WO2002070531A1 - Ascorbic acid 2-phosphate metal salt with low calcium content - Google Patents
Ascorbic acid 2-phosphate metal salt with low calcium content Download PDFInfo
- Publication number
- WO2002070531A1 WO2002070531A1 PCT/JP2002/001926 JP0201926W WO02070531A1 WO 2002070531 A1 WO2002070531 A1 WO 2002070531A1 JP 0201926 W JP0201926 W JP 0201926W WO 02070531 A1 WO02070531 A1 WO 02070531A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ascorbic acid
- salt
- metal salt
- phosphate metal
- compound
- Prior art date
Links
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 95
- 239000002184 metal Substances 0.000 title claims abstract description 95
- 150000003839 salts Chemical class 0.000 title claims abstract description 92
- MIJPAVRNWPDMOR-ZAFYKAAXSA-N L-ascorbic acid 2-phosphate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OP(O)(O)=O)=C1O MIJPAVRNWPDMOR-ZAFYKAAXSA-N 0.000 title claims abstract description 83
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 66
- 239000011575 calcium Substances 0.000 title claims abstract description 66
- 239000000463 material Substances 0.000 claims abstract description 42
- 239000002537 cosmetic Substances 0.000 claims abstract description 40
- 229940043430 calcium compound Drugs 0.000 claims abstract description 28
- 150000001674 calcium compounds Chemical class 0.000 claims abstract description 28
- 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 23
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000007524 organic acids Chemical class 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims description 32
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 28
- 150000002736 metal compounds Chemical class 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 18
- 159000000003 magnesium salts Chemical class 0.000 claims description 15
- 229960005070 ascorbic acid Drugs 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000002211 L-ascorbic acid Substances 0.000 claims description 13
- 235000000069 L-ascorbic acid Nutrition 0.000 claims description 12
- -1 alkali metal salt Chemical class 0.000 claims description 12
- 150000003751 zinc Chemical class 0.000 claims description 11
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 10
- 150000002681 magnesium compounds Chemical class 0.000 claims description 9
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 9
- 239000000347 magnesium hydroxide Substances 0.000 claims description 9
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 9
- 239000003456 ion exchange resin Substances 0.000 claims description 8
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 8
- 239000000395 magnesium oxide Substances 0.000 claims description 8
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 8
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 8
- 229910021645 metal ion Inorganic materials 0.000 claims description 8
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 150000003752 zinc compounds Chemical class 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 7
- 229910001413 alkali metal ion Inorganic materials 0.000 claims description 6
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 claims description 6
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000006210 lotion Substances 0.000 claims description 6
- 230000000865 phosphorylative effect Effects 0.000 claims description 6
- 150000003112 potassium compounds Chemical class 0.000 claims description 6
- 150000003388 sodium compounds Chemical class 0.000 claims description 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
- 159000000000 sodium salts Chemical group 0.000 claims description 5
- 239000003957 anion exchange resin Substances 0.000 claims description 4
- 235000013361 beverage Nutrition 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000003608 titanium Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 12
- 239000002244 precipitate Substances 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 55
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- 239000012535 impurity Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 13
- 238000001556 precipitation Methods 0.000 description 11
- ACFGRWJEQJVZTM-LEJBHHMKSA-L Magnesium L-ascorbic acid-2-phosphate Chemical compound [Mg+2].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1O ACFGRWJEQJVZTM-LEJBHHMKSA-L 0.000 description 10
- 230000008021 deposition Effects 0.000 description 10
- 239000012266 salt solution Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 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
- 229960004106 citric acid Drugs 0.000 description 9
- 235000015165 citric acid Nutrition 0.000 description 9
- 238000013112 stability test Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000008341 cosmetic lotion Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229940058015 1,3-butylene glycol Drugs 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 235000019437 butane-1,3-diol Nutrition 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910044991 metal oxide Inorganic materials 0.000 description 3
- 150000004706 metal oxides Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001339 alkali metal compounds Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 description 2
- 150000004692 metal hydroxides Chemical class 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 150000003609 titanium compounds Chemical class 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- ROFNJLCLYMMXCT-UHFFFAOYSA-N 4-aminohexanoic acid Chemical compound CCC(N)CCC(O)=O ROFNJLCLYMMXCT-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003788 bath preparation Substances 0.000 description 1
- AAFIBPAFMTWDBF-UHFFFAOYSA-N butane-1,3-diol;ethanol Chemical compound CCO.CC(O)CCO AAFIBPAFMTWDBF-UHFFFAOYSA-N 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- VJVOFLWZDWLHNR-MRCUWXFGSA-N icosan-9-yl (z)-docos-13-enoate Chemical compound CCCCCCCCCCCC(CCCCCCCC)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC VJVOFLWZDWLHNR-MRCUWXFGSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 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
- 239000001509 sodium citrate Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229940045920 sodium pyrrolidone carboxylate Drugs 0.000 description 1
- HYRLWUFWDYFEES-UHFFFAOYSA-M sodium;2-oxopyrrolidine-1-carboxylate Chemical compound [Na+].[O-]C(=O)N1CCCC1=O HYRLWUFWDYFEES-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention relates to L-ascorbic acid derivative reduced in the calcium content and a production process therefor. More specifically, the present invention relates to L-ascorbic acid 2-phosphate metal salt having a low calcium content, which is useful as an additive for cosmetic, medical, food and feed materials, widely applicable in various industrial fields and particularly when added to a cosmetic material containing an organic acid, causes no clouding or scarcely precipitates or deposits even in the storage of cosmetic material, and also relates to a production process therefor.
- the L-ascorbic acid (vitamin C) has been heretofore used in various fields such as cosmetics, medical preparations, food and feed because of its various physiological and pharmacological activities such as suppression of lipoperoxide, acceleration of collagen formation, retardation of melanin formation and enhancement of immunity function.
- L-ascorbic acid is known to be unstable to oxygen, heat, light and the like and readily undergo coloration or degradation. Therefore, L-ascorbic acid generally used in the field of cosmetic material is not L- ascorbic acid itself but a derivative improved in the stability against oxygen, heat and the like by forming the hydroxyl group at the 2-position of L-ascorbic acid into a phosphoric ester or a phosphate salt.
- L-ascorbic acid-2-phosphate metal salts, particularly magnesium salt are widely used as a vitamin C derivative having excellent stability and being easily soluble in water.
- L-ascorbic acid 2-phospate metal salts There are know a lot of processes for producing L-ascorbic acid 2-phospate metal salts.
- APM L-ascorbic acid 2-phosphate magnesium salt
- 2-AP L-ascorbic acid-2-phosphate
- JP-B- 52-18191 the term “JP-B” as used herein means an “examined Japanese patent publication”
- JP-A-59-51293 the term “JP- A” as used herein means an "unexamined published Japanese patent application”
- JP-A-2-286693 the term "JP-B” as used herein means an "unexamined published Japanese patent application”
- the thus-obtained APM has a problem in that when blended, for example, in a cosmetic material such as cosmetic lotion, it readily causes clouding, precipitation or deposition during storage. Aggregation of ingredients in the production process of APM has been considered as one of causes therefor. More specifically, in the production of APM, when APM solution is crystallized in a poor solvent such as methanol or dried in a vacuum, aggregation readily occurs and the particle size increases. If this APM increased in the particle size is blended in a cosmetic material, clouding, precipitation or the like is readily caused due to alcohols contained in the cosmetic material.
- Blending of citrate, oxalate, gluconate or alanine in a high concentration only can attain slight retardation of the precipitation or deposition of APM and although the precipitation or deposition of APM may be slightly improved by the use of freeze-dried or spray-dried APM, the effect is not sufficiently high.
- the present invention has been made to solve the above-described problems and one of the object of the present invention is to provide L-ascorbic acid 2-phosphate metal salt having a low calcium content, which causes no clouding and scarcely precipitates or deposits even when added to a cosmetic material or the like having blended therein an organic acid.
- This object of the present invention includes providing a production process therefor.
- Another object of the present invention is to provide a cosmetic material, a medical preparation, a beverage, a food and a feed, each containing L-ascorbic acid 2- phosphate metal salt and being free from generation of clouding, precipitation or deposition.
- the present inventors have newly found this time that the clouding generated, in a cosmetic material during storage of the cosmetic material containing L-ascorbic acid 2-phosphate metal salt is caused by not only the L-ascorbic acid 2-phosphate metal salt deposited due to alcohols contained in the cosmetic material but also by salts produced in the reaction between an organic acid (for example, citric acid) present in the cosmetic material and calcium contained as an impurity in the starting material L-ascorbic acid 2-phosphate metal salt; that clouding is readily generated when this L-ascorbic acid 2- phosphate metal salt has a high calcium content; that the calcium originates in a metal compound used as a starting material; and that when the content of calcium contained as an impurity in the starting metal compound is reduced, a cosmetic lotion or the like free from generation of clouding can be obtained.
- the present invention has been accomplished based on these findings.
- the present invention relates to the following matters.
- An L-ascorbic acid-2-phosphate metal salt with a low calcium content characterized in that the content of a calcium compound is 500 ppm or less in terms of calcium ion.
- L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is a salt of alkaline earth metal other than calcium, alkali metal salt, zinc salt, aluminum salt or titanium salt.
- L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is sodium salt, potassium salt, magnesium salt, zinc salt or aluminum salt.
- L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is potassium salt, magnesium salt or zinc salt.
- a process for producing an L-ascorbic acid-2-phosphate metal salt with a low calcium content wherein the content of a calcium compound is 500 ppm or less in terms of calcium ion said process is characterized by adding a metal compound containing a calcium compound in an amount of 2,000 ppm or less in terms of calcium ion to a solution containing an L-ascorbic acid-2-phosphoric ester.
- a low-clouding cosmetic material characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
- a low-clouding medical preparation characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
- a low-clouding beverage characterized in that the L- ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
- L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention and the production process therefor are described in detail below.
- the high-purity L-ascorbic acid 2-phosphate metal salt with a low calcium content is characterized in that the content of calcium compound as an impurity is 500 ppm or less in terms of calcium ion.
- the L-ascorbic acid-2-phosphate metal salt is a salt of metal other than calcium, preferably a salt of alkaline earth metal other than calcium, alkali metal salt, zinc salt, aluminum salt or titanium salt, more preferably sodium salt, potassium salt, magnesium salt, zinc salt or aluminum salt, still preferably potassium salt, magnesium salt or zinc salt, and most preferably magnesium salt .
- Such the L-ascorbic acid 2-phosphate metal salt causes no clouding and scarcely precipitates or deposits even when added to a cosmetic lotion containing an organic acid such as citric acid, or ethanol . Accordingly, when such the L- ascorbic acid 2-phosphate metal salt is blended, various cosmetic, medical preparations, food and feed materials having excellent storage stability can be obtained.
- the content of calcium compound as an impurity is suitably 500 ppm or less, preferably 300 ppm or less, in terms of calcium ion.
- the calcium compound content exceeds 500 ppm, when the L-ascorbic acid 2- phosphate metal salt is blended in a cosmetic material or the like, a salt is formed with an organic acid (for example, a citric acid) contained in the cosmetic material or the like to readily cause clouding, precipitation or deposition.
- an organic acid for example, a citric acid
- a metal compound containing an impurity calcium compound in the later described amount or less is added to a solution containing an L-ascorbic acid-2-phosphoric ester (2-AP) (this solution is hereinafter sometimes called "a 2-AP- containing solution") .
- the metal compound is a compound of a metal other than calcium, preferably a compound of alkaline earth metal other than calcium, alkali metal compound, zinc compound, aluminum compound or titanium compound, more preferably sodium compound, potassium compound, magnesium compound, zinc compound or aluminum compound, still preferably potassium compound, sodium compound, magnesium compound or zinc compound, and most preferably magnesium compound.
- the finally obtained L-ascorbic acid 2-phosphate metal salt can be reduced in the content of calcium compound as an impurity and by using this L-ascorbic acid 2-phosphate metal salt reduced in the calcium content, a cosmetic lotion or a medical or food material can be prevented from clouding or the like.
- the metal compound may be added to a 2-AP-containing solution and the adding method is not particularly limited insofar as the 2-AP and the metal compound can be contacted and reacted.
- APM In producing APM by, for example, adding a metal compound to a 2-AP-containing solution and thereby reacting 2-AP with the metal compound, a commonly known method described in JP-B-52-18191, JP-A-59-51293, JP-A-2-286693 and the like may be employed.
- the above-described reaction may be performed by adding a metal compound such as metal oxide having a calcium content in a fixed amount or less to a 2- AP-containing solution, adjusting the pH after the addition to 8.5 to 10.5, and allowing the solution to stand at a temperature of 5 to 25°C for 3 to 5 hours.
- a metal compound such as metal oxide having a calcium content in a fixed amount or less
- adjusting the pH after the addition to 8.5 to 10.5
- the 2-AP-containing solution (starting material solution) for use in the present invention is not particularly limited and, for example, the following solutions may be used.
- Examples of the 2-AP-containing solution which can be suitably used include a 2-AP-containing solution obtained by directly phosphorylating an ascorbic acid (see, JP-B-43- 9219, JP-B-45-23746 and JP-A-6-345786) and a 2-AP- containing solution obtained by phosphorylating a 5,6-0- isopropylidene-L-ascorbic acid (see, JP-B-43-9219, JP-B-45- 4497, JP-B-45-30328 and JP-B-59-4438 ) may be preferably used.
- a 2-AP-containing solution produced from an L-ascorbic acid and a phosphoric acid donor under the action of an enzyme or a microorganism see, JP-A-2-42996 may also be used.
- the 2-AP-containing solution can be obtained, for example, by a method where an L-ascorbic acid, an alkali metal hydroxide and a phosphorylating agent are reacted in the presence of water at a pH of 6 to 13, preferably from 6 to 8, and the obtained 2-AP alkali metal salt solution (an alkali metal salt solution of L-ascorbic acid-2-phosphoric ester) is treated with an ion exchange resin to remove metal ion.
- the 2-AP-containing solution can be obtained, for example, by a method where an L- ascorbic acid is dissolved in a mixed solvent of pyridine and water, reacted with a phosphorylating agent such as phosphorus oxychloride while adjusting the pH to 6 to 13, preferably 6 to 8, using an aqueous alkali metal hydroxide solution (for example, an aqueous solution of sodium hydroxide, potassium hydroxide or lithium hydroxide) and at the same time, with the alkali metal hydroxide, and the obtained 2-AP alkali metal salt solution is treated with an ion exchange resin to remove metal ion.
- a aqueous alkali metal hydroxide solution for example, an aqueous solution of sodium hydroxide, potassium hydroxide or lithium hydroxide
- a 2-AP alkali metal salt solution or a 2-AP alkaline earth metal salt solution may be used in place of the 2-AP- containing solution.
- these solutions aqueous solution
- these solutions are preferably subjected to a metal ion-removing treatment (hereinafter sometimes referred to as decation- ization) before use.
- decation- ization a metal ion-removing treatment
- Examples of the decationization method include a method of treating a 2-AP metal salt solution with an appropriate ion exchange resin.
- a 2-AP metal salt solution such as L-ascorbic acid 2-phosphate magnesium salt (APM) is passed through a strongly acidic cation exchange resin and then water is eluted, whereby the cation portion (metal ion) of the 2-AP metal salt solution is exchanged with hydrogen ion, and the metal ion remains on the exchange resin, as a result, a decationized 2-AP solution is obtained.
- APM L-ascorbic acid 2-phosphate magnesium salt
- the 2-AP-containing solution can also be obtained by a general method, for example, where a 2-AP metal salt solution (aqueous solution) is passed through a weakly or moderately basic anion-exchange resin to adsorb 2-AP to the ion exchange resin and at the same time, allow metal ion (cation) such as alkali metal ion or alkaline earth metal ion to flow out, and the adsorbed 2-AP is eluted with an acid such as 0.1 to 2 N dilute hydrochloric acid.
- a 2-AP metal salt solution aqueous solution
- a weakly or moderately basic anion-exchange resin to adsorb 2-AP to the ion exchange resin and at the same time, allow metal ion (cation) such as alkali metal ion or alkaline earth metal ion to flow out, and the adsorbed 2-AP is eluted with an acid such as 0.1 to 2 N dilute hydrochloric acid.
- the metal compound which is used as a starting material in the production process of the L-ascorbic acid 2-phosphate metal salt according to the present invention is, as mentioned above, a compound of a metal other than calcium, preferably a compound of alkaline earth metal other than calcium, alkali metal compound, zinc compound, aluminum compound or titanium compound, more preferably sodium compound, potassium compound, magnesium compound, zinc compound or aluminum compound, still preferably potassium compound, sodium compound, magnesium compound or zinc compound, and most preferably magnesium compound.
- the metal compound is, for instance, metal oxide, metal hydroxide or metal carbonate, and preferably metal oxide or metal hydroxide.
- examples of magnesium compound include, for instance, magnesium oxide, magnesium hydroxide and magnesium carbonate. Among these, magnesium oxide and magnesium hydroxide are preferred.
- the content of calcium compounds as an impurity contained in the metal compound for use in the present invention is suitably 2,000 ppm or less, preferably 1,500 ppm or less, more preferably 750 ppm or less, in terms of calcium ion. If the calcium content in the starting material metal salt exceeds 2,000 ppm, the L- ascorbic acid 2-phosphate metal salt produced using the metal compound has a high calcium concentration and when blended in a cosmetic material or the like, an organic acid (e.g., citric acid) contained in the base material of the cosmetic material reacts with the calcium compound to form a salt, as a result, clouding, precipitation or deposition is readily caused and this is not preferred.
- an organic acid e.g., citric acid
- the obtained L-ascorbic acid 2-phosphate metal salt can have a low calcium content of 500 ppm or less, preferably 300 ppm or less, in terms of calcium ion.
- the L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention does not cause clouding, precipitation or deposition even when added to a cosmetic material having blended therein particularly an organic acid (e.g., citric acid, succinic acid, malic acid, tartaric acid) and stored for a long period of time, and therefore, can be suitably used in various cosmetic materials .
- an organic acid e.g., citric acid, succinic acid, malic acid, tartaric acid
- Examples of the cosmetic material to which the L- ascorbic acid 2-phosphate metal salt with low calcium content obtained by the present invention can be added include : a lotion where citric acid, sodium citrate, g- aminocaproic acid, 1,3-butylene glycol, ethanol, glycerol, polyoxyethylene hydrogenated castor oil, purified water, perfume and the like are blended; a cream where stearic acid, cetanol, 1,3-butylene glycol, parahydroxybenzoic ester, dipentaerythritol fatty ester, purified water, perfume and the like are blended; a milky lotion where stearic acid, cetanol, octyldodecyl erucate, polyoxyethylene tetraoleate and the like are blended; and a pack where dipropylene glycol, sodium pyrrolidone- carboxylate, polyvinyl alcohol, tetrasodium edetate and the like are blended.
- the present invention is not
- the ratio of L-ascorbic acid 2-phosphate metal salt with low calcium content blended to these cosmetic materials varies depending on the amount of organic acid blended, the preparation form and the like but assuming that the entire amount of the cosmetic material is 100 wt%, the ratio is generally from 0.01 to 30 wt%, preferably from 0.1 to 20 wt% in a lotion; generally from 0.01 to 30 wt%, preferably from 0.1 to 15 wt% in a cream; generally from 0.01 to 30 wt%, preferably from 0.1 to 20 wt% in a milky lotion; and generally from 0.01 to 30 wt%, preferably from 0.1 to 15 wt% in a pack.
- the amount of the organic acid contained in the cosmetic material varies depending on the kind of the cosmetic material but is generally from 0.1 to 10 wt%.
- This L-ascorbic acid 2-phosphate metal salt reduced in the calcium content can be suitably used also for medical preparations (e.g., preparation for oral cavity, ophthalmic solution, bath preparation), beverages, feed for animals, food and the like containing particularly an organic acid (e.g., citric acid, succinic acid, malic acid, tartaric acid) and the same effect as in the cosmetic material can be obtained.
- medical preparations e.g., preparation for oral cavity, ophthalmic solution, bath preparation
- beverages feed for animals, food and the like containing particularly an organic acid (e.g., citric acid, succinic acid, malic acid, tartaric acid) and the same effect as in the cosmetic material can be obtained.
- an organic acid e.g., citric acid, succinic acid, malic acid, tartaric acid
- the present invention is described in greater detail below by referring to examples, however, the present invention is not limited to these Examples.
- the invention is described in accordance with the production of L-ascorbic acid 2- phosphate magnesium salt.
- the invention is not limited to magnesium salt, but include the various metal salts of L-ascorbic acid 2-phosphate metal.
- the concentration of calcium compound as an impurity in the starting material magnesium hydroxide and in the final product L-ascorbic acid 2-phosphate magnesium salt was measured by ICP (manufactured by Seiko Instruments K.K.) (similarly measured in Example 2 and Comparative Examples 1 to 2 below) .
- An L-ascorbic acid 2-phosphate magnesium salt as a white dry product was obtained in the same manner as in Example 1 except that magnesium hydroxide having an impurity calcium compound content of 2,500 ppm in terms of calcium ion was used in place of the magnesium hydroxide having an impurity calcium compound content of 500 ppm in terms of calcium ion in Example 1.
- the calcium compound content in this white dry product was 580 ppm.
- in-solution stability tests 1 and 2 described later were performed. In both in-solution stability tests 1 and 2, clouding was observed at room temperature (20°C) and more distinguished clouding was observed at 50°C.
- reaction solution after such adjustment of pH was diluted by adding 6,500 ml of pure water, passed through a column packed with 2,000 ml of a moderately basic anion exchange resin (Amberlite IRA-68, produced by Organo) and then developed with 23,500 ml of 0.05N hydrochloric acid and further with 11,000 ml of 0.2N hydrochloric acid to obtain a fraction containing 2-AP.
- An aqueous solution of this fraction was dialyzed using an electrodialyser (Model DU-Ob, manufactured by Asahi Glass K.K.) until chlorine ion was reduced to 500 ppm.
- An L-ascorbic acid 2-phosphate magnesium salt as a white dry product was obtained in the same manner as in Example 2 except that magnesium oxide having an impurity calcium compound content of 3,000 ppm in terms of calcium ion was used in place of the magnesium oxide having an impurity calcium compound content of 1,000 ppm in terms of calcium ion in Example 2.
- the calcium compound content in this white dry product was 750 ppm in terms of calcium ion.
- in-liquid stability tests described later were performed. As a result, in the in-solution stability test 1, clouding was observed when the dry product was allowed to stand at room temperature, and more distinguished clouding was observed when allowed to stand at 50°C. In the in-liquid stability test 2, distinguished clouding was observed under both conditions of room temperature and 50°C.
- L-ascorbic acid 2-phosphate metal salt with a low calcium content can be produced, where the content of calcium compound as an impurity contained in the L-ascorbic acid 2-phosphate metal salt, giving rise to clouding, precipitation or deposition, is reduced to 500 ppm or less in terms of calcium ion.
- the L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention can be free of clouding, precipitation or deposition during storage either at room temperature or at a high temperature (for example, 50°C) when the L-ascorbic acid 2-phosphate metal salt is blended in a cosmetic material containing particularly an organic acid, and therefore, can be suitably used for this usage.
- this L-ascorbic acid 2-phosphate metal salt can exhibit stability during the same storage as above even when blended in a medical, feed or food material containing particularly an organic acid, and therefore, can be widely used in various industrial fields .
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Abstract
One of the object of the present invention is to provide an L-ascorbic acid 2-phosphate metal salt, which causes no clouding and scarcely precipitates or deposits even when added to a cosmetic material or the like having blended therein an organic acid. Disclosed herein is an L-ascorbic acid-2-phosphate metal salt with a low calcium content characterized in that the content of a calcium compound is 500 ppm or less in terms of calcium ion, and production process thereof.
Description
DESCRI PTION
ASCORBIC ACID 2-PHOS PHATE METAL SALT WITH LOW CALCIUM
CONTENT
CROSS REFERENCES OF RELATED APPLICATION
This application is an application filed under 35 U.S.C. §111 (a) claiming benefit pursuant to 35 U.S.C. §119 (e) (1) of the filing date of Provisional Application 60/275,033 filed on March 13, 2001 pursuant to 35 U.S.C. §111 (b) .
DETAILED DESCRIPTION OF THE INVENTION Application Field in Industry
The present invention relates to L-ascorbic acid derivative reduced in the calcium content and a production process therefor. More specifically, the present invention relates to L-ascorbic acid 2-phosphate metal salt having a low calcium content, which is useful as an additive for cosmetic, medical, food and feed materials, widely applicable in various industrial fields and particularly when added to a cosmetic material containing an organic acid, causes no clouding or scarcely precipitates or deposits even in the storage of cosmetic material, and also relates to a production process therefor.
Background Art
The L-ascorbic acid (vitamin C) has been heretofore used in various fields such as cosmetics, medical
preparations, food and feed because of its various physiological and pharmacological activities such as suppression of lipoperoxide, acceleration of collagen formation, retardation of melanin formation and enhancement of immunity function.
However, L-ascorbic acid is known to be unstable to oxygen, heat, light and the like and readily undergo coloration or degradation. Therefore, L-ascorbic acid generally used in the field of cosmetic material is not L- ascorbic acid itself but a derivative improved in the stability against oxygen, heat and the like by forming the hydroxyl group at the 2-position of L-ascorbic acid into a phosphoric ester or a phosphate salt. Among these derivatives, L-ascorbic acid-2-phosphate metal salts, particularly magnesium salt, are widely used as a vitamin C derivative having excellent stability and being easily soluble in water.
There are know a lot of processes for producing L- ascorbic acid 2-phospate metal salts. As for the process for producing such L-ascorbic acid 2-phosphate magnesium salt (hereinafter sometimes referred to as "APM" ) , for example, a method of reacting L-ascorbic acid-2-phosphate (hereinafter sometimes referred to as "2-AP") with magnesium oxide, magnesium hydroxide, magnesium carbonate or the like to produce L-ascorbic acid 2-phosphate magnesium salt is known. This production process of APM is described in a large number of publications such as JP-B- 52-18191 (the term "JP-B" as used herein means an "examined Japanese patent publication"), JP-A-59-51293 (the term "JP-
A" as used herein means an "unexamined published Japanese patent application") and JP-A-2-286693.
However, the thus-obtained APM has a problem in that when blended, for example, in a cosmetic material such as cosmetic lotion, it readily causes clouding, precipitation or deposition during storage. Aggregation of ingredients in the production process of APM has been considered as one of causes therefor. More specifically, in the production of APM, when APM solution is crystallized in a poor solvent such as methanol or dried in a vacuum, aggregation readily occurs and the particle size increases. If this APM increased in the particle size is blended in a cosmetic material, clouding, precipitation or the like is readily caused due to alcohols contained in the cosmetic material.
In order to prevent such clouding, various methods have been heretofore proposed, for example, a method of blending citrate, oxalate, gluconate or alanine in the above-described cosmetic material to a high concentration (see, JP-A-1-213212, JP-A-4-283593) , a method of freeze- drying the obtained APM before use (see, JP-A-2-231496) , or a method of spray-drying the obtained APM before use (see, JP-A-7-112914) .
Blending of citrate, oxalate, gluconate or alanine in a high concentration only can attain slight retardation of the precipitation or deposition of APM and although the precipitation or deposition of APM may be slightly improved by the use of freeze-dried or spray-dried APM, the effect is not sufficiently high.
The problems associated with precipitation or
deposition are not only specific in APM but also found in various -ascorbic acid 2-phosphate metal salts.
Object of the Invention
The present invention has been made to solve the above-described problems and one of the object of the present invention is to provide L-ascorbic acid 2-phosphate metal salt having a low calcium content, which causes no clouding and scarcely precipitates or deposits even when added to a cosmetic material or the like having blended therein an organic acid. This object of the present invention includes providing a production process therefor.
Another object of the present invention is to provide a cosmetic material, a medical preparation, a beverage, a food and a feed, each containing L-ascorbic acid 2- phosphate metal salt and being free from generation of clouding, precipitation or deposition.
Summary of the Invention
As a result of extensive investigations to solve the above-described problems, the present inventors have newly found this time that the clouding generated, in a cosmetic material during storage of the cosmetic material containing L-ascorbic acid 2-phosphate metal salt is caused by not only the L-ascorbic acid 2-phosphate metal salt deposited due to alcohols contained in the cosmetic material but also by salts produced in the reaction between an organic acid (for example, citric acid) present in the cosmetic material and calcium contained as an impurity in the starting
material L-ascorbic acid 2-phosphate metal salt; that clouding is readily generated when this L-ascorbic acid 2- phosphate metal salt has a high calcium content; that the calcium originates in a metal compound used as a starting material; and that when the content of calcium contained as an impurity in the starting metal compound is reduced, a cosmetic lotion or the like free from generation of clouding can be obtained. The present invention has been accomplished based on these findings.
More specifically, the present invention relates to the following matters.
(1) An L-ascorbic acid-2-phosphate metal salt with a low calcium content characterized in that the content of a calcium compound is 500 ppm or less in terms of calcium ion.
(2) The L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is a salt of alkaline earth metal other than calcium, alkali metal salt, zinc salt, aluminum salt or titanium salt.
(3) The L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is sodium salt, potassium salt, magnesium salt, zinc salt or aluminum salt.
(4) The L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1), wherein the L-ascorbic acid-2-phosphate metal salt is potassium salt, magnesium salt or zinc salt.
(5) The L-ascorbic acid-2-phosphate metal salt with a low calcium content as described in (1) , wherein the L-ascorbic
acid-2-phosphate metal salt is magnesium salt.
(6) A process for producing an L-ascorbic acid-2-phosphate metal salt with a low calcium content wherein the content of a calcium compound is 500 ppm or less in terms of calcium ion, said process is characterized by adding a metal compound containing a calcium compound in an amount of 2,000 ppm or less in terms of calcium ion to a solution containing an L-ascorbic acid-2-phosphoric ester.
(7) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as described in (6), wherein the metal compound is any one of potassium compound, sodium compound, magnesium compound or zinc compound, and the resulting L-ascorbic acid-2- phosphate metal salt is any one of potassium salt, sodium salt, magnesium salt or zinc salt.
(8) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as described in (6), wherein the metal compound is any one of magnesium oxide or magnesium hydroxide, and the resulting L-ascorbic acid-2-phosphate metal salt is magnesium salt.
(9) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as described in any one of (6) to (8), wherein the solution containing an L-ascorbic acid-2-phosphoric ester contains alkali metal ion or alkaline earth metal ion in an amount of 10 ppm or less in terms of the L-ascorbic acid-2- phosphoric ester.
(10) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as
described in (9) , wherein the solution containing an L- ascorbic acid-2-phosphoric ester contains alkali metal ion or alkaline earth metal ion in an amount of 1 ppm or less in terms of the L-ascorbic acid-2-phosphoric ester.
(11) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as described in (9) or (10), wherein the solution containing an L-ascorbic acid-2-phosphoric ester is prepared by a method comprising reacting L-ascorbic acid, an alkali metal hydroxide and phosphorylating agent in the presence of water, and removing metal ion from the resulting solution of L-ascorbic acid-2-phosphate metal salt by using ion exchange resin.
(12) The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as described in (11), wherein the ion exchange resin is weakly or moderately basic anion-exchange resin.
(13) A low-clouding cosmetic material characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
(14) The low-clouding cosmetic material described in (13) , wherein the cosmetic material is lotion.
(15) The low-clouding cosmetic material described in (13) or (14), wherein 0.1 to 10 % by weight of organic acid is blended in the cosmetic material.
(16) A low-clouding medical preparation characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
' (17) A low-clouding beverage characterized in that the L-
ascorbic acid 2-phosphate metal salt with a low calcium content described in (1) is blended.
Specific Description of the Invention
The L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention and the production process therefor are described in detail below.
L-ascorbic Acid 2-Phosphate Metal Salt with Low Calcium Content
The high-purity L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention is characterized in that the content of calcium compound as an impurity is 500 ppm or less in terms of calcium ion. Herein, the L-ascorbic acid-2-phosphate metal salt is a salt of metal other than calcium, preferably a salt of alkaline earth metal other than calcium, alkali metal salt, zinc salt, aluminum salt or titanium salt, more preferably sodium salt, potassium salt, magnesium salt, zinc salt or aluminum salt, still preferably potassium salt, magnesium salt or zinc salt, and most preferably magnesium salt .
Such the L-ascorbic acid 2-phosphate metal salt causes no clouding and scarcely precipitates or deposits even when added to a cosmetic lotion containing an organic acid such as citric acid, or ethanol . Accordingly, when such the L- ascorbic acid 2-phosphate metal salt is blended, various cosmetic, medical preparations, food and feed materials having excellent storage stability can be obtained.
In the highly purified L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention, the content of calcium compound as an impurity is suitably 500 ppm or less, preferably 300 ppm or less, in terms of calcium ion. If the calcium compound content exceeds 500 ppm, when the L-ascorbic acid 2- phosphate metal salt is blended in a cosmetic material or the like, a salt is formed with an organic acid (for example, a citric acid) contained in the cosmetic material or the like to readily cause clouding, precipitation or deposition.
Production of L-Ascorbic Acid 2-Phosphate Metal Salt with Low Calcium Content
In a preferred embodiment of the process for producing an L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention, a metal compound containing an impurity calcium compound in the later described amount or less is added to a solution containing an L-ascorbic acid-2-phosphoric ester (2-AP) (this solution is hereinafter sometimes called "a 2-AP- containing solution") . Herein, the metal compound is a compound of a metal other than calcium, preferably a compound of alkaline earth metal other than calcium, alkali metal compound, zinc compound, aluminum compound or titanium compound, more preferably sodium compound, potassium compound, magnesium compound, zinc compound or aluminum compound, still preferably potassium compound, sodium compound, magnesium compound or zinc compound, and
most preferably magnesium compound.
By adding such the metal compounds, the finally obtained L-ascorbic acid 2-phosphate metal salt can be reduced in the content of calcium compound as an impurity and by using this L-ascorbic acid 2-phosphate metal salt reduced in the calcium content, a cosmetic lotion or a medical or food material can be prevented from clouding or the like.
In the present invention, the metal compound may be added to a 2-AP-containing solution and the adding method is not particularly limited insofar as the 2-AP and the metal compound can be contacted and reacted.
In producing APM by, for example, adding a metal compound to a 2-AP-containing solution and thereby reacting 2-AP with the metal compound, a commonly known method described in JP-B-52-18191, JP-A-59-51293, JP-A-2-286693 and the like may be employed.
More specifically, the above-described reaction may be performed by adding a metal compound such as metal oxide having a calcium content in a fixed amount or less to a 2- AP-containing solution, adjusting the pH after the addition to 8.5 to 10.5, and allowing the solution to stand at a temperature of 5 to 25°C for 3 to 5 hours.
2-AP-Containinq Solution
The 2-AP-containing solution (starting material solution) for use in the present invention is not particularly limited and, for example, the following solutions may be used.
Examples of the 2-AP-containing solution which can be suitably used include a 2-AP-containing solution obtained by directly phosphorylating an ascorbic acid (see, JP-B-43- 9219, JP-B-45-23746 and JP-A-6-345786) and a 2-AP- containing solution obtained by phosphorylating a 5,6-0- isopropylidene-L-ascorbic acid (see, JP-B-43-9219, JP-B-45- 4497, JP-B-45-30328 and JP-B-59-4438 ) may be preferably used. In addition, a 2-AP-containing solution produced from an L-ascorbic acid and a phosphoric acid donor under the action of an enzyme or a microorganism (see, JP-A-2-42996) may also be used.
More specifically, the 2-AP-containing solution can be obtained, for example, by a method where an L-ascorbic acid, an alkali metal hydroxide and a phosphorylating agent are reacted in the presence of water at a pH of 6 to 13, preferably from 6 to 8, and the obtained 2-AP alkali metal salt solution (an alkali metal salt solution of L-ascorbic acid-2-phosphoric ester) is treated with an ion exchange resin to remove metal ion.
Still more specifically, the 2-AP-containing solution can be obtained, for example, by a method where an L- ascorbic acid is dissolved in a mixed solvent of pyridine and water, reacted with a phosphorylating agent such as phosphorus oxychloride while adjusting the pH to 6 to 13, preferably 6 to 8, using an aqueous alkali metal hydroxide solution (for example, an aqueous solution of sodium hydroxide, potassium hydroxide or lithium hydroxide) and at the same time, with the alkali metal hydroxide, and the obtained 2-AP alkali metal salt solution is treated with an
ion exchange resin to remove metal ion.
In the present invention, a 2-AP alkali metal salt solution or a 2-AP alkaline earth metal salt solution (an alkaline earth metal salt solution of L-ascorbic acid-2- phosphoric ester) may be used in place of the 2-AP- containing solution. In this case, these solutions (aqueous solution) are preferably subjected to a metal ion-removing treatment (hereinafter sometimes referred to as decation- ization) before use. Examples of the decationization method include a method of treating a 2-AP metal salt solution with an appropriate ion exchange resin.
More specifically, for example, a 2-AP metal salt solution such as L-ascorbic acid 2-phosphate magnesium salt (APM) is passed through a strongly acidic cation exchange resin and then water is eluted, whereby the cation portion (metal ion) of the 2-AP metal salt solution is exchanged with hydrogen ion, and the metal ion remains on the exchange resin, as a result, a decationized 2-AP solution is obtained. The 2-AP-containing solution can also be obtained by a general method, for example, where a 2-AP metal salt solution (aqueous solution) is passed through a weakly or moderately basic anion-exchange resin to adsorb 2-AP to the ion exchange resin and at the same time, allow metal ion (cation) such as alkali metal ion or alkaline earth metal ion to flow out, and the adsorbed 2-AP is eluted with an acid such as 0.1 to 2 N dilute hydrochloric acid.
In the present invention, the thus-obtained high- purity 2-AP extremely reduced in the metal ion content may
be used, where the content of alkali metal ion or alkaline earth metal ion, such as Na ion or Ca ion, is usually 10 ppm or less, preferably 1 ppm or less in terms of the L- ascorbic acid-2-phosphoric ester.
Metal Compound
The metal compound which is used as a starting material in the production process of the L-ascorbic acid 2-phosphate metal salt according to the present invention is, as mentioned above, a compound of a metal other than calcium, preferably a compound of alkaline earth metal other than calcium, alkali metal compound, zinc compound, aluminum compound or titanium compound, more preferably sodium compound, potassium compound, magnesium compound, zinc compound or aluminum compound, still preferably potassium compound, sodium compound, magnesium compound or zinc compound, and most preferably magnesium compound. The metal compound is, for instance, metal oxide, metal hydroxide or metal carbonate, and preferably metal oxide or metal hydroxide. Accordingly, examples of magnesium compound include, for instance, magnesium oxide, magnesium hydroxide and magnesium carbonate. Among these, magnesium oxide and magnesium hydroxide are preferred.
The content of calcium compounds as an impurity contained in the metal compound for use in the present invention is suitably 2,000 ppm or less, preferably 1,500 ppm or less, more preferably 750 ppm or less, in terms of calcium ion. If the calcium content in the starting material metal salt exceeds 2,000 ppm, the L-
ascorbic acid 2-phosphate metal salt produced using the metal compound has a high calcium concentration and when blended in a cosmetic material or the like, an organic acid (e.g., citric acid) contained in the base material of the cosmetic material reacts with the calcium compound to form a salt, as a result, clouding, precipitation or deposition is readily caused and this is not preferred.
When 2-AP and the metal compound are reacted as such by adding a metal compound having an impurity calcium compound content of 2,000 ppm or less in terms of calcium ion to a 2-AP-containing solution, the obtained L-ascorbic acid 2-phosphate metal salt can have a low calcium content of 500 ppm or less, preferably 300 ppm or less, in terms of calcium ion.
Uses of L-ascorbic Acid 2-phosphate Metal Salt with Low Calcium Content
The L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention does not cause clouding, precipitation or deposition even when added to a cosmetic material having blended therein particularly an organic acid (e.g., citric acid, succinic acid, malic acid, tartaric acid) and stored for a long period of time, and therefore, can be suitably used in various cosmetic materials .
Examples of the cosmetic material to which the L- ascorbic acid 2-phosphate metal salt with low calcium content obtained by the present invention can be added include :
a lotion where citric acid, sodium citrate, g- aminocaproic acid, 1,3-butylene glycol, ethanol, glycerol, polyoxyethylene hydrogenated castor oil, purified water, perfume and the like are blended; a cream where stearic acid, cetanol, 1,3-butylene glycol, parahydroxybenzoic ester, dipentaerythritol fatty ester, purified water, perfume and the like are blended; a milky lotion where stearic acid, cetanol, octyldodecyl erucate, polyoxyethylene tetraoleate and the like are blended; and a pack where dipropylene glycol, sodium pyrrolidone- carboxylate, polyvinyl alcohol, tetrasodium edetate and the like are blended. However, the present invention is not limited thereto.
The ratio of L-ascorbic acid 2-phosphate metal salt with low calcium content blended to these cosmetic materials varies depending on the amount of organic acid blended, the preparation form and the like but assuming that the entire amount of the cosmetic material is 100 wt%, the ratio is generally from 0.01 to 30 wt%, preferably from 0.1 to 20 wt% in a lotion; generally from 0.01 to 30 wt%, preferably from 0.1 to 15 wt% in a cream; generally from 0.01 to 30 wt%, preferably from 0.1 to 20 wt% in a milky lotion; and generally from 0.01 to 30 wt%, preferably from 0.1 to 15 wt% in a pack. The amount of the organic acid contained in the cosmetic material varies depending on the kind of the cosmetic material but is generally from 0.1 to 10 wt%.
This L-ascorbic acid 2-phosphate metal salt reduced in
the calcium content can be suitably used also for medical preparations (e.g., preparation for oral cavity, ophthalmic solution, bath preparation), beverages, feed for animals, food and the like containing particularly an organic acid (e.g., citric acid, succinic acid, malic acid, tartaric acid) and the same effect as in the cosmetic material can be obtained.
Examples
The present invention is described in greater detail below by referring to examples, however, the present invention is not limited to these Examples. In the following examples, the invention is described in accordance with the production of L-ascorbic acid 2- phosphate magnesium salt. However, as mentioned above, the invention is not limited to magnesium salt, but include the various metal salts of L-ascorbic acid 2-phosphate metal.
Example 1
In 368 ml of pure water, 32 g of L-ascorbic acid 2- phosphate magnesium salt was dissolved. The resulting solution was passed through a column packed with 2,000 ml of a strongly acidic cation exchange resin (Amberlite IR- 120B, produced by Organo) and further through 1,200 ml of pure water to obtain 1, 600 ml of an aqueous solution containing only 2-AP. The magnesium ion content of this solution was less than 1 ppm and the content of calcium compound as an impurity was lower than the detection limit.
While keeping this aqueous 2-AP solution at 10°C,
magnesium hydroxide having an impurity calcium compound content of 500 ppm in terms of calcium ion was added to give a pH of 9.2 after the addition. The resulting solution was left standing for 4 hours and the supernatant was filtered to remove insoluble matters. The filtrate solution was concentrated to one-tenth (1/10) and after adding a two-fold amount of methanol, the generated solid portion was collected by filtration. Subsequently, the obtained solid portion (wet body) was recrystallized with water- methanol and then dried to obtain an L-ascorbic acid 2- phosphate magnesium salt as a white dry product. The calcium compound content in this white dry product was 120 ppm in terms of calcium ion. Using this dry product, in-solution stability tests 1 and 2 described later were performed, as a result, clouding was not observed.
The concentration of calcium compound as an impurity in the starting material magnesium hydroxide and in the final product L-ascorbic acid 2-phosphate magnesium salt was measured by ICP (manufactured by Seiko Instruments K.K.) (similarly measured in Example 2 and Comparative Examples 1 to 2 below) .
Comparative Example 1
An L-ascorbic acid 2-phosphate magnesium salt as a white dry product was obtained in the same manner as in Example 1 except that magnesium hydroxide having an impurity calcium compound content of 2,500 ppm in terms of calcium ion was used in place of the magnesium hydroxide having an impurity calcium compound content of 500 ppm in
terms of calcium ion in Example 1. The calcium compound content in this white dry product was 580 ppm. Using this dry product, in-solution stability tests 1 and 2 described later were performed. In both in-solution stability tests 1 and 2, clouding was observed at room temperature (20°C) and more distinguished clouding was observed at 50°C.
Example 2
In a nitrogen atmosphere, 100 g of L-ascorbic acid was added to and dissolved in a mixed solvent containing 1,350 ml of pure water and 150 g of pyridine and after cooling to 0 to 10°C, an aqueous 10% sodium hydroxide solution was added to adjust the pH to about 12. To the resulting solution, 150 g of phosphorus oxychloride was added dropwise and while adjusting the pH to 12 with an aqueous 10% sodium hydroxide solution, a reaction was performed by keeping the temperature at 0 to 10°C. After the completion of dropwise addition, the pH was adjusted to about 7 with 35% hydrochloric acid and pyridine was distilled off under reduced pressure. Thereafter, 35% hydrochloric acid was added to adjust the pH to 4.
The reaction solution after such adjustment of pH was diluted by adding 6,500 ml of pure water, passed through a column packed with 2,000 ml of a moderately basic anion exchange resin (Amberlite IRA-68, produced by Organo) and then developed with 23,500 ml of 0.05N hydrochloric acid and further with 11,000 ml of 0.2N hydrochloric acid to obtain a fraction containing 2-AP. An aqueous solution of this fraction was dialyzed using an
electrodialyser (Model DU-Ob, manufactured by Asahi Glass K.K.) until chlorine ion was reduced to 500 ppm. While keeping the dialysate solution at 15°C, magnesium oxide having an impurity calcium compound content of 1,000 ppm in terms of calcium ion was added to give a pH of 10.1 after the addition. This solution was left standing for 2 hours and the supernatant was filtered to remove insoluble matters. The resulting solution was concentrated to one- tenth (1/10) and after adding a two-fold amount of methanol, the generated solid portion was collected by filtration. The obtained wet body was recrystallized with water- methanol and then dried to obtain an L-ascorbic acid 2- phosphate magnesium salt as a white dry product. The impurity calcium compound content in this white dry product was 280 ppm in terms of calcium ion. Using this dry product, in-solution stability tests 1 and 2 described later were performed, as a result, clouding was not observed.
Comparative Example 2
An L-ascorbic acid 2-phosphate magnesium salt as a white dry product was obtained in the same manner as in Example 2 except that magnesium oxide having an impurity calcium compound content of 3,000 ppm in terms of calcium ion was used in place of the magnesium oxide having an impurity calcium compound content of 1,000 ppm in terms of calcium ion in Example 2. The calcium compound content in this white dry product was 750 ppm in terms of calcium ion. Using this dry product, in-liquid stability tests described later were performed. As a result, in the in-solution
stability test 1, clouding was observed when the dry product was allowed to stand at room temperature, and more distinguished clouding was observed when allowed to stand at 50°C. In the in-liquid stability test 2, distinguished clouding was observed under both conditions of room temperature and 50°C.
In-solution Stability Test 1
Into a 200 ml-volume Erlenmeyer flask, 2 g of a sample (APM), 0.4 g of sodium citrate dihydrate and 0.05 g of citric acid were charged. Thereto, 16 g of glycerol • 1, 3- butylene glycol -ethanol mixed solution (volume ratio: 3:5:8) was added and the resulting solution was stirred for 30 minutes. Thereto, 82 g of pure water was added and the resulting solution was further stirred for 2 hours. After filtering this solution through a filter, a half amount was left standing at room temperature (20°C) for 1 month and the remaining half amount was left standing at 50°C for 10 days. Each solution was observed with an eye on the clouding state.
The observation results are shown in Table 1.
In-solution Stability Test 2
Into a 200 ml-volume Erlenmeyer flask, 2 g of a sample (APM), 0.4 g of sodium citrate dihydrate and 0.05 g of citric acid were charged. Thereto, 15 g of glycerol • 1, 3- butylene glycol • ethanol mixed solution (volume ratio: 3:5:8) was charged and the resulting solution was stirred for 30 minutes. Thereto, 82 g of pure water was added and
further stirred for 2 hours. After filtering this solution through a filter, a half amount was left standing at room temperature (20°C) for 1 month and the remaining half amount was left standing at 50°C for 10 days. Each solution was observed with an eye on the clouding state.
The observation results are shown in Table 1.
Table 1
A* No clouding, B "• Clouded, C: Distinguished Clouding
Effect of the Invention
According to the production process of the present invention, L-ascorbic acid 2-phosphate metal salt with a low calcium content can be produced, where the content of calcium compound as an impurity contained in the L-ascorbic acid 2-phosphate metal salt, giving rise to clouding, precipitation or deposition, is reduced to 500 ppm or less in terms of calcium ion. The L-ascorbic acid 2-phosphate metal salt with a low calcium content according to the present invention can be free of clouding, precipitation or deposition during storage either at room temperature or at a high temperature (for example, 50°C) when the L-ascorbic
acid 2-phosphate metal salt is blended in a cosmetic material containing particularly an organic acid, and therefore, can be suitably used for this usage. Furthermore, this L-ascorbic acid 2-phosphate metal salt can exhibit stability during the same storage as above even when blended in a medical, feed or food material containing particularly an organic acid, and therefore, can be widely used in various industrial fields .
Claims
1. An L-ascorbic acid-2-phosphate metal salt with a low calcium content characterized in that the content of a calcium compound is 500 ppm or less in terms of calcium ion.
2. The L-ascorbic acid-2-phosphate metal salt with a low calcium content as claimed in claim 1, wherein the L- ascorbic acid-2-phosphate metal salt is a salt of alkaline earth metal other than calcium, alkali metal salt, zinc salt, aluminum salt or titanium salt.
3. The L-ascorbic acid-2-phosphate metal salt with a low calcium content as claimed in claim 1, wherein the L- ascorbic acid-2-phosphate metal salt is sodium salt, potassium salt, magnesium salt, zinc salt or aluminum salt.
4. The L-ascorbic acid-2-phosphate metal salt with a low calcium content as claimed in claim 1, wherein the L- ascorbic acid-2-phosphate metal salt is potassium salt, magnesium salt or zinc salt.
5. The L-ascorbic acid-2-phosphate metal salt with a low calcium content as claimed in claim 1, wherein the L- ascorbic acid-2-phosphate metal salt is magnesium salt.
6. A process for producing an L-ascorbic acid-2-phosphate metal salt with a low calcium content wherein the content of a calcium compound is 500 ppm or less in terms of calcium ion, said process is characterized by adding a metal compound containing a calcium compound in an amount of 2,000 ppm or less in terms of calcium ion to a solution containing an L-ascorbic acid-2-phosphoric ester.
7. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in claim 6, wherein the metal compound is any one of potassium compound, sodium compound, magnesium compound or zinc compound, and the resulting L-ascorbic acid-2- phosphate metal salt is any one of potassium salt, sodium salt, magnesium salt or zinc salt.
8. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in claim 6, wherein the metal compound is any one of magnesium oxide or magnesium hydroxide, and the resulting L-ascorbic acid-2-phosphate metal salt is magnesium salt.
9. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in any one of claims 6 to 8, wherein the solution containing an L-ascorbic acid-2-phosphoric ester contains alkali metal ion or alkaline earth metal ion in an amount of 10 ppm or less in terms of the L-ascorbic acid-2- phosphoric ester.
10. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in claim 9, wherein the solution containing an L-ascorbic acid-2-phosphoric ester contains alkali metal ion or alkaline earth metal ion in an amount of 1 ppm or less in terms of the L-ascorbic acid-2-phosphoric ester.
11. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in claim 9 or 10, wherein the solution containing an L- ascorbic acid-2-phosphoric ester is prepared by a method comprising reacting L-ascorbic acid, an alkali metal hydroxide and phosphorylating agent in the presence of water, and removing metal ion from the resulting solution of L-ascorbic acid-2-phosphate metal salt by using ion exchange resin.
12. The process for producing an L-ascorbic acid-2- phosphate metal salt with a low calcium content as claimed in claim 11, wherein the ion exchange resin is weakly or moderately basic anion-exchange resin.
13. A low-clouding cosmetic material characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content claimed in claim 1 is blended.
14. The low-clouding cosmetic material as claimed in claim 13, wherein the cosmetic material is lotion.
15. The low-clouding cosmetic material as claimed in claim 13 or 14, wherein 0.1 to 10 % by weight of organic acid is blended in the cosmetic material.
16. A low-clouding medical preparation characterized in that the L-ascorbic acid 2-phosphate metal salt with a low calcium content claimed in claim 1 is blended.
17. A low-clouding beverage characterized in that the L- ascorbic acid 2-phosphate metal salt with a low calcium content claimed in claim 1 is blended.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/469,527 US20040092485A1 (en) | 2001-03-02 | 2002-03-01 | Ascorbic acid 2-phosphate metal salt with low calcium content |
| EP02701682A EP1368362A1 (en) | 2001-03-02 | 2002-03-01 | Ascorbic acid 2-phosphate metal salt with low calcium content |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001-57982 | 2001-03-02 | ||
| JP2001057982A JP2002255981A (en) | 2001-03-02 | 2001-03-02 | Magnesium salt of ascorbic acid-2-phosphate having reduced content of calcium |
| US27503301P | 2001-03-13 | 2001-03-13 | |
| US60/275,033 | 2001-03-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002070531A1 true WO2002070531A1 (en) | 2002-09-12 |
Family
ID=26610496
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2002/001926 WO2002070531A1 (en) | 2001-03-02 | 2002-03-01 | Ascorbic acid 2-phosphate metal salt with low calcium content |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1368362A1 (en) |
| CN (1) | CN1216061C (en) |
| WO (1) | WO2002070531A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101247834B (en) * | 2005-06-17 | 2013-10-30 | 生命健康科学公司 | Carrier comprising one or more di and/or mono-(electron transfer agent) phosphate derivatives or complexes thereof |
| CN101550163B (en) * | 2008-10-06 | 2011-09-07 | 北京贝丽莱斯生物化学有限公司 | Production process for preparing vitamin C-2-magnesium phosphate from vitamin C-2-magnesium phosphate crude product |
| CN101735274A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Technology for processing vitamin c phosphate magnesium |
| CN101735275A (en) * | 2008-11-18 | 2010-06-16 | 高锦秋 | Method for producing vitamin c phosphate magnesium |
| CN101747376B (en) * | 2010-01-15 | 2012-05-23 | 北京化工大学 | Method for extracting ascorbyl-2-phosphate through bipolar membrane electrodialysis |
| CN108690076A (en) * | 2018-04-19 | 2018-10-23 | 安徽顺利生物有限公司 | The preparation method of the remaining Magnesium L-Ascorbyl Phosphate of organic solvent-free |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63243014A (en) * | 1987-03-31 | 1988-10-07 | Pola Chem Ind Inc | Beautifying and whitening cosmetic |
| JPH02131494A (en) * | 1988-08-25 | 1990-05-21 | Kyowa Hakko Kogyo Co Ltd | Crystal or sodium l-ascorbate 2-phosphate and production thereof |
| US4999437A (en) * | 1989-03-21 | 1991-03-12 | Basf Aktiengesellschaft | Preparation of ascorbic acid 2-phosphate and of 5, 6-isopropylideneascorbic acid and potassium magnesium l-ascorbate 2-phosphate as an advantageous salt of l-ascorbic acid 2- phosphate |
| EP0866069A2 (en) * | 1997-03-18 | 1998-09-23 | F. Hoffmann-La Roche Ag | Preparation of ascorbyl monophosphates |
| EP0884321A1 (en) * | 1997-06-11 | 1998-12-16 | Showa Denko Kabushiki Kaisha | Ascorbic acid 2-phosphate zinc salt and process for manufacturing the same |
| US6121464A (en) * | 1998-07-13 | 2000-09-19 | Basf Ag | Preparation of salts of ascorbyl 2-phosphoric esters |
-
2002
- 2002-03-01 WO PCT/JP2002/001926 patent/WO2002070531A1/en active Application Filing
- 2002-03-01 CN CN 02805868 patent/CN1216061C/en not_active Expired - Lifetime
- 2002-03-01 EP EP02701682A patent/EP1368362A1/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63243014A (en) * | 1987-03-31 | 1988-10-07 | Pola Chem Ind Inc | Beautifying and whitening cosmetic |
| JPH02131494A (en) * | 1988-08-25 | 1990-05-21 | Kyowa Hakko Kogyo Co Ltd | Crystal or sodium l-ascorbate 2-phosphate and production thereof |
| US4999437A (en) * | 1989-03-21 | 1991-03-12 | Basf Aktiengesellschaft | Preparation of ascorbic acid 2-phosphate and of 5, 6-isopropylideneascorbic acid and potassium magnesium l-ascorbate 2-phosphate as an advantageous salt of l-ascorbic acid 2- phosphate |
| EP0866069A2 (en) * | 1997-03-18 | 1998-09-23 | F. Hoffmann-La Roche Ag | Preparation of ascorbyl monophosphates |
| EP0884321A1 (en) * | 1997-06-11 | 1998-12-16 | Showa Denko Kabushiki Kaisha | Ascorbic acid 2-phosphate zinc salt and process for manufacturing the same |
| US6121464A (en) * | 1998-07-13 | 2000-09-19 | Basf Ag | Preparation of salts of ascorbyl 2-phosphoric esters |
Non-Patent Citations (2)
| Title |
|---|
| PATENT ABSTRACTS OF JAPAN vol. 013, no. 049 (C - 565) 3 February 1989 (1989-02-03) * |
| PATENT ABSTRACTS OF JAPAN vol. 014, no. 356 (C - 0745) 2 August 1990 (1990-08-02) * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1494547A (en) | 2004-05-05 |
| CN1216061C (en) | 2005-08-24 |
| EP1368362A1 (en) | 2003-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3979510A (en) | Aluminum-zirconium anti-perspirant systems with complex aluminum buffers | |
| JP3772468B2 (en) | L-ascorbic acid-2-phosphate zinc salt and method for producing the same | |
| EP1368362A1 (en) | Ascorbic acid 2-phosphate metal salt with low calcium content | |
| JP2954640B2 (en) | Lotion | |
| US3947556A (en) | Zinc complexes of basic aluminum chlorides and methods of making same | |
| US4108962A (en) | Process of stabilization of anhydrous dibasic calcium phosphate against fluorine ions with 3-amino-1-hydroxypropane-1,1-diphosphonic acid | |
| EP0040521B1 (en) | Antacid material based on magnesium aluminium hydroxide and the preparation thereof | |
| US20040092485A1 (en) | Ascorbic acid 2-phosphate metal salt with low calcium content | |
| CA1193419A (en) | Process for the manufacture of highly pure trimagnesium phosphate octahydrate of high purity | |
| EP0291960B1 (en) | Novel synthetic aluminum silicate preparation | |
| US3734734A (en) | Deproteinizing protein-containing solutions | |
| JP2810722B2 (en) | Cosmetics | |
| US3506761A (en) | Combinations of aluminum-coordinating therapeutic adjuvants and aluminum chelates and process for making and using the same | |
| EP0020617B1 (en) | Dentifrice | |
| JP4991088B2 (en) | Stabilized derivative of ascorbic acid-3-phosphate | |
| US6420419B1 (en) | L-ascorbic acid 2-phosphate zinc salt and process for manufacturing the same | |
| JP3750160B2 (en) | Amorphous L-ascorbic acid-2-phosphate ester sodium salt and method for producing the same | |
| WO2022082320A1 (en) | Process for obtaining a purified psychoactive alkaloid solution | |
| WO2020170840A1 (en) | CRYSTAL OF POTASSIUM SALT OF 2-O-α-D-GLUCOSYL-L-ASCORBIC ACID AND PRODUCTION METHOD THEREFOR | |
| JP3913278B2 (en) | Method for stabilizing pH of aqueous lactic acid or glycolic acid solution and skin cosmetic | |
| EP0658565A1 (en) | Oral products | |
| US6271397B1 (en) | L-ascorbic acid-2-phosphoric acid potassium crystal and method for producing the same | |
| EP0962461A1 (en) | Crystalline potassium salt of L-ascorbic acid-2-phosphoric acid and method for producting the same | |
| AU2012201606A1 (en) | Crystalline levofolinic acid and process for its preparation | |
| EP1072605B1 (en) | Process for producing ascorbic acid-2-phosphoric ester salts |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2002701682 Country of ref document: EP Ref document number: 10469527 Country of ref document: US Ref document number: 028058682 Country of ref document: CN |
|
| WWP | Wipo information: published in national office |
Ref document number: 2002701682 Country of ref document: EP |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |