニティ, インコーポレイテッド | 摂取可能装置 |
EP3624751A4 (en) * | 2017-05-17 | 2021-03-03 | Massachusetts Institute of Technology | SELF-ALIGNING SYSTEMS, PROCEDURES AND ASSOCIATED COMPONENTS |
US11541015B2 (en) | 2017-05-17 | 2023-01-03 | Massachusetts Institute Of Technology | Self-righting systems, methods, and related components |
US12023406B2 (en) | 2017-06-09 | 2024-07-02 | Lyndra Therapeutics, Inc. | Gastric residence systems with release rate-modulating films |
AU2018290246A1 (en) | 2017-06-21 | 2020-01-30 | Access Vascular, Inc | High strength porous materials incorporating water soluble polymers |
JP2020530494A (ja) | 2017-08-07 | 2020-10-22 | フィンチ セラピューティクス、インコーポレイテッド. | 健康な腸バリアを維持及び回復するための組成物及び方法 |
CN107773554A (zh) * | 2017-09-07 | 2018-03-09 | 华南农业大学 | 一种伊维菌素缓释微囊及其制备方法和应用 |
CN111511338B (zh) * | 2017-09-20 | 2022-11-29 | 林德拉治疗公司 | 胃驻留系统的封装 |
WO2019083483A2 (en) * | 2017-10-11 | 2019-05-02 | Ege Universitesi | VAGINAL IMPLANT |
TWI837082B (zh) * | 2017-11-22 | 2024-04-01 | 美商萊恩卓治療公司 | 用於胃滯留系統之材料架構 |
US11684315B2 (en) * | 2017-11-28 | 2023-06-27 | Massachusetts Institute Of Technology | Gastric resident electronics |
JP7296084B2 (ja) | 2017-12-04 | 2023-06-22 | クレキシオ バイオサイエンシーズ エルティーディー. | 長時間作用型胃滞留システム |
WO2019222570A1 (en) | 2018-05-17 | 2019-11-21 | Massachusetts Institute Of Technology | Systems for electrical stimulation |
US11576860B2 (en) * | 2018-05-31 | 2023-02-14 | Massachusetts Institute Of Technology | Retrieval systems and related methods |
WO2020101737A1 (en) * | 2018-11-15 | 2020-05-22 | Massachusetts Institute Of Technology | Actuating components and related methods |
WO2020102629A1 (en) * | 2018-11-15 | 2020-05-22 | Massachusetts Institute Of Technology | Thermally controlled residence devices |
WO2020106704A2 (en) | 2018-11-19 | 2020-05-28 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
EP3897765A2 (en) * | 2018-12-19 | 2021-10-27 | Access Vascular, Inc. | High strength porous materials for controlled release |
EP3917598A1 (en) | 2019-02-01 | 2021-12-08 | Massachusetts Institute of Technology | Systems and methods for liquid injection |
WO2020257017A1 (en) * | 2019-06-18 | 2020-12-24 | Progenity, Inc. | Ingestible device with component capable of residing in the gastrointestinal tract |
CN110591125B (zh) * | 2019-07-31 | 2021-01-26 | 北京理工大学 | 一种可溶解的三维交联弹性体及其制备和处理方法 |
KR20220087456A (ko) * | 2019-10-01 | 2022-06-24 | 라니 테라퓨틱스, 엘엘씨 | 내강 벽에 제제를 전달하기 위한 자체 크기 조정 장치 |
WO2021092484A1 (en) * | 2019-11-08 | 2021-05-14 | Lyndra, Inc. | Gastric residence systems having arms with controlled stiffness for improved gastric residence |
US20220409528A1 (en) * | 2019-11-08 | 2022-12-29 | Lyndra Therapeutics, Inc. | Gastric residence systems having a filament for improved gastric residence |
JP2022554383A (ja) * | 2019-11-08 | 2022-12-28 | リンドラ セラピューティクス, インコーポレイティド | 胃内滞留システムのための放出速度調節フィルム用製剤 |
US11541216B2 (en) | 2019-11-21 | 2023-01-03 | Massachusetts Institute Of Technology | Methods for manufacturing tissue interfacing components |
WO2021119482A1 (en) | 2019-12-13 | 2021-06-17 | Progenity, Inc. | Ingestible device for delivery of therapeutic agent to the gastrointestinal tract |
US11253534B2 (en) | 2020-03-23 | 2022-02-22 | Sabine Hazan | Method of preventing COVID-19 infection |
US11744866B2 (en) | 2020-03-18 | 2023-09-05 | Sabine Hazan | Methods of preventing and treating COVID-19 infection with probiotics |
US11278520B2 (en) | 2020-03-31 | 2022-03-22 | Sabine Hazan | Method of preventing COVID-19 infection |
WO2021231411A1 (en) * | 2020-05-12 | 2021-11-18 | Massachusetts Institute Of Technology | Gastroretentive articles for alcohol sensing |
WO2022006000A1 (en) | 2020-06-30 | 2022-01-06 | Access Vascular, Inc. | Articles comprising markings and related methods |
CA3187537A1 (en) * | 2020-07-29 | 2022-02-03 | Stephanie REED | Shape-guided controlled release and retention with structures including crosslinked poly(glycerol sebacate) |
JP2024518156A (ja) * | 2021-05-05 | 2024-04-25 | リンドラ セラピューティクス, インコーポレイティド | ブプレノルフィンとナロキソンを含む胃内滞留システム |
CA3229117A1 (en) | 2021-08-19 | 2023-02-23 | Dorit MIMROD | Method of treating parkinson's disease |
WO2024073752A2 (en) * | 2022-09-30 | 2024-04-04 | Lyndra Therapeutics, Inc. | Risperidone dosage regimens with gastric residence systems |
WO2024081793A1 (en) | 2022-10-12 | 2024-04-18 | Massachusetts Institute Of Technology | Ingestible in vivo-assembling drug release formulations and methods |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6226215A (ja) * | 1985-05-10 | 1987-02-04 | メルク エンド カムパニ− インコ−ポレ−テツド | 一定に制御した時間内胃中に保持できる薬剤移送装置 |
JPS6323815A (ja) * | 1986-07-15 | 1988-02-01 | ファイザ−・インコ−ポレ−テッド | 徐放性薬物含有繊維 |
JPH0229268A (ja) * | 1988-05-31 | 1990-01-31 | Pfizer Inc | 薬剤徐放のための胃内停滞システム |
EP0388234A1 (en) * | 1989-03-17 | 1990-09-19 | Carter Holt Harvey Plastic Products Group Limited | A drug administering device for insertion in a body cavity of an animal |
JPH03128934A (ja) * | 1989-09-20 | 1991-05-31 | Merck & Co Inc | 生体内崩壊性熱硬化エラストマー |
JPH03163011A (ja) * | 1989-08-31 | 1991-07-15 | Yamanouchi Pharmaceut Co Ltd | 胃内滞留デバイス |
JP2006518392A (ja) * | 2003-02-19 | 2006-08-10 | ニーモサイエンス ゲーエムベーハー | 胃腸管または泌尿生殖器官エリアのための自己膨張性デバイス |
US20100152410A1 (en) * | 2003-06-04 | 2010-06-17 | Rutgers, The State University Of New Jersey | High molecular weight polymers, devices and method for making and using same |
US20120116285A1 (en) * | 2008-12-27 | 2012-05-10 | Duggirala Chandra S | Devices for treating obesity and methods of using those devices |
Family Cites Families (125)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US415671A (en) * | 1889-11-19 | harris | ||
US3154461A (en) | 1960-03-07 | 1964-10-27 | Minnesota Mining & Mfg | Matte-finish polymeric film and method of forming the same |
AU449029B2 (en) | 1969-08-28 | 1974-04-17 | Commonwealth Scientific And Industrial Research Organisation | Device for administration to ruminants |
JPS5512411B2 (ja) | 1974-03-12 | 1980-04-02 | ||
US4199561A (en) * | 1979-02-26 | 1980-04-22 | The Dow Chemical Company | Coated nutrients and medicaments for veterinary use |
US4451260A (en) | 1982-03-26 | 1984-05-29 | Minnesota Mining And Manufacturing Company | Sustained release oral medicinal delivery device |
US4676507A (en) | 1985-05-06 | 1987-06-30 | Patterson Bruce D | Puzzles forming platonic solids |
EP0202159B1 (en) * | 1985-05-10 | 1991-07-03 | Merck & Co. Inc. | Drug delivery device which can be retained in the stomach for a controlled period of time |
US4735804A (en) | 1985-05-10 | 1988-04-05 | Merck & Co., Inc. | Drug delivery device which can be retained in the stomach for a controlled period of time |
US4767627A (en) * | 1985-05-29 | 1988-08-30 | Merck & Co., Inc. | Drug delivery device which can be retained in the stomach for a controlled period of time |
US4758436A (en) | 1985-05-29 | 1988-07-19 | Merck & Co., Inc. | Drug delivery device which can be retained in the stomach for a controlled period of time |
IL87710A (en) | 1987-09-18 | 1992-06-21 | Ciba Geigy Ag | Covered floating retard form for controlled release in gastric juice |
EP0406315B1 (en) | 1988-03-24 | 1992-11-11 | Bukh Meditec A/S | Controlled release composition |
US5007790A (en) | 1989-04-11 | 1991-04-16 | Depomed Systems, Inc. | Sustained-release oral drug dosage form |
US5369142A (en) * | 1993-01-15 | 1994-11-29 | The Ohio State University | Water soluble polymers containing amino acid residues for dental restoratives |
WO1995003558A1 (en) * | 1993-07-19 | 1995-02-02 | Reflexite Corporation | Retroreflective structure |
DE4406424A1 (de) | 1994-02-28 | 1995-08-31 | Bayer Ag | Expandierbare Arzneiformen |
US6962579B2 (en) | 1995-03-23 | 2005-11-08 | Advanced Animal Technology Limited | Substance delivery device |
WO1996029025A1 (en) | 1995-03-23 | 1996-09-26 | Advanced Animal Technology Limited | Substance delivery device |
TW354451B (en) | 1995-09-18 | 1999-03-11 | Ibm | Method of fabricating cross-linked biobased materials and structures fabricated therewith a method comprising the step of: forming the mixture of polymer and cross-linked agent |
US5840332A (en) | 1996-01-18 | 1998-11-24 | Perio Products Ltd. | Gastrointestinal drug delivery system |
AU2521797A (en) | 1996-04-12 | 1997-11-07 | Japan Atomic Energy Research Institute | Ph-sensitive polymers |
GB9616267D0 (en) | 1996-08-02 | 1996-09-11 | Ranier Ltd | Balloon catheter |
WO1999007342A1 (en) | 1997-08-11 | 1999-02-18 | Alza Corporation | Prolonged release active agent dosage form adapted for gastric retention |
DE19850309A1 (de) | 1998-10-30 | 2000-05-04 | Lohmann Therapie Syst Lts | Expandierbares gastroretensives Therapiesystem mit verlängerter Magenverweildauer |
IL133196A0 (en) | 1999-11-29 | 2001-03-19 | Yissum Res Dev Co | Gastroretentive controlled release pharmaceutical dosage forms |
WO2001091553A1 (en) | 2000-05-26 | 2001-12-06 | Demegen, Inc. | Composite wafer for controlled drug delivery |
US6488962B1 (en) | 2000-06-20 | 2002-12-03 | Depomed, Inc. | Tablet shapes to enhance gastric retention of swellable controlled-release oral dosage forms |
US8158143B2 (en) | 2000-07-14 | 2012-04-17 | Helmholtz-Zentrum Geesthacht Zentrum Fuer Material- Und Kuestenforschung Gmbh | Systems for releasing active ingredients, based on biodegradable or biocompatible polymers with a shape memory effect |
US7803392B2 (en) | 2000-12-27 | 2010-09-28 | University Of Kentucky Research Foundation | pH-Sensitive mucoadhesive film-forming gels and wax-film composites suitable for topical and mucosal delivery of molecules |
US6627206B2 (en) * | 2001-07-25 | 2003-09-30 | Greg A. Lloyd | Method and apparatus for treating obesity and for delivering time-released medicaments |
CN1543337A (zh) | 2001-08-16 | 2004-11-03 | ���ո����ɸߵȽ�����ίԱ�������� | 可膨胀的胃潴留装置 |
US20040219186A1 (en) * | 2001-08-16 | 2004-11-04 | Ayres James W. | Expandable gastric retention device |
CA2409552A1 (en) * | 2001-10-25 | 2003-04-25 | Depomed, Inc. | Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract |
KR100417163B1 (ko) | 2001-11-12 | 2004-02-05 | 한국과학기술연구원 | 마이크로 캡슐형 로봇 |
US20050165136A1 (en) * | 2002-01-23 | 2005-07-28 | Uab Research Foundation | Glass-ionomer cements containing amino acids |
US6960617B2 (en) * | 2002-04-22 | 2005-11-01 | Purdue Research Foundation | Hydrogels having enhanced elasticity and mechanical strength properties |
DE10224352A1 (de) | 2002-06-01 | 2003-12-11 | Mueller Schulte Detlef | Thermosensitive Polymerträger mit veränderbarer physikalischer Struktur für die biochemische Analytik, Diagnostik und Therapie |
GB0214013D0 (en) | 2002-06-18 | 2002-07-31 | Euro Celtique Sa | Pharmaceutical product |
AR040672A1 (es) | 2002-07-25 | 2005-04-13 | Glaxo Group Ltd | Forma de dosificacion farmaceutica multicomponenete, cuerpo apropiado para ser utilizado en la misma y procedimiento para prepararla |
KR20050083750A (ko) | 2002-10-11 | 2005-08-26 | 디포메드 디벨롭먼트 리미티드 | 위-체류성 레보도파 전달 형태 |
JP4497833B2 (ja) | 2003-04-21 | 2010-07-07 | 富士フイルム株式会社 | ポジ型平版印刷版原版 |
CA2527976C (en) | 2003-06-13 | 2011-11-22 | Mnemoscience Gmbh | Stents |
EP1638533A1 (en) | 2003-06-18 | 2006-03-29 | John Michael Newton | Controlled release devices with lumens |
US20090259236A2 (en) | 2003-07-28 | 2009-10-15 | Baronova, Inc. | Gastric retaining devices and methods |
US8048169B2 (en) * | 2003-07-28 | 2011-11-01 | Baronova, Inc. | Pyloric valve obstructing devices and methods |
US7790141B2 (en) * | 2003-08-11 | 2010-09-07 | Pathak Holdings, Llc | Radio-opaque compounds, compositions containing same and methods of their synthesis and use |
US6825308B1 (en) * | 2003-10-29 | 2004-11-30 | Council Of Scientific And Industrial Research | Copolymers and preparation thereof |
CA2549195A1 (en) | 2003-12-09 | 2005-06-23 | Spherics, Inc. | Bioadhesive polymers with catechol functionality |
US20080089933A1 (en) | 2006-10-16 | 2008-04-17 | Amir Alon | Device and method for reducing calorie intake |
CA2567741A1 (en) * | 2004-05-25 | 2006-03-30 | Chimeracore, Inc. | Self-assembling nanoparticle drug delivery system |
DE102004047076A1 (de) | 2004-09-28 | 2006-04-06 | Zimmer Ag | Verfahren zur Herstellung von Polyestern |
IL166183A0 (en) | 2005-01-06 | 2006-01-15 | Yissum Res Dev Co | Novel diagnostic and imaging techniques of the gi tract |
RU2411045C2 (ru) * | 2005-01-27 | 2011-02-10 | Институт Нефтехимического Синтеза Имени А.В. Топчиева Ран | Гидрофильные биологически совместимые адгезивные композиции и их применение |
WO2006084164A2 (en) | 2005-02-01 | 2006-08-10 | Emisphere Technologies, Inc. | Gastric retention and controlled release delivery system |
US7785291B2 (en) | 2005-03-01 | 2010-08-31 | Tulip Medical Ltd. | Bioerodible self-deployable intragastric implants |
US7699863B2 (en) * | 2005-03-01 | 2010-04-20 | Tulip Medical Ltd. | Bioerodible self-deployable intragastric implants |
JP2006323082A (ja) | 2005-05-18 | 2006-11-30 | Canon Inc | 現像剤補給容器 |
US8021384B2 (en) | 2005-07-26 | 2011-09-20 | Ram Weiss | Extending intrabody capsule |
US20090120879A1 (en) | 2005-08-05 | 2009-05-14 | Shiga Prefecture | Material For Transfer Of Substance In Liquid Comprising Polymer Blend |
US20070048383A1 (en) * | 2005-08-25 | 2007-03-01 | Helmus Michael N | Self-assembled endovascular structures |
EP1957052A2 (en) | 2005-10-25 | 2008-08-20 | Pharmascience Inc. | A gastric retention drug delivery system |
EP1945189A4 (en) * | 2005-11-03 | 2012-08-15 | Sun Pharmaceutical Ind Ltd | COATED TABLETS WITH EXTENDED MAGNETIC RETENTION |
US7674396B2 (en) | 2005-11-08 | 2010-03-09 | Plensat Llc | Method and system for treatment of eating disorders |
TR201902010T4 (tr) | 2006-01-18 | 2019-03-21 | Intec Pharma Ltd | Bir ajanın oral alımına yönelik taşıyıcı cihaz. |
WO2007093999A1 (en) | 2006-02-15 | 2007-08-23 | Intec Pharma Ltd. | A gastro-retentive system for the delivery of macromolecules |
WO2007106415A2 (en) * | 2006-03-10 | 2007-09-20 | Massachusetts Institute Of Technology | Triggered self-assembly conjugates and nanosystems |
US7691151B2 (en) | 2006-03-31 | 2010-04-06 | Spiration, Inc. | Articulable Anchor |
US20070264307A1 (en) | 2006-05-15 | 2007-11-15 | Medtronic Vascular, Inc. | Biodegradable Modified Caprolactone Polymers for Fabricating and Coating Medical Devices |
EP1886665A1 (en) | 2006-08-01 | 2008-02-13 | Boehringer Ingelheim Pharma GmbH & Co. KG | Gastro retentive delivery system |
JP2010502591A (ja) | 2006-09-04 | 2010-01-28 | パナセア バイオテック リミテッド | プログラム可能な浮揚性送達技術 |
US20080075766A1 (en) | 2006-09-25 | 2008-03-27 | Shun-Por Li | Multi-core dosage form having transparent outer coating |
CA2673511A1 (en) * | 2006-12-22 | 2008-07-03 | Combinatorx, Incorporated | Pharmaceutical compositions for treatment of parkinson's disease and related disorders |
WO2008140651A2 (en) | 2007-03-13 | 2008-11-20 | Olson Arthur J | Self-assembled polyhedra |
US20100297009A1 (en) * | 2007-03-13 | 2010-11-25 | Technion Research & Development Foundation Ltd. | Self-assembled polyhedral multimeric chemical structures |
US20080249156A1 (en) * | 2007-04-09 | 2008-10-09 | Palepu Nageswara R | Combinations of statins and anti-obesity agent and glitazones |
ES2562878T3 (es) | 2007-05-25 | 2016-03-08 | Indivior Uk Limited | Formulaciones de liberación sostenida de compuestos de risperidona |
US8481076B2 (en) * | 2007-05-25 | 2013-07-09 | Gorham Enterprises Llc | Bariatric magnetic apparatus and method of manufacturing thereof |
US8303573B2 (en) * | 2007-10-17 | 2012-11-06 | The Invention Science Fund I, Llc | Medical or veterinary digestive tract utilization systems and methods |
US8038659B2 (en) | 2007-10-17 | 2011-10-18 | The Invention Science Fund I, Llc | Disintegrating digestive tract interaction system |
AU2009223061B2 (en) | 2008-03-11 | 2014-10-09 | Depomed Inc. | Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic |
US20130273135A1 (en) | 2008-03-25 | 2013-10-17 | University Of Utah Research Foundation | Controlled Release Combination Biomaterials |
EP2276473B1 (en) | 2008-04-18 | 2016-09-14 | Intec Pharma Ltd. | Gastroretentive drug delivery for carbidopa/levodopa |
US9066877B2 (en) * | 2008-04-28 | 2015-06-30 | Eat Little Inc. | Bezoar-forming units for weight control |
US20100256342A1 (en) * | 2008-08-12 | 2010-10-07 | Francis Raymond Salemme | Protein nodes for controlled nanoscale assembly |
JP2012500230A (ja) | 2008-08-18 | 2012-01-05 | 北京天衡▲薬▼物研究院 | 胃内滞留薬物放出システム及びその製造方法と使用 |
WO2010029095A2 (en) | 2008-09-10 | 2010-03-18 | Sandoz Ag | Capsule with soluble blocking element |
WO2010035273A2 (en) | 2008-09-29 | 2010-04-01 | Intec Pharma Ltd. | Novel gastroretentive delivery system |
CA2745741A1 (en) | 2008-12-04 | 2010-06-10 | Intec Pharma Ltd. | Zaleplon gastroretentive drug delivery system |
CN102414116B (zh) | 2009-02-26 | 2015-01-21 | 加利福尼亚大学董事会 | 用于制备尺寸可控的纳米颗粒的超分子方法 |
US8414559B2 (en) | 2009-05-07 | 2013-04-09 | Rainbow Medical Ltd. | Gastroretentive duodenal pill |
DE102009028076A1 (de) | 2009-07-29 | 2011-02-03 | Evonik Röhm Gmbh | Beschichtungsmittel zum Tauchbeschichten von Kapselhälften |
US20110052497A1 (en) * | 2009-08-27 | 2011-03-03 | Taris Biomedical, Inc. | Minimally Invasive Systems and Methods for In Vivo Testing of Materials |
US20110052700A1 (en) | 2009-08-31 | 2011-03-03 | Depomed, Inc. | Gastric retentive pharmaceutical compositions for immediate and extended release of levosulpiride |
WO2011032087A2 (en) | 2009-09-11 | 2011-03-17 | Replication Medical Inc. | Swellable polymeric device for dietary regulation |
WO2011048494A2 (en) | 2009-10-19 | 2011-04-28 | Intec Pharma Ltd. | Novel gastroretentive dosage forms of poorly soluble drugs |
US9421169B2 (en) | 2009-11-20 | 2016-08-23 | Covidien Lp | Oral dosage forms for delivery of therapeutic agents |
CN101711752B (zh) | 2009-11-26 | 2011-09-21 | 中国科学院上海药物研究所 | 一种苯并异噁唑类衍生物的控释制剂及其制备方法 |
JP2013527157A (ja) | 2010-04-15 | 2013-06-27 | ワシントン・ユニバーシティ | プロドラッグ組成物、プロドラッグナノ粒子およびその使用方法 |
US11535510B2 (en) * | 2010-04-27 | 2022-12-27 | The Johns Hopkins University | Self-folding sub-centimeter structures |
BRPI1002601E2 (pt) * | 2010-06-01 | 2020-06-30 | Embrapa Pesquisa Agropecuaria | composição nanoestruturada de uso veterinário para administração de fármacos |
US20120165792A1 (en) | 2010-12-22 | 2012-06-28 | Ethicon Endo-Surgery, Inc. | Pill Catchers |
US20120165793A1 (en) | 2010-12-22 | 2012-06-28 | Ethicon Endo-Surgery, Inc. | Pill Catchers |
US20120165794A1 (en) | 2010-12-22 | 2012-06-28 | Ethicon Endo-Surgery, Inc. | Pill Catchers |
AU2012211960B2 (en) | 2011-02-04 | 2016-12-01 | Taris Biomedical Llc | Implantable device for controlled release of low solubility drug |
US9228859B2 (en) | 2011-09-26 | 2016-01-05 | Northeastern University | Customizable embedded sensors |
US8835507B2 (en) | 2012-02-21 | 2014-09-16 | Vymed Corporation | Adamantane derivatives possessing anti-viral and anti-microbial activity |
US8979887B2 (en) | 2012-02-24 | 2015-03-17 | Elwha Llc | Devices, systems, and methods to control stomach volume |
CA2879282C (en) | 2012-07-16 | 2022-05-03 | Hendrik Jan Cornelis Meijerink | Gastro-retentive drug delivery system |
US9307966B2 (en) | 2012-08-15 | 2016-04-12 | St. Jude Medical Puerto Rico Llc | Vascular closure device anchor |
US20140050784A1 (en) | 2012-08-16 | 2014-02-20 | Teva Pharmaceuticals Usa, Inc. | Pharmaceutical compositions of memantine |
US8746339B2 (en) * | 2012-09-27 | 2014-06-10 | Halliburton Energy Services, Inc. | Triggerable lost circulation material and method of use |
US10441760B2 (en) | 2013-03-01 | 2019-10-15 | The Johns Hopkins University | Self-actuating chemomechanical devices for delivery and extended release of therapeutic agents in the gastrointestinal tract |
CN103654903A (zh) * | 2013-11-27 | 2014-03-26 | 西安交通大学 | 一种用于人体消化道吻合的磁性可降解装置 |
EP3091962B1 (en) | 2013-12-05 | 2022-06-08 | Epitomee Medical Ltd. | Retentive devices and systems for in-situ release of pharmaceutical active agents |
US20170051099A1 (en) | 2014-04-29 | 2017-02-23 | The Brigham And Women's Hospital, Inc. | Polymeric materials for bio-applications |
CN106456550A (zh) | 2014-05-26 | 2017-02-22 | 格吕伦塔尔有限公司 | 避免乙醇剂量倾泻的多颗粒 |
US10485758B2 (en) | 2014-06-02 | 2019-11-26 | Clexio Biosciences Ltd. | Expandable gastroretentive dosage form |
US20170266112A1 (en) | 2014-06-11 | 2017-09-21 | Massachusetts Institute Of Technology | Residence structures and related methods |
EP3155024B1 (en) | 2014-06-11 | 2020-09-16 | Massachusetts Institute Of Technology | Residence structures and related methods |
JP2018515476A (ja) | 2015-05-01 | 2018-06-14 | マサチューセッツ インスティテュート オブ テクノロジー | 誘発性形状記憶誘導デバイス |
AU2016342374B2 (en) | 2015-10-23 | 2022-08-04 | Lyndra Therapeutics, Inc. | Gastric residence systems for sustained release of therapeutic agents and methods of use thereof |
US11992552B2 (en) | 2015-12-08 | 2024-05-28 | Lyndra Therapeutics, Inc. | Geometric configurations for gastric residence systems |
CA3025650A1 (en) | 2016-05-27 | 2017-11-30 | Lyndra, Inc. | Materials architecture for gastric residence systems |
CN110022861B (zh) | 2016-09-30 | 2024-06-28 | 林德拉治疗公司 | 用于金刚烷类药物缓释的胃驻留系统 |
-
2015
- 2015-06-11 EP EP15806017.8A patent/EP3155024B1/en active Active
- 2015-06-11 JP JP2016572445A patent/JP6666858B2/ja active Active
- 2015-06-11 CN CN202211697823.5A patent/CN116370644A/zh active Pending
- 2015-06-11 WO PCT/US2015/035429 patent/WO2015191925A1/en active Application Filing
- 2015-06-11 DK DK15806017.8T patent/DK3155024T3/da active
- 2015-06-11 CA CA2951909A patent/CA2951909C/en active Active
- 2015-06-11 CN CN201580038072.8A patent/CN106573015B/zh active Active
- 2015-06-11 US US15/317,628 patent/US10849853B2/en active Active
- 2015-06-11 EP EP15805932.9A patent/EP3154622B1/en active Active
- 2015-06-11 EP EP15806483.2A patent/EP3154553B1/en active Active
- 2015-06-11 WO PCT/US2015/035425 patent/WO2015191922A1/en active Application Filing
- 2015-06-11 CA CA2951902A patent/CA2951902C/en active Active
- 2015-06-11 CN CN201580038008.XA patent/CN106573999A/zh active Pending
- 2015-06-11 SG SG11201610246PA patent/SG11201610246PA/en unknown
- 2015-06-11 CA CA2951884A patent/CA2951884A1/en active Pending
- 2015-06-11 BR BR112016028957-9A patent/BR112016028957B1/pt active IP Right Grant
- 2015-06-11 US US15/317,601 patent/US10413507B2/en active Active
- 2015-06-11 US US15/317,566 patent/US10182985B2/en active Active
- 2015-06-11 KR KR1020227040906A patent/KR20220162852A/ko not_active Application Discontinuation
- 2015-06-11 CN CN201580038062.4A patent/CN106714893B/zh active Active
- 2015-06-11 JP JP2016572439A patent/JP2017519003A/ja active Pending
- 2015-06-11 BR BR122021018078-4A patent/BR122021018078B1/pt active IP Right Grant
- 2015-06-11 MX MX2016016406A patent/MX2016016406A/es unknown
- 2015-06-11 NZ NZ727659A patent/NZ727659A/en unknown
- 2015-06-11 EP EP20160645.6A patent/EP3725357A1/en active Pending
- 2015-06-11 AU AU2015274456A patent/AU2015274456B2/en active Active
- 2015-06-11 SG SG10201912100SA patent/SG10201912100SA/en unknown
- 2015-06-11 RU RU2017100273A patent/RU2766335C2/ru active
- 2015-06-11 KR KR1020177000698A patent/KR102471095B1/ko active IP Right Grant
- 2015-06-11 WO PCT/US2015/035423 patent/WO2015191920A1/en active Application Filing
- 2015-06-11 JP JP2017517216A patent/JP6681390B2/ja active Active
- 2015-06-11 AU AU2015274453A patent/AU2015274453A1/en not_active Abandoned
- 2015-06-11 ES ES15806017T patent/ES2832334T3/es active Active
- 2015-06-11 AU AU2015274451A patent/AU2015274451C1/en active Active
-
2016
- 2016-12-07 IL IL249435A patent/IL249435B/en active IP Right Grant
- 2016-12-09 MX MX2023005223A patent/MX2023005223A/es unknown
- 2016-12-22 ZA ZA2016/08889A patent/ZA201608889B/en unknown
-
2018
- 2018-11-01 US US16/177,704 patent/US10610482B2/en active Active
- 2018-11-01 US US16/177,687 patent/US20190070108A1/en not_active Abandoned
- 2018-11-01 US US16/177,670 patent/US10532027B2/en active Active
-
2019
- 2019-02-15 US US16/277,516 patent/US10517819B2/en active Active
- 2019-04-09 US US16/379,727 patent/US10517820B2/en active Active
- 2019-07-31 US US16/528,197 patent/US11083690B2/en active Active
- 2019-09-19 AU AU2019232862A patent/AU2019232862A1/en not_active Abandoned
- 2019-11-22 US US16/693,149 patent/US10716752B2/en active Active
- 2019-11-22 US US16/693,121 patent/US10716751B2/en active Active
-
2020
- 2020-01-06 JP JP2020000278A patent/JP2020056042A/ja active Pending
- 2020-01-17 AU AU2020200346A patent/AU2020200346B2/en active Active
- 2020-02-21 JP JP2020028439A patent/JP2020097623A/ja not_active Withdrawn
- 2020-04-20 JP JP2020074561A patent/JP7337746B2/ja active Active
- 2020-06-11 US US16/899,447 patent/US11246829B2/en active Active
- 2020-12-18 US US17/126,835 patent/US11389399B2/en active Active
- 2020-12-18 US US17/126,786 patent/US11077056B2/en active Active
-
2021
- 2021-02-12 US US17/174,458 patent/US11357723B2/en active Active
- 2021-05-14 AU AU2021203086A patent/AU2021203086B2/en active Active
- 2021-12-14 JP JP2021202475A patent/JP7405820B2/ja active Active
-
2022
- 2022-06-09 US US17/836,972 patent/US20230039421A1/en active Pending
- 2022-12-09 JP JP2022197093A patent/JP2023022316A/ja active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6226215A (ja) * | 1985-05-10 | 1987-02-04 | メルク エンド カムパニ− インコ−ポレ−テツド | 一定に制御した時間内胃中に保持できる薬剤移送装置 |
JPS6323815A (ja) * | 1986-07-15 | 1988-02-01 | ファイザ−・インコ−ポレ−テッド | 徐放性薬物含有繊維 |
JPH0229268A (ja) * | 1988-05-31 | 1990-01-31 | Pfizer Inc | 薬剤徐放のための胃内停滞システム |
EP0388234A1 (en) * | 1989-03-17 | 1990-09-19 | Carter Holt Harvey Plastic Products Group Limited | A drug administering device for insertion in a body cavity of an animal |
JPH03163011A (ja) * | 1989-08-31 | 1991-07-15 | Yamanouchi Pharmaceut Co Ltd | 胃内滞留デバイス |
JPH03128934A (ja) * | 1989-09-20 | 1991-05-31 | Merck & Co Inc | 生体内崩壊性熱硬化エラストマー |
JP2006518392A (ja) * | 2003-02-19 | 2006-08-10 | ニーモサイエンス ゲーエムベーハー | 胃腸管または泌尿生殖器官エリアのための自己膨張性デバイス |
US20100152410A1 (en) * | 2003-06-04 | 2010-06-17 | Rutgers, The State University Of New Jersey | High molecular weight polymers, devices and method for making and using same |
US20120116285A1 (en) * | 2008-12-27 | 2012-05-10 | Duggirala Chandra S | Devices for treating obesity and methods of using those devices |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020097623A (ja) * | 2014-06-11 | 2020-06-25 | マサチューセッツ インスティテュート オブ テクノロジー | 滞留構造体および関連方法 |
JP2018515476A (ja) * | 2015-05-01 | 2018-06-14 | マサチューセッツ インスティテュート オブ テクノロジー | 誘発性形状記憶誘導デバイス |
US10953208B2 (en) | 2015-05-01 | 2021-03-23 | Massachusetts Institute Of Technology | Triggerable shape memory induction devices |
JP2019503347A (ja) * | 2015-12-08 | 2019-02-07 | リンドラ,インコーポレイティド | 胃滞留システムのための幾何学的構成 |
JP7030052B2 (ja) | 2015-12-08 | 2022-03-04 | リンドラ セラピューティクス, インコーポレイティド | 胃滞留システムのための幾何学的構成 |
JP2021535090A (ja) * | 2018-08-15 | 2021-12-16 | リンドラ セラピューティクス, インコーポレイティド | 治療薬物の腸内送達のためのシステム |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11357723B2 (en) | Residence structures and related methods | |
US10596110B2 (en) | Residence structures and related methods |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180611 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181220 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190628 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190626 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190930 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200124 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200221 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6666858 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |