CN106309486A - 营养组合物及在制备器官损伤修复药物中的应用 - Google Patents
营养组合物及在制备器官损伤修复药物中的应用 Download PDFInfo
- Publication number
- CN106309486A CN106309486A CN201610720043.6A CN201610720043A CN106309486A CN 106309486 A CN106309486 A CN 106309486A CN 201610720043 A CN201610720043 A CN 201610720043A CN 106309486 A CN106309486 A CN 106309486A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- alimentation composition
- application
- group
- medicine
- 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 64
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 230000008439 repair process Effects 0.000 title claims abstract description 18
- 229940079593 drug Drugs 0.000 title abstract description 5
- 235000015097 nutrients Nutrition 0.000 title abstract description 5
- 230000008816 organ damage Effects 0.000 title abstract 2
- 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 18
- 230000006378 damage Effects 0.000 claims abstract description 18
- 210000000056 organ Anatomy 0.000 claims abstract description 18
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 16
- 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 claims abstract description 16
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims abstract description 14
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 claims abstract description 14
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004471 Glycine Substances 0.000 claims abstract description 8
- 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 claims abstract description 8
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000011575 calcium Substances 0.000 claims abstract description 8
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 8
- 229960000304 folic acid Drugs 0.000 claims abstract description 8
- 235000019152 folic acid Nutrition 0.000 claims abstract description 8
- 239000011724 folic acid Substances 0.000 claims abstract description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002773 nucleotide Substances 0.000 claims abstract description 8
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 8
- 239000011715 vitamin B12 Substances 0.000 claims abstract description 8
- 239000011716 vitamin B2 Substances 0.000 claims abstract description 8
- 239000011726 vitamin B6 Substances 0.000 claims abstract description 8
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 8
- 239000011718 vitamin C Substances 0.000 claims abstract description 8
- 239000011701 zinc Substances 0.000 claims abstract description 8
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 8
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims abstract description 7
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims abstract description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 7
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract description 7
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 7
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract description 7
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 7
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000004472 Lysine Substances 0.000 claims abstract description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 7
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 7
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000004473 Threonine Substances 0.000 claims abstract description 7
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 7
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims abstract description 7
