JP2013508344A

JP2013508344A - 組成物

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Publication number: JP2013508344A
Authority: JP; Japan
Prior art keywords: calcium; salt; metal ion; composition; zinc
Prior art date: 2009-10-21
Legal status : Pending

Application number

JP2012534763A

Other languages

English (en)

Japanese (ja)

Other versions

JP2013508344A5 (cg-RX-API-DMAC7.html

Inventor

マーティン，グレン

Current Assignee

Innovata Ltd

Original Assignee

Innovata Ltd

Priority date

2009-10-21

Filing date

2010-10-21

Publication date

2013-03-07

2010-10-21 Application filed by Innovata Ltd filed Critical Innovata Ltd

2013-03-07 Publication of JP2013508344A publication Critical patent/JP2013508344A/ja

2013-12-05 Publication of JP2013508344A5 publication Critical patent/JP2013508344A5/ja

Status Pending legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 252
150000003839 salts Chemical class 0.000 claims abstract description 222
229910021645 metal ion Inorganic materials 0.000 claims abstract description 172
239000002245 particle Substances 0.000 claims abstract description 147
239000000843 powder Substances 0.000 claims abstract description 116
239000000126 substance Substances 0.000 claims abstract description 72
230000000975 bioactive effect Effects 0.000 claims abstract description 47
229920005862 polyol Polymers 0.000 claims abstract description 17
150000003077 polyols Chemical class 0.000 claims abstract description 17
-1 zinc halide (eg Chemical class 0.000 claims description 137
238000000034 method Methods 0.000 claims description 53
MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 47
239000001527 calcium lactate Substances 0.000 claims description 47
235000011086 calcium lactate Nutrition 0.000 claims description 47
229960002401 calcium lactate Drugs 0.000 claims description 47
150000001875 compounds Chemical class 0.000 claims description 46
239000013543 active substance Substances 0.000 claims description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
239000003814 drug Substances 0.000 claims description 22
239000000463 material Substances 0.000 claims description 22
238000001694 spray drying Methods 0.000 claims description 17
230000036571 hydration Effects 0.000 claims description 16
238000006703 hydration reaction Methods 0.000 claims description 16
239000006185 dispersion Substances 0.000 claims description 15
239000000243 solution Substances 0.000 claims description 15
208000023504 respiratory system disease Diseases 0.000 claims description 14
108090000623 proteins and genes Proteins 0.000 claims description 12
229960005069 calcium Drugs 0.000 claims description 11
239000011575 calcium Substances 0.000 claims description 11
229910052791 calcium Inorganic materials 0.000 claims description 11
108090000765 processed proteins & peptides Proteins 0.000 claims description 11
239000001509 sodium citrate Substances 0.000 claims description 11
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 11
150000003431 steroids Chemical class 0.000 claims description 11
229910052725 zinc Inorganic materials 0.000 claims description 11
239000011701 zinc Substances 0.000 claims description 11
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 10
102000004169 proteins and genes Human genes 0.000 claims description 10
239000002904 solvent Substances 0.000 claims description 10
229960005486 vaccine Drugs 0.000 claims description 10
229920000669 heparin Polymers 0.000 claims description 9
230000002685 pulmonary effect Effects 0.000 claims description 9
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 8
102000004196 processed proteins & peptides Human genes 0.000 claims description 8
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 6
239000001639 calcium acetate Substances 0.000 claims description 6
235000011092 calcium acetate Nutrition 0.000 claims description 6
229960005147 calcium acetate Drugs 0.000 claims description 6
FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 claims description 6
239000001354 calcium citrate Substances 0.000 claims description 6
229960004256 calcium citrate Drugs 0.000 claims description 6
GUPPESBEIQALOS-UHFFFAOYSA-L calcium tartrate Chemical compound [Ca+2].[O-]C(=O)C(O)C(O)C([O-])=O GUPPESBEIQALOS-UHFFFAOYSA-L 0.000 claims description 6
239000001427 calcium tartrate Substances 0.000 claims description 6
235000011035 calcium tartrate Nutrition 0.000 claims description 6
235000013337 tricalcium citrate Nutrition 0.000 claims description 6
BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 claims description 5
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 5
102000004190 Enzymes Human genes 0.000 claims description 5
108090000790 Enzymes Proteins 0.000 claims description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 5
230000002776 aggregation Effects 0.000 claims description 5
229910000019 calcium carbonate Inorganic materials 0.000 claims description 5
229960003563 calcium carbonate Drugs 0.000 claims description 5
235000010216 calcium carbonate Nutrition 0.000 claims description 5
239000004227 calcium gluconate Substances 0.000 claims description 5
235000013927 calcium gluconate Nutrition 0.000 claims description 5
229960004494 calcium gluconate Drugs 0.000 claims description 5
239000004330 calcium propionate Substances 0.000 claims description 5
235000010331 calcium propionate Nutrition 0.000 claims description 5
NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims description 5
XHHXAYSRQQBVFL-UHFFFAOYSA-L calcium;3-carboxy-3-hydroxypentanedioate;2-hydroxypropanoic acid Chemical compound [Ca+2].CC(O)C([O-])=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O XHHXAYSRQQBVFL-UHFFFAOYSA-L 0.000 claims description 5
229960002897 heparin Drugs 0.000 claims description 5
229920001184 polypeptide Polymers 0.000 claims description 5
230000002829 reductive effect Effects 0.000 claims description 5
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 4
238000004220 aggregation Methods 0.000 claims description 4
PWKNEBQRTUXXLT-ZBHRUSISSA-L calcium lactate gluconate Chemical compound [Ca+2].CC(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O PWKNEBQRTUXXLT-ZBHRUSISSA-L 0.000 claims description 4
229940041131 calcium lactate gluconate Drugs 0.000 claims description 4
229940057801 calcium lactate pentahydrate Drugs 0.000 claims description 4
ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 4
QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 claims description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
JCFHGKRSYPTRSS-UHFFFAOYSA-N calcium;2-hydroxypropanoic acid;hydrate Chemical compound O.[Ca].CC(O)C(O)=O JCFHGKRSYPTRSS-UHFFFAOYSA-N 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
150000004683 dihydrates Chemical class 0.000 claims description 4
239000000839 emulsion Substances 0.000 claims description 4
229940050410 gluconate Drugs 0.000 claims description 4
ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims description 4
229960001008 heparin sodium Drugs 0.000 claims description 4
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
230000000069 prophylactic effect Effects 0.000 claims description 4
235000019983 sodium metaphosphate Nutrition 0.000 claims description 4
239000006104 solid solution Substances 0.000 claims description 4
239000000725 suspension Substances 0.000 claims description 4
239000004246 zinc acetate Substances 0.000 claims description 4
VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
BHHYHSUAOQUXJK-UHFFFAOYSA-L zinc fluoride Chemical compound F[Zn]F BHHYHSUAOQUXJK-UHFFFAOYSA-L 0.000 claims description 4
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 4
LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 claims description 3
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 3
108010036949 Cyclosporine Proteins 0.000 claims description 3
229960001265 ciclosporin Drugs 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
150000007522 mineralic acids Chemical class 0.000 claims description 3
229940124597 therapeutic agent Drugs 0.000 claims description 3
229960000257 tiotropium bromide Drugs 0.000 claims description 3
ALWXETURCOIGIZ-UHFFFAOYSA-N 1-nitropropylbenzene Chemical compound CCC([N+]([O-])=O)C1=CC=CC=C1 ALWXETURCOIGIZ-UHFFFAOYSA-N 0.000 claims description 2
RWYRUDPAALLKPX-UHFFFAOYSA-N 2,2-difluoro-n-methylethanamine;hydrochloride Chemical compound Cl.CNCC(F)F RWYRUDPAALLKPX-UHFFFAOYSA-N 0.000 claims description 2
BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 claims description 2
OPSXJNAGCGVGOG-DKWTVANSSA-L Calcium L-aspartate Chemical compound [Ca+2].[O-]C(=O)[C@@H](N)CC([O-])=O OPSXJNAGCGVGOG-DKWTVANSSA-L 0.000 claims description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
239000001749 Calcium fumarate Substances 0.000 claims description 2
UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 claims description 2
XYQRXRFVKUPBQN-UHFFFAOYSA-L Sodium carbonate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]C([O-])=O XYQRXRFVKUPBQN-UHFFFAOYSA-L 0.000 claims description 2
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 2
FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 2
CANRESZKMUPMAE-UHFFFAOYSA-L Zinc lactate Chemical compound [Zn+2].CC(O)C([O-])=O.CC(O)C([O-])=O CANRESZKMUPMAE-UHFFFAOYSA-L 0.000 claims description 2
PWHCIQQGOQTFAE-UHFFFAOYSA-L barium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ba+2] PWHCIQQGOQTFAE-UHFFFAOYSA-L 0.000 claims description 2
229940034055 calcium aspartate Drugs 0.000 claims description 2
239000004301 calcium benzoate Substances 0.000 claims description 2
235000010237 calcium benzoate Nutrition 0.000 claims description 2
229910001622 calcium bromide Inorganic materials 0.000 claims description 2
239000001110 calcium chloride Substances 0.000 claims description 2
229910001628 calcium chloride Inorganic materials 0.000 claims description 2
WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 0.000 claims description 2
WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 2
229910001634 calcium fluoride Inorganic materials 0.000 claims description 2
235000019296 calcium fumarate Nutrition 0.000 claims description 2
229940046413 calcium iodide Drugs 0.000 claims description 2
229910001640 calcium iodide Inorganic materials 0.000 claims description 2
HDRTWMBOUSPQON-ODZAUARKSA-L calcium;(z)-but-2-enedioate Chemical compound [Ca+2].[O-]C(=O)\C=C/C([O-])=O HDRTWMBOUSPQON-ODZAUARKSA-L 0.000 claims description 2
VPWAVWZPVGDNMN-UHFFFAOYSA-L calcium;2,3-dihydroxypropanoate Chemical compound [Ca+2].OCC(O)C([O-])=O.OCC(O)C([O-])=O VPWAVWZPVGDNMN-UHFFFAOYSA-L 0.000 claims description 2
AVVIDTZRJBSXML-UHFFFAOYSA-L calcium;2-carboxyphenolate;dihydrate Chemical compound O.O.[Ca+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O AVVIDTZRJBSXML-UHFFFAOYSA-L 0.000 claims description 2
CHRHZFQUDFAQEQ-UHFFFAOYSA-L calcium;2-hydroxyacetate Chemical compound [Ca+2].OCC([O-])=O.OCC([O-])=O CHRHZFQUDFAQEQ-UHFFFAOYSA-L 0.000 claims description 2
PBUBJNYXWIDFMU-UHFFFAOYSA-L calcium;butanedioate Chemical compound [Ca+2].[O-]C(=O)CCC([O-])=O PBUBJNYXWIDFMU-UHFFFAOYSA-L 0.000 claims description 2
FKYAWWVVKRUUFY-UHFFFAOYSA-L calcium;decanoate Chemical compound [Ca+2].CCCCCCCCCC([O-])=O.CCCCCCCCCC([O-])=O FKYAWWVVKRUUFY-UHFFFAOYSA-L 0.000 claims description 2
HZQXCUSDXIKLGS-UHFFFAOYSA-L calcium;dibenzoate;trihydrate Chemical compound O.O.O.[Ca+2].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 HZQXCUSDXIKLGS-UHFFFAOYSA-L 0.000 claims description 2
