CA2065603C - Stabilized vitamin d preparation - Google Patents
Stabilized vitamin d preparation Download PDFInfo
- Publication number
- CA2065603C CA2065603C CA002065603A CA2065603A CA2065603C CA 2065603 C CA2065603 C CA 2065603C CA 002065603 A CA002065603 A CA 002065603A CA 2065603 A CA2065603 A CA 2065603A CA 2065603 C CA2065603 C CA 2065603C
- Authority
- CA
- Canada
- Prior art keywords
- heat
- vitamin
- labile
- compound
- composition
- 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.)
- Expired - Lifetime
Links
- 229940046008 vitamin d Drugs 0.000 title abstract description 30
- 238000002360 preparation method Methods 0.000 title description 16
- 239000000203 mixture Substances 0.000 claims abstract description 74
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 47
- 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 claims abstract description 43
- 229960002061 ergocalciferol Drugs 0.000 claims abstract description 43
- 239000000126 substance Substances 0.000 claims abstract description 43
- 235000001892 vitamin D2 Nutrition 0.000 claims abstract description 43
- 239000011653 vitamin D2 Substances 0.000 claims abstract description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 239000003960 organic solvent Substances 0.000 claims abstract description 32
- 229920000642 polymer Polymers 0.000 claims abstract description 29
- 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 claims abstract description 22
- -1 vitamin D2 compound Chemical class 0.000 claims description 55
- 229940088594 vitamin Drugs 0.000 claims description 44
- 229930003231 vitamin Natural products 0.000 claims description 44
- 235000013343 vitamin Nutrition 0.000 claims description 44
- 239000011782 vitamin Substances 0.000 claims description 44
- 239000007787 solid Substances 0.000 claims description 31
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 25
- 229910052783 alkali metal Inorganic materials 0.000 claims description 21
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 13
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 13
- 229910000318 alkali metal phosphate Inorganic materials 0.000 claims description 13
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 11
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 235000011180 diphosphates Nutrition 0.000 claims description 11
- 150000001340 alkali metals Chemical class 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 10
- 239000011248 coating agent Substances 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 8
- 229920002126 Acrylic acid copolymer Polymers 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
- CRVGKGJPQYZRPT-UHFFFAOYSA-N diethylamino acetate Chemical compound CCN(CC)OC(C)=O CRVGKGJPQYZRPT-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims 6
- 238000000576 coating method Methods 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 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 abstract description 39
- 229930003316 Vitamin D Natural products 0.000 abstract description 29
- 235000019166 vitamin D Nutrition 0.000 abstract description 29
- 239000011710 vitamin D Substances 0.000 abstract description 29
- 150000003710 vitamin D derivatives Chemical class 0.000 abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 238000000354 decomposition reaction Methods 0.000 abstract description 2
- 238000002845 discoloration Methods 0.000 abstract description 2
- 238000006317 isomerization reaction Methods 0.000 abstract description 2
- 239000007970 homogeneous dispersion Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- 150000003722 vitamin derivatives Chemical class 0.000 description 35
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 14
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 14
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003085 diluting agent Substances 0.000 description 12
- 229920001059 synthetic polymer Polymers 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- 235000005282 vitamin D3 Nutrition 0.000 description 10
- 239000011647 vitamin D3 Substances 0.000 description 10
- 229940021056 vitamin d3 Drugs 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 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 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
- 235000010980 cellulose Nutrition 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 239000001923 methylcellulose Substances 0.000 description 6
- 241000894007 species Species 0.000 description 6
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229960005084 calcitriol Drugs 0.000 description 3
- 239000005018 casein Substances 0.000 description 3
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 3
- 235000021240 caseins Nutrition 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 229920001519 homopolymer Polymers 0.000 description 3
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000000395 magnesium oxide Substances 0.000 description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229940048086 sodium pyrophosphate Drugs 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 description 3
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 3
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 3
- 235000019801 trisodium phosphate Nutrition 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 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 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
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- 239000004375 Dextrin Substances 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
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- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
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- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
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- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
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- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
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- 239000011734 sodium Substances 0.000 description 2
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- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000001238 wet grinding Methods 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
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- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP076210-1991 | 1991-04-09 | ||
| JP7621091 | 1991-04-09 | ||
| JP019099-1992 | 1992-02-04 | ||
| JP1909992 | 1992-02-04 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2065603A1 CA2065603A1 (en) | 1992-10-10 |
| CA2065603C true CA2065603C (en) | 2007-04-03 |
Family
ID=26355908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002065603A Expired - Lifetime CA2065603C (en) | 1991-04-09 | 1992-04-08 | Stabilized vitamin d preparation |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US5487900A (2) |
| EP (1) | EP0508756B1 (2) |
| JP (1) | JPH05279260A (2) |
| KR (1) | KR100231633B1 (2) |
| AT (1) | ATE144424T1 (2) |
| AU (1) | AU649802B2 (2) |
| CA (1) | CA2065603C (2) |
| DE (1) | DE69214704T2 (2) |
| DK (1) | DK0508756T3 (2) |
| ES (1) | ES2094290T3 (2) |
| GR (1) | GR3021892T3 (2) |
| IE (1) | IE75709B1 (2) |
| NZ (1) | NZ242271A (2) |
| TW (1) | TW212761B (2) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19701264A1 (de) * | 1997-01-16 | 1998-07-23 | Kief Lizenz Verwertungsgesells | Heilmittel, enthaltend Betasitosterin und/oder Phytosterol/Betasitosteringemische |
| AU7895601A (en) * | 2000-07-18 | 2002-01-30 | Bone Care Int Inc | Stabilized 1alpha-hydroxy vitamin d |
| AU8252101A (en) * | 2000-08-30 | 2002-03-13 | Chugai Pharmaceutical Co Ltd | Oct preparations |
| JP2005515996A (ja) * | 2001-12-03 | 2005-06-02 | ノバセア インコーポレイティッド | 活性型ビタミンｄ化合物を含む薬学的組成物 |
| US20040058895A1 (en) * | 2002-09-18 | 2004-03-25 | Bone Care International, Inc. | Multi-use vessels for vitamin D formulations |
| US20040053895A1 (en) * | 2002-09-18 | 2004-03-18 | Bone Care International, Inc. | Multi-use vessels for vitamin D formulations |
| US7148211B2 (en) * | 2002-09-18 | 2006-12-12 | Genzyme Corporation | Formulation for lipophilic agents |
| US20050026877A1 (en) * | 2002-12-03 | 2005-02-03 | Novacea, Inc. | Pharmaceutical compositions comprising active vitamin D compounds |
| US20050020546A1 (en) * | 2003-06-11 | 2005-01-27 | Novacea, Inc. | Pharmaceutical compositions comprising active vitamin D compounds |
| US20060189586A1 (en) * | 2003-06-11 | 2006-08-24 | Cleland Jeffrey L | Pharmaceutical compositions comprising active vitamin D compounds |
| CA2624897C (en) * | 2005-10-12 | 2017-02-14 | Proventiv Therapeutics, Llc | Methods and articles for treating 25-hydroxyvitamin d insufficiency and deficiency |
| ES2593047T3 (es) | 2006-02-03 | 2016-12-05 | Opko Renal, Llc | Tratamiento de la insuficiencia y deficiencia de vitamina D con 25-hidroxivitamina D2 y 25-hidroxivitamina D3 |
| ES2670029T3 (es) | 2006-06-21 | 2018-05-29 | Opko Ireland Global Holdings, Ltd. | Terapia usando agente de repleción de la vitamina D y agente de reemplazo de la hormona de la vitamina D |
| US11752158B2 (en) | 2007-04-25 | 2023-09-12 | Eirgen Pharma Ltd. | Method of treating vitamin D insufficiency and deficiency |
| KR20190028822A (ko) | 2007-04-25 | 2019-03-19 | 사이토크로마 인코포레이티드 | 비타민 ｄ 화합물과 밀랍성 담체를 포함하는 경구 조절성 방출 조성물 |
| HUE073014T2 (hu) | 2007-04-25 | 2025-12-28 | Opko Renal Llc | Eljárás a másodlagos hyperparathyreoidismus biztonságos és hatékony kezelésére és megelõzésére krónikus vesebetegség esetén |
| US8592401B2 (en) | 2007-04-25 | 2013-11-26 | Proventiv Therapeutics, Llc | Methods and compounds for vitamin D therapy |
| EP2281058B1 (en) | 2008-04-02 | 2016-06-29 | Opko Ireland Global Holdings, Ltd. | Methods, compositions, uses, and kits useful for vitamin d deficiency and related disorders |
| WO2011123476A1 (en) | 2010-03-29 | 2011-10-06 | Cytochroma Inc. | Methods and compositions for reducing parathyroid levels |
| CA2698160C (en) * | 2010-03-30 | 2017-07-25 | Alphora Research Inc. | Stabilized doxercalciferol and process for manufacturing the same |
| EP2468265A3 (en) * | 2010-12-04 | 2013-01-02 | DEEF Pharmaceutical Industries Co. | Homogeneous preparations containing vitamin D |
| KR101847947B1 (ko) * | 2013-03-15 | 2018-05-28 | 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 | 안정화되고 변형된 비타민 ｄ 방출 제형 |
| US10220047B2 (en) | 2014-08-07 | 2019-03-05 | Opko Ireland Global Holdings, Ltd. | Adjunctive therapy with 25-hydroxyvitamin D and articles therefor |
| JP7032322B2 (ja) | 2016-03-28 | 2022-03-08 | オプコ アイルランド グローバル ホールディングス リミテッド | ビタミンｄ治療法 |
| JP7085105B2 (ja) * | 2016-11-10 | 2022-06-16 | 日産化学株式会社 | ビタミンｄ３誘導体の製剤 |
| JP7603000B2 (ja) * | 2018-08-31 | 2024-12-19 | オプコ アイルランド グローバル ホールディングス リミテッド | ビタミンｄ小児用剤形、製造方法および使用方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59155309A (ja) * | 1983-02-22 | 1984-09-04 | Teijin Ltd | 活性型ビタミンｄ↓３類組成物 |
| JPS6217A (ja) * | 1985-02-14 | 1987-01-06 | Chugai Pharmaceut Co Ltd | 安定な活性型ビタミンｄ３類製剤 |
| DE3612212A1 (de) * | 1986-04-11 | 1987-10-15 | Basf Ag | Verfahren zur herstellung von festen pharmazeutischen formen |
| JP2525478B2 (ja) * | 1989-03-01 | 1996-08-21 | 帝人株式会社 | 安定性の改良された活性型ビタミンｄ▲下３▼類固型製剤 |
| JPH04198129A (ja) * | 1990-11-28 | 1992-07-17 | Sumitomo Pharmaceut Co Ltd | 活性型ビタミンｄ↓３類含有組成物 |
-
1992
- 1992-04-08 DE DE69214704T patent/DE69214704T2/de not_active Expired - Lifetime
- 1992-04-08 IE IE921126A patent/IE75709B1/en not_active IP Right Cessation
- 1992-04-08 CA CA002065603A patent/CA2065603C/en not_active Expired - Lifetime
- 1992-04-08 EP EP92303129A patent/EP0508756B1/en not_active Expired - Lifetime
- 1992-04-08 TW TW081102667A patent/TW212761B/zh active
- 1992-04-08 ES ES92303129T patent/ES2094290T3/es not_active Expired - Lifetime
- 1992-04-08 NZ NZ242271A patent/NZ242271A/en not_active IP Right Cessation
- 1992-04-08 AT AT92303129T patent/ATE144424T1/de not_active IP Right Cessation
- 1992-04-08 DK DK92303129.8T patent/DK0508756T3/da active
- 1992-04-09 AU AU14804/92A patent/AU649802B2/en not_active Ceased
- 1992-04-09 JP JP4088666A patent/JPH05279260A/ja not_active Withdrawn
- 1992-04-09 KR KR1019920005930A patent/KR100231633B1/ko not_active Expired - Fee Related
-
1994
- 1994-02-07 US US08/193,650 patent/US5487900A/en not_active Expired - Lifetime
-
1996
- 1996-12-04 GR GR960403313T patent/GR3021892T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE69214704D1 (de) | 1996-11-28 |
| US5487900A (en) | 1996-01-30 |
| AU649802B2 (en) | 1994-06-02 |
| GR3021892T3 (en) | 1997-03-31 |
| TW212761B (2) | 1993-09-11 |
| DE69214704T2 (de) | 1997-04-17 |
| DK0508756T3 (da) | 1997-03-24 |
| EP0508756A1 (en) | 1992-10-14 |
| IE75709B1 (en) | 1997-09-10 |
| AU1480492A (en) | 1992-10-15 |
| ATE144424T1 (de) | 1996-11-15 |
| KR920019346A (ko) | 1992-11-19 |
| NZ242271A (en) | 1993-10-26 |
| KR100231633B1 (ko) | 1999-11-15 |
| IE921126A1 (en) | 1992-10-21 |
| JPH05279260A (ja) | 1993-10-26 |
| ES2094290T3 (es) | 1997-01-16 |
| CA2065603A1 (en) | 1992-10-10 |
| EP0508756B1 (en) | 1996-10-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |