CN1765882A - Water soluble vitamins D2 preparation method - Google Patents
Water soluble vitamins D2 preparation method Download PDFInfo
- Publication number
- CN1765882A CN1765882A CN 200410040903 CN200410040903A CN1765882A CN 1765882 A CN1765882 A CN 1765882A CN 200410040903 CN200410040903 CN 200410040903 CN 200410040903 A CN200410040903 A CN 200410040903A CN 1765882 A CN1765882 A CN 1765882A
- Authority
- CN
- China
- Prior art keywords
- vitamins
- water
- emulsion
- soluble
- soluble vitamins
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 229940088594 vitamin Drugs 0.000 title description 10
- 229930003231 vitamin Natural products 0.000 title description 10
- 235000013343 vitamin Nutrition 0.000 title description 10
- 239000011782 vitamin Substances 0.000 title description 10
- 239000000839 emulsion Substances 0.000 claims abstract description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- -1 glyceryl fatty acid ester Chemical class 0.000 claims abstract description 27
- 238000003756 stirring Methods 0.000 claims abstract description 21
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 19
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 16
- 239000000194 fatty acid Substances 0.000 claims abstract description 16
- 229930195729 fatty acid Natural products 0.000 claims abstract description 16
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 238000001035 drying Methods 0.000 claims abstract description 11
- 229930006000 Sucrose Natural products 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 7
- 239000005720 sucrose Substances 0.000 claims abstract description 7
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 claims abstract description 5
- 239000011710 vitamin D Substances 0.000 claims description 154
- 235000019166 vitamin D Nutrition 0.000 claims description 154
- 239000000203 mixture Substances 0.000 claims description 42
- 238000009472 formulation Methods 0.000 claims description 24
- 238000004945 emulsification Methods 0.000 claims description 16
- 239000012530 fluid Substances 0.000 claims description 13
- 239000007788 liquid Substances 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 10
- 230000001804 emulsifying effect Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 229920002521 macromolecule Polymers 0.000 claims description 6
- 238000003801 milling Methods 0.000 claims description 5
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 claims description 4
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 claims description 4
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 claims description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000013305 food Nutrition 0.000 abstract description 13
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 8
- 239000008103 glucose Substances 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 abstract description 4
- 239000002775 capsule Substances 0.000 abstract description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 abstract 3
- 229960002061 ergocalciferol Drugs 0.000 abstract 3
- 235000001892 vitamin D2 Nutrition 0.000 abstract 3
- 239000011653 vitamin D2 Substances 0.000 abstract 3
- QSVJYFLQYMVBDR-UHFFFAOYSA-N Ergosterin Natural products C1C(O)CCC2(C)C3=CCC4(C)C(C(C)C=CC(C)C(C)C)CCC4C3=CC=C21 QSVJYFLQYMVBDR-UHFFFAOYSA-N 0.000 abstract 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- DNVPQKQSNYMLRS-APGDWVJJSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-APGDWVJJSA-N 0.000 abstract 1
- 230000001678 irradiating effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000010298 pulverizing process Methods 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 10
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 150000003722 vitamin derivatives Chemical class 0.000 description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 229930003316 Vitamin D Natural products 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 229960005069 calcium Drugs 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 150000003710 vitamin D derivatives Chemical class 0.000 description 6
- 229940046008 vitamin d Drugs 0.000 description 6
- 230000000996 additive effect Effects 0.000 description 5
- 238000005303 weighing Methods 0.000 description 4
- 241000283725 Bos Species 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 208000007442 rickets Diseases 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 208000027219 Deficiency disease Diseases 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 208000037147 Hypercalcaemia Diseases 0.000 description 2
- 206010025476 Malabsorption Diseases 0.000 description 2
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 208000003217 Tetany Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000008452 baby food Nutrition 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 230000000148 hypercalcaemia Effects 0.000 description 2
- 208000030915 hypercalcemia disease Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 208000008822 Ankylosis Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 208000000381 Familial Hypophosphatemia Diseases 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013038 Hypocalcemia Diseases 0.000 description 1
- 208000000038 Hypoparathyroidism Diseases 0.000 description 1
- 208000029663 Hypophosphatemia Diseases 0.000 description 1
- 206010023129 Jaundice cholestatic Diseases 0.000 description 1
- 206010023198 Joint ankylosis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 201000005267 Obstructive Jaundice Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000035467 Pancreatic insufficiency Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 235000013927 calcium gluconate Nutrition 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
- 229960002401 calcium lactate Drugs 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 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
- 244000309466 calf Species 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003278 egg shell Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 230000000705 hypocalcaemia Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 231100000567 intoxicating Toxicity 0.000 description 1
- 230000002673 intoxicating effect Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 235000016236 parenteral nutrition Nutrition 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 208000006078 pseudohypoparathyroidism Diseases 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000002037 soft tissue calcification Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention relates to preparation field of water-soluble vitamin D2, which comprises: adding the medical or food vitamin D2 or vitamin D2 obtained by irradiating ergosterin to break its ninth and tenth bonds into emulsifier of glyceryl fatty acid ester dissolved in ethanol to prepare emulsion of D2; heating and dissolving the macromolecular material, such as glucose, adding sucrose fatty acid ester as emulsifier to stir and obtain the emulsion of carrier reagent for D2; mixing said two solution; drying, pulverizing, and obtaining the product, or as capsule or tablet. This product can be used as drug or food or feed addictive diluted by water with any proportion.
Description
Technical field
The present invention relates to vitamins D
2Field, particularly water-soluble vitamins D
2The preparation method field.
Background technology
Vitamins D
2Be that humans and animals is kept normal activities and one of healthy necessary micro-organic compound, can add vitamins D in right amount in medicine, food and the feed
2Satisfying the human or animal absorbs from the external world regularly.Vitamins D
2It is the main natural form of the vitamins D in plant, found.(referring to Chinese patent 95118188.2).And VITAMIN is divided into two classes according to its solubleness is liposoluble vitamin (A, D, E, K) etc., or water-soluble vitamins (B
1, B
2, B
6, B
12, folic acid, nicotinic acid and vitamins C)] etc.[see " pharmaceutical chemistry " the 15th chapter, one, the classification of VITAMIN (the refined rosy clouds of the central TV university farming doctor king of portion).Because vitamins D
2Water insoluble and be dissolved in fat and fatsolvent, therefore often in food coexist with lipid, also closely related when intestinal absorption with the absorption of lipid, as human or animal during to the malabsorption of lipid, liposoluble vitamin D
2Absorption can reduce, thereby cause corresponding deficiency disease.At vitamins D medically
2Principal indication comprise three aspects, one, be used for the prevention and the treatment of vitamin D deficiency.As: vegan, parenteral nutrition patient, pancreatic insufficiency companion malabsorption syndrome, liver and gall diseases (hepatic disorder, liver cirrhosis, obstructive jaundice), disease of intestine (pimelorrhea, regional enteritis, long-term diarrhea), stomach excision etc.Two, be used for chronic hypocalcemia, hypophosphatemia, rickets and with the treatment of osteomalacia, familial hypophosphatemia and the hypoparathyroidism (postoperative, special property or the Pseudohypoparathyroidism sent out) of chronic renal insufficiency.Three, be used for the treatment of acute and chronic and potential operation back tetany disease and the special property sent out tetany disease.And the animal vitamins D
2The feature of deficiency disease show as: vitamins D
2When not enough, even calcium, phosphorus abundance, animal can not well utilize, and calcium, phosphorus, the magnesium deposition in bone can descend; Hypoplasia of tooth, growth retardation rickets and rickets appear, in the osteogenesis generation obstacle of young animal; Adult animals generation osteoporosis is easily fractured joint deformity; Dam pregnancy period vitamins D
2Excessively shortage can cause newborn young baby's congenital malformation, and dam itself also can suffer damage; The poultry D that is deficient in vitamin
2Can reduce egg productivity and hatching rate, eggshell approaches and easily embrittlement.Therefore under the condition of the artificial mass rearing animal of modern mechanicalization, more need vitamin D Can
2Yet excessive use vitamins D
2Be deleterious, take in heavy dose in a short time or take the overdose vitamins D for a long time according to relevant medical information prompting
2, can cause serious toxic reaction.Vitamins D
2The hypercalcemia of poisoning and to cause can cause general angiosteosis, kidney marl and other soft tissue calcifications, and hypertension induced and renal failure, and above-mentioned untoward reaction pilosity is born in hypercalcemia and during with hyperphosphatemia.Children can cause cessation of growth cessation, see the prolonged application vitamins D repeatly
2Behind every days 1800 units, toxic dose can be different because of individual difference.Even use 10,000 units every day above after the several months, to also intoxicating reaction of normal adult.Vitamins D
2Poisoning can cause death because of kidney, cardiovascular function depletion.Animal pregnancy excess intake vitamins D
2Can cause the young deformity of tire, the animal vitamins D
2Poisoning manifestations is higher urinary calcium, apocleisis, nausea and vomiting, thirsty, diuresis, weak, arthralgia and general disorientation, excessive vitamins D
2Causing that blood calcium is too high makes unnecessary calcium be deposited on heart, blood vessel, joint, pericardium or intestines wall, causes heart failure, ankylosis or enteron aisle illness, in addition dead.Two kinds of principal modes of vitamins D are vitamins Ds
2And vitamins D
3, it is generally acknowledged that they demonstrate similar biological activity, the same metabolism (i.e. activation and katabolism) is arranged, but have data to think; " vitamins D
310～20 times of toxicity to vitamins D
2, this is because vitamins D
3Be easy to be metabolised to 25-hydroxyl-D
3Reason, Trunnel etc. (1990) feed vitamins D, A and E mixture for the milk calf of 15 7～10 ages in days and cross-bred ox, every day Dry Vitamin D3 100 cws 000,000 units, vitamin-E 880,000 units.All as a result oxen all show lassitude, apocleisis, depilation, symptoms such as dysbasia, wherein 6 death after feeding 13～27.To wherein 3 its row dissection discoveries, at Pulmonic internal surface the reddish-brown precipitation thing is arranged, the liver light discolouration.6 oxen in 8 oxen are carried out blood chemical examination, find 25-hydroxyl-D in the blood plasma
3And calcium
2+Concentration obvious rising is all arranged." (referring to people such as " security of liposoluble vitamin additive " author Huang Tao, Chen Xibin, Sheng Jinpeng, Chinese culturing net).According to State Standard of the People's Republic of China GB14880-94 " food enrichment use hygienic standard " to vitamins D (D
2Or D
3) use range and per kilogram usage quantity be defined as; Breast and milky-drinks 10～40 μ g, oleomargarine 125～156 μ g, milk-product 63～125 μ g, infant or baby food 50～100 μ g (1 μ g vitamins D=40 unit vitamin D).And be vitamins D (IU/kg) for vitamins D as the national standard of safe feeding addition, pig 114-240, chicken 200～500, duck 400～900.Because the consumption of vitamins D is a unit with μ g, liposoluble vitamin D
2When mixing, be difficult to the control consumption and be difficult for mixing and cause product defective, therefore, add vitamins D in domestic food or the feedstuff industry with food or feed
2Product few.Vitamins D
2Be about 1800 tons at present global year consumption, wherein about 70% are used for fodder additives.China's annual requirement is about more than 100 ton.Present global vitamins D
2Market is learned company and is controlled by BASF AG, Roche Holding Ag, day Qinghua, mainly supplies Europe and Japanese market, and these VITAMIN are made giant in the VITAMIN in the whole world is sold, and are sold to terminal client by multidimensional and Preblend more than 40%.The retrieval novelty assessment report that provides according to patent information center, Sichuan Province shows through the result for retrieval to China and foreign countries' patent database still to find no water-soluble vitamins D
2The technical information of aspect.
Goal of the invention:
The objective of the invention is at liposoluble vitamin D
2The problems referred to above that exist adopt emulsifying agent with liposoluble vitamin D
2(medical grade, food grade vitamins D
2, or with ergosterol through irradiation make 9,10 bond ruptures and vitamins D
2Crude product), make the water-soluble water-soluble vitamins D of energy
2Method:
Summary of the invention
Water-soluble vitamins D of the present invention
2The preparation method, carry out as follows:
(1) vitamins D
2Emulsification
Emulsifying agent is dissolved in the ethanol, adds vitamins D again
2, vitamins D wherein
2With emulsifying agent, alcoholic acid ratio be 1: (0.2～0.5): 2 (g: g: ml), form vitamins D
2Emulsion.
(2) vitamins D
2The emulsification of carrier formulation
The heating for dissolving in water with macromolecular substance or synthesising biological degradability macromolecular substance adds emulsifying agent again and stirs the companion evenly, and wherein the weight ratio of carrier formulation and emulsifying agent is 1: (0.01～0.02) gets vitamins D
2The emulsion of carrier formulation.
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 65 of carrier formulation ℃～75 ℃ is vitaminize D again
2Emulsion, fully stir the companion evenly, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2
Water-soluble vitamins D of the present invention
2The preparation method preferably scheme be the vitamins D that in step (1), adds
2Be with ergosterol through irradiation make 9,10 bond ruptures and vitamins D
2Crude product.
Water-soluble vitamins D of the present invention
2The better scheme of preparation method be to increase following steps in step (3) back:
(4) drying
With vitamins D
2Mix emulsion fluid is put into the loft drier inner drying, gets block or granulous water-soluble vitamins D
2
(5) with dried bulk or granulous water-soluble vitamins D
2Milling is ground into powdery, obtains powdered water-soluble vitamins D
2
Water-soluble vitamins D of the present invention
2The preparation method, also can carry out as follows:
(1) vitamins D
2Emulsification
Emulsifying agent is dissolved in the ethanol, adds vitamins D again
2, vitamins D wherein
2With emulsifying agent, alcoholic acid ratio be 1: (8～10): (8～10) (g: g: ml), form vitamins D
2Emulsion.
(2) with vitamins D
2Emulsion and carrier formulation mixing and stirring, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2
The emulsifying agent that uses in the above-mentioned steps is the tensio-active agent that contains hydrophilic radical and lipophilic group, and majority is the ester class.Commonly used have glycerine fatty acid fat, sucrose fatty acid ester, Span, propylene glycol fatty acid ester, polyoxyethylene fatty acid sorbitol ester, a polyoxyethylene fatty acid glyceride etc.Also can use emulsifying agents such as sodium lauryl sulphate, polyvinylpyrrolidone.
The macromolecular substance that uses in the above-mentioned steps is glucose, calcium lactate, calcium gluconate etc., and synthesising biological degradability macromolecular substance is liposome, beta-cyclodextrin, agar glycan globule etc.
Adopt the method for the present invention can be with liposoluble vitamin D
2Making can be with the water-soluble water-soluble vitamins D of required arbitrary proportion
2, it can be made liquid, powdery, capsule or tablet, can satisfy fields such as medicine, food, feed to vitamins D
2Application requiring.
Specific embodiment
Embodiment 1:
(1) vitamins D
2Emulsification
The 20g glycerol fatty acid ester is dissolved in the ethanol of 200ml, adds the 100g vitamins D again
2, stir the companion back and form vitamins D
2Emulsion;
(2) vitamins D
2The emulsification of carrier formulation
1000g glucose adding distil water heating for dissolving is added 1% sucrose fatty ester again stir the companion evenly, obtain vitamins D
2The emulsion of carrier formulation;
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 65 of carrier formulation ℃ adds vitamins D again
2Emulsion, stir, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2Finished product can be directly as medicine, and the additive of food or feed uses, and it can be interpreted as required arbitrary proportion by the uniform weighing apparatus of water.
Embodiment 2
(1) vitamins D
2Emulsification
The 50g glycerol fatty acid ester is dissolved in the ethanol of 200ml, adds the 100g vitamins D again
2, stir the back and form vitamins D
2Emulsion;
(2) vitamins D
2The emulsification of carrier formulation
2000g glucose adding distil water heating for dissolving concentrated make the glucose syrup of sugar degree 90% or more, adding 2% sucrose fatty ester again, to stir the companion even, obtains vitamins D
2The emulsion of carrier formulation;
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 75 of carrier formulation ℃ adds vitamins D again
2Emulsion, stir, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2Finished product can be directly as medicine, and the additive of food or feed uses, and it can be interpreted as required arbitrary proportion by the uniform weighing apparatus of water.
Embodiment 3
(1) vitamins D
2Emulsification
The 20g glycerol fatty acid ester is dissolved in the ethanol of 200ml, add again 100g with ergosterol through irradiation make 9,10 bond ruptures and vitamins D
2Crude product stirs the companion back and forms vitamins D
2Emulsion;
(2) vitamins D
2The emulsification of carrier formulation
1000g glucose adding distil water heating for dissolving is added 1% sucrose fatty ester again stir the companion evenly, obtain vitamins D
2The emulsion of carrier formulation;
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 65 of carrier formulation ℃ adds vitamins D again
2Emulsion, stir, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2Finished product can be directly as medicine, and the additive of food or feed uses, and it can be interpreted as required arbitrary proportion by the uniform weighing apparatus of water.
Embodiment 4
(1) vitamins D
2Emulsification
The 50g glycerol fatty acid ester is dissolved in the ethanol of 200ml, adds the 100g vitamins D again
2, stir the back and form vitamins D
2Emulsion;
(2) vitamins D
2The emulsification of carrier formulation
2000g glucose adding distil water heating for dissolving concentrated make the glucose syrup of sugar degree 90% or more, adding 2% sucrose fatty ester again, to stir the companion even, obtains vitamins D
2The emulsion of carrier formulation;
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 75 of carrier formulation ℃ adds vitamins D again
2Emulsion, stir, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2Finished product can be directly as medicine, and the additive of food or feed uses, and it can be interpreted as required arbitrary proportion by the uniform weighing apparatus of water.
(4) drying
With vitamins D
2Mix emulsion fluid is put into the loft drier inner drying, gets block or granulous water-soluble vitamins D
2
(5) with dried bulk or granulous water-soluble vitamins D
2Milling is ground into powdery, obtains powdered water-soluble vitamins D
2
Embodiment 5
(1) vitamins D
2Emulsification
With dissolving in the 1000g polyvinylpyrrolidone adding 1000ml ethanol, add the 50g sodium lauryl sulphate again, mix, and then adding contains the 100g vitamins D
2The 200ml ethanolic soln, mix, vitamins D
2Emulsion;
(2) mixing and emulsifying
With carrier formulation dextrin 2850g and vitamins D
2The emulsion mixing and stirring gets liquid water-soluble vitamins D
2
Embodiment 6
(1) vitamins D
2Emulsification
With dissolving in the 750g polyvinylpyrrolidone adding 800ml ethanol, add the 50g sodium lauryl sulphate again, mix, and then adding contains the 100g vitamins D
2The 200ml ethanolic soln, mix, vitamins D
2Emulsion;
(2) mixing and emulsifying
With carrier formulation dextrin 4100g and vitamins D
2The emulsion mixing and stirring gets liquid water-soluble vitamins D
2
(3) drying
With vitamins D
2Mix emulsion fluid is put into the loft drier inner drying, gets block or granulous water-soluble vitamins D
2
(4) with dried bulk or granulous water-soluble vitamins D
2Milling is ground into powdery, obtains powdered water-soluble vitamins D
2
Claims (6)
1, a kind of water-soluble vitamins D
2The preparation method, it is characterized in that: this method is carried out as follows:
(1) vitamins D
2Emulsification
Emulsifying agent is dissolved in the ethanol, adds vitamins D again
2, vitamins D wherein
2With emulsifying agent, alcoholic acid ratio be 1: (0.2～0.5): 2 (g: g: ml), form vitamins D
2Emulsion;
(2) vitamins D
2The emulsification of carrier formulation
The heating for dissolving in water with macromolecular substance or synthesising biological degradability macromolecular substance adds emulsifying agent again and stirs the companion evenly, and wherein the weight ratio of carrier formulation and emulsifying agent is 1: (0.01～0.02) gets vitamins D
2The emulsion of carrier formulation.
(3) mixing and emulsifying
With vitamins D
2The emulsion temperature adjustment to 65 of carrier formulation ℃～75 ℃ is vitaminize D again
2Emulsion, fully stir the companion evenly, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2
2, the method for claim 1 is characterized in that: the vitamins D that adds in step (1)
2Be with ergosterol through irradiation make 9,10 bond ruptures and vitamins D
2Crude product.
3, method as claimed in claim 1 or 2 is characterized in that increasing following steps in step (3) back:
(4) drying
With vitamins D
2Mix emulsion fluid is put into the loft drier inner drying, gets block or granulous water-soluble vitamins D
2
(5) with dried bulk or granulous water-soluble vitamins D
2Milling is ground into powdery, obtains powdered water-soluble vitamins D
2
4, method as claimed in claim 3 is characterized in that described emulsifying agent is the tensio-active agent that contains hydrophilic radical and lipophilic group, and majority is the ester class; Commonly used have glycerine fatty acid fat, sucrose fatty acid ester, Span, propylene glycol fatty acid ester, polyoxyethylene fatty acid sorbitol ester, a polyoxyethylene fatty acid glyceride etc.; Also can use emulsifying agents such as sodium lauryl sulphate, polyvinylpyrrolidone.
5, a kind of water-soluble vitamins D
2The preparation method, it is characterized in that: this method is carried out as follows:
(1) vitamins D
2Emulsification
Emulsifying agent is dissolved in the ethanol, adds vitamins D again
2, vitamins D wherein
2With emulsifying agent, alcoholic acid ratio be 1: (8～10): (8～10) (g: g: ml), form vitamins D
2Emulsion.
(2) with vitamins D
2Emulsion and carrier formulation mixing and stirring, vitamins D
2Mix emulsion fluid, promptly liquid water-soluble vitamins D
2
6, as method as described in the claim 5, it is characterized in that: increase following steps in step (2) back:
(3) drying
With vitamins D
2Mix emulsion fluid is put into the loft drier inner drying, gets block or granulous water-soluble vitamins D
2
(4) with dried bulk or granulous water-soluble vitamins D
2Milling is ground into powdery, obtains powdered water-soluble vitamins D
2
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100409039A CN100364969C (en) | 2004-10-25 | 2004-10-25 | Water soluble vitamins D2 preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100409039A CN100364969C (en) | 2004-10-25 | 2004-10-25 | Water soluble vitamins D2 preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1765882A true CN1765882A (en) | 2006-05-03 |
| CN100364969C CN100364969C (en) | 2008-01-30 |
Family
ID=36742024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100409039A Expired - Lifetime CN100364969C (en) | 2004-10-25 | 2004-10-25 | Water soluble vitamins D2 preparation method |
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| Country | Link |
|---|---|
| CN (1) | CN100364969C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302168A (en) * | 2011-05-19 | 2012-01-04 | 四川内江汇鑫制药有限公司 | Vitamin D2 oil and preparation method thereof |
| CN107156456A (en) * | 2017-05-15 | 2017-09-15 | 南京群汇化工有限公司 | 25 hydroxycholecalciferol inclusion compounds and its preparation method and application |
| CN114230499A (en) * | 2021-12-20 | 2022-03-25 | 四川内江汇鑫制药有限公司 | Water-soluble vitamin D2Preparation method of (1) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59122424A (en) * | 1982-12-29 | 1984-07-14 | Riken Vitamin Co Ltd | Vitamin a composition and its preparation |
| JPS62281855A (en) * | 1986-05-29 | 1987-12-07 | Daikin Ind Ltd | Clathrate compound containing vitamin, vitamin derivative or hormone |
-
2004
- 2004-10-25 CN CNB2004100409039A patent/CN100364969C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302168A (en) * | 2011-05-19 | 2012-01-04 | 四川内江汇鑫制药有限公司 | Vitamin D2 oil and preparation method thereof |
| CN102302168B (en) * | 2011-05-19 | 2012-09-05 | 四川内江汇鑫制药有限公司 | Vitamin d2 oil and preparation method thereof |
| CN107156456A (en) * | 2017-05-15 | 2017-09-15 | 南京群汇化工有限公司 | 25 hydroxycholecalciferol inclusion compounds and its preparation method and application |
| CN114230499A (en) * | 2021-12-20 | 2022-03-25 | 四川内江汇鑫制药有限公司 | Water-soluble vitamin D2Preparation method of (1) |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100364969C (en) | 2008-01-30 |
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Assignee: Sichuan Neijiang Huixin Pharmaceutical Co.,Ltd. Assignor: Chen Guoping Contract record no.: 2011510000262 Denomination of invention: Method for preparing water soluble vitamin D[sub]2[/sub] Granted publication date: 20080130 License type: Exclusive License Open date: 20060503 Record date: 20110908 |
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| TR01 | Transfer of patent right |
Effective date of registration: 20180807 Address after: 641000 185 Gonghe street, Baima Town, Shizhong District, Neijiang, Sichuan Patentee after: Sichuan Neijiang Huixin Pharmaceutical Co.,Ltd. Address before: 641000 188 Forest Farm Road, Baima Town, Neijiang, Sichuan (Sichuan Xing Ming Tai Machinery Co., Ltd.) Patentee before: Chen Guoping |