CN1035241A - 稳定的抗坏血酸组合物 - Google Patents
稳定的抗坏血酸组合物 Download PDFInfo
- Publication number
- CN1035241A CN1035241A CN88108526.XA CN88108526A CN1035241A CN 1035241 A CN1035241 A CN 1035241A CN 88108526 A CN88108526 A CN 88108526A CN 1035241 A CN1035241 A CN 1035241A
- Authority
- CN
- China
- Prior art keywords
- ascorbic acid
- metal compound
- powder
- sodium
- alkali metal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims abstract description 42
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 18
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 18
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 18
- 150000001341 alkaline earth metal compounds Chemical class 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 21
- 238000002425 crystallisation Methods 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- 150000001339 alkali metal compounds Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 4
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 2
- 125000002587 enol group Chemical group 0.000 claims 1
- 239000000654 additive Substances 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract description 2
- 239000000843 powder Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 15
- 229910000765 intermetallic Inorganic materials 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- -1 organic acid alkali metal salt Chemical class 0.000 description 7
- KIDXYAWWICJAFK-UHFFFAOYSA-N O.[Na].OC Chemical compound O.[Na].OC KIDXYAWWICJAFK-UHFFFAOYSA-N 0.000 description 5
- 150000001447 alkali salts Chemical class 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 229940047036 calcium ascorbate Drugs 0.000 description 3
- 239000011692 calcium ascorbate Substances 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 150000002736 metal compounds Chemical class 0.000 description 3
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 3
- 229960005055 sodium ascorbate Drugs 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 235000011572 Pyrus ussuriensis Nutrition 0.000 description 2
- 244000173166 Pyrus ussuriensis Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 235000010376 calcium ascorbate Nutrition 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FXXMDJFRMDVSCF-RXSVEWSESA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;hydrate Chemical compound O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O FXXMDJFRMDVSCF-RXSVEWSESA-N 0.000 description 1
- RYDFXSRVZBYYJV-TYYBGVCCSA-N (e)-but-2-enedioic acid;sodium Chemical compound [Na].OC(=O)\C=C\C(O)=O RYDFXSRVZBYYJV-TYYBGVCCSA-N 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- NTJPVVKEZMOHNU-UHFFFAOYSA-N 6-(oxan-4-yl)-1h-indazole Chemical compound C1COCCC1C1=CC=C(C=NN2)C2=C1 NTJPVVKEZMOHNU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- YERHKTRISAQYDH-UHFFFAOYSA-M CO.C(C1=CC=CC=C1)(=O)[O-].[Na+] Chemical compound CO.C(C1=CC=CC=C1)(=O)[O-].[Na+] YERHKTRISAQYDH-UHFFFAOYSA-M 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- FYBLWUVZITWWEZ-UHFFFAOYSA-N Cl.[Ca] Chemical compound Cl.[Ca] FYBLWUVZITWWEZ-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 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 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 229960004256 calcium citrate Drugs 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000010331 calcium propionate Nutrition 0.000 description 1
