JP6459129B2 - Ferric pyrophosphate-containing powder and method for producing the same - Google Patents
Ferric pyrophosphate-containing powder and method for producing the same Download PDFInfo
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- JP6459129B2 JP6459129B2 JP2015082107A JP2015082107A JP6459129B2 JP 6459129 B2 JP6459129 B2 JP 6459129B2 JP 2015082107 A JP2015082107 A JP 2015082107A JP 2015082107 A JP2015082107 A JP 2015082107A JP 6459129 B2 JP6459129 B2 JP 6459129B2
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- ferric pyrophosphate
- iron
- pyrophosphate
- ferric
- containing powder
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- CADNYOZXMIKYPR-UHFFFAOYSA-B ferric pyrophosphate Chemical compound [Fe+3].[Fe+3].[Fe+3].[Fe+3].[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O CADNYOZXMIKYPR-UHFFFAOYSA-B 0.000 title claims description 82
- 239000011706 ferric diphosphate Substances 0.000 title claims description 79
- 235000007144 ferric diphosphate Nutrition 0.000 title claims description 79
- 229940036404 ferric pyrophosphate Drugs 0.000 title claims description 79
- 239000000843 powder Substances 0.000 title claims description 69
- 238000004519 manufacturing process Methods 0.000 title claims description 16
- 239000011148 porous material Substances 0.000 claims description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
- 239000002002 slurry Substances 0.000 claims description 16
- 239000007795 chemical reaction product Substances 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 13
- 235000011180 diphosphates Nutrition 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 6
- 239000003125 aqueous solvent Substances 0.000 claims description 5
- 159000000014 iron salts Chemical class 0.000 claims description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 150000004760 silicates Chemical class 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 147
- 229910052742 iron Inorganic materials 0.000 description 66
- 239000000523 sample Substances 0.000 description 29
- 239000012086 standard solution Substances 0.000 description 29
- 239000007788 liquid Substances 0.000 description 18
- 238000001035 drying Methods 0.000 description 17
- 239000007864 aqueous solution Substances 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 230000032683 aging Effects 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 14
- 238000010521 absorption reaction Methods 0.000 description 13
- 238000010828 elution Methods 0.000 description 13
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 13
- 239000004115 Sodium Silicate Substances 0.000 description 12
- 235000019795 sodium metasilicate Nutrition 0.000 description 12
- 229910052911 sodium silicate Inorganic materials 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 238000010298 pulverizing process Methods 0.000 description 11
- 238000000926 separation method Methods 0.000 description 11
- 210000002784 stomach Anatomy 0.000 description 11
- 150000002505 iron Chemical class 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 210000001198 duodenum Anatomy 0.000 description 8
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229940048084 pyrophosphate Drugs 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 7
- 229940048086 sodium pyrophosphate Drugs 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 7
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229910017604 nitric acid Inorganic materials 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 206010022971 Iron Deficiencies Diseases 0.000 description 5
- 239000012736 aqueous medium Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 5
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- 229910021642 ultra pure water Inorganic materials 0.000 description 5
- 239000012498 ultrapure water Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000007502 anemia Diseases 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 210000004211 gastric acid Anatomy 0.000 description 4
- -1 iron ions Chemical class 0.000 description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 4
- 235000019353 potassium silicate Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 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
- 238000011156 evaluation Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- 229910052753 mercury Inorganic materials 0.000 description 3
- 229910052913 potassium silicate Inorganic materials 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 229910052727 yttrium Inorganic materials 0.000 description 3
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 238000009616 inductively coupled plasma Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- PAZHGORSDKKUPI-UHFFFAOYSA-N lithium metasilicate Chemical compound [Li+].[Li+].[O-][Si]([O-])=O PAZHGORSDKKUPI-UHFFFAOYSA-N 0.000 description 2
- 229910052912 lithium silicate Inorganic materials 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 235000019629 palatability Nutrition 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000001321 subclavian vein Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241001061225 Arcos Species 0.000 description 1
- 238000004438 BET method Methods 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 1
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- XGGLLRJQCZROSE-UHFFFAOYSA-K ammonium iron(iii) sulfate Chemical compound [NH4+].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O XGGLLRJQCZROSE-UHFFFAOYSA-K 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- PLKYGPRDCKGEJH-UHFFFAOYSA-N azane;2-hydroxypropane-1,2,3-tricarboxylic acid;iron Chemical compound N.[Fe].OC(=O)CC(O)(C(O)=O)CC(O)=O PLKYGPRDCKGEJH-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002354 inductively-coupled plasma atomic emission spectroscopy Methods 0.000 description 1
- 238000007603 infrared drying Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940082629 iron antianemic preparations Drugs 0.000 description 1
- 235000014413 iron hydroxide Nutrition 0.000 description 1
- PVFSDGKDKFSOTB-UHFFFAOYSA-K iron(3+);triacetate Chemical compound [Fe+3].CC([O-])=O.CC([O-])=O.CC([O-])=O PVFSDGKDKFSOTB-UHFFFAOYSA-K 0.000 description 1
- WHRBSMVATPCWLU-UHFFFAOYSA-K iron(3+);triformate Chemical compound [Fe+3].[O-]C=O.[O-]C=O.[O-]C=O WHRBSMVATPCWLU-UHFFFAOYSA-K 0.000 description 1
- NPFOYSMITVOQOS-UHFFFAOYSA-K iron(III) citrate Chemical compound [Fe+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NPFOYSMITVOQOS-UHFFFAOYSA-K 0.000 description 1
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229940042126 oral powder Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- MVGWWCXDTHXKTR-UHFFFAOYSA-J tetralithium;phosphonato phosphate Chemical compound [Li+].[Li+].[Li+].[Li+].[O-]P([O-])(=O)OP([O-])([O-])=O MVGWWCXDTHXKTR-UHFFFAOYSA-J 0.000 description 1
- POWFTOSLLWLEBN-UHFFFAOYSA-N tetrasodium;silicate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-][Si]([O-])([O-])[O-] POWFTOSLLWLEBN-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000007601 warm air drying Methods 0.000 description 1
Description
本発明は、経口により鉄分を体内に補給するための鉄補給用食品等に用いられるピロリン酸第二鉄含有粉末とその製造方法に関する。 The present invention relates to a ferric pyrophosphate-containing powder used for iron supplementary food for supplementing iron in the body orally and a method for producing the same.
近年、人体の疾病予防又は健康維持に関して、ミネラルの摂取不足が原因の一つとして指摘されており、それに関連して種々のミネラルの役割が研究・分析により解明されつつある。その中でも、鉄分は、人体内の鉄の約７０％が酸素運搬を行っているヘモグロビンのヘム鉄に存在している。鉄不足になるとヘモグロビンの量が減少して酸素運搬能が減少し、貧血を発症する。貧血等の鉄欠乏症は、全人口のうち２０億人が罹っているといわれている。鉄欠乏症になると、貧血の発症だけでなく、妊婦においては低体重児の出生、小児では発達遅延、異常行動等を引き起こすといわれている。これらの疾患に対する治療方法としては、主として、鉄分を補給することにより鉄の体内吸収量を増加させる手法がとられている。 In recent years, insufficient intake of minerals has been pointed out as one of the causes for disease prevention or health maintenance of the human body, and the role of various minerals is being elucidated by research and analysis in relation to this. Among them, iron is present in heme iron of hemoglobin in which about 70% of iron in the human body carries oxygen. When iron is deficient, the amount of hemoglobin decreases, oxygen transport capacity decreases, and anemia develops. Iron deficiency such as anemia is said to affect 2 billion people in the total population. Iron deficiency is said to cause not only the onset of anemia, but also birth of low-weight infants in pregnant women, developmental delay, abnormal behavior, etc. in children. As a treatment method for these diseases, a technique of increasing the amount of iron absorbed in the body by supplementing iron is mainly used.
鉄の体内への吸収は、二価の鉄イオン（Ｆｅ２＋）が十二指腸で吸収されるとされている。このメカニズムを考慮し、鉄欠乏症を緩和ないしは治癒するための食品又は医薬品が開発されている。例えば、清涼飲料水、粉ミルク、サプリメント、医薬品等に鉄剤が配合された製品が提供されている。鉄剤としては、可溶性鉄塩又は水不溶性鉄塩を主成分とするものが使用されているが、特に可溶性塩が汎用されている。ところが、可溶性鉄塩は、鉄味が強く、経口用として嗜好性に問題があることに加え、イオン化した鉄の胃壁への侵襲による副作用が問題となる。このため、近年においては、不溶性鉄塩が使用されるようになり、その中でもピロリン酸第二鉄が脚光を浴びている。 As for absorption of iron into the body, divalent iron ions (Fe 2+ ) are absorbed by the duodenum. In consideration of this mechanism, foods or pharmaceuticals have been developed to alleviate or cure iron deficiency. For example, products in which an iron preparation is blended with soft drinks, powdered milk, supplements, pharmaceuticals, and the like are provided. As the iron agent, those containing a soluble iron salt or a water-insoluble iron salt as a main component are used, and particularly soluble salts are widely used. However, the soluble iron salt has a strong iron taste and has a problem of palatability for oral use, and also has a side effect due to the invasion of the ionized iron into the stomach wall. For this reason, insoluble iron salts have come to be used in recent years, and among these, ferric pyrophosphate is in the spotlight.
鉄の吸収性に関係する作用が、胃及び十二指腸での鉄の溶出である。胃での鉄の溶出を抑制し、十二指腸で溶出することができれば、十二指腸で溶出する量が増えて生体吸収性の向上が期待できる。さらには、可溶性鉄塩と異なり、胃への侵襲の問題を緩和ないしは防止できると言える。一方、ピロリン酸第二鉄のような不溶性鉄塩は、比較的に胃での障害を引き起こしにくいものの、鉄の溶出性が悪いため、生体吸収性が低い。このような問題を解消するために、例えばピロリン酸第二鉄を可溶化するようにキレート鉄製剤が開発されているが、胃で鉄の溶出が生じる結果、嘔吐、下痢及び食欲不振の原因になるおそれがある。このため、ピロリン酸第二鉄を含む鉄剤に対して種々の改良技術が提案されている。 An action related to iron absorption is the dissolution of iron in the stomach and duodenum. If the elution of iron in the stomach can be suppressed and it can be eluted in the duodenum, the amount of elution in the duodenum will increase, and an improvement in bioabsorbability can be expected. Furthermore, unlike soluble iron salts, it can be said that the problem of stomach invasion can be alleviated or prevented. On the other hand, insoluble iron salts such as ferric pyrophosphate are relatively less likely to cause damage in the stomach, but have poor bioabsorbability due to poor iron elution. In order to solve such problems, chelated iron preparations have been developed to solubilize ferric pyrophosphate, for example, but the dissolution of iron in the stomach results in vomiting, diarrhea and loss of appetite. There is a risk. For this reason, various improved techniques have been proposed for iron agents containing ferric pyrophosphate.
例えば、食品添加物として使用しているピロリン酸第二鉄に分散剤を添加してピロリン酸第二鉄の微粒子を調製することにより、分散性を向上させて鉄の風味を抑制したピロリン酸第二鉄製剤が提案されている（特許文献１）。 For example, by adding a dispersing agent to ferric pyrophosphate used as a food additive to prepare fine particles of ferric pyrophosphate, the dispersibility is improved and the iron flavor is suppressed. A ferric preparation has been proposed (Patent Document 1).
その他にも、ピロリン酸第二鉄の生体吸収性に関する研究成果が報告されている。例えば、強熱減量を変化させたピロリン酸第二鉄の生体吸収性の評価（非特許文献１）、平均粒子径を変化させたピロリン酸第二鉄の生体吸収性の評価（非特許文献２）が行われている。 In addition, research results on bioabsorbability of ferric pyrophosphate have been reported. For example, evaluation of bioabsorbability of ferric pyrophosphate with reduced ignition loss (Non-patent document 1), evaluation of bioabsorbability of ferric pyrophosphate with changed average particle diameter (non-patent document 2) ) Is done.
しかしながら、特許文献１の技術では、食品添加物製剤に含まれるピロリン酸第二鉄の配合量が少ないため、鉄を摂取する際には大量の食品添加物製剤を服用しなければならない。さらには、微粒子化するために、ビーズミル等を用いて粉砕していることから、ビーズ又は装置からのコンタミネーションのリスクが高くなる。 However, in the technique of Patent Document 1, since the amount of ferric pyrophosphate contained in the food additive preparation is small, a large amount of food additive preparation must be taken when ingesting iron. Furthermore, since the particles are pulverized using a bead mill or the like in order to form fine particles, the risk of contamination from beads or an apparatus increases.
非特許文献１の技術では、強熱減量を変化させてピロリン酸第二鉄の生体吸収性を評価し、ピロリン酸第二鉄の強熱減量が高いほど生体吸収性は高くなることが報告されているが、その生体吸収性は十分ではない。 In the technique of Non-Patent Document 1, it is reported that the bioabsorbability of ferric pyrophosphate is evaluated by changing the ignition loss, and the bioabsorbability increases as the ignition loss of ferric pyrophosphate increases. However, its bioresorbability is not sufficient.
非特許文献２の技術では、平均粒子径を変化させてピロリン酸第二鉄の生体吸収性を評価し、ピロリン酸第二鉄の平均粒子径を小さくするほど生体吸収性は高くなることが報告されているものの、生体吸収性の劇的な改善には至っていない。 In the technique of Non-Patent Document 2, the bioabsorbability of ferric pyrophosphate is evaluated by changing the average particle diameter, and it is reported that the bioabsorbability increases as the average particle diameter of ferric pyrophosphate decreases. However, the bioabsorbability has not improved dramatically.
従って、本発明の主な目的は、経口用鉄剤の主成分として高い鉄分吸収性が得られるピロリン酸第二鉄含有粉末を提供することにある。 Accordingly, a main object of the present invention is to provide a ferric pyrophosphate-containing powder that can obtain high iron content as a main component of an oral iron preparation.
本発明者らは、従来技術の問題点に鑑みて鋭意研究を重ねた結果、特定の組成及び物性を有するピロリン酸第二鉄含有粉末が上記目的を達成できることを見出し、本発明を完成するに至った。 As a result of intensive studies in view of the problems of the prior art, the present inventors have found that a ferric pyrophosphate-containing powder having a specific composition and physical properties can achieve the above-mentioned object, and to complete the present invention. It came.
すなわち、本発明は、下記のピロリン酸第二鉄含有粉末及びその製造方法に係る。
１． ピロリン酸第二鉄を含む粉末であって、
（１）モード径（最頻細孔直径）が３００ｎｍ以下であり、
（２）全細孔容積中に占める細孔直径１００〜２１０ｎｍの細孔容積の割合が６０〜８０％である、
ことを特徴とするピロリン酸第二鉄含有粉末。
２． 比表面積が２５ｍ２／ｇ以上である、前記項１記載のピロリン酸第二鉄含有粉末。
３． 外部表面積が２０ｍ２／ｇ以上である、前記項１又は２に記載のピロリン酸第二鉄含有粉末。
４． 平均粒子径が５μｍ以上である、前記項１〜３のいずれかに記載のピロリン酸第二鉄含有粉末。
５． ピロリン酸第二鉄の含有量が９０重量％以上である、前記項１〜４のいずれかに記載のピロリン酸第二鉄含有粉末。
６． ピロリン酸第二鉄及びケイ素成分を含むピロリン酸第二鉄含有粉末を製造する方法であって、
水性溶媒中に水溶性鉄塩、ピロリン酸塩及びケイ酸塩を添加及び混合することにより、これらの反応生成物を含む水性スラリーを調製する工程
を含むことを特徴とするピロリン酸第二鉄含有粉末の製造方法。
That is, this invention relates to the following ferric pyrophosphate containing powder and its manufacturing method.
1. A powder comprising ferric pyrophosphate,
(1) The mode diameter (moderate pore diameter) is 300 nm or less,
(2) The ratio of the pore volume having a pore diameter of 100 to 210 nm in the total pore volume is 60 to 80%.
A ferric pyrophosphate-containing powder characterized by that.
2. Item 2. The ferric pyrophosphate-containing powder according to Item 1, wherein the specific surface area is 25 m 2 / g or more.
3. Item 3. The ferric pyrophosphate-containing powder according to Item 1 or 2, wherein the external surface area is 20 m 2 / g or more.
4). Item 4. The ferric pyrophosphate-containing powder according to any one of Items 1 to 3, wherein the average particle size is 5 μm or more.
5. Item 5. The ferric pyrophosphate-containing powder according to any one of Items 1 to 4, wherein the content of ferric pyrophosphate is 90% by weight or more.
6). A method for producing a ferric pyrophosphate-containing powder comprising ferric pyrophosphate and a silicon component, comprising:
Ferric pyrophosphate containing, comprising the step of preparing an aqueous slurry containing these reaction products by adding and mixing water soluble iron salts, pyrophosphates and silicates in an aqueous solvent Powder manufacturing method.
本発明のピロリン酸第二鉄含有粉末では、特定の細孔容積及びモード径（最頻細孔直径）を兼ね備えた細孔構造を有するので、鉄の溶出性に関し、ｐＨ１．２の水に対する溶出を低く抑える一方、ｐＨ３．０の水に対する溶出性を高めることができる。すなわち、本発明粉末を経口により服用した際、胃内では鉄イオンの溶出を効果的に抑制しつつ、十二指腸では胃内と比較して鉄の溶出性が高いことにより高い吸収性を得ることが期待できる。これにより、胃での障害が少なく、体内に鉄分がより吸収されやすい経口型粉末を提供することができる。 The ferric pyrophosphate-containing powder of the present invention has a pore structure that has both a specific pore volume and a mode diameter (moderate pore diameter). While keeping the pH low, it is possible to enhance the dissolution property with respect to water having a pH of 3.0. That is, when the powder of the present invention is taken orally, it effectively suppresses the elution of iron ions in the stomach, while the duodenum can obtain a high absorbability due to its higher iron elution than in the stomach. I can expect. As a result, it is possible to provide an oral powder that is less damaged by the stomach and more easily absorbs iron in the body.
このような特徴を有する本発明粉末は、そのまま経口摂取・経口投与できるほか、例えば食品又はサプリメント、医薬品、医薬部外品等の各種の製品に配合したうえで好適に使用することもできる。 The powder of the present invention having such characteristics can be ingested or administered as it is, and can be suitably used after blended with various products such as foods or supplements, pharmaceuticals, quasi drugs and the like.
本発明の製造方法では、特に所定量のケイ酸塩を反応系に存在させることにより、上記のような特定の細孔構造をより確実に形成させることができるので、本発明粉末をより確実かつ効率的に製造することができる。 In the production method of the present invention, the specific pore structure as described above can be more reliably formed by the presence of a predetermined amount of silicate in the reaction system. It can be manufactured efficiently.
１．ピロリン酸第二鉄含有粉末
本発明のピロリン酸第二鉄含有粉末（本発明粉末）は、ピロリン酸第二鉄を含む粉末であって、
（１）モード径（最頻細孔直径）が３００ｎｍ以下であり、
（２）細孔直径１００〜３００ｎｍの細孔容積（全細孔容積）中に占める細孔直径１００〜２１０ｎｍの細孔容積の割合が６０〜８０％である、
ことを特徴とする。
1. Ferric pyrophosphate-containing powder The ferric pyrophosphate-containing powder of the present invention (the present powder) is a powder containing ferric pyrophosphate,
(1) The mode diameter (moderate pore diameter) is 300 nm or less,
(2) The ratio of the pore volume with a pore diameter of 100 to 210 nm in the pore volume with a pore diameter of 100 to 300 nm (total pore volume) is 60 to 80%.
It is characterized by that.
一般に、ピロリン酸第二鉄は化学式Ｆｅ４（Ｐ２Ｏ７）３で示される化合物である。これに対し、本発明粉末は、ピロリン酸第二鉄とそれ以外の成分（第三成分）とが複合化（一体的に固定化）した成分から構成されるものであるので、上記のような混合物とは明確に区別されるものである。 Generally, ferric pyrophosphate is a compound represented by the chemical formula Fe 4 (P 2 O 7 ) 3 . On the other hand, the powder of the present invention is composed of components in which ferric pyrophosphate and other components (third component) are complexed (integrated and fixed), so that A distinction is made from mixtures.
本発明粉末では、本発明粉末を構成する個々の粒子中にピロリン酸第二鉄と第三成分とが複合化した成分が含まれる。このような粉末は、後記に示すような製造方法によってより確実に製造することができる。 In the powder of the present invention, a component in which ferric pyrophosphate and a third component are combined is included in each particle constituting the powder of the present invention. Such a powder can be more reliably produced by a production method as described below.
また、前記のピロリン酸第二鉄と第三成分とが複合化した成分は、通常は非晶質体である。従って、例えばＸ線回折分析では第三成分による明確なピークは認められない。 The component in which the ferric pyrophosphate and the third component are combined is usually an amorphous body. Therefore, for example, in X-ray diffraction analysis, a clear peak due to the third component is not recognized.
本発明粉末におけるピロリン酸第二鉄の含有量は通常９０重量％以上であり、特に９５重量％以上であることが好ましい。ピロリン酸第二鉄の含有量の上限値は限定的でないが、通常は９９重量％程度とすれば良い。第三成分としては、上記のような細孔構造（すなわち、細孔容積及びモード径）が形成される限りは特に限定されず、通常は出発原料由来の成分であることが好ましく、例えばケイ素等が含まれる。 The content of ferric pyrophosphate in the powder of the present invention is usually 90% by weight or more, and particularly preferably 95% by weight or more. Although the upper limit of the content of ferric pyrophosphate is not limited, it is usually about 99% by weight. The third component is not particularly limited as long as the pore structure (that is, pore volume and mode diameter) as described above is formed, and is usually preferably a component derived from a starting material, such as silicon. Is included.
本発明粉末におけるモード径（最頻細孔直径）が３００ｎｍ以下であり、特に１５０〜２１０ｎｍであることが望ましい。すなわち、本発明粉末を構成する粒子が有する細孔におけるモード径が上記範囲内にあることが好ましい。また、本発明粉末の全細孔容積に占める細孔直径１００〜２１０ｎｍの細孔容積の割合が６０〜８０％であり、特に６０〜７５％であることが望ましい。 The mode diameter (moderate pore diameter) in the powder of the present invention is 300 nm or less, and particularly preferably 150 to 210 nm. That is, the mode diameter in the pores of the particles constituting the powder of the present invention is preferably in the above range. Further, the ratio of the pore volume having a pore diameter of 100 to 210 nm in the total pore volume of the powder of the present invention is 60 to 80%, and particularly preferably 60 to 75%.
本発明粉末では、特に、上記のような特定のモード径及び細孔容積の割合という２つの物性を兼ね備えることにより、次のような効果を得ることができる。すなわち、本発明粉末を構成する粒子の内部で細孔が発達した多孔性の細孔構造が形成されることによって、高い鉄分吸収性を発揮することができる。これは、次のようなメカニズムによるものと考えられる。モード径が水の毛管凝縮が生じる直径より小さくなると、毛細管現象が起こりやすく細孔内部への水の浸透性が高まるとともに、当該細孔の容積が大きい場合には細孔内部における水の保持量も多くなり、ピロリン酸第二鉄含有粉末内で水との接触性が高まり、保持水中への鉄の溶出が容易になる。ピロリン酸第二鉄はその特性上、ｐＨ１．２での溶解性はｐＨ３．０でのそれと比較して低いことから、ピロリン酸第二鉄含有粉末の細孔構造を特定の範囲とすることで細孔内での水の保持量を高め、ピロリン酸第二鉄自身の酸溶解特性によりｐＨ１．２に対するｐＨ３．０での溶出性（溶出率）を高めることが期待できる。すなわち、消化管内部での溶解性を想定した場合、経口服用されたピロリン酸第二鉄含有粉末は、胃酸（ｐＨ１．２）と接触した際にその細孔内に胃酸が浸透し、細孔内部に胃酸が保持された状態で十二指腸（ｐＨ３．０）に到達すると、細孔内で胃酸が一部中和されながらｐＨ３．０の酸性液と置換され、この際にピロリン酸第二鉄自身の溶解とともに細孔構造が崩壊し、これに伴い鉄イオンが消化管内に溶出されることにより腸管から体内へ吸収される。従って、本発明粉末によれば、胃での鉄の溶出を抑制することともに、十二指腸での鉄の溶出を促進するという効果が期待できる。 In the powder of the present invention, the following effects can be obtained by combining the two physical properties of the specific mode diameter and the pore volume ratio as described above. That is, high iron content absorbability can be exhibited by forming a porous pore structure in which pores are developed inside the particles constituting the powder of the present invention. This is thought to be due to the following mechanism. When the mode diameter is smaller than the diameter at which capillary condensation of water occurs, capillarity easily occurs and the water permeability into the pores increases, and when the pore volume is large, the amount of water retained inside the pores The contact with water in the ferric pyrophosphate-containing powder is increased, and the elution of iron into the retained water is facilitated. Ferric pyrophosphate has low solubility at pH 1.2 compared to that at pH 3.0 due to its characteristics. Therefore, by setting the pore structure of ferric pyrophosphate-containing powder within a specific range. It can be expected that the amount of water retained in the pores is increased, and the dissolution property (dissolution rate) at pH 3.0 with respect to pH 1.2 is enhanced by the acid solubility characteristics of ferric pyrophosphate itself. That is, assuming solubility in the digestive tract, the ferric pyrophosphate-containing powder taken orally penetrates into the pores of gastric acid when contacted with gastric acid (pH 1.2). When reaching the duodenum (pH 3.0) while gastric acid is retained inside, the gastric acid is partially neutralized in the pores and replaced with an acidic solution of pH 3.0. At this time, ferric pyrophosphate itself The pore structure collapses along with the dissolution of iron, and iron ions are eluted into the digestive tract and are absorbed from the intestinal tract into the body. Therefore, according to the powder of the present invention, it is possible to expect the effects of suppressing the elution of iron in the stomach and promoting the elution of iron in the duodenum.
本発明粉末の性状は、通常は粉末（乾燥粉末）の形態をとり得るが、この場合の平均粒径は限定されないが、通常は１〜１００μｍ程度とし、特に１〜５０μｍとすることが好ましい。なお、必要に応じて、水等を含む液状媒体に本発明粉末を分散させることにより分散液、ペースト等の液体の形態で使用することもできる。 The properties of the powder of the present invention can usually be in the form of a powder (dry powder), but the average particle size in this case is not limited, but is usually about 1 to 100 μm, particularly preferably 1 to 50 μm. In addition, it can also be used with liquid forms, such as a dispersion liquid and a paste, by dispersing this invention powder in the liquid medium containing water etc. as needed.
本発明粉末の比表面積は限定的でないが、通常は２０ｍ２/ｇ以上であり、特に２５ｍ２/ｇ以上とすることが本発明の効果の見地より好ましい。また、外部比表面積は、通常は１５ｍ２/ｇ以上とし、特に２０ｍ２/ｇ以上とすることが好ましい。これによって、水との接触面積が広くなるため、水に馴染みやすくなる。 The specific surface area of the powder of the present invention is not limited, but is usually 20 m 2 / g or more, and particularly preferably 25 m 2 / g or more from the viewpoint of the effect of the present invention. Further, the external specific surface area is usually 15 m 2 / g or more, and particularly preferably 20 m 2 / g or more. Thereby, since the contact area with water becomes large, it becomes easy to become familiar with water.
本発明粉末は、経口用として好適に用いることができる。従って、そのまま経口型鉄剤（鉄補給用）として使用することができるほか、他の成分（溶媒、増粘剤、賦形剤、着色料、香料等の添加物）とともに製剤化して鉄補給製剤として使用することもできる。また、一般的な食品、サプリメント、医薬品等の補助成分として用いることもできる。 The powder of the present invention can be suitably used for oral use. Therefore, it can be used as it is as an oral iron supplement (for iron supplementation), or formulated with other ingredients (solvents, thickeners, excipients, coloring agents, fragrances, etc.) as an iron supplement formulation. It can also be used. Moreover, it can also be used as an auxiliary component for general foods, supplements, pharmaceuticals and the like.
２．ピロリン酸第二鉄含有粉末の製造方法
本発明は、ピロリン酸第二鉄及びケイ素成分を含むピロリン酸第二鉄含有粉末を製造する方法であって、
水性溶媒中に水溶性鉄塩、ピロリン酸塩及びケイ酸塩を添加及び混合することにより、これらの反応生成物を含む水性スラリーを調製する工程（反応工程）
を含むことを特徴とするピロリン酸第二鉄含有粉末の製造方法を包含する。
2. The present invention relates to a method for producing a ferric pyrophosphate-containing powder containing ferric pyrophosphate and a silicon component,
A step of preparing an aqueous slurry containing these reaction products by adding and mixing water-soluble iron salt, pyrophosphate and silicate in an aqueous solvent (reaction step)
The manufacturing method of the ferric pyrophosphate containing powder characterized by including this.
反応工程
反応工程では、水性溶媒中に水溶性鉄塩、ピロリン酸塩及びケイ酸塩を添加及び混合することにより、これらの反応生成物を含む水性スラリーを調製する。すなわち、水性溶媒中において、出発原料である水溶性鉄塩、ピロリン酸塩及びケイ酸塩の反応生成物を生成させるに際し、これら出発原料の反応生成物を含む水性スラリーを調製する
Reaction Step In the reaction step, an aqueous slurry containing these reaction products is prepared by adding and mixing a water-soluble iron salt, pyrophosphate and silicate in an aqueous solvent. That is, when producing reaction products of water-soluble iron salt, pyrophosphate and silicate which are starting materials in an aqueous solvent, an aqueous slurry containing the reaction products of these starting materials is prepared.
水溶性鉄塩としては、特に限定されるものではなく、例えば塩化第二鉄、硫酸第二鉄、硫酸第二鉄アンモニウム、硝酸第二鉄、臭化第二鉄、ギ酸第二鉄、酢酸第二鉄、クエン酸鉄、クエン酸鉄アンモニウム等が挙げられる。特に、塩化第二鉄、硫酸第二鉄、硝酸第二鉄等の少なくとも１種が好ましく、その中でも塩化第二鉄及び硫酸第二鉄の少なくとも１種がより好ましい。最も好ましいのは塩化第二鉄である。 The water-soluble iron salt is not particularly limited. For example, ferric chloride, ferric sulfate, ammonium ferric sulfate, ferric nitrate, ferric bromide, ferric formate, ferric acetate Examples thereof include diiron, iron citrate, and ammonium iron citrate. In particular, at least one of ferric chloride, ferric sulfate, ferric nitrate and the like is preferable, and among them, at least one of ferric chloride and ferric sulfate is more preferable. Most preferred is ferric chloride.
ピロリン酸塩としては、特に限定されるものではなく、例えばピロリン酸ナトリウム、ピロリン酸カリウム、ピロリン酸リチウム、酸性ピロリン酸ナトリウム、酸性ピロリン酸カリウム等が挙げられる。特に、ピロリン酸ナトリウム、ピロリン酸カリウム、酸性ピロリン酸ナトリウム等の少なくとも１種が好ましく、さらにはピロリン酸ナトリウム及びピロリン酸カリウムの少なくとも１種が好ましく、ピロリン酸ナトリウムが最も好ましい。 The pyrophosphate is not particularly limited, and examples thereof include sodium pyrophosphate, potassium pyrophosphate, lithium pyrophosphate, acidic sodium pyrophosphate, acidic potassium pyrophosphate, and the like. In particular, at least one of sodium pyrophosphate, potassium pyrophosphate, acidic sodium pyrophosphate, and the like is preferable, at least one of sodium pyrophosphate and potassium pyrophosphate is more preferable, and sodium pyrophosphate is most preferable.
ケイ酸塩としては、特に限定されるものではなく、例えばメタケイ酸ナトリウム、オルトケイ酸ナトリウム、メタ二ケイ酸ナトリウム、メタケイ酸カリウム、メタケイ酸リチウム、コロイダルシリカ、水ガラスが挙げられ、好ましいのはメタケイ酸ナトリウム、メタケイ酸カリウム、メタケイ酸リチウムであり、さらに好ましいのはメタケイ酸ナトリウム、メタケイ酸カリウムであり、最も好ましいのは、メタケイ酸ナトリウムである。 The silicate is not particularly limited, and examples thereof include sodium metasilicate, sodium orthosilicate, sodium metadisilicate, potassium metasilicate, lithium metasilicate, colloidal silica, and water glass. Sodium metasilicate, potassium metasilicate, and lithium metasilicate are more preferable. Sodium metasilicate and potassium metasilicate are more preferable, and sodium metasilicate is most preferable.
水性媒体としては、水及び水溶性有機溶媒の少なくとも１種を好適に使用することができる。水溶性有機溶媒としては、例えばメタノール、エタノール、プロパノール等のアルコール類を好ましく使用することができる。本発明では、特に水を用いることが好ましい。水性媒体の使用量は特に制限されず、通常は反応生成物の固形分濃度が０．１〜４０重量％、さらに好ましくは０．３〜５０重量％程度となるように適宜調製すれば良い。 As the aqueous medium, at least one of water and a water-soluble organic solvent can be suitably used. As the water-soluble organic solvent, for example, alcohols such as methanol, ethanol and propanol can be preferably used. In the present invention, it is particularly preferable to use water. The amount of the aqueous medium used is not particularly limited, and it may be appropriately adjusted so that the solid content concentration of the reaction product is usually about 0.1 to 40% by weight, more preferably about 0.3 to 50% by weight.
本発明の製造方法では、水性媒体に水溶液鉄塩、ピロリン酸塩及びケイ酸塩を配合する方法であっても良いし、これらを予め水溶液の形態としたうえで添加及び混合しても良い。この場合の各水溶液の濃度は限定的ではないが、通常は水溶液鉄塩では１〜２ｍｏｌ/Ｌ、ピロリン酸塩では０．１〜１ｍｏｌ/Ｌ、ケイ酸塩では０．０１〜０．１５ｍｏｌ/Ｌ程度の範囲内とすれば良い。 In the production method of the present invention, a method of blending an aqueous iron salt, pyrophosphate and silicate into an aqueous medium may be used, or these may be added and mixed in the form of an aqueous solution in advance. The concentration of each aqueous solution in this case is not limited, but is usually 1 to 2 mol / L for an aqueous iron salt, 0.1 to 1 mol / L for pyrophosphate, and 0.01 to 0.15 mol / L for silicate. It may be within a range of about L.
また、本発明では、必要に応じて水性媒体中にｐＨ調整剤等を適宜配合することもできる。ｐＨ調整剤としては、例えばフッ化水素酸、塩酸、臭化水素酸、ヨウ化水素酸、硫酸、硝酸、リン酸、酢酸、クエン酸、シュウ酸、塩化アルミニウム、水酸化リチウム、水酸化ナトリウム、水酸化カリウム、アンモニア水等を用いることができる。 Moreover, in this invention, a pH adjuster etc. can also be suitably mix | blended with an aqueous medium as needed. Examples of the pH adjuster include hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, citric acid, oxalic acid, aluminum chloride, lithium hydroxide, sodium hydroxide, Potassium hydroxide, aqueous ammonia, etc. can be used.
本発明の製造方法においては、これら所定の割合となるように秤量された出発原料を水性媒体中で混合し、反応させることによって、所望の反応生成物を含む水性スラリーを得ることができる。原料仕込み量として、例えば、（Ｆｅ＋Ｓｉ）／Ｐモル比が０．７０〜０．８５の範囲内で適宜設定すれば良い。 In the production method of the present invention, an aqueous slurry containing a desired reaction product can be obtained by mixing and reacting the starting materials weighed so as to have a predetermined ratio in an aqueous medium. What is necessary is just to set suitably as raw material preparation amount, for example in the range whose (Fe + Si) / P molar ratio is 0.70-0.85.
反応温度は、特に限定的ではなく、例えば５〜５０℃、特に１５〜３５℃の範囲内で適宜設定すれば良い。また、反応雰囲気としては特に限定的ではないが、大気中（大気圧下）とすれば良い。 The reaction temperature is not particularly limited, and may be appropriately set within a range of, for example, 5 to 50 ° C., particularly 15 to 35 ° C. The reaction atmosphere is not particularly limited, but may be in the atmosphere (under atmospheric pressure).
また、本発明の製造方法において、すべての出発原料を添加した後の反応生成物を含む水性スラリーのｐＨは、水酸化鉄等の副生成物の生成を抑制するという点において、２．０〜５．０となるように調整することが好ましい。 In the production method of the present invention, the pH of the aqueous slurry containing the reaction product after adding all starting materials is 2.0 to 2.0 in that it suppresses the production of by-products such as iron hydroxide. It is preferable to adjust so that it may be set to 5.0.
このようにして反応生成物を含む水性スラリーが得られるが、必要に応じてさらに熟成工程を実施することもできる。熟成工程では、出発原料の添加がすべて完了した後の混合液を一定時間撹拌し続けることによって実施することができる。これにより、ピロリン酸第二鉄の生成反応を促進することができる。熟成工程の温度は通常５〜８０℃程度とすれば良く、特に１０〜５０℃とすることが好ましい。また、熟成時間は、出発原料の添加がすべて完了した直後から０．１５〜５時間程度とすれば良く、特に０．１５〜１時間とすることが好ましい。 In this way, an aqueous slurry containing the reaction product is obtained, but an aging step can be further carried out if necessary. The aging step can be carried out by continuing to stir the mixed solution after completion of all the addition of the starting materials for a certain period of time. Thereby, the production | generation reaction of ferric pyrophosphate can be accelerated | stimulated. The temperature of the aging step is usually about 5 to 80 ° C., and preferably 10 to 50 ° C. The aging time may be about 0.15 to 5 hours immediately after all the starting materials have been added, and particularly preferably 0.15 to 1 hour.
なお、熟成工程における上記水性スラリーの固形分濃度は特に限定されないが、通常は１〜２０重量％程度とし、特に３〜１５重量％とすることが好ましい。固形分濃度を調整するために脱水又は水の添加を適宜実施することもできる。 The solid content concentration of the aqueous slurry in the aging step is not particularly limited, but is usually about 1 to 20% by weight, and particularly preferably 3 to 15% by weight. In order to adjust the solid content concentration, dehydration or addition of water may be appropriately performed.
その他の工程
前記の水性スラリーは、通常は反応生成物である本発明粉末が分散した液体であるので、そのまま使用することもできるが、必要に応じて固液分離工程、水洗工程、乾燥工程、粉砕・分級工程等のいずれかの工程に供することもできる。
Other steps The aqueous slurry is usually a liquid in which the powder of the present invention, which is a reaction product, is dispersed, and can be used as it is, but if necessary, a solid-liquid separation step, a water washing step, a drying step, It can also be subjected to any step such as pulverization / classification step.
固液分離工程
固液分離工程では、前記水性スラリーを固液分離することによって固形分を回収する。固液分離方法は、公知の方法に従えば良く、例えばろ過、遠心分離等の各種の脱水方法を採用することができる。
Solid-liquid separation step In the solid-liquid separation step, the solid content is recovered by solid-liquid separation of the aqueous slurry. The solid-liquid separation method may follow a known method, and various dehydration methods such as filtration and centrifugation can be employed.
水洗工程
前記水性スラリーは、固液分離工程の前工程及び／又は後工程として水洗工程を実施することもできる。水洗工程により、反応生成物中に含まれる副生成物、不純物等が含まれる場合、これらを効果的に除去することができる。
Water Washing Process The aqueous slurry can be subjected to a water washing process as a pre-process and / or a post-process of the solid-liquid separation process. When the by-product, impurities, etc. contained in the reaction product are contained in the water washing step, these can be effectively removed.
水洗工程は、固液分離工程と交互に繰り返すことにより好適に実施することができる。従って、水洗工程は、例えば加圧ろ過、減圧濾過、真空ろ過、自然ろ過、遠心ろ過等の一般的なろ過方法により水性スラリーを脱水し、得られた固形分を一般的な水洗設備を用いることにより水で洗浄を行った後、例えばフィルタープレス、遠心分離機等を用いることにより固液分離するという一連の工程を１回又は２回以上実施すれば良い。 The water washing step can be suitably performed by alternately repeating the solid-liquid separation step. Accordingly, in the water washing step, the aqueous slurry is dehydrated by a general filtration method such as pressure filtration, vacuum filtration, vacuum filtration, natural filtration, and centrifugal filtration, and the obtained solid content is used with a common water washing facility. After washing with water, a series of steps of solid-liquid separation using, for example, a filter press, a centrifuge, etc. may be performed once or twice or more.
なお、水洗工程の終点は、例えばフィルタープレス等による場合、水洗ろ液の導電率（２２℃）を１００〜２００μＳ/ｃｍとすれば良く、さらに好ましくは１００〜１５０μＳ/ｃｍとすれば良い。 The end point of the washing step may be, for example, a filter press or the like, and the conductivity (22 ° C.) of the washing filtrate may be 100 to 200 μS / cm, and more preferably 100 to 150 μS / cm.
乾燥工程
固液分離後又は水洗工程後の固形分は、必要に応じて乾燥工程に供することができる。乾燥温度は２０〜４００℃の範囲内で適宜設定すれば良いが、特に８０〜１２０℃で行うのが好ましい。乾燥時間は、乾燥温度により適時設定することができるが、強熱減量で３０％以下、特に好ましくは２０％以下になるように乾燥時間を設定することが好ましい。
Drying Step The solid content after the solid-liquid separation or the water washing step can be subjected to a drying step as necessary. The drying temperature may be appropriately set within the range of 20 to 400 ° C, but it is particularly preferably 80 to 120 ° C. The drying time can be set as appropriate depending on the drying temperature, but it is preferable to set the drying time so that the loss on ignition is 30% or less, particularly preferably 20% or less.
乾燥方法としては限定的でなく、例えば温風乾燥、赤外線乾燥、ホットプレート乾燥、真空乾燥、吸引乾燥と蒸気乾燥、温純水引上げ乾燥・マランゴニ乾燥・エアナイフ水切り・スピン乾燥、ロール乾燥が「液きり」等の一般的な方法を用いることにより乾燥することができ、例えば、静置式の棚段・箱形乾燥機、スプレードライヤー、バンド乾燥機、真空乾燥機、凍結乾燥機、マイクロ波乾燥機、ドラムドライヤー、流動乾燥機等の一般的な乾燥設備を用いることができる。 The drying method is not limited. For example, warm air drying, infrared drying, hot plate drying, vacuum drying, suction drying and steam drying, hot pure water pulling drying, Marangoni drying, air knife draining, spin drying, and roll drying are “liquid”. Can be dried by using a general method such as a stationary shelf / box dryer, spray dryer, band dryer, vacuum dryer, freeze dryer, microwave dryer, drum General drying equipment such as a dryer and a fluid dryer can be used.
粉砕工程
生成した本発明粉末は、必要に応じて粉砕することができる。粉砕方法としては、例えば乾式粉砕、湿式粉砕、凍結粉砕等の一般的な方法を用いることができる。粉砕装置としても、例えばジェットミル、フェザーミル、ハンマーミル、パルペライザー、ボールミル、ビーズミル等一般的な設備で粉砕を行うことができる。粉砕の程度は、粉砕後の平均粒子径が１〜１００μｍ程度、特に１〜５０μｍとすることが好ましい。なお、所望の粒子径に調整するために、粉砕物を適宜分級することもできる。
Pulverization step The produced powder of the present invention can be pulverized as necessary. As a pulverization method, general methods such as dry pulverization, wet pulverization, and freeze pulverization can be used. As the pulverization apparatus, for example, pulverization can be performed using general equipment such as a jet mill, a feather mill, a hammer mill, a pulverizer, a ball mill, and a bead mill. The degree of pulverization is preferably such that the average particle diameter after pulverization is about 1 to 100 μm, particularly 1 to 50 μm. In addition, in order to adjust to a desired particle diameter, a pulverized material can also be classified suitably.
分散工程
前記１．で説明したように、本発明粉末を液体の形態（分散体）で使用する場合は、固液分離工程、水洗工程、乾燥工程、粉砕工程等のいずれかの工程で得られた本発明粉末又はその水性スラリーを用いて、その分散体を調製すれば良い。分散体の調製に際しては、例えば撹拌機、乳化機、湿式粉砕機、遊星ボールミル等の公知の装置を用いることができる。また、分散性を高めるための分散剤のほか、各種の添加剤を適宜配合しても良い。
Dispersion step As described above, when the powder of the present invention is used in a liquid form (dispersion), the powder of the present invention obtained in any one of the solid-liquid separation process, the water washing process, the drying process, the pulverization process, etc. The dispersion may be prepared using the aqueous slurry. In preparing the dispersion, known devices such as a stirrer, an emulsifier, a wet pulverizer, and a planetary ball mill can be used. In addition to a dispersant for enhancing dispersibility, various additives may be appropriately blended.
以下に実施例及び比較例を示し、本発明の特徴をより具体的に説明する。ただし、本発明の範囲は、実施例に限定されない。なお、実施例中に記載の「％」「ｐｐｍ」はそれぞれ「重量％」「重量ｐｐｍ」を意味する。 The features of the present invention will be described more specifically with reference to the following examples and comparative examples. However, the scope of the present invention is not limited to the examples. In the examples, “%” and “ppm” mean “wt%” and “wt ppm”, respectively.
実施例１
１Ｌの容器に２４０ｍＬの水を量りとり、０．９１ｍｏｌ/Ｌの硫酸第二鉄水溶液、０．５５ｍｏｌ/Ｌのピロリン酸ナトリウム水溶液及び０．１１ｍｏｌ/Ｌのメタケイ酸ナトリウム水溶液を原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．７７になるように前記水に添加して４００ｒｐｍで撹拌した。添加終了後、室温で１０分間攪拌して熟成を行い、反応生成物を含む水性スラリーを得た。熟成終了後の最終ｐＨは３．４であった。熟成後、この水性スラリーをろ過して脱水し、水洗した。得られた反応生成物を乾燥器に入れ、１０５℃にて１６時間乾燥し、乾燥品を卓上ミルにて粉砕することにより試料１を得た。
Example 1
240 mL of water is weighed into a 1 L container, and 0.91 mol / L ferric sulfate aqueous solution, 0.55 mol / L sodium pyrophosphate aqueous solution and 0.11 mol / L sodium metasilicate aqueous solution are charged as raw materials in a molar ratio ( Fe + Si) / P was added to the water so as to be 0.77 and stirred at 400 rpm. After completion of the addition, the mixture was aged by stirring for 10 minutes at room temperature to obtain an aqueous slurry containing the reaction product. The final pH after aging was 3.4. After aging, this aqueous slurry was filtered to dehydrate and washed with water. The obtained reaction product was put into a drier, dried at 105 ° C. for 16 hours, and the dried product was pulverized with a table mill to obtain Sample 1.
実施例２
メタケイ酸ナトリウム水溶液を０．０６ｍｏＬ／Ｌにして、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．７２になるように調整したほかは、実施例１と同様にして試料２を得た。熟成終了後のｐＨは２．５であった。
Example 2
Sample 2 was obtained in the same manner as in Example 1 except that the sodium metasilicate aqueous solution was adjusted to 0.06 mol / L and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.72. The pH after aging was 2.5.
実施例３
メタケイ酸ナトリウム水溶液を０．１７ｍｏＬ／Ｌにして、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．８２になるように調整したほかは、実施例１と同様にして試料３を得た。熟成終了後のｐＨは４．２であった。
Example 3
Sample 3 was obtained in the same manner as in Example 1, except that the sodium metasilicate aqueous solution was adjusted to 0.17 mol / L and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.82. The pH after completion of aging was 4.2.
実施例４
塩化第二鉄水溶液を１．８１ｍｏＬ／Ｌ、及びメタケイ酸ナトリウム水溶液を０．１７ｍｏＬ／Ｌにして、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．８２になるように調整したほかは、実施例１と同様にして試料４を得た。熟成終了後のｐＨは４．１であった。
Example 4
Except that the ferric chloride aqueous solution was 1.81 mol / L and the sodium metasilicate aqueous solution was 0.17 mol / L, and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.82, the examples Sample 4 was obtained in the same manner as in Example 1. The pH after completion of aging was 4.1.
実施例５
塩化第二鉄水溶液を１．８１ｍｏＬ／Ｌ、及びメタケイ酸ナトリウム水溶液を０．１５ｍｏＬ／Ｌにとし、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．８２になるように調整したほかは、実施例１と同様にして試料５を得た。熟成終了後のｐＨは３．６であった。
Example 5
Except that the ferric chloride aqueous solution was adjusted to 1.81 mol / L and the sodium metasilicate aqueous solution to 0.15 mol / L, and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.82, the examples Sample 5 was obtained in the same manner as in Example 1. The pH after completion of aging was 3.6.
実施例６
塩化第二鉄水溶液を１．３６ｍｏＬ／Ｌ、硫酸第二鉄水溶液を０．２３ｍｏＬ／Ｌ、及びメタケイ酸ナトリウム水溶液を０．１７ｍｏＬ／Ｌにして、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．８２になるように調整したほかは、実施例１と同様にして試料６を得た。熟成終了後のｐＨは４．０であった。
Example 6
The ferric chloride aqueous solution was 1.36 mol / L, the ferric sulfate aqueous solution was 0.23 mol / L, and the sodium metasilicate aqueous solution was 0.17 mol / L, and the raw material charge molar ratio (Fe + Si) / P was 0.00. Sample 6 was obtained in the same manner as in Example 1 except that the amount was adjusted to 82. The pH after aging was 4.0.
比較例１
メタケイ酸ナトリウム水溶液は添加せず、塩化第二鉄溶液を１．８１ｍｏｌ/Ｌにして、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．６７になるように調整したほかは、実施例１と同様にして試料７を得た。熟成終了後のｐＨは１．７であった。
Comparative Example 1
The same as in Example 1 except that the sodium metasilicate aqueous solution was not added, the ferric chloride solution was adjusted to 1.81 mol / L, and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.67. Thus, sample 7 was obtained. The pH after completion of aging was 1.7.
比較例２
メタケイ酸ナトリウム水溶液は添加せず、原料仕込みモル比（Ｆｅ＋Ｓｉ）／Ｐが０．６７になるように調整したほかは、実施例１と同様にして試料８を得た。熟成終了後のｐＨは２．２であった。
Comparative Example 2
Sample 8 was obtained in the same manner as in Example 1 except that the sodium metasilicate aqueous solution was not added and the raw material charge molar ratio (Fe + Si) / P was adjusted to 0.67. The pH after aging was 2.2.
比較例３〜５
比較例３として、富田製薬株式会社製「食品添加物 ピロリン酸第二鉄」（Ｌｏｔ Ｎｏ.：Ｌ２０８１６）（試料９）を用いた。比較例４として、ポールローマン社製「ピロリン酸第二鉄」（試料１０）を用いた。比較例５として、米山化学工業株式会社製「ピロリン酸第二鉄」（Ｌｏｔ Ｎｏ.：４０８０４４）（試料１１）を用いた。
Comparative Examples 3-5
As Comparative Example 3, “Food additive ferric pyrophosphate” (Lot No .: L20816) (Sample 9) manufactured by Tomita Pharmaceutical Co., Ltd. was used. As Comparative Example 4, “Ferric pyrophosphate” (sample 10) manufactured by Paul Roman was used. As Comparative Example 5, “Ferric pyrophosphate” (Lot No .: 408044) (Sample 11) manufactured by Yoneyama Chemical Co., Ltd. was used.
試験例１
実施例及び比較例の各試料について、モード径（最頻細孔直径）、細孔直径１００〜２１０ｎｍの細孔容積、全細孔容積、ＢＥＴ比表面積、外部表面積、平均粒子径、ピロリン酸第二鉄含量、強熱減量をそれぞれ測定した。その結果を表１〜２及び図１〜１１に示す。なお、各測定は、以下に記載する方法に従って実施した。
Test example 1
For each sample of Example and Comparative Example, mode diameter (moderate pore diameter), pore volume of 100-210 nm pore diameter, total pore volume, BET specific surface area, external surface area, average particle diameter, pyrophosphate number The ferric content and loss on ignition were measured respectively. The results are shown in Tables 1-2 and FIGS. Each measurement was performed according to the method described below.
（１）モード径、細孔直径１００〜２１０ｎｍの細孔容積、全細孔容積
水銀ポロシメータ（Ｑｕａｎｔａｃｈｒｏｍｅ社製「ＰｏｒｅＭａｓｔｅｒ ６０ＧＴ」）を用いて以下の条件で測定を行った。
測定及び解析：試料０．０５ｇを正確に量り、測定セルに封入し、水銀圧入下で水銀の吸着等温線を求め、細孔直径（モード径）のピーク位置、細孔直径１００ｎｍから２１０ｎｍの細孔容積、全細孔容積を算出した。
(1) Mode diameter, pore volume with a pore diameter of 100 to 210 nm, total pore volume A mercury porosimeter (“PoreMaster 60GT” manufactured by Quantachrome) was used under the following conditions.
Measurement and analysis: Accurately weigh 0.05 g of sample, enclose it in a measurement cell, obtain mercury adsorption isotherm under mercury intrusion, peak position of pore diameter (mode diameter), fine pore diameter from 100 nm to 210 nm The pore volume and total pore volume were calculated.
（２）全細孔容積中に占める細孔直径１００〜２１０ｎｍの細孔容積の割合
試験例１の（１）で算出した細孔直径１００から２１０ｎｍの細孔容積ａ（ｃｃ/ｇ）と全細孔容積ｂ（ｃｃ/ｇ）により、下記の式にて全細孔容積中に占める細孔直径１００〜２１０ｎｍの細孔容積の割合（占有率）を算出した。
占有率（％）＝ａ／ｂ×１００
(2) Proportion of pore volume having a pore diameter of 100 to 210 nm in the total pore volume Pore volume a (cc / g) having a pore diameter of 100 to 210 nm calculated in (1) of Test Example 1 and the total volume From the pore volume b (cc / g), the ratio (occupancy) of the pore volume having a pore diameter of 100 to 210 nm in the total pore volume was calculated by the following formula.
Occupancy rate (%) = a / b × 100
（３）ＢＥＴ比表面積
高速比表面積細孔分布測定装置（Ｑｕａｎｔａｃｈｒｏｍｅ社製「ＮＯＶＡ−４２００ｅ」）にて以下の操作条件で測定を行った。
前処理：試料０．８ｇを正確に量り、吸着管に封入し、１０５℃で１時間脱気した。
測定及び解析：液体窒素ガス温度下で窒素ガスの吸着等温線を求め、その吸着等温線を用いて多点ＢＥＴ法により比表面積を算出した。
(3) BET specific surface area It measured on the following operating conditions with the high-speed specific surface area pore-distribution measuring apparatus ("NOVA-4200e" by Quantachrome).
Pretreatment: 0.8 g of sample was accurately weighed, sealed in an adsorption tube, and degassed at 105 ° C. for 1 hour.
Measurement and analysis: An adsorption isotherm of nitrogen gas was determined under liquid nitrogen gas temperature, and a specific surface area was calculated by the multipoint BET method using the adsorption isotherm.
（４）外部表面積
高速比表面積細孔分布測定装置（Ｑｕａｎｔａｃｈｒｏｍｅ社製「ＮＯＶＡ−４２００ｅ」）にて以下の操作条件で測定を行った。
前処理：試料０．８ｇを正確に量り、吸着管に封入し、１０５℃にて３時間脱気した。
測定及び解析：液体窒素ガス温度下で窒素ガスの吸着等温線を求め、その吸着等温線を用いてＶ−ｔプロット法にて外部表面積を算出した。
(4) External surface area Measurement was performed under the following operating conditions using a high-speed specific surface area pore distribution measuring apparatus (“NOVA-4200e” manufactured by Quantachrome).
Pretreatment: 0.8 g of sample was accurately weighed, sealed in an adsorption tube, and deaerated at 105 ° C. for 3 hours.
Measurement and analysis: An adsorption isotherm of nitrogen gas was determined under liquid nitrogen gas temperature, and an external surface area was calculated by the Vt plot method using the adsorption isotherm.
（５）平均粒子径
試料を３分間超音波攪拌（超音波出力４０Ｗ）した後に水中に分散させてレーザー回折法により水溶媒中にて測定を行った。測定装置としてＭｉｃｒｏｔｒａｃ社製「ＭＩＣＲＯＴＲＡＣ ＭＴ３３００ＥＸII」を用いた。
(5) Average particle diameter The sample was ultrasonically stirred for 3 minutes (ultrasonic output 40 W), then dispersed in water and measured in a water solvent by laser diffraction. As a measuring apparatus, “MICROTRAC MT3300EXII” manufactured by Microtrac was used.
（６）ピロリン酸第二鉄含量
試料を強熱し、直ちにその約０．３ｇを精密に量り、塩酸（１→２）２０ｍＬを加えて溶かし、水２０ｍＬで共栓フラスコに移した。次に、ヨウ化カリウム３ｇを加え、直ちに密栓して暗所に１５分間放置した後、水１００ｍＬを加え、デンプン試液を加えて遊離したヨウ素を０．１ｍｏｌ/Ｌチオ硫酸ナトリウム溶液で滴定した（ｃ ｍＬ）。
別に、共栓フラスコに塩酸（１→２）２０ｍＬと水２０ｍＬを入れて、ヨウ化カリウム３ｇを加え、直ちに密栓して暗所に１５分間放置した後、水１００ｍＬを加え、デンプン試液を加えて遊離したヨウ素を０．１ｍｏｌ/Ｌチオ硫酸ナトリウム溶液で滴定し、これを空試験とした。滴定量から次式を用いて、ピロリン酸第二鉄含有粉末１ｇ中のピロリン酸第二鉄の含量を算出した（ｄ ｍＬ）。
ピロリン酸第二鉄含量（％）＝（（ｃ−ｄ）×０．０１８６３／採取量（ｇ））×１００
(6) Ferric pyrophosphate content The sample was ignited, and about 0.3 g of the sample was immediately measured accurately, dissolved by adding 20 mL of hydrochloric acid (1 → 2), and transferred to a stoppered flask with 20 mL of water. Next, 3 g of potassium iodide was added, immediately sealed and allowed to stand in the dark for 15 minutes, and then 100 mL of water was added, and the free iodine was titrated with a 0.1 mol / L sodium thiosulfate solution by adding starch test solution ( c mL).
Separately, 20 mL of hydrochloric acid (1 → 2) and 20 mL of water were added to a stoppered flask, 3 g of potassium iodide was added, immediately sealed and allowed to stand in the dark for 15 minutes, then 100 mL of water was added, and starch test solution was added. The liberated iodine was titrated with a 0.1 mol / L sodium thiosulfate solution, and this was used as a blank test. The content of ferric pyrophosphate in 1 g of ferric pyrophosphate-containing powder was calculated from the titration amount using the following formula (d mL).
Ferric pyrophosphate content (%) = ((cd) × 0.01863 / collected amount (g)) × 100
（７）強熱減量
試料１ｇを正確に量り取り、５００℃で１時間強熱させ、強熱前後の重量の差から強熱減量を算出した。
(7) Ignition loss The sample 1 g was accurately weighed and ignited at 500 ° C. for 1 hour, and the ignition loss was calculated from the difference in weight before and after ignition.
試験例２
実施例１〜６及び比較例１〜５で得られた試料について鉄の溶出性を評価した。溶出試験は、表３に示す試験条件に従って実施した。なお、各測定は、以下に記載する方法に従って実施した。
Test example 2
The samples obtained in Examples 1 to 6 and Comparative Examples 1 to 5 were evaluated for iron elution. The dissolution test was performed according to the test conditions shown in Table 3. Each measurement was performed according to the method described below.
＜試料溶液の調製＞
溶出試験採取液４ｍＬ、希硝酸１ｍＬ、及びイットリウム標準液（１００ｐｐｍ）１ｍＬをメスフラスコに正確に量りとり、超純水で正確に２０ｍＬとし、これを試料溶液とした。
＜標準溶液の調製＞
鉄標準液（１０ｐｐｍ）：
原子吸光分析用鉄標準液（１００ｐｐｍ）５ｍＬ、及び希硝酸１ｍＬをメスフラスコに正確に量りとり、超純水を加えて５０ｍＬとした。
鉄標準液（１ｐｐｍ）：
調製した鉄標準液（１０ｐｐｍ）５ｍＬ、及び希硝酸１ｍＬをメスフラスコに正確に量りとり、超純水を加えて５０ｍＬとした。
標準溶液（ａ）（ブランク）：
イットリウム標準液（１００ｐｐｍ）１ｍＬ、及び希硝酸１ｍＬをメスフラスコに正確に量りとり、超純水を加えて２０ｍＬとした。
標準溶液（ｂ）（Ｆｅ：０．１ｐｐｍ）：
イットリウム標準液（１００ｐｐｍ）１ｍＬ、希硝酸１ｍＬ、及び鉄標準液（１ｐｐｍ）２ｍＬをメスフラスコに正確に量りとり、超純水を加えて２０ｍＬとした。
標準溶液（ｃ）（Ｆｅ：０．５ｐｐｍ）：
標準液として、鉄標準液（１０ｐｐｍ）１ｍＬを正確に量りとったほかは、標準溶液（ｂ）と同様にして調製した。
標準溶液（ｄ）（Ｆｅ：１ｐｐｍ）：
標準液として、鉄標準液（１０ｐｐｍ）２ｍＬを正確に量りとったほかは、標準溶液（ｂ）と同様にして調製した。
標準溶液（ｅ）（Ｆｅ：５ｐｐｍ）：
標準液として、原子吸光分析用鉄標準液（１００ｐｐｍ）１ｍＬを正確に量りとったほかは、標準溶液（ｂ）と同様にして調製した。
標準溶液（ｆ）（Ｆｅ：１５ｐｐｍ）：
標準液として、原子吸光分析用鉄標準液（１００ｐｐｍ）３ｍＬを正確に量りとったほかは、標準溶液（ｂ）と同様にして調製した。
＜測定方法＞
誘導結合プラズマ発光分光分析法（ＩＣＰ）検量線法
検出波長：２５９．９４１ｎｍ
標準溶液（ａ）、（ｂ）、（ｃ）、（ｄ）、（ｅ）、（ｆ）の順に強度を測定し、検量線を作成した。次に、試料溶液の強度を測定し、得られた強度から測定液中の鉄濃度に換算し、溶出率を次式１で算出した。表４に溶出試験液第１液（ｐＨ １．２）の結果、及び薄めたＭｃＩｌｖａｉｎｅ（ｐＨ ３．０）の結果を示す。
溶出率（％）＝（（ｅ×５）／（試験仕込量（ｍｇ）×（ピロリン酸第二鉄含量／１００）×４×５５．８５／７４５．２２））×１００ （式１）
（但し、ｃ＝測定液中の鉄濃度 （ｐｐｍ））
ＩＣＰ： ＳＰＥＣＴＲＯ ＡＲＣＯＳ（エスアイアイ・ナノテクノロジー株式会社）
原子吸光分析用鉄標準液：和光純薬工業株式会社
<Preparation of sample solution>
4 mL of the elution test collection solution, 1 mL of dilute nitric acid, and 1 mL of yttrium standard solution (100 ppm) were accurately weighed into a volumetric flask and made exactly 20 mL with ultrapure water, which was used as a sample solution.
<Preparation of standard solution>
Iron standard solution (10 ppm):
5 mL of an iron standard solution for atomic absorption analysis (100 ppm) and 1 mL of dilute nitric acid were accurately weighed into a measuring flask, and ultrapure water was added to make 50 mL.
Iron standard solution (1 ppm):
The prepared iron standard solution (10 ppm) 5 mL and dilute nitric acid 1 mL were accurately weighed into a volumetric flask, and ultrapure water was added to make 50 mL.
