CN101072565A - 对营养缺乏的肾病患者进行补充的方法和组合物 - Google Patents
对营养缺乏的肾病患者进行补充的方法和组合物 Download PDFInfo
- Publication number
- CN101072565A CN101072565A CNA2005800421870A CN200580042187A CN101072565A CN 101072565 A CN101072565 A CN 101072565A CN A2005800421870 A CNA2005800421870 A CN A2005800421870A CN 200580042187 A CN200580042187 A CN 200580042187A CN 101072565 A CN101072565 A CN 101072565A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- compositions
- patient
- interpolation
- zinc
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 139
- 238000000034 method Methods 0.000 title claims abstract description 74
- 208000002720 Malnutrition Diseases 0.000 title claims abstract description 25
- 235000018343 nutrient deficiency Nutrition 0.000 title abstract description 3
- 230000009469 supplementation Effects 0.000 title description 7
- 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 claims abstract description 78
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 72
- 208000017169 kidney disease Diseases 0.000 claims abstract description 47
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 39
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 39
- 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 claims abstract description 39
- 229940046009 vitamin E Drugs 0.000 claims abstract description 39
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 39
- 239000011709 vitamin E Substances 0.000 claims abstract description 39
- 239000011701 zinc Substances 0.000 claims abstract description 39
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 39
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000011669 selenium Substances 0.000 claims abstract description 34
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 34
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 33
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 33
- 239000011718 vitamin C Substances 0.000 claims abstract description 33
- 229940088594 vitamin Drugs 0.000 claims abstract description 20
- 229930003231 vitamin Natural products 0.000 claims abstract description 20
- 235000013343 vitamin Nutrition 0.000 claims abstract description 20
- 239000011782 vitamin Substances 0.000 claims abstract description 20
- 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 claims description 66
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 48
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 48
- 229960003512 nicotinic acid Drugs 0.000 claims description 40
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims description 38
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 37
- 229930003270 Vitamin B Natural products 0.000 claims description 35
- 235000019156 vitamin B Nutrition 0.000 claims description 35
- 239000011720 vitamin B Substances 0.000 claims description 35
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 claims description 34
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 34
- 229930003779 Vitamin B12 Natural products 0.000 claims description 33
- 229960003495 thiamine Drugs 0.000 claims description 33
- 235000019163 vitamin B12 Nutrition 0.000 claims description 33
- 239000011715 vitamin B12 Substances 0.000 claims description 33
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 32
- 229930003537 Vitamin B3 Natural products 0.000 claims description 32
- 229960002685 biotin Drugs 0.000 claims description 32
- 235000020958 biotin Nutrition 0.000 claims description 32
- 239000011616 biotin Substances 0.000 claims description 32
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 32
- 229960002477 riboflavin Drugs 0.000 claims description 32
- 235000019160 vitamin B3 Nutrition 0.000 claims description 32
- 239000011708 vitamin B3 Substances 0.000 claims description 32
- 229930003451 Vitamin B1 Natural products 0.000 claims description 31
- 229930003571 Vitamin B5 Natural products 0.000 claims description 31
- 229960002079 calcium pantothenate Drugs 0.000 claims description 31
- 208000020832 chronic kidney disease Diseases 0.000 claims description 31
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 31
- 235000010374 vitamin B1 Nutrition 0.000 claims description 31
- 239000011691 vitamin B1 Substances 0.000 claims description 31
- 235000009492 vitamin B5 Nutrition 0.000 claims description 31
- 239000011675 vitamin B5 Substances 0.000 claims description 31
- 235000019158 vitamin B6 Nutrition 0.000 claims description 31
- 239000011726 vitamin B6 Substances 0.000 claims description 31
- 229940011671 vitamin b6 Drugs 0.000 claims description 31
- 229930003471 Vitamin B2 Natural products 0.000 claims description 30
- 235000019164 vitamin B2 Nutrition 0.000 claims description 30
- 239000011716 vitamin B2 Substances 0.000 claims description 30
- 238000000502 dialysis Methods 0.000 claims description 23
- 235000000824 malnutrition Nutrition 0.000 claims description 20
- 230000001071 malnutrition Effects 0.000 claims description 20
- 208000015380 nutritional deficiency disease Diseases 0.000 claims description 20
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 18
- 201000000523 end stage renal failure Diseases 0.000 claims description 17
- 208000028208 end stage renal disease Diseases 0.000 claims description 16
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 15
- 239000011707 mineral Substances 0.000 claims description 15
- 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 claims description 14
- 235000020805 dietary restrictions Nutrition 0.000 claims description 12
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 10
- 201000006370 kidney failure Diseases 0.000 claims description 10
- 230000036542 oxidative stress Effects 0.000 claims description 10
- 230000002969 morbid Effects 0.000 claims description 9
- 230000003203 everyday effect Effects 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 4
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 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 36
- 235000019152 folic acid Nutrition 0.000 description 24
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 24
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 23
- KNXVOGGZOFOROK-UHFFFAOYSA-N trimagnesium;dioxido(oxo)silane;hydroxy-oxido-oxosilane Chemical compound [Mg+2].[Mg+2].[Mg+2].O[Si]([O-])=O.O[Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O KNXVOGGZOFOROK-UHFFFAOYSA-N 0.000 description 22
- 125000002252 acyl group Chemical group 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 239000011724 folic acid Substances 0.000 description 21
- 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 15
- 239000002775 capsule Substances 0.000 description 15
- 229960000304 folic acid Drugs 0.000 description 15
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 14
- 210000003734 kidney Anatomy 0.000 description 13
- 235000010755 mineral Nutrition 0.000 description 13
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 239000005515 coenzyme Substances 0.000 description 11
- 235000016709 nutrition Nutrition 0.000 description 11
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000004060 metabolic process Effects 0.000 description 10
- 235000005911 diet Nutrition 0.000 description 9
- 230000037213 diet Effects 0.000 description 8
- 239000011664 nicotinic acid Substances 0.000 description 8
- 235000001968 nicotinic acid Nutrition 0.000 description 8
- 230000006378 damage Effects 0.000 description 7
- 229940055726 pantothenic acid Drugs 0.000 description 7
- 235000019161 pantothenic acid Nutrition 0.000 description 7
- 239000011713 pantothenic acid Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000011677 pyridoxine Substances 0.000 description 7
- 235000008160 pyridoxine Nutrition 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229940014144 folate Drugs 0.000 description 6
- 230000035764 nutrition Effects 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 235000020905 low-protein-diet Nutrition 0.000 description 5
- 239000007937 lozenge Substances 0.000 description 5
- 208000037157 Azotemia Diseases 0.000 description 4
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 4
- ANVAOWXLWRTKGA-XHGAXZNDSA-N all-trans-alpha-carotene Chemical compound CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1C(C)=CCCC1(C)C ANVAOWXLWRTKGA-XHGAXZNDSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000003907 kidney function Effects 0.000 description 4
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000005239 tubule Anatomy 0.000 description 4
- 208000009852 uremia Diseases 0.000 description 4
- ZNOVTXRBGFNYRX-STQMWFEESA-N (6S)-5-methyltetrahydrofolic acid Chemical compound C([C@@H]1N(C=2C(=O)N=C(N)NC=2NC1)C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-STQMWFEESA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical group CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 125000000659 L-selenomethionine group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])[Se]C([H])([H])[H] 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 102000014701 Transketolase Human genes 0.000 description 3
- 108010043652 Transketolase Proteins 0.000 description 3
- 229930003316 Vitamin D Natural products 0.000 description 3
- 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 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 3
- 239000005516 coenzyme A Substances 0.000 description 3
- 229940093530 coenzyme a Drugs 0.000 description 3
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 3
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 3
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 3
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 3
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 3
- 150000002224 folic acids Chemical class 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000000627 niacin group Chemical group 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 125000001452 riboflavin group Chemical group 0.000 description 3
- 150000003900 succinic acid esters Chemical class 0.000 description 3
- 230000009967 tasteless effect Effects 0.000 description 3
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical group [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 235000019166 vitamin D Nutrition 0.000 description 3
- 239000011710 vitamin D Substances 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 229940046008 vitamin d Drugs 0.000 description 3
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 2
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 2
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- 229930003756 Vitamin B7 Natural products 0.000 description 2
- 235000009392 Vitis Nutrition 0.000 description 2
- 241000219095 Vitis Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 description 2
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 208000012998 acute renal failure Diseases 0.000 description 2
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 2
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 description 2
- 239000011795 alpha-carotene Substances 0.000 description 2
- 235000003903 alpha-carotene Nutrition 0.000 description 2
- ANVAOWXLWRTKGA-HLLMEWEMSA-N alpha-carotene Natural products C(=C\C=C\C=C(/C=C/C=C(\C=C\C=1C(C)(C)CCCC=1C)/C)\C)(\C=C\C=C(/C=C/[C@H]1C(C)=CCCC1(C)C)\C)/C ANVAOWXLWRTKGA-HLLMEWEMSA-N 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000021028 berry Nutrition 0.000 description 2
- 235000013734 beta-carotene Nutrition 0.000 description 2
- 239000011648 beta-carotene Substances 0.000 description 2
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 2
- 229960002747 betacarotene Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037058 blood plasma level Effects 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 235000000639 cyanocobalamin Nutrition 0.000 description 2
- 239000011666 cyanocobalamin Substances 0.000 description 2
- 229960002104 cyanocobalamin Drugs 0.000 description 2
- 125000002235 cyanocobalamin group Chemical group 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 208000016097 disease of metabolism Diseases 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000003969 glutathione Nutrition 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 229940094952 green tea extract Drugs 0.000 description 2
- 235000020688 green tea extract Nutrition 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- 235000012661 lycopene Nutrition 0.000 description 2
- 239000001751 lycopene Substances 0.000 description 2
- 229960004999 lycopene Drugs 0.000 description 2
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 229910052748 manganese Inorganic materials 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000011585 methylcobalamin Substances 0.000 description 2
- 235000007672 methylcobalamin Nutrition 0.000 description 2
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 2
- 210000000885 nephron Anatomy 0.000 description 2
- 230000007830 nerve conduction Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- CCHNOBQMQBSRHQ-UHFFFAOYSA-N phosphoric acid;7h-purin-6-amine Chemical compound OP(O)(O)=O.NC1=NC=NC2=C1NC=N2 CCHNOBQMQBSRHQ-UHFFFAOYSA-N 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 2
- 235000005875 quercetin Nutrition 0.000 description 2
- 229960001285 quercetin Drugs 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 235000019192 riboflavin Nutrition 0.000 description 2
- 239000002151 riboflavin Substances 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000005460 tetrahydrofolate Substances 0.000 description 2
- 235000019157 thiamine Nutrition 0.000 description 2
- 239000011721 thiamine Substances 0.000 description 2
- 229960002663 thioctic acid Drugs 0.000 description 2
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 2
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 2
- 235000000112 undernutrition Nutrition 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 235000011912 vitamin B7 Nutrition 0.000 description 2
- 239000011735 vitamin B7 Substances 0.000 description 2
- 235000010930 zeaxanthin Nutrition 0.000 description 2
- 239000001775 zeaxanthin Substances 0.000 description 2
- 229940043269 zeaxanthin Drugs 0.000 description 2
- RNWHGQJWIACOKP-UHFFFAOYSA-N zinc;oxygen(2-) Chemical group [O-2].[Zn+2] RNWHGQJWIACOKP-UHFFFAOYSA-N 0.000 description 2
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- OAJLVMGLJZXSGX-NDSREFPTSA-L (2r,3s,4s,5r)-2-(6-aminopurin-9-yl)-5-methanidyloxolane-3,4-diol;cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12 Chemical compound [Co+3].O[C@H]1[C@H](O)[C@@H]([CH2-])O[C@H]1N1C2=NC=NC(N)=C2N=C1.C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O OAJLVMGLJZXSGX-NDSREFPTSA-L 0.000 description 1
- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 1
- LDHMAVIPBRSVRG-UHFFFAOYSA-O 1-methylnicotinamide Chemical compound C[N+]1=CC=CC(C(N)=O)=C1 LDHMAVIPBRSVRG-UHFFFAOYSA-O 0.000 description 1
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- YXXURDJTDAAEPH-UHFFFAOYSA-N 2-aminopropanethioic s-acid Chemical compound CC(N)C(S)=O YXXURDJTDAAEPH-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 208000003918 Acute Kidney Tubular Necrosis Diseases 0.000 description 1
- 208000024985 Alport syndrome Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010073644 Cystathionine beta-synthase Proteins 0.000 description 1
- 102000020018 Cystathionine gamma-Lyase Human genes 0.000 description 1
- 108010045283 Cystathionine gamma-lyase Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 108091027757 Deoxyribozyme Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010018374 Glomerulonephritis minimal lesion Diseases 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 208000004883 Lipoid Nephrosis Diseases 0.000 description 1
- 206010061291 Mineral deficiency Diseases 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-O 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010029400 Nicotinic acid deficiency Diseases 0.000 description 1
- 206010048757 Oncocytoma Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000002063 Oxyphilic Adenoma Diseases 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- 208000004531 Renal Artery Obstruction Diseases 0.000 description 1
- 206010038378 Renal artery stenosis Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 206010038540 Renal tubular necrosis Diseases 0.000 description 1
- RJFAYQIBOAGBLC-BYPYZUCNSA-N Selenium-L-methionine Chemical compound C[Se]CC[C@H](N)C(O)=O RJFAYQIBOAGBLC-BYPYZUCNSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
- 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 1
- 206010046326 Uraemic encephalopathy Diseases 0.000 description 1
- 206010046337 Urate nephropathy Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010047612 Vitamin B2 deficiency Diseases 0.000 description 1
- 208000003056 Vitamin B6 deficiency Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000489 anti-atherogenic effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- -1 antiseptic Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 201000007590 ariboflavinosis Diseases 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940086763 ascorbic acid 100 mg Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000009172 bursting Effects 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol 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)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- 229940088129 calcium pantothenate 10 mg Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000021196 dietary intervention Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- 125000003929 folic acid group Chemical group 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100000852 glomerular disease Toxicity 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 208000003215 hereditary nephritis Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000000640 hydroxylating effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 201000006334 interstitial nephritis Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 150000002742 methionines Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 201000000173 nephrocalcinosis Diseases 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229940101270 nicotinamide adenine dinucleotide (nad) Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
- XEEVLJKYYUVTRC-UHFFFAOYSA-N oxomalonic acid Chemical compound OC(=O)C(=O)C(O)=O XEEVLJKYYUVTRC-UHFFFAOYSA-N 0.000 description 1
- 230000008557 oxygen metabolism Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 230000004108 pentose phosphate pathway Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- 229960001327 pyridoxal phosphate Drugs 0.000 description 1
- ZMJGSOSNSPKHNH-UHFFFAOYSA-N pyridoxamine 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(CN)=C1O ZMJGSOSNSPKHNH-UHFFFAOYSA-N 0.000 description 1
- 229940086387 pyridoxine hydrochloride 30 mg Drugs 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000004223 riboflavin deficiency Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229960002718 selenomethionine Drugs 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000019191 thiamine mononitrate Nutrition 0.000 description 1
- 239000011748 thiamine mononitrate Substances 0.000 description 1
- 229960004860 thiamine mononitrate Drugs 0.000 description 1
- 229940053678 thiamine mononitrate 3 mg Drugs 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 239000002441 uremic toxin Substances 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000002550 vasoactive agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- 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
-
- 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
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/32—Manganese; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及一种包含多种维生素和矿物质的组合物,还涉及一种使用该组合物治疗肾脏病及其并发症的治疗方法。特别地,该方法包括对肾脏疾病患者施用包含维生素C、维生素E、复合维生素B、硒和锌的组合物。
Description
本申请为部分后续申请,并根据35U.S.C§120要求2000年9月27日提交的美国专利申请09/671,283的优先权,并在此将其全文一并引入作为参考。
技术领域
本发明涉及一种包含多种维生素和矿物质的组合物,还涉及一种使用该组合物治疗肾脏病及其并发症的治疗方法。
背景技术
肾脏具有三个主要的生理功能,即排泄、代谢和内分泌功能。然而,水分、矿物质和其他营养物质的调节与代谢是肾脏最重要的功能。代谢废物的排泄包括尿素、肌酐、尿酸、血红蛋白降解产物和激素代谢产物都是通过肾脏来完成的。肾脏还通过分泌血管活性物质如肾素,参与动脉血压的调节。另外,肾脏能够分泌促进红细胞产生的红细胞生成素,并能够产生1,25-二羟维生素D3,即维生素D的活性形式。患肾脏疾病时,上述任何一种功能都有可能受到损害,从而导致患者营养状态的失衡。医学生理学315(Guyton &Hall,第9版.1996)。
肾脏疾病是导致死亡的主要原因之一,每年有数百万人发病。一般情况下,肾脏疾病可以分为两种类型:1)急性肾衰竭和2)慢性肾衰竭。急性肾衰竭的特征为肾脏功能突然降低或丧失。相反,慢性肾衰竭是指肾脏功能逐渐丧失,通常为潜在病理现象的结果。例如,免疫系统疾病如红斑狼疮;代谢疾病如糖尿病和高血压;和感染性疾病如结核都可以导致慢性肾衰竭。随着肾功能的逐步恶化,患者发展为终末期肾衰竭(ESRD)而最终需要进行透析治疗或移植。Id,431页。
患有典型的慢性肾衰竭的患者将发展为全身水肿、酸中毒、尿毒症和血液中氮代谢物产物堆积。为了减轻上述症状,患者需要进行饮食治疗或透析。对肾脏疾病患者采取的限制蛋白饮食通常将导致维生素如叶酸、B族维生素和维生素C的缺乏。营养和肾脏手册42(Mitch & Klahr,编著,第3版.1998)(以下称“手册”)。此外,透析过程本身也可除去维生素和营养物质。患有慢性肾衰竭的患者,其胃肠对维生素的吸收也发生改变。Makoff,25Miner.Electrolyte Metabol.349-351(1999)。
采用肾脏病的限制饮食将会导致微量元素如锌和硒的缺乏。在患有蛋白尿的患者体内,与蛋白质结合度较高的矿物质将大量的流失。Zima等等.,17Blood Purif.182-186(1999)。此外,已经证实患者在接受透析后,血浆中硒的浓度有所降低。手册,43页。较差的营养状况和维生素、矿物质水平的不足将导致肾脏疾病患者极易患有贫血、感染和心血管疾病;或使已有疾病如高血脂、骨质疏松和病毒性肝炎发生恶化。Modern Nutrition in Health andDisease,1447(Shils等,编著,第9版.1999)。
营养干预是慢性肾脏疾病和终末期肾脏疾病治疗的关键。饮食治疗应该维持或改善肾脏疾病患者的营养状况;和减少或防止由肾衰竭所引起的尿毒症和产生的代谢毒素。在提供有效营养治疗的同时,简化复杂的食物疗法是一项挑战。在此描述的营养组合物及相关治疗方法还包括对肾脏疾病患者进行限制饮食时所缺乏的多种维生素和矿物质。因此,本发明提供的组合物及治疗方法通过简单的方法满足了肾脏疾病患者的营养需求。
发明内容
本发明提供一种营养组合物和使用该组合物对患有肾脏疾病的患者进行治疗的方法。特别地,本发明公开了一种包含大量维生素和矿物质的新型组合物,该组合物能够用于对患有肾脏疾病、肾功能不全、终末期肾脏疾病的患者所具有的营养缺乏状况进行补充。本发明所述的组合物还可以用作接受透析或限制饮食治疗的患者的营养增补剂。此外,该组合物还能够用于治疗导致氧化应激增加、胆固醇水平提高或同型半胱氨酸水平提高的各种疾病状态的营养缺乏。
本发明所述组合物包含大量的维生素和矿物质,能够改善患者的营养状况。本发明所述组合物中含有的维生素包括维生素C、维生素E、维生素B1、维生素B2、维生素B3、维生素B5、维生素B6、维生素B12、生物素和维生素B9。本发明所述组合物中含有的矿物质包括硒和锌。
本发明一实施方式中,该组合物可以包含一种或多种抗坏血酸形式的维生素C;d-α-生育酚琥珀酸酯或d-α-生育酚醋酸酯形式的维生素E;硫胺一硝酸盐形式的维生素B1;核黄素形式的维生素B2;烟酰胺或烟酸形式的维生素B3;泛酸(右旋泛酸钙)形式的维生素B5;盐酸吡哆醇形式的维生素B6;氰钴胺素性质的维生素B12;生物素;叶片酸、叶酸、甲基叶酸、叶酸酯和/或一种或多种叶酸酯的天然异构体包括(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、10-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物和5-亚胺甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物形式的维生素B9;L-硒代蛋氨酸形式的硒;和L-Optizinic Z M L-200 Interhelth9TM或氧化锌形式的锌。
本发明另一实施方式中,该组合物可基本上不含有其他未在以上段落中进行描述的添加的维生素和矿物质。例如,本发明所述组合物可基本上不含有添加的α-胡萝卜素;基本上不含有添加的β-胡萝卜素;基本上不含有添加的叶黄素;基本上不含有添加的番茄红素;基本上不含有添加的玉米黄素;基本上不含有添加的维生素B4;基本上不含有添加的维生素B7;基本上不含有添加的维生素B8;基本上不含有添加的维生素B10;基本上不含有添加的维生素B11;基本上不含有添加的维生素D;基本上不含有添加的钙;基本上不含有添加的铬;基本上不含有添加的铁;基本上不含有添加的镁;基本上不含有添加的铜;基本上不含有添加的锰;基本上不含有添加的硼;基本上不含有添加的无味大蒜;基本上不含有添加的辅酶Q-10;基本上不含有添加的L-肉碱;基本上不含有添加的葡萄籽提取物;基本上不含有添加的绿茶提取物;基本上不含有添加的栎精;基本上不含有添加的山楂果提取物;和/或基本上不含有添加的α-硫辛酸。
本发明另一具体实施方式中,本发明所述组合物可以基本上不含有添加的维生素C;基本上不含有添加的维生素E;基本上不含有添加的维生素B1;基本上不含有添加的维生素B2;基本上不含有添加的维生素B3;基本上不含有添加的维生素B5;基本上不含有添加的维生素B6;基本上不含有添加的维生素B12;基本上不含有添加的生物素;基本上不含有添加的维生素B9;基本上不含有添加的硒;和/或基本上不含有添加的锌。
本发明另一具体实施方式中,该组合物可以包含约60mg至约140mg的维生素C;约40IU至约80IU的维生素E;约1.5mg至约4.5mg的维生素B1;约1mg至约3mg的维生素B2;约10mg至约30mg的维生素B3;约5mg至约15mg的维生素B5;约18mg至约42mg的维生素B6;约500μg至约1500μg的维生素B12;约150μg至约450μg的生物素;约3mg至约8mg的维生素B9;约35μg至约105μg的硒;和约10mg至约30mg的锌的组合物。
另一优选实施方式中,本发明所述组合物可以包含约80mg至约120mg的维生素C;约48IU至约72IU的维生素E;约2.4mg至约3.6mg的维生素B1;约1.6mg至约2.4mg的维生素B2;约16mg至约24mg的维生素B3;约8mg至约12mg的维生素B5;约24mg至约36mg的维生素B6;约800μg至约1200μg的维生素B12;约240μg至约360μg的生物素;约4.4mg至约6.6mg的维生素B9;约56μg至约84μg的硒;和约16mg至约24mg的锌。
另一实施方式中,本发明所述组合物可以包含约90mg至约110mg的维生素C;约54IU至约66IU的维生素E;约2.7mg至约3.3mg的维生素B1;约1.8mg至约2.2mg的维生素B2;约18mg至约22mg的维生素B3;约9mg至约11mg的维生素B5;约27mg至约33mg的维生素B6;约900μg至约1100μg的维生素B12;约270μg至约330μg的生物素;约4.95mg至约6.05mg的维生素B9;约63μg至约77μg的硒;和约18mg至约22mg的锌。
本发明另一优选实施方式中,该组合物可以包含约100mg的维生素C;约60IU的维生素E;约3mg的维生素B1;约2mg的维生素B2;约20mg的维生素B3;约10mg的维生素B5;约30mg的维生素B6;约12μg的维生素B12;约300μg的生物素;约5.5mg的维生素B9;约70μg的硒;和约20mg的锌。
刚才所描述的本发明实施方式可以每日施用于患者。这些实施方式还可以为口服给药的方式,并且还可以包含药学上可接受的载体。可以考虑使用这些配方以治疗患者的营养缺乏,所述患者由于肾脏疾病、终末期肾脏疾病、肾功能不全、透析治疗、饮食限制或导致氧化应激增加、胆固醇水平提高和/或同型半胱氨酸水平提高的其他疾病状态而需要此类治疗。
本发明还包括对患有营养缺乏的患者的营养缺乏进行补充的方法,所述营养缺乏是由于患者患有肾脏疾病、终末期肾脏疾病、肾功能不全、透析治疗、饮食限制或导致氧化应激的增加、胆固醇水平的提高和/或同型半胱氨酸水平的提高的其他疾病状态所引起的。本发明所述的方法还可以使用能够用作对接受透析治疗或限制饮食的患者进行营养补充的组合物。在一实施方式中,本发明所述的方法可以使用包含维生素C、维生素E、复合维生素B、硒和锌的组合物。特别地,本发明所述的方法可以使用包含维生素C、维生素E、维生素B1、维生素B2、维生素B3、维生素B5、维生素B6、维生素B12、生物素、维生素B9、硒和锌的组合物。
在一实施方式中,本发明所述的方法可以使用包含一种或多种抗坏血酸形式的维生素C;d-α-生育酚琥珀酸酯或d-α-生育酚醋酸酯形式的维生素E;硫胺一硝酸盐素形式的维生素B1;核黄素形式的维生素B2;烟酰胺或烟酸形式的维生素B3;泛酸(右旋泛酸钙)形式的维生素B5;盐酸吡哆醇形式的维生素B6;氰钴胺素形式的维生素B12;生物素;叶片酸、叶酸、甲基叶酸、叶酸酯和/或一种或多种叶酸酯的天然异构体包括(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、10-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物和5-亚胺甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物形式的维生素B9;L-硒代蛋氨酸形式的硒;和L-Optizinic Z M L-200 Interhelth9TM或氧化锌形式的锌的组合物。
本发明另一实施方式中,该方法可以使用基本上不含有任何未在以上段落中进行描述的添加的维生素和矿物质。例如,本发明所述的方法可以使用基本上不含有添加的α-胡萝卜素;基本上不含有添加的β-胡萝卜素;基本上不含有添加的叶黄素;基本上不含有添加的番茄红素;基本上不含有添加的玉米黄素;基本上不含有添加的维生素B4;基本上不含有添加的维生素B7;基本上不含有添加的维生素B8;基本上不含有添加的维生素B10;基本上不含有添加的维生素B11;基本上不含有添加的维生素D;基本上不含有添加的钙;基本上不含有添加的铬;基本上不含有添加的铁;基本上不含有添加的镁;基本上不含有添加的铜;基本上不含有添加的锰;基本上不含有添加的硼;基本上不含有添加的无味大蒜;基本上不含有添加的辅酶Q-10;基本上不含有添加的L-肉碱;基本上不含有添加的葡萄籽提取物;基本上不含有添加的绿茶提取物;基本上不含有添加的栎精;基本上不含有添加的山楂果提取物;和/或基本上不含有添加的α-硫辛酸的组合物。
另一具体实施方式中,本发明所述的方法可以使用基本上不含有添加的维生素C;基本上不含有添加的维生素E;基本上不含有添加的维生素B1;基本上不含有添加的维生素B2;基本上不含有添加的维生素B3;基本上不含有添加的维生素B5;基本上不含有添加的维生素B6;基本上不含有添加的维生素B12;基本上不含有添加的生物素;基本上不含有添加的维生素B9;基本上不含有添加的硒;和/或基本上不含有添加的锌的组合物。
另一实施方式中,本发明所述的方法可以使用包含约60mg至约140mg的维生素C;约40IU至约80IU的维生素E;约1.5mg至约4.5mg的维生素B1;约1mg至约3mg的维生素B2;约10mg至约30mg的维生素B3;约5mg至约15mg的维生素B5;约18mg至约42mg的维生素B6;约500μg至约1500μg的维生素B12;约150μg至约450μg的生物素;约3mg至约8mg的维生素B9;约35μg至约105μg的硒;和约10mg至约30mg的锌的组合物。
另一具体实施方式中,该方法可以使用包含约80mg至约120mg的维生素C;约48IU至约72IU的维生素E;约2.4mg至约3.6mg的维生素B1;约1.6mg至约2.4mg的维生素B2;约16mg至约24mg的维生素B3;约8mg至约12mg的维生素B5;约24mg至约36mg的维生素B6;约800μg至约1200μg的维生素B12;约240μg至约360μg的生物素;约4.4mg至约6.6mg的维生素B9;约56μg至约84μg的硒;和约16mg至约24mg的锌的组合物。
本发明另一实施方式中,该方法可以使用包含约90mg至约110mg的维生素C;约54IU至约66IU的维生素E;约2.7mg至约3.3mg的维生素B1;约1.8mg至约2.2mg的维生素B2;约18mg至约22mg的维生素B3;约9mg至约11mg的维生素B5;约27mg至约33mg的维生素B6;约900μg至约1100μg的维生素B12;约270μg至约330μg的生物素;约4.95mg至约6.05mg的维生素B9;约63μg至约77μg的硒;和约18mg至约22mg的锌的组合物。
在一特别优选实施方式中,该方法可以使用包含约100mg的维生素C;约60IU的维生素E;约3mg的维生素B1;约2mg的维生素B2;约20mg的维生素B3;约10mg的维生素B5;约30mg的维生素B6;约12μg的维生素B12;约300μg的生物素;约5.5mg的维生素B9;约70μg的硒;和约20mg锌的组合物。
本发明所述方法包括使用本发明所述组合物对患者进行每日给药。该方法可以考虑使用包含药学上可接受载体的口服给药组合物。可以考虑使用这些配方以治疗患者由于肾脏疾病、终末期肾脏疾病、肾功能不全、透析治疗、饮食限制或其他疾病状态引起的营养缺乏。该组合物还可以用于治疗导致氧化应激增加、胆固醇水平提高和/或同型半胱氨酸水平提高的任何疾病状态下的营养缺乏。
本发明的其他目的、特征和优点将通过以下详细描述进行说明。虽然已指出本发明的具体实施方式,但本发明还提供了仅起到说明目的的详细描述和特殊实施例。因此,本发明还包括在本发明精神和范围内,本领域技术人员通过此详细的描述而进行的各种改变和修改。
具体实施方式
应当理解为本发明不限制于在此描述的特殊方法、方案、填充剂、赋形剂等,因为其可以进行改变。还应当理解为在此所使用的术语仅起到说明具体实施方式的目的,而不是用于限制本发明的范围。应注意的是,在此所用的和所附权利要求书中所用的单数形式“一”和“该”包括复数代词,除非文中另外明确指出。因此,例如一维生素应理解为一种或多种维生素,并且还包括本领域技术人员所公知的与其等效的维生素等。
除非另有定义,在此所用的所有技术和科学术语与属于本发明领域内的普通技术人员理解的含义相同。虽然任何与在此描述的方法和材料相似或等效的方法和材料都可以用于实施或检验本发明,但本发明仍对具体方法、设备和材料进行了描述。
由于复杂的代谢和生物化学的变化,除了饮食限制外个体肾脏疾病的营养治疗需要独特的配方。所述饮食限制通常导致生命所需的营养如维生素C、维生素E、复合维生素B和锌的浓度降低。Rocco等,7J.RenalNutr.17-24(1997)。此外,患有终末期肾脏疾病的患者通常患有尿毒症,尿毒症将导致氧化应激的增加、自由基的产生、影响食欲和改变机体利用营养的能力。Tetta等,17 Blood Purif.118-126(1999)。透析过程还将导致必要营养物的缺失。Stein等,3 Blood Purif.52-62(1985)。本发明提供的新型组合物及其相关方法含有独特的维生素和矿物质混合物,能够用于对患有肾脏疾病的患者进行营养补充。
术语“肾脏疾病”为一般性表述,其包括一系列影响肾脏的病症。术语“肾脏疾病患者”包括患有肾脏疾病的患者。一般而言,根据患病的形态学部位,肾脏疾病分为肾小球型、小管型和血管型。肾小球为分支和网结毛细管的网状结构,能够从血液中过滤蛋白质、毒素和其它物质。包括免疫、血管和代谢疾病的副作用在内的很多因素都能够导致肾小球的伤害。肾小球疾病包括肾小球肾炎、肾病综合征、脂性肾病(lipoid nephrosis)、肾小球硬化症、Berger肾病和遗传性肾炎,但并不限制于此。Robbins Pathologic Basis of Disease942(Cotran等,第6版.1999)。
肾脏的小管从肾小球过滤液中吸收养分并转至血液中。由于小管上皮细胞对局部缺血和毒素特别敏感,因此,小管极易遭受损伤。小管的患病状态包括急性肾小管坏死、小管间质性肾炎、肾盂肾炎、尿酸性肾病和肾钙沉着症,但并不限制于此。Id.968-980页。
充分血管化的肾脏接收约25%的心输出量,全身血管疾病如血管炎和高血压对肾脏血管产生副作用。其它肾脏血管疾病包括良性肾硬化、肾动脉狭窄、血栓性微血管病、溶血性尿毒症综合征和镰状细胞病,但并不限制于此。Id.981-987页。此外,肿瘤如嗜酸细胞瘤和肾细胞癌也能够对肾脏功能造成损伤。Id.991-994页。无论源自何种病因,以上所描述的多种疾病最终将转变为慢性肾脏疾病和终末期肾脏疾病。
慢性肾功能衰竭患者的血清维生素C水平明显降低。血清维生素C水平的降低正是由于低钾饮食和减少食物摄入量所引起的。Marumo等,Int.J.Artif.Organs 17-24(1986)。肾脏疾病的低钾饮食通常限制富含钾和维生素C的水果和蔬菜的摄入。维生素C主要的生化作用在于作为由金属催化的羟基化反应的协同底物,并且在与过氧化物羟基和单态氧的直接相互作用中起到抗氧化的作用。此外,维生素C能够对叶酸和维生素E起到抗氧化保护的作用。Recommended Dietary Allowances 115(National Reserch Council,第10版.,1989)(以下称为“RDA”)。本发明的一具体实施方式中,所含有的维生素C可以为抗坏血酸的形式。另一具体实施方式中,维生素C的含量可以为约60mg至约140mg。另一具体实施方式中,维生素C的含量可以为约80mg至约120mg。另一具体实施方式中,维生素C的含量可以为约90mg至约110mg。在一优选实施方式中,维生素C的含量可以为100mg。
维生素E为一种生物膜中的抗氧化剂,其可以保护磷脂膜免于氧化应激的损伤。RDA,99-101页。维生素E还可以作为抗动脉粥样硬化的制剂,研究表明增加维生素E的摄入量可以降低冠心病患病危险。Stampfer等.,328Engl.J.Med.1444-1449(1993)。在慢性肾衰竭患者和接受透析治疗的患者中,维生素E的水平较低。Taccone-Gallucci等.,27 Clin.Nephrol.238-241(1987);Ito等.,217 JAMA 699(1971)。此外,业已证实典型的肾病饮食中缺乏维生素E。Ono,40 Nephron 440-445(1985)。此外,动脉粥样硬化性心血管疾病是导致患有终末期肾脏疾病患者死亡的根本原因。Maiorca,等.,43KidneyInt.S4-S10(1993)。本发明一具体实施方式中,含有d-α-生育酚醋酸酯形式的维生素E。另一具体实施方式中,含有相同摩尔数的d-α-生育酚琥珀酸酯形式的维生素E。另一具体实施方式中,维生素E的含量为约40IU至约80IU。另一具体实施方式中,维生素E的含量为约48IU至约72IU。另一具体实施方式中,维生素E的含量为约54IU至约66IU。在一优选实施方式中,维生素E的含量为约60IU。
硫胺素(维生素B1)为α-酮酸氧化脱羧作用和酮糖移转酶的辅酶,并作为戊糖磷酸途径的组成部分。硫胺素的活性受到叶酸酯缺乏和营养不良的限制。RDA,123页。低蛋白饮食的慢性肾衰竭患者表现出硫胺素缺乏的情况。Porrini等.,59 Int.J.Vitam.Nutr.Res.304-308(1989)。此外,透析治疗患者的红细胞转酮醇酶的活性受到影响。Descombes等.,43 Kidney Int.1319-1328(1993)。因此,为了改善任何潜在的硫胺素缺乏的情况,本发明一具体实施方式中,含有硫胺一硝酸盐形式的维生素B1。本发明另一具体实施方式中,维生素B1的含量为约1.5mg至约4.5mg。本发明另一具体实施方式中,维生素B1的含量为约2.4mg至约3.6mg。本发明另一具体实施方式中,维生素B1的含量为约2.7mg至约3.3mg。本发明一优选实施方式中,维生素B1的含量为约3mg。
核黄素(维生素B2)为两种黄素辅酶,即黄素单核甘酸(FMN)和黄素腺嘌呤二核苷酸(FAD)的组成部分。包括烟酸及吡哆醇的转化在内的许多氧化还原反应都包括该黄素辅酶。RDA,132页。已证实低蛋白饮食的肾病患者存在核黄素缺乏的现象。Porrini等.,59 Int.J.Vitam.Nutr.Res.304-308(1989);Stein等.,3 Blood Purif.52-62(1985)。发现患者还出现角膜的血管化和皮肤炎的症状,说明患者缺乏核黄素。手册,116页。因此,本发明一具体实施方式中,含有核黄素形式的维生素B2。另一具体实施方式中,维生素B2的含量为约1mg至约3mg。另一具体实施方式中,维生素B2的含量为约1.6mg至约2.4mg。另一具体实施方式中,维生素B2的含量为约1.8mg至约2.2mg。另一实施方式中,维生素B2的含量为约2mg。
烟酰胺腺嘌呤二核苷酸(NAD)和烟酰胺腺嘌呤二核苷酸磷酸(NADP)为烟酸(维生素B3)的活性辅酶。在大量的酶反应中都含有该辅酶,例如糖酵解、脂肪酸的代谢和类固醇的合成。吡哆醇、核黄素和叶酸的合成同样需要烟酸存在。RDA,137页。施用烟酸能够降低总胆固醇、低密度脂蛋白和极低密度脂蛋白水平,而提高高密度脂蛋白胆固醇水平。Henkin等.,Am.J.Med.239-246(1991)。透析患者存在烟酸缺乏的状况,并且业已证实肾脏疾病的低蛋白饮食将导致烟酸含量的降低。DeBari等.,39Am.J.Clin.Nutr.410-415(1984);Mackenzie等.,5 Proc.Eur.Dial.Transplant.Assoc.172-178(1968)。为了使肾脏疾病患者能够维持适当的烟酸水平,本发明一具体实施方式中,含有烟酸形式的维生素B3。本发明另一具体实施方式中,含有相同摩尔数的烟酰胺形式的维生素B3。本发明另一具体实施方式中,维生素B3的量为约10mg至约30mg。本发明另一具体实施方式中,维生素B3的量为约16mg至约24mg。本发明另一具体实施方式中,维生素B3的量为约18mg至约22mg。本发明另一实施方式中,维生素B3的量为约20mg。
泛酸(维生素B5)为脂肪酸、胆固醇、类固醇激素和神经传递介质合成所需的辅酶A大分子的组成部分。复合辅酶A还在膜蛋白的乙酰化和酰化过程中起作用。RDA,169页。肾脏疾病患者采取的典型低蛋白饮食仅能提供极少量的泛酸。此外,接受透析治疗的患者的泛酸血浆水平明显降低。Meckenzie等.,5 Proc.Eur.Dial.Transplant.Assoc.172-178(1968)。因此,为了改善肾脏疾病患者存在的泛酸缺乏的状况,本发明一具体实施方式中含有右旋泛酸钙形式的维生素B5。另一具体实施方式中,维生素B5的含量为约5mg至约15mg。另一具体实施方式中,维生素B5的含量为约8mg至约12mg。另一具体实施方式中,维生素B5的含量为约9mg至约11mg。另一实施方式中,维生素B5的含量为约10mg。
吡哆醇(维生素B6)、5-磷酸吡哆醛(PLP)和5-磷酸吡哆胺的活性形式为多种酶的辅酶,该活性形式对糖异生、烟酸的形成和红细胞的代谢是必需的。RDA.,142-143。与接受透析的患者一样,成人和儿童肾衰竭患者维生素B6缺乏的发病率极高。Stein等.,3 Blood Purif.52-62(1985);Stockberger等.,7Nutr.Res.1021-1030(1987);Descombes等.,43 Kidney Int.1319-1328(1993)。低蛋白饮食中通常仅含有极少量的吡哆醇。Kopple等.,19 KidneyInt.694-704(1981)。与肾衰竭表现出的血浆和组织中草酸浓度升高一样,泛酸的缺乏应归因于肾脏疾病患者的免疫功能被抑制。Dobblestein等.,5 Kiney Int.233-239(1974);Morgan等.,46 Nephron 253-257(1987)。
此外,还暗示指出吡哆醇的缺乏对肾脏疾病患者体内的同型半胱氨酸起作用。吡哆醇为胱硫醚合成酶和胱硫醚酶的辅酶,这两种酶能够催化甲硫氨酸形成半胱氨酸。同型半胱氨酸在此过程中作为中间体,而升高的同型半胱氨酸血浆水平对血管疾病而言是一种危险因素。Robinson等.,94 Circulation2743-2748(1996)。然而,建议通过施用吡哆醇以降低同型半胱氨酸水平。Bostom等,49 Kidney Int.147-152(1996)。因此,本发明一具体实施方式中,含有盐酸吡哆醇形式的维生素B6。另一具体实施方式中,维生素B6的含量为约18mg至约42mg。另一具体实施方式中,维生素B6的含量为约24mg至约36mg。另一具体实施方式中,维生素B6的含量为约27mg至约33mg。然而另一实施方式中,维生素B6的含量为约30mg。
氰钴胺素(维生素B12)为可以转化成活性辅酶、甲基钴胺素和5’-脱氧腺苷钴胺素的钴胺素的药学形式。这些辅酶对叶酸的代谢、辅酶A的转化和髓磷脂的合成是必需的。例如,甲基钴胺素能够催化DNA合成过程中叶酸酯辅助因子的脱甲基作用。缺少脱甲基作用将导致叶酸的缺乏。RDA,159-160页。此外,维生素B12对叶酸在组织内的传输是必需的。RDA,150页。已发现慢性肾衰竭患者和接受透析的患者存在维生素B12缺乏的现象。此外,还发现接受透析患者的神经传导速率较慢。Rostand 29Am.J.Clin.Res.691-697(1976)。基于这些发现,维生素B12补充给药法可以作为对任何一种营养缺失进行补充的方法。此外,由于维生素B12在叶酸代谢中起作用,因此,补充给药法能够有效的调节肾脏疾病患者的同型半胱氨酸水平。因而,本发明一具体实施方式中,含有氰钴胺素形式的维生素B12。另一具体实施方式中,维生素B12的含量为约500μg至约1500μg。另一具体实施方式中,维生素B12的含量为约800μg至约1200μg。另一具体实施方式中,维生素B12的含量为约900μg至约1100μg。在一优选实施方式中,维生素B12的含量为约1000μg。
生物素可以作为多种羧化酶的辅酶,因此,在糖异生、脂肪酸代谢和氨基酸代谢中起重要的作用。RDA,166页。生物素能够抑制尿毒症毒素对微管蛋白聚合作用的影响。Braguer等,57 Nphron 192-196(1991)。此外,更多证据表明慢性肾衰竭患者和接受透析的患者存在生物素缺乏加重的危险。Mackenzie等,5 Proc.Eur.Dial.Transplant.Assoc.172-178(1968)。在众多诊断为尿毒症性脑病和尿毒症性神经病的透析患者中,可以通过生物素的给药以减缓上述疾病的症状。Yatzidis等,305 N.Engl.J.Med.764(1981)。本发明一具体实施方式中,生物素的含量为约150μg至约450μg。本发明另一具体实施方式中,生物素的含量为约240μg至约360μg。本发明一优选具体实施方式中,生物素的含量为约270μg至约330μg。另一实施方式中,生物素的含量为约300μg。
活性形式为四氢叶酸酯的叶酸(维生素B9)为一种辅酶,该辅酶参与甲基集团的转移并且在DNA合成、嘌呤合成和氨基酸合成中起作用,如甘氨酸向丝氨酸的转化和同型半胱氨酸向甲硫氨酸的转化。慢性肾衰竭患者在四氢叶酸酯的吸收受到损害和患有尿毒症的情况下,叶酸的代谢将发生改变。Said等,6 Acta Vitaminol.Enzymol.339-346(1984)。进一步地说,肾脏疾病患者实施的饮食通常情况下为叶酸含量较低,并且对肾衰竭患者的给药也可以抑制叶酸的活性。Stein等,3 Blood Purif.52-62(1985)。Cunningham等,282 Br.Med.J1582(1981)。慢性肾衰竭患者中,与同型半胱胺酸有关的疾病的发病率很高,并且存在发展为动脉粥样硬化的危险,显示出叶酸的补充对上述情况的调节是一种有效的方法并且还能够提供心脏保护的作用。Robinson等,94Circulation 2743-2748(1996)。因此,本发明一具体实施方式中,含有叶酸形式的维生素B9。另一实施方式中,含有叶片酸、叶酸、甲基叶酸、叶酸酯和/或一种或多种叶酸酯的天然异构体包括(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、10-甲酰基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物、5,10-亚甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物和5-亚胺甲基-(6S)-四氢叶酸或其聚谷氨酰衍生物形式的维生素B9。另一具体实施方式中,维生素B9的含量为约3mg至约8mg。另一具体实施方式中,维生素B9的含量为约4.4mg至约6.6mg。另一具体实施方式中,维生素B9的含量为约4.95mg至约6.05mg。另一实施方式中,维生素B9的含量为约5.5mg。
硒为抗氧化酶和谷胱甘肽过氧化物酶的一种组成部分,硒在控制氧代谢,特别在催化过氧化氢分解的过程起重要作用。Burk,3 Annu.Rev.Nutr.53-70(1983)。谷胱甘肽过氧化物酶能够抑制自由基的产生并且能够降低膜组织包括血管系统的氧化损伤危险。Holben,99 J.Am.Diet.Assoc.836-843(1999)。糖尿病患者的氧化应激水平高是由于糖尿病和肾脏疾病共同作用的结果。Kedziora-Kornatowska,等,11Nephrol.Dial.Transplant.2829-2832(1998)。在透析治疗过程中硒将流失,并且由于蛋白限制饮食,食入硒的量不能满足人体需求。许多研究表明,在透析患者中血浆硒、硒依赖性酶水平明显降低,并且脂质过氧化作用显著增加。Smith等,7 J.Renal Nutr.69-72(1997);Zima等,16Blood Purif.253-260(1998)。业已证实通过口服和静脉进行硒的补充在降低氧化应激产物水平的同时,能够有效的提高肾脏疾病患者的硒水平和免疫功能。Temple等,10 J.Renal Nutr.16(2000)。因此,本发明一实施方式中,该组合物含有L-硒代蛋氨酸形式的硒。另一具体实施方式中,硒的含量为约35μg至约105μg。另一具体实施方式中,硒的含量为约56μg至约84μg。另一具体实施方式中,硒的含量为约63μg至约77μg。另一实施方式中,硒的含量为约70μg。
存在有超过200种含锌金属酶,包括醛醇缩合酶、乙醇脱氢酶、RNA聚合酶和蛋白激酶C。因此,锌对多数代谢活性起重要的作用,例如核甘酸的生成、蛋白质的合成和免疫系统的改善。Zima等,17 Blood Purif.182-186(1999)。许多研究表明,在接受透析的患者和患有肾脏疾病的患者中,血浆锌的水平有明显降低。Thomson等,23 Kidney Int.9-14(1983);Muirhead等,6 Am.J.Nephrol.422-426(1986)。已有研究表明,锌的补充能够显著缓解肾脏疾病患者的临床症状数量,如无味、神经传导速度和阳痿,并提出锌的营养补充能够修复细胞性免疫和淋巴细胞功能的损伤。Zima等,17 Blood Purif.182-186(1999)。本发明一具体实施方式中,含有L-Optizinic Z M L-200Interhelth9TM形式的锌。另一具体实施方式中,锌的含量为约10mg至约30mg。另一具体实施方式中,锌的含量为约16mg至约24mg。另一具体实施方式中,锌的含量为约18mg至约22mg。另一实施方式中,锌的含量为约20mg。
本发明所述组合物适合对患者进行给药,并且提供这种营养补充可以缓解肾脏疾病患者维生素和矿物质缺乏的状况。本发明所述组合物的优选剂量可以含有一种或多种囊片以用于人体口服给药。如使用多种囊片时,各囊片彼此可以相同,或每种囊片仅含有所述组合物的某些组分,以使各种不同的囊片相结合时含有本发明所述的组合物。
本发明所述的组合物是指作用于人体各种代谢系统和生物应答的多种必要的维生素和矿物质的联合体。本发明所述的组分优选合成在可以为固体粉末、囊片、片剂、锭剂、丸剂、胶囊或液体形式的组合物中,本发明所述的组分可以单独进行给药也可与其它适合的组合一起进行给药。例如,根据给药的实际情况,本发明所述的组合物可以以一种或多种囊片或锭剂的形式进行给药。各种维生素和矿物质都能够商业获得,可以形成单一组合物的形式或形成能够进行共同给药的多重组合物的形式。
为了制备本发明所述的组合物,可以根据现有制剂技术将各种活性组分通过合适的载体直接进行混合而形成。根据给药的所需制剂的不同如,口服、舌下、鼻腔、局部或肠外的给药,所述载体可以广泛的选自各种形式的载体。所述组合物可以含有1至3种囊片或锭剂,每种囊片或锭剂种所含的组合物彼此相同。
将所述组合物制备为能够通过口服给药形式的过程中,可以使用任何常规介质。例如,可以使用含有水、油、乙醇、芳香剂、防腐剂、着色剂等的液体制剂介质。载体如淀粉、蔗糖、稀释剂、粒化剂、润滑剂、粘合剂、崩裂剂等等都可以用于制备口服固体制剂(如,粉末、囊片、丸剂、片剂、胶囊和锭剂)。同时还可以使用控释剂型。由于其给药的方便性,使用具有方便特性载体的囊片、片剂、丸剂和胶囊为最适合口服给药的剂型。如果需要,可以通过标准法将片剂制备成糖衣片或肠溶片。
通过以下非限制性的实施例对本发明进行更加详细的说明。
实施例1
采用本领域技术人员公知的标准方法制备含有下列组分的组合物囊片:
抗坏血酸 100mg
d-α-生育酚琥珀酸酯 60IU
硫胺一硝酸盐 3mg
核黄素 2mg
烟酸 20mg
右旋泛酸钙 10mg
盐酸吡哆醇 30mg
氰钴胺素 1000μg
生物素 30μg
叶酸 5.5mg
L-硒代蛋氨酸 70μg
L-Optizinic Z M L-200 Interhelth9TM 20mg
医师推荐剂量为每天1片。
实施例2
检测本发明的组合物对患有终末期肾脏疾病(ESRD)患者的治疗效果。本检测的目的在于测定通过口服给药的该组合物是否改善了患者的营养缺乏状况。
进行超过20个月的双盲、安慰剂对照研究。选择总共60名,年龄为40-85岁,患有终末期肾脏疾病的患者(男30人,女30人)。进行初期营养状况的判定。通过分光光度计和比色法检测维生素C、硒和锌水平。通过免疫放射分析法检测维生素B9和维生素B12水平。通过高效液相色谱法检测生物素和维生素B6水平。通过检测尿液中的N’-甲基烟酰胺和吡啶来测定维生素B3水平。通过过氧化物溶血检测来测定维生素E水平,通过检测红细胞转酮酶的活性来测定维生素B1水平。通过检测红细胞谷胱甘肽还原酶的活性测定维生素B2水平,通过检测辅酶A的活性来测定维生素B5水平。
将60名患者分为两组,每组有15名男性患者,15名女性患者。第一组中,对每个患者施用实施例1所述的组合物,且给药量为每日1-2片。第二组中(对照),对每个患者施用安慰剂,且给药量为每日1-2片。
在上述12个月期间内,每月对各个患者的营养状况进行评测,所得数据通过多元线性回归和标准Student氏t检验进行评价。在各分析中,输出变量的基线值在模型中作为共变量。通过Weigel & Narvaez,12对照临床试验378-94(1991)所述的方法检测共变量相互作用效应的处理效果。如无明显相互作用效应,该相互作用组将从模型中除去。通过观察具有假设值的剩余曲线,来评价常态回归模型假设和剩余变量共性回归模型假设。在给药18、12和6周时具有明显疗效,并仅在观察到明显疗效的情况下,依次向更早期的阶段进行初期效果检测。通过配对t检验来评价每组中基线的变化。此外,通过对基线测量和可测量患者的特征进行变量分析来评估两组患者间的共性。所有统计过程均采用统计分析系统来完成(SAS Institute Inc.,Cary,NC)。所有统计检测中α均为0.05。
在检测完成时,经治疗的患者的营养状况表现出明显的统计学改善,而在对照组患者中则未有改善。经治疗的患者和对照组患者间营养状况的差别十分显著。因此,本试验证明了本发明所述的组合物通过口服给药能够有效的用于对患有终末期肾脏疾病的患者进行治疗。
所有上述引用的参考文献和出版物的公开内容以全文的形式并入本发明作为参考,并且与其分别并入本发明作为参考的范围相同。在不背离本发明精神和范围的情况下,本领域技术人员可以对本发明所描述的方法和组合物进行各种修改和改变。虽然在优选的具体实施方式中对本发明进行了描述,但不应理解为,如权利要求所述的本发明限制于此实施方式。实际上,对本领域技术人员是显而易见的各种对实施本发明方法的修改,都包括在以下权利要求的范围内。
Claims (62)
1、一种用于在有此需要的患者或人中对营养缺乏进行补充的组合物,该组合物包含约60mg至约140mg的维生素C;约40IU至约80IU的维生素E;约1.5mg至约4.5mg的维生素B1;约1mg至约3mg的维生素B2;约10mg至约30mg的维生素B3;约5mg至约15mg的维生素B5;约18mg至约42mg的维生素B6;约500μg至约1500μg的维生素B12;约150μg至约450μg的生物素;约3mg至约8mg的维生素B9;约35μg至约105μg的硒;和约10mg至约30mg的锌。
2、一种用于在有此需要的患者或人中对营养缺乏进行补充的组合物,该组合物包含约80mg至约120mg的维生素C;约48IU至约72IU的维生素E;约2.4mg至约3.6mg的维生素B1;约1.6mg至约2.4mg的维生素B2;约16mg至约24mg的维生素B3;约8mg至约12mg的维生素B5;约24mg至约36mg的维生素B6;约800μg至约1200μg的维生素B12;约240μg至约360μg的生物素;约4.4mg至约6.6mg的维生素B9;约56μg至约84μg的硒;和约16mg至约24mg的锌。
3、一种用于在有此需要的患者或人中对营养缺乏进行补充的组合物,该组合物包含约90mg至约110mg的维生素C;约54IU至约66IU的维生素E;约2.7mg至约3.3mg的维生素B1;约1.8mg至约2.2mg的维生素B2;约18mg至约22mg的维生素B3;约9mg至约11mg的维生素B5;约27mg至约33mg的维生素B6;约900μg至约1100μg的维生素B12;约270μg至约330μg的生物素;约4.95mg至约6.05mg的维生素B9;约63μg至约77μg的硒;和约18mg至约22mg的锌。
4、根据权利要求1所述的组合物,其中,所述组合物包含约100mg的维生素C。
5、根据权利要求1所述的组合物,其中,所述组合物包含约60IU的维生素E。
6、根据权利要求1所述的组合物,其中,所述组合物包含约3mg的维生素B1。
7、根据权利要求1所述的组合物,其中,所述组合物包含约2mg的维生素B2。
8、根据权利要求1所述的组合物,其中,所述组合物包含约20mg的维生素B3。
9、根据权利要求1所述的组合物,其中,所述组合物包含约10mg的维生素B5。
10、根据权利要求1所述的组合物,其中,所述组合物包含约30mg的维生素B6。
11、根据权利要求1所述的组合物,其中,所述组合物包含约1000μg的维生素B12。
12、根据权利要求1所述的组合物,其中,所述组合物包含约300μg的生物素。
13、根据权利要求1所述的组合物,其中,所述组合物包含约5.5mg的维生素B9。
14、根据权利要求1所述的组合物,其中,所述组合物包含约70μg的硒。
15、根据权利要求1所述的组合物,其中,所述组合物包含约20mg的锌。
16、根据权利要求1所述的组合物,其中,所述组合物包含约100mg的维生素C;约60IU的维生素E;约3mg的维生素B1;约2mg的维生素B2;约20mg的维生素B3;约10mg的维生素B5;约30mg的维生素B6;约1000μg的维生素B12;约300μg的生物素;约5.5mg的维生素B9;约70μg的硒;和约20mg的锌。
17、根据权利要求1所述的组合物,其中,所述组合物基本上不含其它添加的维生素和矿物质。
18、根据权利要求1所述的组合物,其中,所述组合物用于每日施用于所述患者。
19、根据权利要求1所述的组合物,其中,所述组合物用于口服施用于所述患者。
20、根据权利要求1所述的组合物,其中,所述组合物还包含药学上可接受的载体。
21、根据权利要求1所述的组合物,其中,所述组合物用于施用于患有肾脏疾病的患者。
22、根据权利要求21所述的组合物,其中,所述肾脏疾病为终末期肾脏疾病。
23、根据权利要求1所述的组合物,其中,所述组合物用于施用于肾功能不全的患者。
24、根据权利要求1所述的组合物,其中,所述组合物用于施用于接受透析治疗的患者。
25、根据权利要求1所述的组合物,其中,所述营养缺乏为饮食限制的结果。
26、根据权利要求1所述的组合物,其中,所述营养缺乏为疾病状态的结果。
27、根据权利要求26所述的组合物,其中,所述疾病状态为肾脏疾病。
28、根据权利要求27所述的组合物,其中,所述肾脏疾病为终末期肾脏疾病。
29、根据权利要求1所述的组合物,其中,所述营养缺乏为透析治疗的结果。
30、根据权利要求26所述的组合物,其中,所述疾病状态导致所述患者的氧化应激增加。
31、根据权利要求26所述的组合物,其中,所述疾病状态导致所述患者的胆固醇水平提高。
32、一种对患者的营养缺乏进行补充的方法,该方法包括给所述患者施用包含约60mg至约140mg的维生素C;约40IU至约80IU的维生素E;约1.5mg至约4.5mg的维生素B1;约1mg至约3mg的维生素B2;约10mg至约30mg的维生素B3;约5mg至约15mg的维生素B5;约18mg至约42mg的维生素B6;约500μg至约1500μg的维生素B12;约150μg至约450μg的生物素;约3mg至约8mg的维生素B9;约35μg至约105μg的硒;和约10mg至约30mg锌的组合物。
33、一种对患者的营养缺乏进行补充的方法,该方法包括给所述患者施用包含约80mg至约120mg的维生素C;约48IU至约72IU的维生素E;约2.4mg至约3.6mg的维生素B1;约1.6mg至约2.4mg的维生素B2;约16mg至约24mg的维生素B3;约8mg至约12mg的维生素B5;约24mg至约36mg的维生素B6;约800μg至约1200μg的维生素B12;约240μg至约360μg的生物素;约4.4mg至约6.6mg的维生素B9;约56μg至约84μg的硒;和约16mg至约24mg锌的组合物。
34、一种对患者的营养缺乏进行补充的方法,该方法包括给所述患者施用包含约90mg至约110mg的维生素C;约54IU至约66IU的维生素E;约2.7mg至约3.3mg的维生素B1;约1.8mg至约2.2mg的维生素B2;约18mg至约22mg的维生素B3;约9mg至约11mg的维生素B5;约27mg至约33mg的维生素B6;约900μg至约1100μg的维生素B12;约270μg至约330μg的生物素;约4.95mg至约6.05mg的维生素B9;约63μg至约77μg的硒;和约18mg至约22mg锌的组合物。
35、根据权利要求32所述的方法,其中,所述组合物包含约100mg的维生素C。
36、根据权利要求32所述的方法,其中,所述组合物包含约60IU的维生素E。
37、根据权利要求32所述的方法,其中,所述组合物包含约3mg的维生素B1。
38、根据权利要求32所述的方法,其中,所述组合物包含约2mg的维生素B2。
39、根据权利要求32所述的方法,其中,所述组合物包含约20mg的维生素B3。
40、根据权利要求32所述的方法,其中,所述组合物包含约10mg的维生素B5。
41、根据权利要求32所述的方法,其中,所述组合物包含约30mg的维生素B6。
42、根据权利要求32所述的方法,其中,所述组合物包含约1000μg的维生素B12。
43、根据权利要求32所述的方法,其中,所述组合物包含约300μg的生物素。
44、根据权利要求32所述的方法,其中,所述组合物包含约5.5mg的维生素B9。
45、根据权利要求32所述的方法,其中,所述组合物包含约70μg的硒。
46、根据权利要求32所述的方法,其中,所述组合物包含约20mg的锌。
47、根据权利要求32所述的方法,其中,所述组合物包含约100mg的维生素C;约60IU的维生素E;约3mg的维生素B1;约2mg的维生素B2;约20mg的维生素B3;约10mg的维生素B5;约30mg的维生素B6;约1000μg的维生素B12;约300μg的生物素;约5.5mg的维生素B9;约70μg的硒;和约20mg的锌。
48、根据权利要求32所述的方法,其中,所述组合物基本上不含其它添加的维生素和矿物质。
49、根据权利要求32所述的方法,其中,所述组合物用于每日施用于所述患者。
50、根据权利要求32所述的方法,其中,所述组合物用于口服施用于所述患者。
51、根据权利要求32所述的方法,其中,所述组合物还包含药学上可接受的载体。
52、根据权利要求32所述的方法,其中,所述组合物用于施用于患有肾脏疾病的患者。
53、根据权利要求52所述的方法,其中,所述肾脏疾病为终末期肾脏疾病。
54、根据权利要求32所述的方法,其中,所述组合物用于施用于肾功能不全的患者。
55、根据权利要求32所述的方法,其中,所述组合物用于施用于接受透析治疗的患者。
56、根据权利要求32所述的方法,其中,所述营养缺乏为饮食限制的结果。
57、根据权利要求32所述的方法,其中,所述营养缺乏为疾病状态的结果。
58、根据权利要求57所述的方法,其中,所述疾病状态为肾脏疾病。
59、根据权利要求58所述的方法,其中,所述肾脏疾病为终末期肾脏疾病。
60、根据权利要求32所述的方法,其中,所述营养缺乏为透析治疗的结果。
61、根据权利要求57所述的方法,其中,所述疾病状态导致所述患者的氧化应激增加。
62、根据权利要求57所述的方法,其中,所述疾病状态导致所述患者的胆固醇水平提高。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/964,754 | 2004-10-15 | ||
US10/964,754 US7696219B2 (en) | 2000-09-27 | 2004-10-15 | Method and composition for supplementation of nutritional deficiences in renal patients |
Publications (1)
Publication Number | Publication Date |
---|---|
CN101072565A true CN101072565A (zh) | 2007-11-14 |
Family
ID=36203372
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2005800421870A Pending CN101072565A (zh) | 2004-10-15 | 2005-09-22 | 对营养缺乏的肾病患者进行补充的方法和组合物 |
Country Status (6)
Country | Link |
---|---|
US (2) | US7696219B2 (zh) |
EP (1) | EP1802309A4 (zh) |
JP (1) | JP2008516948A (zh) |
KR (1) | KR20070083734A (zh) |
CN (1) | CN101072565A (zh) |
WO (1) | WO2006044101A2 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110944648A (zh) * | 2017-07-26 | 2020-03-31 | Ams高级医疗补充剂公司 | 用于治疗或预防已经受胃袖状手术的患者中的维生素缺乏和矿物质缺乏的药物组合物 |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7901710B2 (en) | 2005-08-04 | 2011-03-08 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
US8202546B2 (en) | 2005-08-04 | 2012-06-19 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
US8263137B2 (en) | 2005-08-04 | 2012-09-11 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
US7998500B2 (en) | 2005-08-04 | 2011-08-16 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
BRPI0713999A2 (pt) * | 2006-07-06 | 2012-11-20 | Bayer Schering Pharma Ag | produÇço farmacÊutica para contracepÇço e para reduÇço do risco de malformaÇÕes congÊnitas |
JP5463011B2 (ja) * | 2008-04-30 | 2014-04-09 | 扶桑薬品工業株式会社 | 透析患者用栄養補助剤 |
US8535660B1 (en) | 2008-05-27 | 2013-09-17 | Argent Development Group, Llc | Nutritional supplements for pregnant women |
US20100047363A1 (en) * | 2008-11-07 | 2010-02-25 | John Wigneswaran | Nutritional supplement for patients with chronic kidney disease |
US20110135753A1 (en) * | 2009-12-04 | 2011-06-09 | John Wigneswaran | Nutritional Supplement For Patients With Chronic Heart Failure |
WO2012029655A1 (ja) * | 2010-08-30 | 2012-03-08 | 国立大学法人東北大学 | 血液透析痙攣抑制剤 |
US8183227B1 (en) | 2011-07-07 | 2012-05-22 | Chemo S. A. France | Compositions, kits and methods for nutrition supplementation |
US8168611B1 (en) | 2011-09-29 | 2012-05-01 | Chemo S.A. France | Compositions, kits and methods for nutrition supplementation |
JP6535322B2 (ja) | 2013-05-08 | 2019-06-26 | ガンブロ・ルンディア・エービーGambro Lundia Ab | 透析製剤 |
CN105530947A (zh) * | 2013-09-13 | 2016-04-27 | 株式会社明治 | 用于减轻蛋白质异化或促进蛋白质同化的制剂 |
KR101692546B1 (ko) * | 2015-08-05 | 2017-01-05 | 연세대학교 산학협력단 | 갑상선 질환 완화용 복합비타민 조성물 |
SE542106C2 (en) * | 2016-08-26 | 2020-02-25 | Atif M Dabdoub | Dietary macro/micronutritional supplement for patients undergoing kidney dialysis |
US11484579B2 (en) | 2017-11-29 | 2022-11-01 | Edgar L Hull | Vitamins and alpha keto acid compositions for use in a treatment program for chronic kidney disease patients |
WO2019108809A2 (en) | 2017-11-29 | 2019-06-06 | Hull Edgar L Jr | Alpha keto acid compositions for treating hypo-albuminemia |
EP3799724B1 (en) * | 2019-10-02 | 2022-08-17 | Hull, Edgar, L., Jr. | Vitamins and alpha keto acid compositions for use in a treatment program for chronic kidney disease patients |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3160564A (en) * | 1961-12-19 | 1964-12-08 | Merck & Co Inc | Multi-vitamin composition containing pantothenamide |
US6090414A (en) * | 1970-05-20 | 2000-07-18 | Life Science Labs, Inc. | Method and composition to reduce cancer incidence |
US4357343A (en) * | 1981-06-26 | 1982-11-02 | Baxter Travenol Laboratories, Inc. | Nutritional composition for management of renal failure |
NL8403433A (nl) * | 1984-11-09 | 1986-06-02 | Holland Melkunie | Voedingssuppletiepreparaat op basis van melkbestanddelen. |
US4740373A (en) * | 1986-05-27 | 1988-04-26 | Usv Pharmaceutical Corporation | Stabilization of multivitamin/trace elements formulations |
US4804535A (en) * | 1986-05-27 | 1989-02-14 | Rorer Pharmaceutical Corporation | Stabilization of multivitamin/trace elements formulations |
US4945083A (en) | 1986-06-03 | 1990-07-31 | Jansen Jr Christian J | Safe oral folic-acid-containing vitamin preparation |
US4940658A (en) * | 1986-11-20 | 1990-07-10 | University Patents, Inc. | Assay for sulfhydryl amino acids and methods for detecting and distinguishing cobalamin and folic acid deficency |
US5374560A (en) * | 1989-04-03 | 1994-12-20 | The University Of Colorado, Inc. | Method for screening and distinguishing between cobalamin and folic acid deficiency based on assay for cystathionine and 2-methylcitric acid |
US5563126A (en) * | 1986-11-20 | 1996-10-08 | Metabolite Laboratories | Method for treatment and prevention of deficiencies of vitamins B12, folic acid, and B6 |
US5457055A (en) * | 1986-11-20 | 1995-10-10 | The University Of Colorado Foundation | Diagnostic method for cobalamin deficiency |
US5438017A (en) * | 1989-05-01 | 1995-08-01 | The University Of Colorado Foundation, Inc. | Assays for sulfhydryl amino acids and methylmalonic acid and their application to diagnosis of cobalamin deficiency |
US4957938A (en) * | 1989-06-21 | 1990-09-18 | Abbott Laboratories | Nutritional formulation for the treatment of renal disease |
US4945803A (en) * | 1989-09-15 | 1990-08-07 | Norwood Paul J | Double beat bass drum pedal assembly |
DE4002204A1 (de) * | 1990-01-26 | 1991-08-01 | Westfalen Milchwerke | Diaetetisches nahrungsmittel fuer patienten mit niereninsuffizienz |
US5132113A (en) | 1990-10-26 | 1992-07-21 | Maurizio Luca | Nutritional composition containing essential amino acids |
US5108767A (en) * | 1991-06-10 | 1992-04-28 | Abbott Laboratories | Liquid nutritional product for persons receiving renal dialysis |
US5278329A (en) * | 1992-02-21 | 1994-01-11 | Zinpro Corporation | L-form 1:1 metal methionine complexes |
EP0662825B1 (en) * | 1992-09-23 | 2003-03-19 | Kv Pharmaceutical Corporation | Multi-vitamin and mineral supplement for pregnant women |
CA2089607C (en) * | 1992-11-05 | 1997-11-04 | Ranjit K. Chandra | Nutritional supplement for the elderly |
US6207651B1 (en) | 1996-08-02 | 2001-03-27 | Metabolite Laboratories | Method for treatment and prevention of deficiencies of vitamins B12, folic acid, and B6 |
US5795873A (en) * | 1992-12-29 | 1998-08-18 | Metabolite Laboratories, Inc. | Method for treatment and prevention of deficiencies of vitamins B12, folic acid and B6 |
US5869084A (en) * | 1994-06-20 | 1999-02-09 | K-V Pharmaceuticals Co. | Multi-vitamin and mineral supplements for women |
US5514382A (en) * | 1994-10-17 | 1996-05-07 | Sultenfuss; Sherry | Daily vitamin and mineral supplement for women |
US5728678A (en) * | 1995-06-06 | 1998-03-17 | Nestec Ltd. | Method and composition for providing nutrition to a renal failure patient |
US5626884A (en) * | 1995-08-18 | 1997-05-06 | Lockett; Curtis G. | Treatment of sickle cell disease |
WO1997037670A1 (en) * | 1996-04-10 | 1997-10-16 | Chronorx, Llc | Unit dosage forms, containing magnesium, vitamin c, vitamin e, folate and selenium, for treatment of vasoconstriction and related conditions |
US20020015742A1 (en) * | 1998-09-11 | 2002-02-07 | Jackson Sherry D. | Method of dietary supplementation |
US5976568A (en) * | 1997-02-21 | 1999-11-02 | Medical Doctors' Research Institute, Inc. | Modular system of dietary supplement compositions for optimizing health benefits and methods |
JPH11238488A (ja) * | 1997-06-06 | 1999-08-31 | Toshiba Lighting & Technology Corp | メタルハライド放電ランプ、メタルハライド放電ランプ点灯装置および照明装置 |
EP0891719A1 (en) | 1997-07-14 | 1999-01-20 | N.V. Nutricia | Nutritional composition containing methionine |
US5877171A (en) * | 1997-07-28 | 1999-03-02 | Mcleod; Malcolm N. | Method of treating pre-menstrual syndrome using chromium |
JP2001513370A (ja) * | 1997-08-07 | 2001-09-04 | グプタ,アジャイ | 水溶性ビタミン及び栄養素を含む透析溶液 |
US6054128A (en) * | 1997-09-29 | 2000-04-25 | Wakat; Diane | Dietary supplements for the cardiovascular system |
GB9722361D0 (en) * | 1997-10-24 | 1997-12-17 | Pharma Nord Uk Ltd | Pharmaceutical formulation for treating liver disorders |
US5922704A (en) * | 1997-12-24 | 1999-07-13 | Feeling Fine Company Llc | Optimal nutritional supplement for men |
US6130244A (en) * | 1998-02-25 | 2000-10-10 | Abbott Laboratories | Product and method to reduce stress induced immune suppression |
US6048846A (en) * | 1998-02-26 | 2000-04-11 | Cochran; Timothy M. | Compositions used in human treatment |
US6197340B1 (en) * | 1998-05-28 | 2001-03-06 | Medical Research Institute | Controlled release lipoic acid |
US6245360B1 (en) * | 1998-06-26 | 2001-06-12 | John S. Markowitz | Nutritional supplement |
US6103756A (en) * | 1999-08-11 | 2000-08-15 | Vitacost Inc. | Ocular orally ingested composition for prevention and treatment of individuals |
AU2001234782A1 (en) * | 2000-02-02 | 2001-08-14 | Metagenics, Inc. | Compositions and methods for promoting healthy joints |
JP4339979B2 (ja) * | 2000-02-28 | 2009-10-07 | 雪印乳業株式会社 | 葉酸及び/又はビタミンb12−ラクトフェリン類複合物 |
US6361800B1 (en) * | 2000-04-13 | 2002-03-26 | Cooper Concepts, Inc. | Multi-vitamin and mineral supplement |
US6299896B1 (en) * | 2000-04-13 | 2001-10-09 | Cooper Concepts, Inc. | Multi-vitamin and mineral supplement |
US6995166B1 (en) * | 2000-09-27 | 2006-02-07 | Everett Laboratories, Inc. | Method and composition for supplementation of nutritional deficiencies in renal patients |
-
2004
- 2004-10-15 US US10/964,754 patent/US7696219B2/en not_active Expired - Fee Related
-
2005
- 2005-09-22 KR KR1020077008957A patent/KR20070083734A/ko not_active Application Discontinuation
- 2005-09-22 JP JP2007536703A patent/JP2008516948A/ja active Pending
- 2005-09-22 WO PCT/US2005/033913 patent/WO2006044101A2/en active Application Filing
- 2005-09-22 CN CNA2005800421870A patent/CN101072565A/zh active Pending
- 2005-09-22 EP EP05800433A patent/EP1802309A4/en not_active Withdrawn
-
2010
- 2010-04-12 US US12/758,333 patent/US20100196508A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110944648A (zh) * | 2017-07-26 | 2020-03-31 | Ams高级医疗补充剂公司 | 用于治疗或预防已经受胃袖状手术的患者中的维生素缺乏和矿物质缺乏的药物组合物 |
Also Published As
Publication number | Publication date |
---|---|
WO2006044101A2 (en) | 2006-04-27 |
US20100196508A1 (en) | 2010-08-05 |
US20050100613A1 (en) | 2005-05-12 |
KR20070083734A (ko) | 2007-08-24 |
US7696219B2 (en) | 2010-04-13 |
JP2008516948A (ja) | 2008-05-22 |
WO2006044101A3 (en) | 2006-09-21 |
EP1802309A2 (en) | 2007-07-04 |
EP1802309A4 (en) | 2010-01-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101072565A (zh) | 对营养缺乏的肾病患者进行补充的方法和组合物 | |
Vanek et al. | ASPEN position paper: recommendations for changes in commercially available parenteral multivitamin and multi–trace element products | |
US6562378B1 (en) | Nutritional supplement for adolescents | |
US7901710B2 (en) | Nutritional supplement for use under physiologically stressful conditions | |
US8911798B2 (en) | Multivitamin and mineral compositions for individuals having renal disease | |
WO2006020739A2 (en) | Compositions and methods for nutrition supplementation | |
PL190526B1 (pl) | Leczniczo-odżywczy preparat dla osób chorych na cukrzycę | |
NZ532550A (en) | Compositions incorporating (-)-hydroxycitric acid, chromium, and gymnemic acid, and related methods for promoting healthy body weight and improving related health factors | |
US6995166B1 (en) | Method and composition for supplementation of nutritional deficiencies in renal patients | |
US6565891B1 (en) | Nutritional supplement for children | |
WO2001056572A1 (en) | Compositions and methods for promoting healthy joints | |
CA2505103A1 (en) | Nutritional supplement for adults | |
CA2505043A1 (en) | Nutritional supplement for infants | |
WO2014022886A1 (en) | A method, use, and dietary supplement composition for at least treating an atopic or non-atopic disorder in a patient | |
JP5931324B2 (ja) | がん化学療法時に起こる酸化ストレス及び/又は副作用の軽減あるいはがん化学療法時の栄養状態を改善するための組成物 | |
US20040137080A1 (en) | Multivitamin regimen for renal patients | |
US20130064924A1 (en) | Nutritional supplement for use under physiologically stressful conditions | |
Rivlin | Vitamin Defi ciencies | |
US20170239275A1 (en) | Compositions Containing Vitamin D and Magnesium | |
Reid | Hazards Associated with Nutrient Fortification | |
Rivlin | 14 Vitamin Deficiencies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20071114 |