- 239000004330 calcium propionate Substances 0.000 description 1
- 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 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 229910002090 carbon oxide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- IDAGXRIGDWCIET-SDFKWCIISA-L disodium;(2s,3s,4s,5r)-2,3,4,5-tetrahydroxyhexanedioate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IDAGXRIGDWCIET-SDFKWCIISA-L 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 235000016337 monopotassium tartrate Nutrition 0.000 description 1
- 235000019321 monosodium tartrate Nutrition 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229940086065 potassium hydrogentartrate Drugs 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000003918 potentiometric titration Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940119126 sodium bitartrate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 description 1
- 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 1
- 239000004320 sodium erythorbate Substances 0.000 description 1
- 235000010352 sodium erythorbate Nutrition 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 229940068459 sodium pantothenate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 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 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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Abstract
含有一种微量碱金属化合物或碱土金属化合物的抗坏血酸的组合物在变色方面是非常稳定的，甚至在长时间贮存后也不会变黄。
并且该组合物可以通过添加仅仅是微量的添加剂而容易地获得。
Description
本发明涉及稳定的抗坏血酸组合物，该组合物不随时间而发生诸如变色这样的变化，还介绍了该粉末的生产方法。
目前采用的含有抗坏血酸或其盐的配方，为防止变质，含有各种稳定剂。例如，为了含有抗坏血酸的片剂的稳定性添加了山梨糖或乳糖（USP3，446，894），为了抗坏血酸钙的水溶液的稳定性而添加了半脱氨酸或硫羟乳酸（USP2，442，461）。
研磨结晶抗坏血酸而获得的抗坏血酸粉末，有一个稳定性的问题，因为在通常大气中它随着时间发生变化，并且比原晶体更容易变黄。为解决这些问题，要在密封的惰性气体下贮存这些粉末，还曾尝试过在脱水剂存在下贮存。
作为发明人对抗坏血酸组合物稳定性的研究结果，发明人已发现，在只要有微量碱金属化合物或碱土金属化合物存在时，制备很稳定的抗坏血酸合成物就足够了。
即本发明介绍了（1）含有其量约为100ppm或更少的碱金属化合物或碱土金属化合物的稳定的抗坏血酸组合物。（2）生产稳定的抗坏血酸粉末的方法，该方法包括在以其量约为100ppm或更少的碱金属化合物或碱土金属化合物的存在下，研磨抗坏血酸晶体。
可以用本发明的组合物制成各种类型制品。如粉末剂，颗粒剂，微粒剂，片剂等等。该组合物对制备抗坏血酸粉末是特别有用的。
用于本发明的碱金属化合物和碱土金属化合物包括有机酸的碱金属盐和碱土金属盐，无机酸的碱金属盐和碱土金属盐，及碱金属和碱土金属的氢氧化物。组成这些盐和氢氧化物的碱金属包括钾和钠，以及这样的碱土金属包括钙和镁。
有机酸的碱金属盐和碱土金属盐包括芳族碳酸盐，例如苯甲酸钠;饱和与不饱和的脂肪族碳酸盐，例如乙酸钠，琥珀酸钠，山梨糖酸钾，山梨糖酸钠，富马酸钠，丙酸钠及丙酸钙，氧化碳酸盐类，例如柠檬酸钠，柠檬酸钙，葡糖酸钙，酒石酸氢钾，酒石酸氢钠，乳酸钠，乳酸钙、苹果酸钠，泛酸钙及泛酸钠，氨基酸盐例如L-谷氨酸钠，烯醇酸类例如异抗坏血酸钠，L-抗坏血酸钠及L-抗坏血酸钙。
无机酸的碱金属盐和碱土金属盐包括盐酸盐，硫酸盐，硝酸盐，碳酸盐和磷酸盐，例如氯化钠，氯化钙，氯化镁，硝酸钠，硝酸钾，硫酸钠，硫酸钙，硫酸镁，碳酸钾，碳酸钠，碳酸钙，碳酸镁，硫代硫酸钠，焦磷酸钾，焦磷酸钠，磷酸钾，磷酸钠及磷酸钙。
碱金属和碱土金属的氢氧化合物包括氢氧化钠和氢氧化钙。
在碱金属化合物和碱土金属化合物（以下简称为金属化合物）中，可食用的有机酸碱金属盐和碱土金属盐，特别是烯醇酸的盐类，及氢氧化钠是可推荐的。
被组合到该组合物中的金属混合物的量为100PPm或更少;甚至0.5～50ppm的该化合物对于其稳定性就足够了。这些化合物更可推荐的量约为1～10ppm。
上述的任一种金属化合物与抗坏血酸粉末的混合，是通过例如在金属化合物存在下通过研磨抗坏血酸晶体进行的。该方法将产生一个很稳定的抗坏血酸组合物。促使金属化合物存在于抗坏血酸晶体中的方法包括：（a）均匀地将金属化合物添加到结晶中形成混合物，（b）用一些方法，例如用金属化合物溶液（例如水溶液，在诸如甲醇这样的醇中的溶液，在酮中如甲基乙基酮中的溶液）代替通常在结晶时用来洗涤结晶的甲醇，然后用抽滤或离心法除去溶剂，并干燥，得到已附加了金属化合物的结晶。（c）在含有金属化合物的溶液中结晶抗坏血酸，得到已和金属化合物结合的晶体。在这些方法中，方法（b）是特别令人满意的。要包括在抗坏血酸组合物中的金属化合物的量在方法（a）中可由加入的量的量选择来控制，在方法（b）中，通过溶液中的金属化合物的浓度以及要除去的溶液的量来控制，在方法（c）中通过溶液的浓度来控制。方法（b）中的金属化合物在溶液中适宜浓度为约0.01～5W/V%。