Standard solution (a) (blank):
1 mL of yttrium standard solution (100 ppm) and 1 mL of dilute nitric acid were accurately weighed into a volumetric flask, and ultrapure water was added to make 20 mL.
Standard solution (b) (Fe: 0.1 ppm):
1 mL of yttrium standard solution (100 ppm), 1 mL of dilute nitric acid, and 2 mL of iron standard solution (1 ppm) were accurately weighed into a volumetric flask, and ultrapure water was added to make 20 mL.
Standard solution (c) (Fe: 0.5 ppm):
A standard solution was prepared in the same manner as the standard solution (b) except that 1 mL of an iron standard solution (10 ppm) was accurately weighed.
Standard solution (d) (Fe: 1 ppm):
A standard solution was prepared in the same manner as the standard solution (b) except that 2 mL of an iron standard solution (10 ppm) was accurately weighed.
Standard solution (e) (Fe: 5 ppm):
A standard solution was prepared in the same manner as the standard solution (b) except that 1 mL of an iron standard solution for atomic absorption analysis (100 ppm) was accurately weighed.
Standard solution (f) (Fe: 15 ppm):
A standard solution was prepared in the same manner as the standard solution (b) except that 3 mL of an iron standard solution for atomic absorption analysis (100 ppm) was accurately weighed.
<Measurement method>
Inductively coupled plasma optical emission spectrometry (ICP) calibration curve method Detection wavelength: 259.941 nm
Intensities were measured in the order of standard solutions (a), (b), (c), (d), (e), and (f) to prepare a calibration curve. Next, the strength of the sample solution was measured, and the obtained strength was converted to the iron concentration in the measurement solution, and the elution rate was calculated by the following formula 1. Table 4 shows the results of the first dissolution test solution (pH 1.2) and the diluted McIlvine (pH 3.0).
Dissolution rate (%) = ((e × 5) / (test charge (mg) × (ferric pyrophosphate content / 100) × 4 × 55.85 / 745.22)) × 100 (Formula 1)
(However, c = iron concentration in the measuring solution (ppm))
ICP: SPECTRO ARCOS (SII Nanotechnology Inc.)
Iron standard solution for atomic absorption analysis: Wako Pure Chemical Industries, Ltd.
鉄はイオンの状態で十二指腸から吸収されること、及び鉄イオンが胃で溶出すると吸収量の低下を引き起こすことが想定される。そこで、本発明では、鉄分吸収率（％）を次式２で規定し、その吸収率を確認した。その結果を表４に示す。
鉄分吸収率（％）＝（１００−ｐＨ１．２での６０分後の溶出率）×ｐＨ３．０での６０分後の溶出率／１００ （式２）
It is assumed that iron is absorbed from the duodenum in the form of ions and that the amount of iron ion that is absorbed in the stomach causes a decrease in absorption. Therefore, in the present invention, the iron absorption rate (%) is defined by the following formula 2, and the absorption rate was confirmed. The results are shown in Table 4.
Iron absorption rate (%) = (elution rate after 60 minutes at 100-pH 1.2) × elution rate after 60 minutes at pH 3.0 / 100 (formula 2)
試験例３
試料１及び試料９を用い、鉄の吸収性を動物試験により評価した。その結果を表５〜６に示す。評価方法は、以下に示す通りである。
Test example 3
Using Sample 1 and Sample 9, the absorbability of iron was evaluated by an animal test. The results are shown in Tables 5-6. The evaluation method is as shown below.
４週齢のＳＤ系雄ラット１群５匹に低Ｆｅ飼料（ＡＩＮ‐９３Ｇベース）粉末飼料（日本クレア株式会社製）を２週間摂食させ、鉄欠乏状態にした。低Ｆｅ飼料（ＡＩＮ‐９３Ｇベース）粉末飼料摂食２週間後、麻酔下にて鎖骨下静脈から採血を行い、血清分離を行った後、血清中における鉄濃度（血清鉄）、総鉄結合能（ＴＩＢＣ）、及び末梢血の指標として使用される鉄飽和率（ＴＳＡＴ）をそれぞれ測定した。また、血液中のヘモグロビン濃度（Ｈｂ）も測定したところ、血清鉄３０．８μｇ/ｄＬ、ＴＩＢＣ７６６．６μｇ/ｄＬ、Ｈｂ８．８ｇ/ｄＬ、ＴＳＡＴ４．０％であり、鉄欠乏ラットであることを確認した。その後、低Ｆｅ飼料（ＡＩＮ‐９３Ｇベース）粉末飼料に試料１及び試料９をラット１匹あたり３００ｍｇ鉄/ｋｇ相当量になるように混ぜ、この混餌飼料を７日間自由摂食させ、自由摂食後、３日と７日経過後に麻酔下にて鎖骨下静脈から採血を行い、血清分離を行った後、血清中における血清鉄、ＴＩＢＣを測定した。また、血液中のＨｂも測定した。 A group of five 4-week-old SD male rats were fed a low-Fe diet (AIN-93G base) powdered diet (manufactured by CLEA Japan, Inc.) for 2 weeks to make them iron-deficient. Two weeks after feeding a low-Fe diet (AIN-93G based) powdered diet, blood was collected from the subclavian vein under anesthesia, serum was separated, serum iron concentration (serum iron), total iron binding capacity (TIBC) and iron saturation (TSAT) used as an indicator of peripheral blood were measured respectively. In addition, blood hemoglobin concentration (Hb) was also measured, and serum iron was 30.8 μg / dL, TIBC766.6 μg / dL, Hb 8.8 g / dL, TSAT 4.0%, and it was confirmed that the rats were iron-deficient rats. did. After that, sample 1 and sample 9 were mixed with low-Fe feed (AIN-93G base) powdered feed so that the equivalent of 300 mg iron / kg per rat was allowed to eat freely for 7 days. After 3 days and 7 days, blood was collected from the subclavian vein under anesthesia, and after serum separation, serum iron and TIBC in the serum were measured. Moreover, Hb in the blood was also measured.
表５〜６の結果からも明らかなように、鉄欠乏状態に比べて、各ピロリン酸第二鉄含有粉末を投与することにより、鉄欠乏が回復していることがわかる。その中でも、３日目のＨｂに関し、試料１は試料９に比べると高くなっていることがわかる。さらに、ＴＳＡＴを比較すると、試料９は投与日数が経過してもＴＳＡＴの減少率が低いものの、試料１はその減少率が高い。つまり、試料１は、試料９に比して、鉄の吸収速度が速く、吸収された鉄が造血系の合成に使用され、定常状態に達する期間が短く、貧血状態からの回復時間が短縮されることが考えられる。これより、本発明品は、鉄の吸収性が改善されたピロリン酸第二鉄組成物であることがわかる。 As is clear from the results in Tables 5 to 6, it can be seen that iron deficiency is recovered by administering each ferric pyrophosphate-containing powder as compared with the iron deficient state. Among them, it can be seen that Sample 1 is higher than Sample 9 with respect to Hb on the third day. Further, comparing TSAT, Sample 9 has a low TSAT reduction rate even after the number of administration days, but Sample 1 has a high reduction rate. That is, the sample 1 has a faster iron absorption rate than the sample 9, and the absorbed iron is used for the synthesis of the hematopoietic system, the period for reaching the steady state is short, and the recovery time from the anemia state is shortened. It can be considered. From this, it can be seen that the product of the present invention is a ferric pyrophosphate composition with improved iron absorption.
本発明粉末では、高い鉄分吸収性が得られるので、各種製剤の製剤化の簡便化、使用量の低減及び鉄欠乏症患者への投与量の低減が可能となる。さらには、本発明粉末を用いることによって、嗜好性及び胃腸障害の問題が緩和ないしは回避された食品、医薬品、化粧品等を提供することができる。 In the powder of the present invention, high iron absorption is obtained, so that it is possible to simplify the formulation of various preparations, reduce the amount used, and reduce the dose to patients with iron deficiency. Furthermore, by using the powder of the present invention, it is possible to provide foods, pharmaceuticals, cosmetics and the like in which the problems of palatability and gastrointestinal disorders are alleviated or avoided.
Claims (6)
（１）モード径（最頻細孔直径）が３００ｎｍ以下であり、
（２）全細孔容積中に占める細孔直径１００〜２１０ｎｍの細孔容積の割合が６０〜８０％である、
ことを特徴とするピロリン酸第二鉄含有粉末。 A powder comprising ferric pyrophosphate,
(1) The mode diameter (moderate pore diameter) is 300 nm or less,
(2) The ratio of the pore volume having a pore diameter of 100 to 210 nm in the total pore volume is 60 to 80%.
A ferric pyrophosphate-containing powder characterized by that.
水性溶媒中に水溶性鉄塩、ピロリン酸塩及びケイ酸塩を添加及び混合することにより、これらの反応生成物を含む水性スラリーを調製する工程
を含むことを特徴とするピロリン酸第二鉄含有粉末の製造方法。 A method for producing a ferric pyrophosphate-containing powder comprising ferric pyrophosphate and a silicon component, comprising:
Ferric pyrophosphate containing, comprising the step of preparing an aqueous slurry containing these reaction products by adding and mixing water soluble iron salts, pyrophosphates and silicates in an aqueous solvent Powder manufacturing method.
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