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims abstract description 7
- 229910052804 chromium Inorganic materials 0.000 claims abstract description 7
- 239000011651 chromium Substances 0.000 claims abstract description 7
- 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 abstract description 7
- 229910052802 copper Inorganic materials 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims abstract description 7
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract description 7
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960000310 isoleucine Drugs 0.000 claims abstract description 7
- 239000011777 magnesium Substances 0.000 claims abstract description 7
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 7
- 235000001968 nicotinic acid Nutrition 0.000 claims abstract description 7
- 229960003512 nicotinic acid Drugs 0.000 claims abstract description 7
- 239000011664 nicotinic acid Substances 0.000 claims abstract description 7
- 229960005010 orotic acid Drugs 0.000 claims abstract description 7
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000011591 potassium Substances 0.000 claims abstract description 7
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 7
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 7
- 239000011669 selenium Substances 0.000 claims abstract description 7
- 239000008347 soybean phospholipid Substances 0.000 claims abstract description 7
- 229960003080 taurine Drugs 0.000 claims abstract description 7
- 239000004474 valine Substances 0.000 claims abstract description 7
- 235000019155 vitamin A Nutrition 0.000 claims abstract description 7
- 239000011719 vitamin A Substances 0.000 claims abstract description 7
- 229940045997 vitamin a Drugs 0.000 claims abstract description 7
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims abstract description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 6
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims abstract description 6
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229930003316 Vitamin D Natural products 0.000 claims abstract description 6
- 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 claims abstract description 6
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 6
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 6
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims abstract description 6
- 229960000367 inositol Drugs 0.000 claims abstract description 6
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims abstract description 6
- 235000019166 vitamin D Nutrition 0.000 claims abstract description 6
- 239000011710 vitamin D Substances 0.000 claims abstract description 6
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 6
- 229940046008 vitamin d Drugs 0.000 claims abstract description 6
- 239000004475 Arginine Substances 0.000 claims abstract description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 5
- 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 abstract description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229930182817 methionine Natural products 0.000 claims abstract description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 16
- 208000014674 injury Diseases 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 7
- 239000011572 manganese Substances 0.000 claims description 7
- 229910052748 manganese Inorganic materials 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 206010061363 Skeletal injury Diseases 0.000 claims description 5
- 239000000470 constituent Substances 0.000 claims description 5
- 206010061481 Renal injury Diseases 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 208000037806 kidney injury Diseases 0.000 claims description 4
- 230000003902 lesion Effects 0.000 claims description 4
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims description 4
- 102000004452 Arginase Human genes 0.000 claims description 3
- 108700024123 Arginases Proteins 0.000 claims description 3
- 206010041649 Splenic injury Diseases 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- LURVIJVAAIIEQT-RGMNGODLSA-N [S].C(CC)N[C@@H](CCO)C(=O)O Chemical compound [S].C(CC)N[C@@H](CCO)C(=O)O LURVIJVAAIIEQT-RGMNGODLSA-N 0.000 claims 1
- 210000000952 spleen Anatomy 0.000 abstract description 12
- 210000004185 liver Anatomy 0.000 abstract description 11
- 210000000130 stem cell Anatomy 0.000 abstract description 11
- 210000003734 kidney Anatomy 0.000 abstract description 9
- 210000004556 brain Anatomy 0.000 abstract description 8
- 210000003958 hematopoietic stem cell Anatomy 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 230000035755 proliferation Effects 0.000 abstract description 3
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 abstract 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract 1
- 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 abstract 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 abstract 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 abstract 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract 1
- 239000006035 Tryptophane Substances 0.000 abstract 1
- 229930003779 Vitamin B12 Natural products 0.000 abstract 1
- 229930003471 Vitamin B2 Natural products 0.000 abstract 1
- 229910052742 iron Inorganic materials 0.000 abstract 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 abstract 1
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 abstract 1
- 229960002477 riboflavin Drugs 0.000 abstract 1
- 210000002356 skeleton Anatomy 0.000 abstract 1
- 229960004799 tryptophan Drugs 0.000 abstract 1
- 235000019163 vitamin B12 Nutrition 0.000 abstract 1
- 235000019164 vitamin B2 Nutrition 0.000 abstract 1
- 235000019158 vitamin B6 Nutrition 0.000 abstract 1
- 229940011671 vitamin b6 Drugs 0.000 abstract 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 66
- 241000700159 Rattus Species 0.000 description 48
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 15
- 239000007788 liquid Substances 0.000 description 15
- 230000006698 induction Effects 0.000 description 13
- 238000000034 method Methods 0.000 description 12
- 210000001185 bone marrow Anatomy 0.000 description 11
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 11
- 238000004043 dyeing Methods 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 9
- 210000005259 peripheral blood Anatomy 0.000 description 9
- 210000000988 bone and bone Anatomy 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 210000000963 osteoblast Anatomy 0.000 description 8
- 239000011886 peripheral blood Substances 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000010586 diagram Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000012531 culture fluid Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000003995 blood forming stem cell Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 210000001772 blood platelet Anatomy 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000004026 insulin derivative Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 210000005087 mononuclear cell Anatomy 0.000 description 3
- 238000003305 oral gavage Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 210000000689 upper leg 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
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 101150018889 FABP4 gene Proteins 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical class Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 230000002293 adipogenic effect Effects 0.000 description 2
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 101150053306 bglap gene Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 208000037890 multiple organ injury Diseases 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000004072 osteoblast differentiation Effects 0.000 description 2
- 230000001582 osteoblastic effect Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 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 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- TUFFYSFVSYUHPA-UHFFFAOYSA-M rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C(C=CC(N)=C2)C2=[O+]C2=C1C=CC(N)=C2 TUFFYSFVSYUHPA-UHFFFAOYSA-M 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 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 1
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AQGDXJQRVOCUQX-UHFFFAOYSA-N N.[S] Chemical compound N.[S] AQGDXJQRVOCUQX-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 235000009392 Vitis Nutrition 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 208000034777 Vitreous degeneration Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 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
- 210000000601 blood cell Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229940097572 chloromycetin Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003013 erythroid precursor cell Anatomy 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 210000001280 germinal center Anatomy 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical group C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 239000008518 lycium barbarum polysaccharide Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000001501 megacaryocyte Anatomy 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000013441 quality evaluation Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000003462 vein Anatomy 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
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 201000011288 vitreous syneresis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000004018 waxing Methods 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
-
- 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
- A61K31/59—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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- 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
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
-
- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
-
- 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
- A61K33/26—Iron; Compounds thereof
-
- 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
- A61K33/30—Zinc; Compounds thereof
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明本发明公开一种营养组合物及在制备器官损伤修复药物中的应用,是由赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸、色氨酸、精氨酸、组氨酸、甘氨酸、天冬氨酸、亮氨酸、异亮氨酸、缬氨酸、丝氨酸、谷氨酰胺、牛磺酸、乳清酸、核苷酸、维生素A 、维生素D、维生素B2、维生素B6、维生素B12、烟酸、叶酸、维生素C、铁、锌、锰、铜、硒、铬、钾、钙、镁、肌醇及大豆磷脂按比例配制而成,具有促进造血干细胞增殖等作用且可肝脏损伤、脾脏损伤、肾脏损伤、大脑损伤及骨骼损伤等具有修复作用,无毒、无副作用,避免给予外源性干细胞进行器官修复所存在的麻烦。
Description
技术领域
本发明涉及一种营养组合物及用途,尤其是一种具有促进造血干细胞增殖等作用且可对多种器官损伤恢复的营养组合物及在制备器官损伤修复药物中的应用。
背景技术
正常情况下,生物体受到创伤后会行使自我修复功能,这种修复功能在很大程度上依赖于体内的干细胞完成。但是,机体内自我修复功能是非常有限的,如无法在组织器官严重器质性损伤的情况下修复,现有方法是通过给予外源性干细胞进行器官修复。然而,要实现将干细胞变成药物还有许多的关键问题需要解决,例如,如何保持干细胞经过体外大规模培养后的分化能力、遗传特征、致瘤性和稳定性;建立与药效作用相关的体外生物学评价方法;筛选保持活细胞稳定的药物制剂配方;选择剂型及包装材料;规范储存、冷链运输条件;建立干细胞产品的技术标准及质量评价体系;摸索临床前药物有效性评价体系、安全性评价体系等等,比较麻烦。
专利号为200710012788.8的中国发明专利公开了一种“促进造血干细胞增殖与血红蛋白合成的营养组合物”。该营养组合物的原料及重量比如下:核苷酸90~110、精氨酸20~30、赖氨酸20~30、半胱氨酸10~20、甘氨酸25~35、组氨酸20~30、卵磷脂110~130、脑磷脂50~70、维生素E 0.4~0.6、维生素C 5~7、叶酸0.02~0.04、维生素B2 0.05~0.07、维生素B6 0.07~0.08、维生素B12 0.0001~0.0002、铁0.5~1.5、锌0.5~0.7、锰0.4~0.6、枸杞多糖14~16、葡萄籽提取物14~16。可明显提高血中血红蛋白(Hb)、红细胞(RBC)、白细胞(WBC)及血小板(Plt)数量;可刺激骨髓造血干细胞的增殖,使造血干细胞明显增多;明显提高细胞内线粒体数目。但是仅对肝、脾两个器官的损伤具有恢复作用。
发明内容
本发明是为了解决现有技术所存在的上述技术问题,提供一种具有促进造血干细胞增殖等作用且可对多种器官损伤恢复的营养组合物及在制备器官损伤修复药物中的应用。
本发明的技术解决方案是:一种营养组合物,其特征在于各组分质量比如下:赖氨酸200~1200、甲硫氨酸100~1600、苯丙氨酸150~1400、苏氨酸50~600、色氨酸50~400、精氨酸200~1500、组氨酸100~1000、甘氨酸100~600、天冬氨酸100~600、亮氨酸100~600、异亮氨酸100~600、缬氨酸100~800、丝氨酸100~400、谷氨酰胺200~600、牛磺酸100~500、乳清酸100~300、核苷酸200~1200、维生素A 0.2~0.6、维生素D 0.002~0.006、维生素B2 1~4、维生素B6 1~4、维生素B12 0.001~0.006、烟酸 5~20、叶酸0.01~1.2、维生素C 50~150、铁2~10、锌2~10、锰2~10、铜 0.5~2、硒0.01~0.1、铬0.01~0.02、钾10~300、钙100~300、镁100~200、肌醇50~60、大豆磷脂100~2500。
各组分最佳质量比如下:赖氨酸600、甲硫氨酸800、苯丙氨酸700、苏氨酸300、色氨酸200、精氨酸760、组氨酸500、甘氨酸300、天冬氨酸300、亮氨酸300、异亮氨酸300、缬氨酸400、丝氨酸200、谷氨酰胺300、牛磺酸500、乳清酸300、核苷酸400、维生素A 0.6、维生素D0.006、维生素B22、维生素B62、维生素B12 0.004、烟酸12、叶酸0.9、维生素C100、铁10、锌10、锰 8、铜2、硒0.1、铬 0.02、钾 300、钙300、镁 200、肌醇60、大豆磷脂1200。
上述营养组合物在制备器官损伤修复药物中的应用。
上述营养组合物在制备肝脏损伤修复药物中的应用。
上述营养组合物在制备脾脏损伤修复药物中的应用。
上述营养组合物在制备肾脏损伤修复药物中的应用。
上述营养组合物在制备大脑损伤修复药物中的应用。
上述营养组合物在制备骨骼损伤修复药物中的应用。
本发明的营养组合物具有促进造血干细胞增殖等作用且可对肝脏损伤、脾脏损伤、肾脏损伤、大脑损伤及骨骼损伤等具有修复作用,可应用于制备器官损伤修复药物,无毒、无副作用,避免给予外源性干细胞进行器官修复所存在的麻烦。
附图说明
图1是本发明实施例对再障大鼠体重的影响示意图。
图2 是本发明实施例对再障大鼠肝、脾、肾、脑的影响示意图(HE染色)。
图3 是本发明实施例对再障大鼠肠、肌肉的影响示意图(HE染色)。
图4是本发明各实验组的肾切片透射电镜图。
图5是本发明实施例对再障大鼠骨髓间充质干细胞生长的影响示意图。
图6是本发明各实验组脂肪细胞的诱导及成脂细胞相关基因的表达示意图。
图7是本发明各实验组成骨细胞的诱导及成骨细胞相关基因的表达示意图。
图8时本发明实施例对再障大鼠骨髓造血细胞的影响示意图。
具体实施方式
实施例1:本发明的营养组合物各组分质量(mg)比如下:赖氨酸200~1200、甲硫氨酸100~1600、苯丙氨酸150~1400、苏氨酸50~600、色氨酸50~400、精氨酸200~1500、组氨酸100~1000、甘氨酸100~600、天冬氨酸100~600、亮氨酸100~600、异亮氨酸100~600、缬氨酸100~800、丝氨酸100~400、谷氨酰胺200~600、牛磺酸100~500、乳清酸100~300、核苷酸200~1200、维生素A 0.2~0.6、维生素D 0.002~0.006、维生素B2 1~4、维生素B6 1~4、维生素B120.001~0.006、烟酸 5~20、叶酸0.01~1.2、维生素C 50~150、铁2~10、锌2~10、锰2~10、铜 0.5~2、硒0.01~0.1、铬0.01~0.02、钾10~300、钙100~300、镁100~200、肌醇50~60、大豆磷脂100~2500。
实施例2:各组分质量(mg)比如下:赖氨酸600、甲硫氨酸800、苯丙氨酸700、苏氨酸300、色氨酸200、精氨酸760、组氨酸500、甘氨酸300、天冬氨酸300、亮氨酸300、异亮氨酸300、缬氨酸400、丝氨酸200、谷氨酰胺300、牛磺酸500、乳清酸300、核苷酸400、维生素A0.6、维生素D0.006、维生素B22、维生素B62、维生素B12 0.004、烟酸12、叶酸0.9、维生素C100、铁10、锌10、锰 8、铜2、硒0.1、铬 0.02、钾 300、钙300、镁 200、肌醇60、大豆磷脂1200。
所述营养组合物对肝脏损伤、脾脏损伤、肾脏损伤、大脑损伤及骨骼损伤等具有修复作用,可在制备器官损伤恢复药物中应用。
实施例1、2原料来源如下表:
实验:
一.再生障碍性贫血大鼠模型的建立
本实验采用SD大鼠。实验步骤:第一天X射线2.5Gy照射后,于第4、6、8天分别给予环磷酰胺35mg/kg,氯霉素45 mg/kg腹腔注射。第15天重复以上步骤。以单纯等量生理盐水相应部位注射为正常对照组。
实验分组:根据动物药理学的药品剂量和综合试验的设计分析,分为:①正常对照组;②再障模型组;③实施例2营养组合物高剂量组,以2266.95mg/kg.d对大鼠灌胃;④实施例2营养组合物中剂量组,以1511.3mg/kg.d对大鼠灌胃;⑤实施例2营养组合物低剂量组,以1057.91mg/kg.d对大鼠灌胃。
试验流程:首先,按前述再障大鼠模型的建立方法建立模型,从第5天开始,营养组合物高、中、低剂量组分别以相应剂量对大鼠进行灌胃,每天一次,直至第60天,拉颈处死大鼠,采样进行检测。同时每日进行整体观察,测量体重。
二.实验方法
1. 外周血检测
各实验组第60天, 称重动物,经眼眶取血,采用全自动血细胞分析仪测定外周血血红蛋白含量、红细胞、白细胞及血小板数;显微镜下观察外周血涂片。
2.***(Epo)检测
酶标板每孔加入标准液,对照液及预先用样品稀释液稀释的待测样品100ul,封板,37°C孵育90分钟。反应后甩干孔内液体后,将准备好的生物素抗小鼠EPO抗体工作液按每孔100ul依次加入(TMB空白显色孔除外),封板后37°C反应60分钟,0.01M PBS洗涤3次,每次浸泡1分钟左右。加入准备好的亲和素-过氧化物酶复合物工作液按每孔100ul依次加入(TMB空白显色孔除外),37°C反应30分钟。按每孔90µl依次加入已在37℃中平衡30分钟TMB显色液,37°C避光反应,每孔100µl依次加入TMB终止液。用酶标仪于450nm波长处读取吸光度(OD值), 根据标准曲线测得样本Epo浓度(pg/ml)。
3. 骨髓检测
颈椎脱臼处死大鼠, 分离双侧股骨打开骨髓腔进行骨髓涂片、骨髓单个核细胞计数、骨髓病理检查、骨髓间充质干细胞增殖及分化趋势的分析。
4. 骨髓间充质干细胞(BMSCs)的分离提取
SD大鼠腹腔注射***后脱颈处死,75% 乙醇浸泡大鼠20 min;无菌取双后肢,放入75% 的乙醇中浸泡5 min;清除下肢肌肉,从膝关节断离股骨,剪开股骨两端;用10 mL注射器吸取10% 胎牛血清的F-12K培养液冲洗骨髓腔,收集骨髓冲洗液,制成单细胞悬液,200目筛网滤过后以1×108接种于培养瓶中。置于37°C、5% CO2培养箱中培养。72 小时首次更换培养液,去除未贴壁细胞,以后每隔2天换液1次。当细胞铺满整个培养瓶底面积的80%~90%时,传代培养。
5.间充质干细胞(BMSCs)的成脂诱导分化
成脂诱导法:将分离纯化的骨髓间充质干细胞常规培养,消化传代,以1×105/孔的密度,400ul/孔接种于预先放置有盖玻片的6孔培养板中,制备细胞爬片,当细胞生长达80%融合时,加入10%的胎牛血清、1μmol/L***、0.5 mmol/L IBMX、10 mg/L牛胰岛素的H-DMEM诱导3天,再用10% 的胎牛血清、10 mg/L牛胰岛素的H-DMEM处理1天,如此循环3次后,用10%的胎牛血清、10 mg/L牛胰岛素的H-DMEM处理7天,每隔三四天换液1次。对照组始终加入含体积分数为10% 的胎牛血清、10 mg/L牛胰岛素的H-DMEM,每隔三四天换液1次。诱导后细胞用PBS洗涤2~3次,10% 甲醛室温固定40min。PBS洗2~3次,饱和油红O染液用一蒸水以3:2稀释,室温染色30min,PBS洗数次直至无肉眼观察到沉渣,光镜观察。
6. 间充质干细胞(BMSCs)成骨细胞培养及鉴定
取P2代骨髓间充质干细胞,按2×105个/孔接种于12孔板,当细胞贴壁生长达80% 融合时,吸除孔中培养液,换为成骨细胞诱导液 (含高糖DMEM、体积分数为10% 胎牛血清、10-8mol/L***、10-2 mol/L β-甘油磷酸钠、50 mg/L抗坏血酸),每3天更换诱导液1次。培养14天后,吸除培养液,PBS洗2次,10%甲醛室温固定40 min,PBS洗3次,加入0.1% 茜红素(3:2稀释),室温染色10min,去除染液,PBS洗3次后,显微镜下观察。
7. RNA提取和RT-PCR分析
常规应用Trizol 法提取各标本的总RNA,紫外分光光度计测定A260和A280,以检测RNA含量和纯度,并置放于-70°C保存。
反转录体系20μl,包含样品RNA 1μl,按照TaKaRa 的反转录试剂盒提供的说明书进行操作。反转录反应条件为:65°C 1min,30°C 5min,65°C 15min,98°C 5min,5°C 5min。
PCR反应体系50 μl,包含反转录液10 μl。PCR反应条件: 94°C预变性1min;97°C变性 20s,64°C退火20s,72°C 20s延伸,循环30次;72°C 延伸5min,4°C恒定。取5μl PCR扩增产物经1%琼脂糖凝胶电泳, 紫外灯下凝胶成像。
8. 透射电镜观察
将大鼠部分肝、脾、脑、肾组织标本上取不同部位的3张切片进行透射电镜(JEM-100CXE型) 超微结构的观察,每张切片分别随机观察5-6个部位,并按相同放大倍数摄片,每组随机抽取l0张照片,采用Epson微机和Summa Sketch PIus 数字化仪,并使用Sigmascan软件,对各组照片作电镜图像的形态进行分析,同时计数线粒体的平均数目。
9. 线粒体膜电位测定
细胞(5×105个)接种于25cm2培养瓶中, 37℃培养24 h后,加入不同浓度的姜黄素分别作用1 h和 6 h 后,收获细胞,PBS洗两遍,重悬于2ml 含1.0 µM 罗丹明123的新鲜培养液中,37°C 水浴振摇孵育10 min,离心去掉细胞,荧光比色计测定培养液中罗丹明123的强度,激发波长490 nm,发射波长520 nm,结果以细胞吸收的罗丹明123的荧光强度表示。
10. 线粒体DNA含量测定
将骨髓单个核细胞(5×107)、新鲜组织肝脏、脾、脑、肾匀浆、裂解、离心,获取线粒体。按照DNA提取试剂盒说明提取线粒体中的DNA,采用紫外分光光度计测量其含量。计算公式如下:
DNA浓度(μg/μl)= A260 × 50μg/ml × 稀释倍数 × 10-3
11. 病理学观察
将大鼠部分肝、脾、脑、肾、肠、肌肉置于4 %多聚甲醛中固定,依次经过常规脱水、石蜡浸泡包埋、切片、HE 染色, 显微镜观察各组织细胞的形态结构。
12. 免疫组化染色
石蜡切片脱蜡、水化;PBS洗2-3次各5分钟;3% H2O2(80%甲醇)滴加在玻片上,室温静置10分钟;PBS洗2-3次各5分钟;抗原修复;PBS洗2-3次各5分钟;滴加正常山羊血清封闭液,室温20分钟。甩去多余液体,滴加一抗50μl,4°C过夜。过夜后需在37°C复温45分钟。PBS洗3次各5分钟;滴加二抗40-50μl,室温静置,或37°C 1小时;PBS洗3次各5分钟;DAB显色5-10分钟,在显微镜下掌握染色程度;PBS或自来水冲洗10分钟;苏木精复染2分钟,盐酸酒精分化;自来水冲洗10-15分钟;脱水、透明、封片、镜检。
13. 流式细胞仪分析
取大鼠左胫骨,去除表面肌肉组织,修剪骨垢,用18 号针***胫骨踝端,用PBS 5mL 冲洗入试管内,以200目筛网过滤。1000 r/min 离心 5min,弃上清液。将细胞加入5mLPercoll分离液(相对比重1.073g/L),2000r/min,离心25min,取中间单个核细胞层。PBS洗涤后调整单个核细胞数为l×106/管,每样本3管,测定管加入FITC标记的CD34或CD45抗体,37°C孵育2小时。然后PBS洗涤一次。用流式细胞仪检测表达CD34/45阳性细胞数量变化,以标记抗体呈阳性的细胞百分率作为表达CD34/45 蛋白(骨髓造血干细胞标志物)的计量标准。同时以只加标记荧光素的羊抗兔IgG和不加抗体的细胞作阴性对照。
14. 蛋白芯片分析
将大鼠部分骨髓单个核细胞、骨髓间充质干细胞、肝脏组织进行蛋白芯片分析,此部分工作由上海康城公司完成。
15. 统计学分析
所有数据均用SPSS 17.0软件进行统计分析。每一项分析至少有三次结果。数值用均数±SD表示,采用t检验。P<0.05认为有显著性差异,并在统计学上有意义。
三、实验结果
(一)营养组合物对再障大鼠全身情况的影响
与正常对照组相比,再障模型组大鼠自6天起陆续出现皮毛松弛蓬乱,光泽度降低,部分大鼠有脱毛及皮损。同时大鼠消瘦、精神渐显不佳,唇色眼睑苍白、活动减少、少食、体重下降。其中再障模型组大鼠体重(218.23±33.52 g)与正常对照组(366.54±49.68 g,*p<0.05)相比下降明显。
不同剂量的营养组合物组与再障模型组比较,大鼠精神状态渐佳,进食量增大,体重增加(见图1)。表明营养组合物对再生障碍性贫血小鼠全身有显著恢复作用。
(二)营养组合物对再障大鼠外周血的影响
与正常对照组相比,再障模型组外周血中红细胞 (RBC)、白细胞 (WBC)、血小板 (PLT)及血红蛋白 (Hb) 均显著下降 (表 1,#p<0.05);不同剂量营养组合物组与再障模型组比较,其外周血中各项指标均显著升高 (表 1,*p<0.05),并呈量效依赖性。
与正常对照组相比,再障模型组大鼠***(EPO)含量明显升高,且EPO与 RBC、 Hb的降低呈负相关,r=-0.91及r=-0.93(*p<0.05),表明EPO水平与再障骨髓红系生成能力降低,EPO反应性能力减弱,EPO呈代偿性升高有关。(表1,*p<0.01)。EPO是一种重要的造血调控因子,具有促进红系祖细胞增殖、分化和成熟,维持外周血中红细胞,血红蛋白恒定的作用,血液中EPO水平能反映机体中的红细胞生成能力。而不同剂量的营养组合物组与再障模型组比较,***(Epo)由于代偿作用含量降低 (*p<0.01);并呈剂量-效应关系。
以上结果提示,营养组合物对再障大鼠外周血各种血细胞有促进升高作用。
表1营养组合物对再障大鼠外周血的影响
# P<0.05 再障组与正常组;*P<0.05 营养组合物组与再障组
(三)本发明实施例营养组合物对再障大鼠器官损伤修复的影响
1.对于肝、脾、肾、脑、肠及肌肉等器官损伤修复的影响
从图2可以看出:
肝的病理切片HE染色显示,与正常对照组相比,再障模型组大鼠肝脏组织小叶结构欠清晰,肝细胞核固缩,染色质深染,肝血窦及中央静脉扩张,充血。不同剂量的营养组合物组与再障模型组比较, 肝脏组织小叶结构明显清晰,肝细胞形态接近正常。
脾的病理切片HE染色显示,与正常对照组相比,再障模型组大鼠脾脏略微肿大,脾组织结构疏松,脾小体个数减少,生发中心不明显,白髓减少,脾血窦扩张、充血,部分区域可见脾小动脉壁增厚及玻璃样变。不同剂量的营养组合物组与再障模型组比较,脾小体数量增多,白髓增多。
肾的病理切片HE染色显示,与正常对照组相比,再障模型组大鼠肾小球体积减小,部分大小不一,肾小管水肿。不同剂量的营养组合物组与再障模型组比较,肾小球体积趋于正常,肾小管水肿减轻。
脑的病理切片HE染色显示,与正常对照组相比,再障模型组大鼠脑部海马区域的神经元细胞排列紊乱。不同剂量的营养组合物组与再障模型组比较,神经元细胞排列趋于整齐。
从图3中可以看出:
肠、肌肉的组织切片显示未见明显变化。
图4是本发明各实验组的肾切片透射电镜图。从图4可以看出:与正常对照组相比,再障模型组大鼠肾小球基底膜足突大面积融合;不同剂量的营养组合物组与再障模型组比较, 大鼠肾小球基底膜足突融合程度减低,排列趋于正常。
结果显示,本发明实施例营养组合物对再障大鼠肝、脾、肾、脑损伤有显著恢复作用。
2.对于骨骼损伤修复的影响
2.1 本发明实施例营养组合物对再障大鼠骨髓间充质干细胞生长的影响
各组骨髓间充质干细胞增殖能力结果见图5,再障组显著低于正常组,低剂量组与再障组无差异,中剂量组,高剂量组与再障组有明显差异。
2.2 本发明实施例对再障大鼠骨髓间充质干细胞分化趋势的影响
2.2.1 脂肪细胞的诱导及成脂细胞相关基因的表达
如图6所示:
正常组,再障组,高剂量组,中剂量组和低剂量组P2代骨髓间充质干细胞分别用成脂肪细胞诱导培养液进行诱导培养,再障组诱导形成的脂肪滴出现时间 第7天早于正常组第12d左右。继续诱导培养,脂肪滴明显增大并发生融合。诱导19天后,融合的脂肪滴被油红O染色为明亮的红色;显微镜下观察,再障组骨髓间充质干细胞成脂肪细胞分化诱导能力高于正常组,营养组合物处理再障大鼠后,间充质干细胞成脂肪细胞分化诱导能力下降,且随着营养组合物剂量增加而下降,表明营养组合物减弱再障大鼠间充质干细胞成脂肪细胞分化诱导能力。
为更客观地比较营养组合物对大鼠骨髓间充质干细胞成脂肪细胞的影响,进一步检测了成脂肪细胞相关基因Pparr mRNA,Fabp4 mRNA的表达水平。结果显示,Fabp4和Pparr的表达水平与营养组合物干预的计量呈负相关。
以上结果表明再障组与正常对照组相比,再障鼠骨髓间充质干细胞向脂肪细胞分化能力增强;而营养组合物干预后,再障鼠骨髓间充质干细胞向成脂细胞分化能力减弱。
2.2.2 成骨细胞的诱导及成骨细胞相关基因的表达
如图7所示:
正常组,再障组,高剂量组,中剂量组和低剂量组P2代骨髓间充质干细胞分别用成骨细胞诱导培养液诱导培养,连续培养5~7天,可见细胞集落中心出现黑色沉积物,14天后茜红素染色。再障组骨髓间充质干细胞黑色沉积物出现较晚,钙结节数量明显少于正常组。营养组合物处理再障大鼠后,间充质干细胞成骨细胞分化诱导能力增强,且随着营养组合物剂量增加而增加,表明营养组合物能增强再障大鼠间充质干细胞成骨细胞分化诱导能力。
为比较营养组合物对再障大鼠骨髓间充质干细胞成骨细胞过程的影响,进一步检测了成骨细胞相关基因mRNA和Bglap mRNA的表达水平。结果显示,Alp和Bglap的表达水平与营养组合物干预的计量呈正相关。
结果表明再障组与正常照组相比,再障鼠骨髓间充质干细胞向成骨细胞分化能力减弱;而营养组合物干预后,再障鼠骨髓间充质干细胞向成骨细胞分化能力增强。
2.3 本发明实施例对再障大鼠骨髓造血细胞的影响
骨髓涂片(图8)显示,与正常对照组相比,再障模型组大鼠部分骨髓涂片出现油滴,骨髓全面衰竭呈增生障碍,造血细胞减少,非造血细胞增多;成熟红细胞大小一致,无明显淡染区;巨核细胞缺如,血小板减少,散在分布(图8A);骨髓单个核细胞计数显示,再障模型组明显低于正常对照组(图8B、表2)。各营养组合物组与再障模型组比较,骨髓病理变化逐渐改善,骨髓细胞明显增多(图8A);各营养组合物组单个核细胞数明显高于再障模型组(图8B、表2)。
表2
# P<0.05 再障组与正常组;*P<0.05 营养组合物组与再障组
结果显示,营养组合物可促进再障大鼠骨髓造血细胞的增殖,对再障大鼠骨髓损伤状态有显著修复作用。
综上所述,本发明实施例营养组合物对再障大鼠骨骼损伤状态有显著修复作用。
Claims (8)
1.一种营养组合物,其特征在于各组分质量比如下:赖氨酸200~1200、甲硫氨酸100~1600、苯丙氨酸150~1400、苏氨酸50~600、色氨酸50~400、精氨酸200~1500、组氨酸100~1000、甘氨酸100~600、天冬氨酸100~600、亮氨酸100~600、异亮氨酸100~600、缬氨酸100~800、丝氨酸100~400、谷氨酰胺200~600、牛磺酸100~500、乳清酸100~300、核苷酸200~1200、维生素A 0.2~0.6、维生素D 0.002~0.006、维生素B2 1~4、维生素B6 1~4、维生素B12 0.001~0.006、烟酸 5~20、叶酸0.01~1.2、维生素C 50~150、铁2~10、锌2~10、锰2~10、铜 0.5~2、硒0.01~0.1、铬0.01~0.02、钾10~300、钙100~300、镁100~200、肌醇50~60、大豆磷脂100~2500。
2.根据权利要求1所述的营养组合物,其特征在于各组分质量比如下:赖氨酸600、甲硫氨酸800、苯丙氨酸700、苏氨酸300、色氨酸200、精氨酸760、组氨酸500、甘氨酸300、天冬氨酸300、亮氨酸300、异亮氨酸300、缬氨酸400、丝氨酸200、谷氨酰胺300、牛磺酸500、乳清酸300、核苷酸400、维生素A 0.6、维生素D0.006、维生素B22、维生素B62、维生素B12 0.004、烟酸12、叶酸0.9、维生素C100、铁10、锌10、锰 8、铜2、硒0.1、铬 0.02、钾 300、钙300、镁 200、肌醇60、大豆磷脂1200。
3.一种如权利要求1或2所述营养组合物在制备器官损伤修复药物中的应用。
4.根据权利要求3所述营养组合物在制备器官损伤修复药物中的应用,其特征在于在制备肝脏损伤修复药物中的应用。
5.根据权利要求3所述营养组合物在制备器官损伤修复药物中的应用,其特征在于在制备脾脏损伤修复药物中的应用。
6.根据权利要求3所述营养组合物在制备器官损伤修复药物中的应用,其特征在于在制备肾脏损伤修复药物中的应用。
7.根据权利要求3所述营养组合物在制备器官损伤修复药物中的应用,其特征在于在制备大脑损伤修复药物中的应用。
8.根据权利要求3所述营养组合物在制备器官损伤修复药物中的应用,其特征在于在制备骨骼损伤修复药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610720043.6A CN106309486A (zh) | 2016-08-25 | 2016-08-25 | 营养组合物及在制备器官损伤修复药物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610720043.6A CN106309486A (zh) | 2016-08-25 | 2016-08-25 | 营养组合物及在制备器官损伤修复药物中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106309486A true CN106309486A (zh) | 2017-01-11 |
Family
ID=57790234
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610720043.6A Pending CN106309486A (zh) | 2016-08-25 | 2016-08-25 | 营养组合物及在制备器官损伤修复药物中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106309486A (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1298701A (zh) * | 1999-12-03 | 2001-06-13 | 中国人民解放军军事医学科学院放射医学研究所 | 新型复合氨基酸组合物 |
CN101172140A (zh) * | 2007-09-11 | 2008-05-07 | 珍奥集团股份有限公司 | 促进造血干细胞增殖与血红蛋白合成的营养组合物 |
CN101780183A (zh) * | 2010-03-22 | 2010-07-21 | 珍奥集团股份有限公司 | 营养组合物在制备促进肝脏干细胞增殖药物中的应用 |
CN102038952A (zh) * | 2009-10-16 | 2011-05-04 | 唐一源 | 一种提高神经细胞生存能力的组合物及其用途 |
CN102772407A (zh) * | 2012-08-01 | 2012-11-14 | 岳茂兴 | 一种促进神经损伤修复的药物组合物及其应用 |
-
2016
- 2016-08-25 CN CN201610720043.6A patent/CN106309486A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1298701A (zh) * | 1999-12-03 | 2001-06-13 | 中国人民解放军军事医学科学院放射医学研究所 | 新型复合氨基酸组合物 |
CN101172140A (zh) * | 2007-09-11 | 2008-05-07 | 珍奥集团股份有限公司 | 促进造血干细胞增殖与血红蛋白合成的营养组合物 |
CN102038952A (zh) * | 2009-10-16 | 2011-05-04 | 唐一源 | 一种提高神经细胞生存能力的组合物及其用途 |
CN101780183A (zh) * | 2010-03-22 | 2010-07-21 | 珍奥集团股份有限公司 | 营养组合物在制备促进肝脏干细胞增殖药物中的应用 |
CN102772407A (zh) * | 2012-08-01 | 2012-11-14 | 岳茂兴 | 一种促进神经损伤修复的药物组合物及其应用 |
Non-Patent Citations (3)
Title |
---|
于新、胡林子编著: "《大豆加工副产物的综合利用》", 30 June 2013 * |
姜忠丽主编: "《食品营养与安全卫生学》", 31 August 2010 * |
苗小艳等: "营养组合物对再生障碍性贫血小鼠细胞线粒体形态及跨膜电位的影响", 《解剖科学进展》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Huxley et al. | The elements of experimental embryology | |
CN101788480B (zh) | 基于荧光标记的肝毒性物质筛选和评价方法 | |
Monsma et al. | FluoroMyelin™ Red is a bright, photostable and non-toxic fluorescent stain for live imaging of myelin | |
CN106109491A (zh) | 营养组合物及在制备治疗再生障碍性贫血药物中的应用 | |
Rosas-Hernandez et al. | Isolation and culture of brain microvascular endothelial cells for in vitro blood-brain barrier studies | |
CN104745526B (zh) | 一种斑马鱼原代胚胎细胞体外分化为心肌细胞的新方法 | |
CN106344611A (zh) | 营养组合物及在制备促进干细胞增殖药物中的应用 | |
Öztan | The hypothalamic neurosecretory system of a poeciliid fish, Platypoecilus maculatus and its sterile hybrid backcross with Xiphophorus helleri | |
CN106309486A (zh) | 营养组合物及在制备器官损伤修复药物中的应用 | |
CN106109492A (zh) | 营养组合物及在制备线粒体增殖、线粒体基因损伤修复药物中的应用 | |
Prasad et al. | Number and nuclear morphology of TH+ and TH− neurons in the mouse ventral midbrain using epifluorescence stereology | |
CN109481425A (zh) | 仙鹤草酚b作为tfeb核转位诱导剂的应用 | |
Badal et al. | Live imaging and quantitative analysis of organelle transport in sensory neurons of Aplysia Californica | |
CN101780183B (zh) | 营养组合物在制备促进肝脏干细胞增殖药物中的应用 | |
Chiavegatto et al. | Cell Viability, mitotic index and callus morphology of Byrsonima verbascifolia (Malpighiaceae) | |
CN113546070A (zh) | 低聚茋类单体化合物Isohop在制备提高动物脂肪沉积的产品中的用途 | |
CN113521055A (zh) | 低聚茋类单体化合物VitD在制备提高动物脂肪沉积的产品中的用途 | |
CN106265734A (zh) | 营养组合物及在制备基因损伤恢复药物中的应用 | |
CN106929560A (zh) | 一种利用热带爪蟾胚胎测定化学品发育毒性的方法 | |
LeClair | The Last Half Century of Fish Explant and Organ Culture | |
Shilpa et al. | First record of Araneus viridiventris Yaginuma, 1969 (Araneae: Araneidae) from India with redescription of the female | |
Yoosuf et al. | Mutagenicity assessment of sunset yellow on chromosomal aberrations and whole genome dna strand breaks in Allium cepa | |
CN105232590A (zh) | 具有促神经干细胞增殖活性的诃子乙醇提取物及其应用 | |
Hanan | Studies of the retrocerebral complex in the honey bee: Part I: Anatomy and histology | |
CN103961339B (zh) | 新女贞子苷在抗阿霉素心肌毒性中的应用及以新女贞子苷为主要活性成分的药物组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170111 |