BURFOJRYLQGPSB-UHFFFAOYSA-L calcium;heptanoate Chemical compound [Ca+2].CCCCCCC([O-])=O.CCCCCCC([O-])=O BURFOJRYLQGPSB-UHFFFAOYSA-L 0.000 claims description 2
YZLMERHFSCVBKZ-UHFFFAOYSA-L calcium;pentanoate Chemical compound [Ca+2].CCCCC([O-])=O.CCCCC([O-])=O YZLMERHFSCVBKZ-UHFFFAOYSA-L 0.000 claims description 2
MLMODXBPCNLAGP-UHFFFAOYSA-L calcium;propanedioate Chemical compound [Ca+2].[O-]C(=O)CC([O-])=O MLMODXBPCNLAGP-UHFFFAOYSA-L 0.000 claims description 2
JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 claims description 2
229930182912 cyclosporin Natural products 0.000 claims description 2
ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 claims description 2
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
XGVYXURUHKYWND-UHFFFAOYSA-L disodium sulfate octahydrate Chemical compound O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O XGVYXURUHKYWND-UHFFFAOYSA-L 0.000 claims description 2
MYEGRIHQBUXGCK-UHFFFAOYSA-L disodium;sulfate;dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O MYEGRIHQBUXGCK-UHFFFAOYSA-L 0.000 claims description 2
MFGZXPGKKJMZIY-UHFFFAOYSA-N ethyl 5-amino-1-(4-sulfamoylphenyl)pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=C(S(N)(=O)=O)C=C1 MFGZXPGKKJMZIY-UHFFFAOYSA-N 0.000 claims description 2
230000001747 exhibiting effect Effects 0.000 claims description 2
229940125721 immunosuppressive agent Drugs 0.000 claims description 2
239000003018 immunosuppressive agent Substances 0.000 claims description 2
239000001755 magnesium gluconate Substances 0.000 claims description 2
235000015778 magnesium gluconate Nutrition 0.000 claims description 2
229960003035 magnesium gluconate Drugs 0.000 claims description 2
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 2
229940061634 magnesium sulfate heptahydrate Drugs 0.000 claims description 2
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 2
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims description 2
229910000343 potassium bisulfate Inorganic materials 0.000 claims description 2
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 claims description 2
235000017281 sodium acetate Nutrition 0.000 claims description 2
229940087562 sodium acetate trihydrate Drugs 0.000 claims description 2
229940018038 sodium carbonate decahydrate Drugs 0.000 claims description 2
PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 claims description 2
BSHCFHLQFXHMSH-UHFFFAOYSA-M sodium;periodate;trihydrate Chemical compound O.O.O.[Na+].[O-]I(=O)(=O)=O BSHCFHLQFXHMSH-UHFFFAOYSA-M 0.000 claims description 2
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 2
229960001967 tacrolimus Drugs 0.000 claims description 2
229940102001 zinc bromide Drugs 0.000 claims description 2
239000011667 zinc carbonate Substances 0.000 claims description 2
235000004416 zinc carbonate Nutrition 0.000 claims description 2
229910000010 zinc carbonate Inorganic materials 0.000 claims description 2
239000011592 zinc chloride Substances 0.000 claims description 2
235000005074 zinc chloride Nutrition 0.000 claims description 2
239000011576 zinc lactate Substances 0.000 claims description 2
235000000193 zinc lactate Nutrition 0.000 claims description 2
229940050168 zinc lactate Drugs 0.000 claims description 2
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
229960001763 zinc sulfate Drugs 0.000 claims description 2
QWCKCWSBAUZZLF-UHFFFAOYSA-L zinc sulfate hexahydrate Chemical compound O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O QWCKCWSBAUZZLF-UHFFFAOYSA-L 0.000 claims description 2
VRGNUPCISFMPEM-ZVGUSBNCSA-L zinc;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Zn+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VRGNUPCISFMPEM-ZVGUSBNCSA-L 0.000 claims description 2
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