在下一步骤中，有金属化合物存在的抗坏血酸结晶在减压或在一空气流中加热干燥，并研磨。研磨抗坏血酸结晶用一个通常的粉磨机进行，例如锤磨机和喷射型碾磨机。
稳定的抗坏血酸粉末可通过用这种粉磨机研磨成100目（JISZ8801）或更小的细粉来获得，这种细粉，可通过用本发明的方法稳定。
在本发明中含有一微量的碱金属化合物或碱土金属化合物的抗坏血酸组合物，对变色是很稳定的，甚至在长时间贮存之后也不会变黄，用本发明的方法，通过加入微量的添加剂就可容易地获得稳定的抗坏血酸组合物;因此，本方法在工业上是很有用的。
本发明将用以下实例更具体地进行说明。
实例1
抗坏血酸水浆，其中抗坏血酸以结晶形式存在，通过吸滤得到200g湿的结晶。在室温（20-25℃下，用200ml0.02W/V%的氢氧化钠甲醇溶液喷洒吸滤瓶上的结晶。然后，用吸滤法除去该溶液。在其中已有氢氧化钠存在的结晶在减压下干燥，并用锤磨机（由Fuji Powal Co.Ltd制造）研磨，得到190g200目的抗坏血酸粉末。该粉末含有约4ppm的钠。
实例2
除用200ml0。1W/V%的抗坏血酸钠水-甲醇溶液（水/甲醇为1/100）代替实例1中的200ml氢氧化钠甲醇溶液外，用类似于实例1的方法处理得到190g100目的抗坏血酸粉末。该粉末含有约30ppm的抗坏血酸钠。
实例3
除用200ml0.1W/V%苯甲酸钠甲醇溶液代替实例1中的200ml氢氧化钠甲醇溶液外，用类似于实例1的方法处理，得到185g100目的抗坏血酸粉末。该粉末约含35ppm的苯甲酸钠。
实例4
除用150ml0.02W/V%冷却的氢氧化钙水溶液代替实例1中的200ml氢氧化钠甲醇溶液外，用类似于实例1的方法处理，得到180g100目抗坏血酸粉末。该粉末约含3ppm钙。
实例5
除用150ml0.01W/V%冷却的抗坏盐酸钙水溶液代替实例1中的200ml氢氧化钠甲醇溶液外，用同实例1的方法处理得到180g100目抗坏血酸粉末。该粉末约含35ppm抗坏血酸钙。
实例实验
把从实例1到5中获得的一种抗坏血酸粉末制品10g溶解于纯水中，得到50ml水溶液，在400nm测定其吸光度。用研磨机研磨抗坏血酸晶体，获得的粉末用来作为对照物。用同样的方法测定在密闭容器中贮存三年之后的六种粉末制品。测验结果总结在下表中
实例 UU吸光度（400nm） 5Cm 槽
刚制备的粉末 贮存三年后的粉末
1 0.016 0.043
2 0.016 0.044
3 0.015 0.054
4 0.015 0.059
5 0.015 0.051
对照物 0.015 0.261
在400nm的吸光度是显粉末黄色的特征，因此，它证明了本发明的抗坏血酸粉末制品是很稳定的，难以变成黄色。
对实例1-5中得到的各种粉末的氯离子浓度进行测量，氯离子是粉末的一种污染。用通常的电位滴定法未能检测到。
各种粉末含氯离子的量至少不能多于2.0ppm。
Claims (5)
1、一种抗坏血酸组合物，该组合物含有其量约为100ppm或更少的碱金属化合物或碱土金属化合物。
2、根据权利要求1的组合物，其特征为所说的碱金属化合物或碱土金属化合物是一种有机酸盐。
3、根据权利2的组合物，其特征为所说的有机酸盐为烯醇式酸的盐。
4、一种生产稳定的抗坏血酸粉末的方法，它包括在其量约为100ppm或更少的碱金属化合物或碱土金属化合物存在下，研磨抗坏血酸结晶。
5、一种生产稳定的抗坏血酸组合物的方法，它包括将抗坏血酸与一种碱金属化合物或者一种碱土金属化合物进行混合，其中一种碱金属化合物或一种碱土金属化合物的量是大约100ppm或更少。
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| CN102564981A (zh) * | 2011-12-23 | 2012-07-11 | 河北维尔康制药有限公司 | 一种检测抗坏血酸钙溶液颜色的方法 |
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| DE59201206D1 (de) * | 1991-01-28 | 1995-03-02 | Hoffmann La Roche | Vitamin enthaltende Formulierungen und deren Herstellung. |
| US5292534A (en) * | 1992-03-25 | 1994-03-08 | Valentine Enterprises, Inc. | Sustained release composition and method utilizing xanthan gum and an active ingredient |
| US5204114A (en) * | 1992-03-30 | 1993-04-20 | Health Maintenance Programs, Inc. | Methods of manufacturing high dosage glutathione the tablets and capsules produced thereby |
| JPH0987177A (ja) * | 1995-09-20 | 1997-03-31 | Green Cross Corp:The | 安定なビタミンｃ製剤 |
| US6020367A (en) * | 1997-12-02 | 2000-02-01 | Avon Products, Inc. | Supersaturated ascorbic acid solutions |
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| US2442461A (en) * | 1944-03-09 | 1948-06-01 | Hoffmann La Roche | Stable solutions of calcium ascorbate |
| US3116204A (en) * | 1961-11-09 | 1963-12-31 | Merck & Co Inc | Pharmaceutical compositions and method of preparing the same |
| US3446894A (en) * | 1966-09-15 | 1969-05-27 | Hoffmann La Roche | Stabilization of vitamin c tablets |
| US3773930A (en) * | 1971-03-23 | 1973-11-20 | Johnson & Johnson | Amino acid composition |
| US3973032A (en) * | 1975-09-19 | 1976-08-03 | Board Of Regents, State Of Florida For And On Behalf Of The University Of Florida | Treatment of citrus tree diseases |
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| CN102564981A (zh) * | 2011-12-23 | 2012-07-11 | 河北维尔康制药有限公司 | 一种检测抗坏血酸钙溶液颜色的方法 |
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