JP5509503B2 - ビタミンdと25−ヒドロキシビタミンd3の組み合わせ - Google Patents
ビタミンdと25−ヒドロキシビタミンd3の組み合わせ Download PDFInfo
- Publication number
- JP5509503B2 JP5509503B2 JP2010546331A JP2010546331A JP5509503B2 JP 5509503 B2 JP5509503 B2 JP 5509503B2 JP 2010546331 A JP2010546331 A JP 2010546331A JP 2010546331 A JP2010546331 A JP 2010546331A JP 5509503 B2 JP5509503 B2 JP 5509503B2
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- composition
- oil
- dose
- combination
- 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.)
- Active
Links
- 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 title claims description 161
- 229930003316 Vitamin D Natural products 0.000 title claims description 109
- 235000019166 vitamin D Nutrition 0.000 title claims description 109
- 239000011710 vitamin D Substances 0.000 title claims description 109
- 150000003710 vitamin D derivatives Chemical class 0.000 title claims description 109
- 229940046008 vitamin d Drugs 0.000 title claims description 109
- JWUBBDSIWDLEOM-UHFFFAOYSA-N 25-Hydroxycholecalciferol Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CCC1=C JWUBBDSIWDLEOM-UHFFFAOYSA-N 0.000 title claims description 18
- JWUBBDSIWDLEOM-DCHLRESJSA-N 25-Hydroxyvitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C/C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DCHLRESJSA-N 0.000 title description 8
- JWUBBDSIWDLEOM-NQZHSCJISA-N 25-hydroxy-3 epi cholecalciferol Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@H](O)CCC1=C JWUBBDSIWDLEOM-NQZHSCJISA-N 0.000 title description 8
- 239000000203 mixture Substances 0.000 claims description 69
- 235000015872 dietary supplement Nutrition 0.000 claims description 14
- 239000003963 antioxidant agent Substances 0.000 claims description 13
- 235000013305 food Nutrition 0.000 claims description 12
- 239000002775 capsule Substances 0.000 claims description 9
- 241000282412 Homo Species 0.000 claims description 8
- 230000003078 antioxidant effect Effects 0.000 claims description 8
- 206010047626 Vitamin D Deficiency Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000011324 bead Substances 0.000 claims 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 57
- 235000005282 vitamin D3 Nutrition 0.000 description 52
- 239000011647 vitamin D3 Substances 0.000 description 52
- 229940021056 vitamin d3 Drugs 0.000 description 52
- 239000003921 oil Substances 0.000 description 46
- 235000019198 oils Nutrition 0.000 description 45
- 108090000623 proteins and genes Proteins 0.000 description 32
- 239000000839 emulsion Substances 0.000 description 28
- 238000000034 method Methods 0.000 description 24
- 239000000523 sample Substances 0.000 description 22
- 238000011282 treatment Methods 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 15
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 14
- 230000036470 plasma concentration Effects 0.000 description 13
- 235000006708 antioxidants Nutrition 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 229920002774 Maltodextrin Chemical class 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000005913 Maltodextrin Chemical class 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229940035034 maltodextrin Drugs 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000002354 daily effect Effects 0.000 description 9
- 210000002027 skeletal muscle Anatomy 0.000 description 9
- 239000007921 spray Substances 0.000 description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 229910052791 calcium Inorganic materials 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 108010010803 Gelatin Proteins 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229940109239 creatinine Drugs 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 235000010378 sodium ascorbate Nutrition 0.000 description 7
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 7
- 229960005055 sodium ascorbate Drugs 0.000 description 7
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 7
- 235000019698 starch Nutrition 0.000 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 description 7
- 229920000881 Modified starch Polymers 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 235000019426 modified starch Nutrition 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 description 5
- 238000013019 agitation Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 5
- 239000008393 encapsulating agent Substances 0.000 description 5
- 229960002061 ergocalciferol Drugs 0.000 description 5
- 238000000265 homogenisation Methods 0.000 description 5
- 210000003141 lower extremity Anatomy 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 235000001892 vitamin D2 Nutrition 0.000 description 5
- 239000011653 vitamin D2 Substances 0.000 description 5
- JWUBBDSIWDLEOM-XHQRYOPUSA-N (3e)-3-[(2e)-2-[1-(6-hydroxy-6-methylheptan-2-yl)-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol Chemical compound C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2\C1=C\C=C1/CC(O)CCC1=C JWUBBDSIWDLEOM-XHQRYOPUSA-N 0.000 description 4
- -1 25-OH D3 Substances 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 235000021318 Calcifediol Nutrition 0.000 description 4
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 4
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 4
- 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 description 4
- 239000004368 Modified starch Substances 0.000 description 4
- 235000019482 Palm oil Nutrition 0.000 description 4
- 108090000445 Parathyroid hormone Proteins 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 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 4
- 229920001971 elastomer Polymers 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 238000002493 microarray Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 239000002540 palm oil Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000005060 rubber Substances 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 229960000984 tocofersolan Drugs 0.000 description 4
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 4
- 239000011732 tocopherol Substances 0.000 description 4
- 229930003799 tocopherol Natural products 0.000 description 4
- 125000002640 tocopherol group Chemical class 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 244000061456 Solanum tuberosum Species 0.000 description 3
- 235000002595 Solanum tuberosum Nutrition 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 235000019149 tocopherols Nutrition 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 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
- 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 102000003982 Parathyroid hormone Human genes 0.000 description 2
- 102100036893 Parathyroid hormone Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- JWUBBDSIWDLEOM-DTOXIADCSA-N calcidiol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DTOXIADCSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical class 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 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000005976 liver dysfunction Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 239000000199 parathyroid hormone Substances 0.000 description 2
- 229960001319 parathyroid hormone Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 235000013594 poultry meat Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000025185 skeletal muscle atrophy Effects 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 229960003885 sodium benzoate Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 235000020799 vitamin D status Nutrition 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 229920002245 Dextrose equivalent Polymers 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 235000014755 Eruca sativa Nutrition 0.000 description 1
- 244000024675 Eruca sativa Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920001732 Lignosulfonate Chemical class 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010049416 Short-bowel syndrome Diseases 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000050760 Vitamin D-binding protein Human genes 0.000 description 1
- 101710179590 Vitamin D-binding protein Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Chemical class 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940022704 alburx Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol 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)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
- 229960002535 alfacalcidol Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 229940124605 anti-osteoporosis drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000010480 babassu oil Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 230000037118 bone strength Effects 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229960004361 calcifediol Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 210000003278 egg shell Anatomy 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002834 estrogen receptor modulator Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001007 flame atomic emission spectroscopy Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 229920003087 methylethyl cellulose Polymers 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000020939 nutritional additive Nutrition 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 235000019865 palm kernel oil Nutrition 0.000 description 1
- 239000003346 palm kernel oil Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001277 pectin Chemical class 0.000 description 1
- 239000001814 pectin Chemical class 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- 208000001076 sarcopenia Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 102000009310 vitamin D receptors Human genes 0.000 description 1
- 108050000156 vitamin D receptors Proteins 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Nutrition Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
本発明は、ビタミンD(コレカルシフェロール/および/またはエルゴカルシフェロール)と25−ヒドロキシビタミンD3(カルシフェジオール)を含む組成物ならびに、その組成物を用いて、少なくともビタミンDの濃度、バイオアベイラビリティ、代謝または有効性に影響を与えるための使用法に関する。
ビタミンD(エルゴカルシフェロールおよびコレカルシフェロールなど)とは、それぞれの生物活性によって定義される脂溶性化合物の総称である。ビタミンDの欠乏によって、子どもではくる病、成人では骨軟化症が起こる。しかしながら、数ヶ月間にわたって1日あたりの推奨摂取量(すなわち、ビタミンD5〜15μgまたは200〜600IU)の100倍を超えて慢性的に摂取すると、毒性が生じる可能性がある。ビタミンDの場合、「毒性の閾値は体重1kgあたり1日で500〜600mcgである。通常、成人はRDAの3倍を超えて長期間消費すべきではない」(Garrison & Somer, The Nutrition Desk Reference, Third Ed., McGraw−Hill, pg. 82, 1997)。高カルシウム血症は、25−ヒドロキシビタミンDの血中濃度が375nmol/Lを超えると生じることがある。最近になって、ビタミンDの安全な上限レベルは少なくとも250μg/日(10’000IU)であることが確認された(Hathcockら Am.J Clin. Nutr. 85:6〜18, 2007)。このような健康補助食品を摂取すると、25−ヒドロキシビタミンDの血中濃度が約200nmol/Lになることが明らかになっている。
ビタミンDと25−OH D3の組み合わせを人に投与した場合、意外なことに血漿25−OH Dの増加によって相乗的に増加することが見いだされている。この効果は短時間で観察され、最初の6時間程度が最も顕著である。さらに、血漿レベルの増加は約206時間にわたって持続する。このため、本発明は、ヒトの医薬品として使用する、ビタミンD(コレカルシフェロールおよび/またはエルゴカルシフェロール)と25−OH D3(カルシフェジオール)の組み合わせを含む。このような組成物の1つの考えられる用途に、抗骨粗鬆症薬としての使い方があるが、本発明の組み合わせは、ビタミンDまたは25−OH D欠乏が関連している徴候であれば、どのようなものに対しても適している。
1)25−OH Dの迅速かつ相乗的な血漿応答が生じる。
2)予想外に顕著かつ長時間にわたる血漿25−OH Dレベルの定常化につながる。これらは、ビタミンD欠乏の特に重要な治療目標すなわち、すべてのビタミンD依存性組織の十分な供給を保証するための最適以下のビタミンDの状態と長期かつ安定した血漿濃度を速やかに回復することである。
毎日.2種類の有効成分を別々に投与する場合の本発明による組成物は、ビタミンDまたは25−OH D3を、約1μg〜約50μg、好ましくは約5μgおよび25μgの量で含有する。あるいは、ビタミンDと25−OH D3の両方を含む1日の単回投与量に、各有効成分を、約1μg〜約50μg、好ましくは約5μgおよび25μgの量で含有する。
この組み合わせの生物活性の増加を実証するために、ビタミンD、25−OH D3、組み合わせに曝露した筋肉組織の遺伝子チップ解析を実施した。詳細については、マウス後肢懸垂モデルを用いて実施例2にあげておく。ここから分かるように、2つの組み合わせを送達すると、個々に投与した場合よりも活性化または制御される(上方制御または下方制御のいずれか)遺伝子数が劇的に増加する。現時点で、ビタミンDの大部分が摂取および肝臓での処理時に25−OH Dに変換されると考えられているため、これは意外な結果である。
[実施例1]
[製剤および治験]
[製剤]
[材料および方法]
25−OH D3の噴霧乾燥製剤を粉末として提供した。要約すると、25−OH D3およびDL−α−トコフェロールを中鎖トリグリセリドの油に溶解させた後、化工デンプン、スクロース、アスコルビン酸ナトリウムの水溶液に乳化した。このエマルションを二酸化ケイ素の存在下にて噴霧乾燥器で微粒化した。水分含有量(LDO)が4%未満になったら、得られた粉末を回収し、400μmで篩過した。これをアルミ製の袋に包装して封止した後、15℃未満の乾燥した場所で保管し、製造から12ヶ月以内に使用した。
・17.300kgの水(WBI)
・13.460kgの食品用化工デンプン(CAPSUL HS)
・3.270kgのスクロース
・0.730kgのアスコルビン酸ナトリウム
・0.550kgのBERGABEST MCT油60/40
・0.049kgのカルシフェジオール(HY−D USP)
・0.183kgのDL−α−トコフェロール
[被験者]
インフォームドコンセントを用いて健康な閉経後の女性(50〜70歳)を募集し、以下の基準でふるい分けた。血清25−OH Dが20nmol/L〜50nmol/L、肥満度指数18kg/m2〜27kg/m2、血圧146/95mm Hg未満、血清カルシウム2.6nmol/L未満、空腹時グルコース100mg/dl未満、1週間に3回を超えて激しい運動をしない、高血圧症の治療歴なし、骨代謝に影響する高用量ビタミンDまたはカルシウムサプリメントまたは薬物(ビスホスホネート、カルシトニン、エストロゲン受容体調節因子、ホルモン補充療法、副甲状腺ホルモン)の使用歴なし、研究中は「日当たりの良い」場所に足を運ばない。
目的は、ヒトに投与したビタミンDおよび25−OH D3の薬物動態特性を研究および比較することであった。両方の物質を等しい量で調査した。レジメンは、25−OH D3を20μg/日(またはそれに相当する量を週ベースで)とする。25−OH Dの既存の最大基線濃度が50nmol/Lになったら、Ca2+恒常性の乱れが観察される範囲に被験者が近づくとは思われない。比較目的で、等モル量のビタミンDまたは25−OH D3のいずれかを投与する必要があった。ビタミンDの投与に関しては、バックグラウンドのばらつきに影響されず、参加者にとっての有効用量を提供するのに十分な用量であると思われる。
1. 25−OH D3 20μg
2. ビタミンD3 20μg(800IU)
毎週:16回投与
3. 25−OH D3 140μg
4. ビタミンD3 140μg(5600IU)
ボーラス:単回投与
5. 25−OH D3 140μg
6. ビタミンD3 140μg(5600IU)
ボーラス:組み合わせ投与
7. D3および25(OH)D3 140μg(5600IU)+140μg
表1に、投与量140μgの25−OH D3、投与量140μgのビタミンDまたは併用投与量140μgの25−OH D3+140μgのビタミンD後の血漿25−OH Dレベルの増加を示す。血液試料については、表記の時間スケジュールで採取した。
[遺伝子チップデータ]
この研究の目的は、尾部懸垂が動物の負荷軽減した後肢の骨格筋萎縮につながる、BalbCマウスを用いる骨格筋萎縮モデルにおいて、ビタミンD3、25−OH D3、ビタミンD3と25−OH D3の組み合わせによる効果を試験することであった。当初、このモデルはヒトの宇宙飛行を模するためにラットで確立され、他の科学技術分野でも骨格筋質量または骨の喪失の研究に一般に用いられている。結果は、サルコペニア(加齢に伴う骨格筋の質量と力の変性喪失)または骨格筋の運動不足(骨折、外科手術または外傷による長期の床上安静後など)などのヒトでの症状を示すものとみなされる。
1.対照群:後肢負荷軽減(HU)
2.ビタミンD3群:HU+ビタミンD3での処理
3.25−OH D3群:HU+25−OH D3での処理
4.ビタミンD+25−OH D3群:HU+ビタミンD3および25−OH D3(組み合わせ)での処理
1.対照群はビヒクル(ゼラチン)を摂取
2.D3群はビタミンD3(50μg/kg/bw)を摂取
3.25−OH D3群は25−OH D3(50μg/kg/bw)を摂取
4.組み合わせ群はビタミンD3+25−OH D3(50+50μg/kg/bw)を摂取
1.25−OH D3とビタミンD3とを組み合わせると、25−OH D3よりも多くの遺伝子のプローブセットが変化する。結果として、ビタミンD3(表1)よりも多くの遺伝子のプローブセットが変化する。
a.HU対照群と比較して、組み合わせ処理(D3+25−ヒドロキシビタミンD3)を実施した群では、25−OH D3だけで処理を実施した群(1263)よりも有意に多くの遺伝子のプローブセットが変化した(1745)。
HU対照群と比較して、25−OH D3で処理した群では、ビタミンD3での処理を実施した群(385)よりも有意に多くの遺伝子のプローブセットが変化した(1263)エラー!参照ソース見つからず。
a.25−OH D3群で発現の異なる約61%の遺伝子のプローブセットが、25−OH D3+ビタミンD3群でも発現が異なる(1263のうち769、図2)
b.ビタミンD3群で発現の異なる約46%の遺伝子のプローブセットが、25−OH D3+ビタミンD3群でも発現が異なる(385のうち177、図3)
c.図4、図6、図7に示すように、25−OH D3とビタミンD3の組み合わせ処理が、筋肉発達過程の遺伝子に最も有意な影響がある。
d.関与する遺伝子は、骨格筋における以下のメインカテゴリのうちの一部である:筋肉収縮、筋肉発達、筋肉維持(表)。
Claims (9)
- ビタミンDと25−OHビタミンD3とを含み、ビタミンD対25−OHビタミンD3の用量比が6:1〜1:6である、ヒトで使用するのに適した医薬組成物。
- 薬学的に許容される酸化防止剤と、少なくとも1種の薬学的に許容されるキャリアとを、錠剤、カプセルまたは注射可能な形態でさらに含む、請求項1に記載の組成物。
- 噴霧乾燥ビーズレット組成物またはカプセル化ビーズ組成物である、請求項1又は2に記載の組成物。
- 25−OHビタミンD3およびビタミンDを用いて、25−OHビタミンD欠乏に関連する症候を軽減するために使用する、ヒト用の薬を製造する使用法であって、ビタミンD対25−OHビタミンD3の用量比が6:1〜1:6である、使用法。
- 25−OHビタミンD3及びビタミンDを含む、ヒトで使用するのに適した栄養補給食品、栄養補助食品または食品であって、
ビタミンD対25−OHビタミンD3の用量比が6:1〜1:6である、栄養補給食品、栄養補助食品または食品。 - 多数回分の投与量の
a)ビタミンDと、
b)25−OHビタミンD3と、
を含み、ビタミンD対25−OHビタミンD3の用量比が6:1〜1:6である、キット。 - 容器と、組成物を投与量としてヒトに投与するための指示書とからなる群から選択される少なくとも1つの要素をさらに含む、請求項6に記載のキット。
- 少なくとも7回分の投与量が含まれる、請求項6又は7に記載のキット。
- 少なくとも30回分の投与量が含まれる、請求項8に記載のキット。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2851008P | 2008-02-13 | 2008-02-13 | |
US61/028,510 | 2008-02-13 | ||
US3167108P | 2008-02-26 | 2008-02-26 | |
US61/031,671 | 2008-02-26 | ||
US3692808P | 2008-03-15 | 2008-03-15 | |
US61/036,928 | 2008-03-15 | ||
PCT/EP2009/051636 WO2009101132A1 (en) | 2008-02-13 | 2009-02-12 | Combination of vitamin d and 25-hydroxyvitamin d 3 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011512342A JP2011512342A (ja) | 2011-04-21 |
JP5509503B2 true JP5509503B2 (ja) | 2014-06-04 |
Family
ID=40577766
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010546331A Active JP5509503B2 (ja) | 2008-02-13 | 2009-02-12 | ビタミンdと25−ヒドロキシビタミンd3の組み合わせ |
Country Status (11)
Country | Link |
---|---|
US (2) | US20120196057A1 (ja) |
EP (1) | EP2240183A1 (ja) |
JP (1) | JP5509503B2 (ja) |
KR (2) | KR20100126375A (ja) |
CN (2) | CN101951920A (ja) |
AU (1) | AU2009214049B2 (ja) |
BR (1) | BRPI0907952B1 (ja) |
EA (1) | EA201001283A1 (ja) |
IL (1) | IL207589A (ja) |
MX (1) | MX2010008894A (ja) |
WO (1) | WO2009101132A1 (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2882048C (en) | 2006-02-03 | 2020-03-24 | Proventiv Therapeutics, Llc | Treating vitamin d insufficiency and deficiency with 25-hydroxyvitamin d2 and 25-hydroxyvitamin d3 |
PL2679228T3 (pl) | 2006-06-21 | 2018-07-31 | Opko Ireland Global Holdings, Ltd. | Terapia z użyciem środka do uzupełniania witaminy D i środka do zastępowania hormonami witaminy D |
WO2008134523A1 (en) | 2007-04-25 | 2008-11-06 | Proventiv Therapeutics, Llc | Method of safely and effectively treating and preventing secondary hyperparathyroidism in chronic kidney disease |
ES2403107T3 (es) | 2007-04-25 | 2013-05-14 | Cytochroma Inc. | Método de tratamiento de insuficiencia y deficiencia de vitamina D |
EP3542792B1 (en) | 2007-04-25 | 2023-06-28 | EirGen Pharma Ltd. | Controlled release 25-hydroxyvitamin d |
US8962239B2 (en) | 2008-04-02 | 2015-02-24 | Opko Renal, Llc | Methods useful for vitamin D deficiency and related disorders |
HUE048464T2 (hu) | 2010-03-29 | 2020-07-28 | Opko Ireland Global Holdings Ltd | Módszerek és készítmények mellékpajzsmirigy szintjének csökkentésére |
ES2712740T3 (es) | 2010-12-06 | 2019-05-14 | Dsm Ip Assets Bv | Tratamiento de afecciones asociadas con eotaxina incrementada con 25-hidroxivitamina D3 |
KR101847947B1 (ko) | 2013-03-15 | 2018-05-28 | 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 | 안정화되고 변형된 비타민 d 방출 제형 |
CN105208878A (zh) * | 2013-03-27 | 2015-12-30 | 帝斯曼知识产权资产管理有限公司 | 25-羟基维生素d3用于增强执行功能的用途 |
CA2957240A1 (en) | 2014-08-07 | 2016-02-11 | Opko Ireland Global Holdings, Ltd. | Adjunctive therapy with 25-hydroxyvitamin d |
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 |
CN108902985A (zh) * | 2018-06-08 | 2018-11-30 | 唐飞 | 25-羟基维生素d3在制备保健食品中的应用 |
US20230248744A1 (en) * | 2020-04-07 | 2023-08-10 | Carbogen Amcis B.V. | 25-hydroxyvitamin d2 and/or d3 for use in obesity |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US970203A (en) * | 1905-08-03 | 1910-09-13 | Sebastian Ziani De Ferranti | Spinning-machine. |
US5043170A (en) * | 1989-02-14 | 1991-08-27 | Hoffmann-La Roche Inc. | Animal feed composition containing a vitamin D metabolite |
WO1990009179A1 (en) * | 1989-02-16 | 1990-08-23 | University Of Georgia Research Foundation, Inc. | Treatment of tibial dyschondroplasia |
US20040043971A1 (en) * | 1995-04-03 | 2004-03-04 | Bone Care International, Inc. | Method of treating and preventing hyperparathyroidism with active vitamin D analogs |
US7632518B2 (en) * | 2002-01-15 | 2009-12-15 | Dsm Ip Assets B.V. | 25-hydroxy vitamin D3 compositions |
JP2005531532A (ja) * | 2002-04-05 | 2005-10-20 | メルク エンド カムパニー インコーポレーテッド | アレンドロナートおよびビタミンd製剤を用いる骨吸収阻害法 |
EP1662896B1 (en) * | 2003-09-22 | 2012-10-24 | DSM IP Assets B.V. | Vitamin containing pet food compositions |
ES2392823T3 (es) * | 2003-09-22 | 2012-12-14 | Dsm Ip Assets B.V. | Uso de compuestos de vitamina D |
US7212141B2 (en) * | 2005-07-11 | 2007-05-01 | Intel Corporation | Filter with gain |
JP5566026B2 (ja) * | 2005-08-18 | 2014-08-06 | ディーエスエム アイピー アセッツ ビー.ブイ. | 動物の雄の生殖能力を改善するための25−ヒドロキシビタミンd3の使用 |
ES2567595T3 (es) * | 2005-10-12 | 2016-04-25 | Opko Renal, Llc | Métodos y artículos para tratar la insuficiencia y la deficiencia de 25-hidroxivitamina D |
ATE476104T1 (de) * | 2005-11-25 | 2010-08-15 | Dsm Ip Assets Bv | Verwendung von 25-hydroxy-vitamin d3 zur verbesserung der vitalität von tieren |
CA2882048C (en) * | 2006-02-03 | 2020-03-24 | Proventiv Therapeutics, Llc | Treating vitamin d insufficiency and deficiency with 25-hydroxyvitamin d2 and 25-hydroxyvitamin d3 |
WO2008134523A1 (en) * | 2007-04-25 | 2008-11-06 | Proventiv Therapeutics, Llc | Method of safely and effectively treating and preventing secondary hyperparathyroidism in chronic kidney disease |
ES2403107T3 (es) * | 2007-04-25 | 2013-05-14 | Cytochroma Inc. | Método de tratamiento de insuficiencia y deficiencia de vitamina D |
EP3542792B1 (en) * | 2007-04-25 | 2023-06-28 | EirGen Pharma Ltd. | Controlled release 25-hydroxyvitamin d |
-
2009
- 2009-02-12 CN CN2009801052617A patent/CN101951920A/zh active Pending
- 2009-02-12 WO PCT/EP2009/051636 patent/WO2009101132A1/en active Application Filing
- 2009-02-12 JP JP2010546331A patent/JP5509503B2/ja active Active
- 2009-02-12 BR BRPI0907952-1A patent/BRPI0907952B1/pt active IP Right Grant
- 2009-02-12 EP EP09711093A patent/EP2240183A1/en not_active Withdrawn
- 2009-02-12 EA EA201001283A patent/EA201001283A1/ru unknown
- 2009-02-12 MX MX2010008894A patent/MX2010008894A/es active IP Right Grant
- 2009-02-12 KR KR1020107020252A patent/KR20100126375A/ko active Search and Examination
- 2009-02-12 AU AU2009214049A patent/AU2009214049B2/en active Active
- 2009-02-12 KR KR1020157033816A patent/KR20150139629A/ko not_active Application Discontinuation
- 2009-02-12 CN CN201610066797.4A patent/CN106214683A/zh active Pending
-
2010
- 2010-08-12 IL IL207589A patent/IL207589A/en active IP Right Grant
-
2012
- 2012-04-13 US US13/446,128 patent/US20120196057A1/en not_active Abandoned
-
2016
- 2016-07-20 US US15/214,666 patent/US20160324877A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
BRPI0907952B1 (pt) | 2023-12-05 |
JP2011512342A (ja) | 2011-04-21 |
AU2009214049B2 (en) | 2014-02-06 |
EP2240183A1 (en) | 2010-10-20 |
MX2010008894A (es) | 2010-11-05 |
KR20100126375A (ko) | 2010-12-01 |
IL207589A (en) | 2017-10-31 |
IL207589A0 (en) | 2010-12-30 |
AU2009214049A1 (en) | 2009-08-20 |
KR20150139629A (ko) | 2015-12-11 |
WO2009101132A1 (en) | 2009-08-20 |
CN101951920A (zh) | 2011-01-19 |
CN106214683A (zh) | 2016-12-14 |
EA201001283A1 (ru) | 2011-08-30 |
BRPI0907952A2 (pt) | 2015-08-04 |
US20120196057A1 (en) | 2012-08-02 |
US20160324877A1 (en) | 2016-11-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5509503B2 (ja) | ビタミンdと25−ヒドロキシビタミンd3の組み合わせ | |
JP5593550B2 (ja) | ヒトの筋生理に影響を与えるための25−ヒドロキシビタミンd3の使用 | |
JP5509504B2 (ja) | 骨塩密度を改善し、骨粗鬆症を治療するための25−ヒドロキシ−ビタミンd3とビタミンd3の併用 | |
JP5691072B2 (ja) | 25−ヒドロキシビタミンd3を用いた高血糖の治療 | |
JP2011511826A (ja) | 25−ヒドロキシビタミンd3を用いた高血圧症の治療 | |
US20110052707A1 (en) | Combination of vitamin d and 25-hydroxyvitamin d 3 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120127 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130702 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131001 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131029 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140225 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140307 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5509503 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |