JP6422855B2 - インスリンおよびインスリン類似体の薬物動態及び薬力学、ならびに注射部位の疼痛を調節するためのマグネシウム組成物 - Google Patents
インスリンおよびインスリン類似体の薬物動態及び薬力学、ならびに注射部位の疼痛を調節するためのマグネシウム組成物 Download PDFInfo
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- JP6422855B2 JP6422855B2 JP2015505989A JP2015505989A JP6422855B2 JP 6422855 B2 JP6422855 B2 JP 6422855B2 JP 2015505989 A JP2015505989 A JP 2015505989A JP 2015505989 A JP2015505989 A JP 2015505989A JP 6422855 B2 JP6422855 B2 JP 6422855B2
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- insulin
- formulation
- magnesium
- edta
- acid
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims description 579
- 102000004877 Insulin Human genes 0.000 title claims description 286
- 108090001061 Insulin Proteins 0.000 title claims description 284
- 229940125396 insulin Drugs 0.000 title claims description 279
- 239000000203 mixture Substances 0.000 title claims description 180
- 239000011777 magnesium Substances 0.000 title claims description 48
- 229910052749 magnesium Inorganic materials 0.000 title claims description 27
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 title claims description 24
- 230000003285 pharmacodynamic effect Effects 0.000 title description 21
- 206010022086 Injection site pain Diseases 0.000 title description 2
- 238000009472 formulation Methods 0.000 claims description 157
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 150
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical group CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 claims description 75
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 70
- 238000002347 injection Methods 0.000 claims description 64
- 239000007924 injection Substances 0.000 claims description 64
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 59
- 229960004106 citric acid Drugs 0.000 claims description 47
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 43
- 206010012601 diabetes mellitus Diseases 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 35
- 239000002738 chelating agent Substances 0.000 claims description 33
- 235000011187 glycerol Nutrition 0.000 claims description 33
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 32
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 32
- 150000002681 magnesium compounds Chemical class 0.000 claims description 26
- 229940091250 magnesium supplement Drugs 0.000 claims description 26
- 239000001509 sodium citrate Substances 0.000 claims description 24
- 159000000003 magnesium salts Chemical class 0.000 claims description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 22
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 20
- 229910052725 zinc Inorganic materials 0.000 claims description 19
- 239000011701 zinc Substances 0.000 claims description 19
- 206010054266 Injection site discomfort Diseases 0.000 claims description 18
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 16
- 239000000654 additive Substances 0.000 claims description 13
- 239000000178 monomer Substances 0.000 claims description 13
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 12
- 239000001110 calcium chloride Substances 0.000 claims description 12
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 12
- 239000004026 insulin derivative Substances 0.000 claims description 12
- -1 magnesium halide Chemical class 0.000 claims description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 11
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 8
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical group [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 8
- 229940038773 trisodium citrate Drugs 0.000 claims description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 238000004090 dissolution Methods 0.000 claims description 7
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 6
- 239000000539 dimer Substances 0.000 claims description 6
- 239000000395 magnesium oxide Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 5
- 230000000996 additive effect Effects 0.000 claims description 5
- 229960004543 anhydrous citric acid Drugs 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 claims description 4
- FCKYPQBAHLOOJQ-UHFFFAOYSA-N Cyclohexane-1,2-diaminetetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)C1CCCCC1N(CC(O)=O)CC(O)=O FCKYPQBAHLOOJQ-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- 239000001361 adipic acid Substances 0.000 claims description 3
- 235000011037 adipic acid Nutrition 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- XZTWHWHGBBCSMX-UHFFFAOYSA-J dimagnesium;phosphonato phosphate Chemical compound [Mg+2].[Mg+2].[O-]P([O-])(=O)OP([O-])([O-])=O XZTWHWHGBBCSMX-UHFFFAOYSA-J 0.000 claims description 3
- 239000001530 fumaric acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 3
- 239000011654 magnesium acetate Substances 0.000 claims description 3
- 235000011285 magnesium acetate Nutrition 0.000 claims description 3
- 229940069446 magnesium acetate Drugs 0.000 claims description 3
- 229960001983 magnesium aspartate Drugs 0.000 claims description 3
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000004337 magnesium citrate Substances 0.000 claims description 3
- 229960005336 magnesium citrate Drugs 0.000 claims description 3
- 235000002538 magnesium citrate Nutrition 0.000 claims description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical group [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 3
- 239000001755 magnesium gluconate Substances 0.000 claims description 3
- 235000015778 magnesium gluconate Nutrition 0.000 claims description 3
- 229960003035 magnesium gluconate Drugs 0.000 claims description 3
- 239000000347 magnesium hydroxide Substances 0.000 claims description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 3
- OVGXLJDWSLQDRT-UHFFFAOYSA-L magnesium lactate Chemical compound [Mg+2].CC(O)C([O-])=O.CC(O)C([O-])=O OVGXLJDWSLQDRT-UHFFFAOYSA-L 0.000 claims description 3
- 239000000626 magnesium lactate Substances 0.000 claims description 3
- 235000015229 magnesium lactate Nutrition 0.000 claims description 3
- 229960004658 magnesium lactate Drugs 0.000 claims description 3
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 claims description 3
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 claims description 3
- IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 claims description 3
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 claims description 3
- 239000011976 maleic acid Substances 0.000 claims description 3
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 3
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 2
- 229950007919 egtazic acid Drugs 0.000 claims description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 claims description 2
- 235000019136 lipoic acid Nutrition 0.000 claims description 2
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 claims description 2
- 229960002663 thioctic acid Drugs 0.000 claims description 2
- 230000000087 stabilizing effect Effects 0.000 claims 2
- RNMCCPMYXUKHAZ-UHFFFAOYSA-N 2-[3,3-diamino-1,2,2-tris(carboxymethyl)cyclohexyl]acetic acid Chemical compound NC1(N)CCCC(CC(O)=O)(CC(O)=O)C1(CC(O)=O)CC(O)=O RNMCCPMYXUKHAZ-UHFFFAOYSA-N 0.000 claims 1
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 claims 1
- 125000002734 organomagnesium group Chemical group 0.000 claims 1
- 230000006641 stabilisation Effects 0.000 claims 1
- 238000011105 stabilization Methods 0.000 claims 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 claims 1
- 108010065920 Insulin Lispro Proteins 0.000 description 66
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 66
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- 239000008103 glucose Substances 0.000 description 48
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 47
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- 239000011575 calcium Substances 0.000 description 18
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- 244000309715 mini pig Species 0.000 description 14
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 12
- 210000000496 pancreas Anatomy 0.000 description 11
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
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- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US61/624,844 | 2012-04-16 | ||
| US201261704066P | 2012-09-21 | 2012-09-21 | |
| US61/704,066 | 2012-09-21 | ||
| US13/826,806 | 2013-03-14 | ||
| US13/826,806 US9381247B2 (en) | 2012-04-16 | 2013-03-14 | Magnesium compositions for modulating the pharmacokinetics and pharmacodynamics of insulin and insulin analogs, and injection site pain |
| PCT/US2013/036742 WO2013158618A1 (en) | 2012-04-16 | 2013-04-16 | Magnesium compositions for modulating the pharmacokinetics and pharmacodynamics of insulin and insulin analogs, and injection site pain |
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Families Citing this family (34)
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| WO2014076423A1 (fr) | 2012-11-13 | 2014-05-22 | Adocia | Formulation à action rapide d'insuline comprenant un composé anionique substitué |
| WO2015106269A2 (en) * | 2014-01-13 | 2015-07-16 | Thermalin Diabetes, Llc | Rapid action insulin formulations and pharmaceutical delivery systems |
| US20150273022A1 (en) * | 2014-02-10 | 2015-10-01 | Biodel Inc. | Stabilized ultra-rapid-acting insulin formulations |
| JO3624B1 (ar) * | 2014-05-08 | 2020-08-27 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| EP3659651A3 (en) | 2014-07-10 | 2020-10-14 | Companion Medical, Inc. | Medicine administering system including injection pen and companion device |
| AR102869A1 (es) | 2014-12-16 | 2017-03-29 | Lilly Co Eli | Composiciones de insulina de rápida acción |
| EP3247720A4 (en) * | 2015-01-20 | 2018-06-06 | Case Western Reserve University | Insulin analogues with selective signaling properties and reduced mitogenicity |
| JO3749B1 (ar) | 2015-08-27 | 2021-01-31 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| WO2017132577A1 (en) | 2016-01-29 | 2017-08-03 | Companion Medical, Inc. | Automatic medication delivery tracking |
| GB201607918D0 (en) | 2016-05-06 | 2016-06-22 | Arecor Ltd | Novel formulations |
| GB201707189D0 (en) * | 2017-05-05 | 2017-06-21 | Arecor Ltd | Novel formulations |
| CN110662551B (zh) | 2017-06-01 | 2023-07-18 | 伊莱利利公司 | 速效胰岛素组合物 |
| EP3635591A4 (en) | 2017-06-09 | 2021-03-24 | Companion Medical, Inc. | SMART DRUG DELIVERY SYSTEMS AND PROCESSES |
| EP3694583A4 (en) * | 2017-10-12 | 2021-08-04 | Companion Medical, Inc. | INTELLIGENT DRUG DELIVERY SYSTEMS AND METHODS FOR DOSAGE RECOMMENDATION AND ADMINISTRATION |
| US10987464B2 (en) | 2017-12-12 | 2021-04-27 | Bigfoot Biomedical, Inc. | Pen cap for insulin injection pens and associated methods and systems |
| US11464459B2 (en) | 2017-12-12 | 2022-10-11 | Bigfoot Biomedical, Inc. | User interface for diabetes management systems including flash glucose monitor |
| CN111788635A (zh) | 2017-12-12 | 2020-10-16 | 比格福特生物医学有限公司 | 治疗管理系统、方法和设备 |
| US11077243B2 (en) | 2017-12-12 | 2021-08-03 | Bigfoot Biomedical, Inc. | Devices, systems, and methods for estimating active medication from injections |
| US11197964B2 (en) | 2017-12-12 | 2021-12-14 | Bigfoot Biomedical, Inc. | Pen cap for medication injection pen having temperature sensor |
| US11083852B2 (en) | 2017-12-12 | 2021-08-10 | Bigfoot Biomedical, Inc. | Insulin injection assistance systems, methods, and devices |
| US11116899B2 (en) | 2017-12-12 | 2021-09-14 | Bigfoot Biomedical, Inc. | User interface for diabetes management systems and devices |
| CA3094237A1 (en) | 2018-04-04 | 2019-10-10 | Arecor Limited | Medical infusion pump system for the delivery of an insulin compound |
| US10898653B2 (en) | 2018-05-08 | 2021-01-26 | Companion Medical, Inc. | Intelligent medication delivery systems and methods for dose setting and dispensing monitoring |
| US11664107B2 (en) | 2018-05-08 | 2023-05-30 | Medtronic Minimed, Inc. | Intelligent medication delivery systems and methods using a prescription-regulated software application |
| USD893020S1 (en) | 2018-05-11 | 2020-08-11 | Companion Medical, Inc. | Injection pen |
| USD892819S1 (en) | 2018-06-20 | 2020-08-11 | Companion Medical, Inc. | Display screen with graphical user interface |
| US11587663B2 (en) | 2018-06-20 | 2023-02-21 | Medtronic Minimed, Inc. | Intelligent medication delivery systems and methods for medicine dose calculation and reporting |
| FR3083985A1 (fr) | 2018-07-23 | 2020-01-24 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| WO2019243627A1 (fr) | 2018-06-23 | 2019-12-26 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| FR3083984A1 (fr) | 2018-07-23 | 2020-01-24 | Adocia | Dispositif pour injecter une solution d'insuline(s) |
| US12205699B1 (en) | 2018-10-30 | 2025-01-21 | Bigfoot Biomedical, Inc. | Method of pairing therapy devices using shared secrets, and related systems, methods and devices |
| US11948671B2 (en) | 2019-04-11 | 2024-04-02 | Medtronic Minimed, Inc. | Intelligent accessories for medicine dispensing device |
| CN116847869A (zh) * | 2020-10-08 | 2023-10-03 | 美商玛丽莫里斯博士联合有限责任公司 | 用于治疗和预防1型糖尿病的方法和组合物 |
| US11701473B2 (en) | 2021-06-23 | 2023-07-18 | Medtronic Minimed, Inc. | Reusable injection pens |
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| US4196196A (en) | 1978-06-19 | 1980-04-01 | Tiholiz Ivan C | Divalen/monovalent bipolar cation therapy for enhancement of tissue perfusion and reperfusion in disease states |
| DK503386D0 (da) * | 1986-10-20 | 1986-10-20 | Novo Industri As | Peptidpraeparater |
| PH23446A (en) * | 1986-10-20 | 1989-08-07 | Novo Industri As | Peptide preparations |
| EP2243827B2 (en) | 1996-08-30 | 2017-11-22 | Life Technologies Corporation | Serum-free mammalian cell culture medium, and uses thereof |
| DE69924232D1 (de) | 1998-01-09 | 2005-04-21 | Novo Nordisk As | Stabilisierte insulin-zubereitungen |
| US20080085298A1 (en) | 2004-03-12 | 2008-04-10 | Biodel, Inc. | Rapid Mucosal Gel or Film Insulin Compositions |
| US20080090753A1 (en) | 2004-03-12 | 2008-04-17 | Biodel, Inc. | Rapid Acting Injectable Insulin Compositions |
| PL1740154T3 (pl) | 2004-03-12 | 2009-11-30 | Biodel Inc | Kompozycje insuliny o ulepszonym wchłanianiu |
| US20080096800A1 (en) | 2004-03-12 | 2008-04-24 | Biodel, Inc. | Rapid mucosal gel or film insulin compositions |
| AU2008216612B2 (en) | 2007-02-17 | 2014-12-04 | President And Fellows Of Harvard College | Compositions and method for tissue preservation |
| TWI394580B (zh) * | 2008-04-28 | 2013-05-01 | Halozyme Inc | 超快起作用胰島素組成物 |
| US9060927B2 (en) * | 2009-03-03 | 2015-06-23 | Biodel Inc. | Insulin formulations for rapid uptake |
| FR2943538B1 (fr) * | 2009-03-27 | 2011-05-20 | Adocia | Formulation a action rapide d'insuline recombinante humaine |
| WO2012006283A1 (en) | 2010-07-07 | 2012-01-12 | Biodel Inc. | Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of insulin |
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| HK1207577A1 (en) | 2016-02-05 |
| CA2869883A1 (en) | 2013-10-24 |
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