CN106265696A - 使用复合维生素b、c组合物促进胃肠系统动力的方法 - Google Patents
使用复合维生素b、c组合物促进胃肠系统动力的方法 Download PDFInfo
- Publication number
- CN106265696A CN106265696A CN201510321294.2A CN201510321294A CN106265696A CN 106265696 A CN106265696 A CN 106265696A CN 201510321294 A CN201510321294 A CN 201510321294A CN 106265696 A CN106265696 A CN 106265696A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- compositions
- parts
- compound
- acid
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 66
- 235000019156 vitamin B Nutrition 0.000 title claims abstract description 65
- 239000011720 vitamin B Substances 0.000 title claims abstract description 65
- 229930003270 Vitamin B Natural products 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title description 21
- 239000000203 mixture Substances 0.000 claims abstract description 102
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 230000002265 prevention Effects 0.000 claims abstract description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 114
- 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 105
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 100
- 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 description 82
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 76
- 229960003512 nicotinic acid Drugs 0.000 claims description 75
- 229960003495 thiamine Drugs 0.000 claims description 73
- 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 69
- 229960002477 riboflavin Drugs 0.000 claims description 69
- 229940088594 vitamin Drugs 0.000 claims description 58
- 229930003231 vitamin Natural products 0.000 claims description 58
- 235000013343 vitamin Nutrition 0.000 claims description 58
- 239000011782 vitamin Substances 0.000 claims description 58
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 50
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 48
- 229930003268 Vitamin C Natural products 0.000 claims description 48
- 235000019154 vitamin C Nutrition 0.000 claims description 48
- 239000011718 vitamin C Substances 0.000 claims description 48
- 235000019152 folic acid Nutrition 0.000 claims description 42
- 239000011724 folic acid Substances 0.000 claims description 42
- 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 description 41
- 229960000304 folic acid Drugs 0.000 claims description 41
- 235000001968 nicotinic acid Nutrition 0.000 claims description 39
- 239000011664 nicotinic acid Substances 0.000 claims description 39
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 38
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 38
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 37
- 235000019157 thiamine Nutrition 0.000 claims description 37
- 239000011721 thiamine Substances 0.000 claims description 37
- 235000019158 vitamin B6 Nutrition 0.000 claims description 37
- 239000011726 vitamin B6 Substances 0.000 claims description 37
- 229940011671 vitamin b6 Drugs 0.000 claims description 37
- 229930003451 Vitamin B1 Natural products 0.000 claims description 36
- 229930003537 Vitamin B3 Natural products 0.000 claims description 36
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 36
- 235000010374 vitamin B1 Nutrition 0.000 claims description 36
- 239000011691 vitamin B1 Substances 0.000 claims description 36
- 235000019160 vitamin B3 Nutrition 0.000 claims description 36
- 239000011708 vitamin B3 Substances 0.000 claims description 36
- 229930003471 Vitamin B2 Natural products 0.000 claims description 35
- 235000019164 vitamin B2 Nutrition 0.000 claims description 35
- 239000011716 vitamin B2 Substances 0.000 claims description 35
- 235000019192 riboflavin Nutrition 0.000 claims description 34
- 239000002151 riboflavin Substances 0.000 claims description 34
- 235000021470 vitamin B5 (pantothenic acid) Nutrition 0.000 claims description 32
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 27
- 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 description 23
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 claims description 23
- 229960004874 choline bitartrate Drugs 0.000 claims description 23
- 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 description 23
- 229960000367 inositol Drugs 0.000 claims description 23
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 23
- 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 21
- 229930003779 Vitamin B12 Natural products 0.000 claims description 20
- 235000019163 vitamin B12 Nutrition 0.000 claims description 20
- 239000011715 vitamin B12 Substances 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 18
- 241001597008 Nomeidae Species 0.000 claims description 17
- 229940046001 vitamin b complex Drugs 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 8
- -1 vitamin C glucose compound Chemical class 0.000 claims description 8
- 229960001231 choline Drugs 0.000 claims description 5
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 235000013402 health food Nutrition 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 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 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- YRWWOAFMPXPHEJ-OFBPEYICSA-K sodium L-ascorbic acid 2-phosphate Chemical compound [Na+].[Na+].[Na+].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1[O-] YRWWOAFMPXPHEJ-OFBPEYICSA-K 0.000 claims description 2
- 229960005055 sodium ascorbate Drugs 0.000 claims description 2
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 2
- 206010017943 Gastrointestinal conditions Diseases 0.000 claims 1
- 229920000388 Polyphosphate Polymers 0.000 claims 1
- 239000001205 polyphosphate Substances 0.000 claims 1
- 235000011176 polyphosphates Nutrition 0.000 claims 1
- 235000021467 vitamin B7(Biotin) Nutrition 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 14
- 230000001737 promoting effect Effects 0.000 abstract description 5
- 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 82
- 229960002685 biotin Drugs 0.000 description 40
- 235000020958 biotin Nutrition 0.000 description 40
- 239000011616 biotin Substances 0.000 description 40
- 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 description 35
- 230000000968 intestinal effect Effects 0.000 description 31
- 239000000976 ink Substances 0.000 description 24
- 206010010774 Constipation Diseases 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 229960001571 loperamide Drugs 0.000 description 16
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 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 12
- 241001465754 Metazoa Species 0.000 description 12
- 230000001141 propulsive effect Effects 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 10
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 9
- 208000002551 irritable bowel syndrome Diseases 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000003805 vibration mixing Methods 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000002496 gastric effect Effects 0.000 description 8
- 210000000813 small intestine Anatomy 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000005515 coenzyme Substances 0.000 description 7
- 238000000227 grinding Methods 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- FGXWKSZFVQUSTL-UHFFFAOYSA-N domperidone Chemical compound C12=CC=CC=C2NC(=O)N1CCCN(CC1)CCC1N1C2=CC=C(Cl)C=C2NC1=O FGXWKSZFVQUSTL-UHFFFAOYSA-N 0.000 description 6
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 6
- 238000003304 gavage Methods 0.000 description 6
- 230000004060 metabolic process Effects 0.000 description 6
- 229940055726 pantothenic acid Drugs 0.000 description 6
- 235000019161 pantothenic acid Nutrition 0.000 description 6
- 239000011713 pantothenic acid Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 206010012735 Diarrhoea Diseases 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- QQQIECGTIMUVDS-UHFFFAOYSA-N N-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=C(OCCN(C)C)C=C1 QQQIECGTIMUVDS-UHFFFAOYSA-N 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 208000010643 digestive system disease Diseases 0.000 description 5
- 229960001253 domperidone Drugs 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 208000018685 gastrointestinal system disease Diseases 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 210000001187 pylorus Anatomy 0.000 description 5
- 239000013558 reference substance Substances 0.000 description 5
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000000711 cancerogenic effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 201000006549 dyspepsia Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000030136 gastric emptying Effects 0.000 description 4
- 229960005302 itopride Drugs 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical group O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000010254 subcutaneous injection Methods 0.000 description 4
- 239000007929 subcutaneous injection Substances 0.000 description 4
- OVBPIULPVIDEAO-GFCCVEGCSA-N (2r)-2-[[4-[(2-amino-4-oxo-1h-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic 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-GFCCVEGCSA-N 0.000 description 3
- 206010021518 Impaired gastric emptying Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 229930003571 Vitamin B5 Natural products 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000036528 appetite Effects 0.000 description 3
- 235000019789 appetite Nutrition 0.000 description 3
- 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 description 3
- 229960002079 calcium pantothenate Drugs 0.000 description 3
- 231100000357 carcinogen Toxicity 0.000 description 3
- 239000003183 carcinogenic agent Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000002249 digestive system Anatomy 0.000 description 3
- 230000037149 energy metabolism Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000011768 flavin mononucleotide Substances 0.000 description 3
- 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 3
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 3
- 208000001288 gastroparesis Diseases 0.000 description 3
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 3
- 229960004503 metoclopramide Drugs 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 235000009492 vitamin B5 Nutrition 0.000 description 3
- 239000011675 vitamin B5 Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010002065 Anaemia megaloblastic Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 208000000682 Megaloblastic Anemia Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 102000003946 Prolactin Human genes 0.000 description 2
- 108010057464 Prolactin Proteins 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229930003756 Vitamin B7 Natural products 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 2
- 229960004099 azithromycin Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 238000000556 factor analysis Methods 0.000 description 2
- 229960002428 fentanyl Drugs 0.000 description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 2
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 2
- 229960000240 hydrocodone Drugs 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000004001 inositols Chemical class 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 231100001016 megaloblastic anemia Toxicity 0.000 description 2
- 210000000713 mesentery Anatomy 0.000 description 2
- 229960001797 methadone Drugs 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000008855 peristalsis Effects 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 229940097325 prolactin Drugs 0.000 description 2
- 210000004203 pyloric antrum Anatomy 0.000 description 2
- NHZMQXZHNVQTQA-UHFFFAOYSA-N pyridoxamine Chemical compound CC1=NC=C(CO)C(CN)=C1O NHZMQXZHNVQTQA-UHFFFAOYSA-N 0.000 description 2
- 235000008160 pyridoxine Nutrition 0.000 description 2
- 239000011677 pyridoxine Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000000515 tooth Anatomy 0.000 description 2
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 235000011912 vitamin B7 Nutrition 0.000 description 2
- 239000011735 vitamin B7 Substances 0.000 description 2
- OAJLVMGLJZXSGX-CXGXMSGESA-L (2r,3r,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] 1-[3-[(4z,9z,14z)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8 Chemical compound [Co+3].O[C@@H]1[C@H](O)[C@@H]([CH2-])O[C@H]1N1C2=NC=NC(N)=C2N=C1.O([C@H]1[C@H]([C@H](O[C@@H]1CO)N1C2=CC(C)=C(C)C=C2N=C1)O)P([O-])(=O)OC(C)CNC(=O)CCC1(C)C(CC(N)=O)C2[N-]\C1=C(C)/C(C(C\1(C)C)CCC(N)=O)=N/C/1=C\C(C(C/1(CC(N)=O)C)CCC(N)=O)=N\C\1=C(C)/C1=NC2(C)C(C)(CC(N)=O)C1CCC(N)=O OAJLVMGLJZXSGX-CXGXMSGESA-L 0.000 description 1
- 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 description 1
- 101710161460 3-oxoacyl-[acyl-carrier-protein] synthase Proteins 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000037088 Chromosome Breakage Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 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 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000027219 Deficiency disease Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010016880 Folate deficiency Diseases 0.000 description 1
- 208000010188 Folic Acid Deficiency Diseases 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000005232 Glossitis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 208000019255 Menstrual disease 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-N NADP 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](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010057071 Rectal tenesmus Diseases 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 241000218636 Thuja Species 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 208000019790 abdominal distention Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 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 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 230000001989 choleretic effect Effects 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000005886 chromosome breakage Effects 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 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 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 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 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229940013640 flavin mononucleotide Drugs 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- 125000003929 folic acid group Chemical group 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- 230000002607 hemopoietic effect Effects 0.000 description 1
- 210000000514 hepatopancreas Anatomy 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000037345 metabolism of vitamins Effects 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 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 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 230000014653 neuromuscular process Effects 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 235000008151 pyridoxamine Nutrition 0.000 description 1
- 239000011699 pyridoxamine Substances 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000012271 tenesmus Diseases 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940082632 vitamin b12 and folic acid Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 230000003313 weakening effect Effects 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
- A61K31/335—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
- 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
- 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
-
- 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
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- 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
- A61K31/70—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及一种复合维生素BC组合物,尤其是一种促进胃肠系统动力的复合维生素BC组合物。该组合物适用于预防和/或治疗与胃肠动力匮乏相关的状态或疾病。
Description
技术领域
本发明涉及一种维生素B、C组合物,尤其是一种促进胃肠系统动力的复合维生素B、C组合物。该组合物适用于预防和/或治疗与胃肠动力匮乏相关的状态或疾病。
背景技术
现在,人们生活压力普遍加大,生活节奏加快,竞争日益激烈,胃肠道疾患或胃肠不适者越来越多,其起因是多方面的,其症状也各有不同。
胃肠(gastrointestinal,GI)动力是经由消化系统输送营养物之协调的神经肌肉进程。可参与胃食管反流病、胃轻瘫(例如,糖尿病性和手术后的胃轻瘫)、肠易激综合征(IBS)、肠梗阻和便秘(例如,功能性或药物引起的便秘)之胃肠系统动力削弱是工业化国家最大的医疗保健负担之一。鉴于上述情况,有效促进胃肠系统动力是亟需的并且将成为本领域中的进展。
功能性消化不良(functional dyspepsia)及慢性胃炎常有腹部饱胀感、上腹痛、恶心、食欲减退等症状,胃肠道动力障碍引起胃排空延缓是这类症状发生的一个重要原因。而且胃肠道动力障碍易导致IBS。现治疗胃肠动力的药物有甲氧氯普胺、多潘立酮和伊托必利。
以往治疗胃肠疾病的药物很多,但疗效好且无副作用者甚少,尤其是即可作长期保健作用,又很好改善胃肠道功能促进胃肠动力及减缓胃肠不适症状的药物或保健品更是少之又少。
如之前所述的(1)甲氧氯普胺,该药为多巴胺受体阻断药,具有强大的中枢性镇吐和胃肠道兴奋作用。该药可抑制胃平滑肌松弛,使胃肠平滑肌对胆碱能的反应增加,胃排空加快,增加胃窦部时相活性。此外,该药尚有刺激催乳激素释放的作用。甲氧氯普胺的副作用较常见昏睡、烦躁不安、倦怠无力,另该药大剂量或长期应用可能因阻断多巴胺受体,表现为帕金森综合症的症状。(2)多潘立酮是外周性多巴胺受体拮抗剂,可促进上胃肠道的蠕动和张力恢复正常,促进胃排空,增加胃窦和十二指肠肠运动,协调幽门的收缩,同时也能增强食道的蠕动和食道下端括约肌的张力。由于它对血脑屏障的渗透力差,对脑内多巴胺受体几乎无拮抗作用,国外有静脉大剂量注射引起癫痫发作的报道(国内无此制剂),但该药是一种强有力的催乳激素释放药,可能导致月经失调。(3)伊托必利具多巴胺受体阻滞和乙酰胆碱酯酶抑制的双重作用,通过刺激内源性乙酰胆碱释放并抑制其水解而增强胃与十二指肠运动,促进胃排空,并具有中度镇吐作用。老年或高龄患者慎用此药。
维生素B都是水溶性维生素,多数是辅酶,参与体内糖、蛋白质和脂肪的代谢。
维维生素B1(硫胺素)能促进肠胃蠕动,增加食欲。维生素B1可抑制胆碱酯酶对乙酰胆碱的水解作用。B1缺乏时,该酶活性增高,加速乙酰胆碱的水解。乙酰胆碱是传递神经冲动的重要物质,它缺乏时,可使神经传导障碍,尤其影响支配胃肠道、腺体等处的神经传导,造成胃肠蠕动缓慢、腹胀、消化腺分泌减少,使食欲减低。
维生素B2是体内黄素酶类辅基的组成部分。可转化为黄素单核苷酸(FMN)和黄素腺嘌呤二核苷酸(FAD),均为组织呼吸的重要辅酶,在酶系统中起递氢的作用,参与糖、蛋白质、脂肪代谢,并能维持正常视觉功能。另外维生素B2可激活维生素B6,使色氨酸转换为烟酸,可能与维持红细胞的完整性有关。它能维持和改善上皮组织,如消化道黏膜组织的健康。当人体缺少B2,尤其是严重缺乏时,人体腔道的粘膜层就会出现问题,引起粘膜病变,增强化学致癌物的致癌作用。因此维生素B2可防治癌症。
维生素B3(烟酸)在体内构成脱氢酶的辅酶,是B族维生素中人体需要量最多者,它不但是维持消化系统健康的维生素,也能减轻胃肠障碍。烟酸在人体内转化为烟酰胺,烟酰胺是辅酶Ⅰ和辅酶Ⅱ的组成部分,参与体内脂质代谢,组织呼吸的氧化过程和糖类无氧分解的过程。可促进消化系统的健康,减轻胃肠障碍,有效减轻便秘症状。若其缺乏时,可引起口角炎、舌炎、腹泻等,腹泻是本病的典型症状,早期多患便秘,其后因肠壁、消化腺体、肠壁及黏膜、绒毛的萎缩和肠炎的发生常有腹泻,大便呈水样或糊状,量多而有恶臭,也可带血,如病变接近肛门可出现里急后重。腹泻往往严重和难治,可合并吸收障碍。
维生素B5(泛酸)的活性形式是辅酶A,在体内是酰基载体,参与糖、脂肪、蛋白质的代谢。它们是协同作用,调节新陈代谢,维持皮肤和肌肉的健康,增进免疫系统和神经系统的功能,促进细胞生长和分裂(包括促进红血球的产生,预防贫血发生)。缺乏维生素B5的症状有食欲不振、消化不良,易患十二指肠溃疡。
维生素B6包括吡哆醇、吡哆醛和吡哆胺3种,可互相转化。在体内与ATP经酶作用转变成有生理活性的多种酶的辅酶,从而参与氨基酸及脂肪的多种代谢功能。与维生素B1合用,有较强的止痛作用,维生素B12可增强两者联用的止痛效果,缓解因外周神经疾病和脊髓疾病所致的疼痛。有研究报道维生素B6与阿奇霉素混合静滴可减轻阿奇霉素对胃肠道副作用。主要作用在人体的血液、肌肉、神经、皮肤等。功能有抗体的合成、消化系统中胃酸的制造、脂肪与蛋白质利用(尤其在减肥时应补充)、维持钠/钾平衡(稳定神经系统)。维生素B6缺乏损害细胞并影响体液免疫功能,给予维生素B6可提高免疫力,减少体内致癌物,有一定的防癌作用。
维生素B7,又称维生素H、生物素、辅酶R,参与体内的脂肪酸和碳水化合物的代谢;促进蛋白质的合成;还参与维生素B12、叶酸、泛酸的代谢;促进尿素合成与排泄。增强机体的免疫反应和感染的抵抗力,稳定正常组织的溶酶体膜,维持机体的体液免疫、细胞免疫并影响一系列细胞因子的分泌,提高人体免疫功能。减轻肛周湿疹和瘙痒的症状。生物素侧链羧基可通过酰胺键与酶的赖氨酸残基相连。生物素是羧基载体,还参与维生素B12、叶酸、泛酸的代谢。
维生素B9(叶酸),由蝶啶、对氨基苯甲酸及谷氨酸残基组成的水溶性B族维生素。本药由肠道吸收后,经门静脉进人肝脏,在肝内二氢叶酸还原酶的作用下,转变为具有活性的四氢叶酸。四氢叶酸是体内转移“一碳基团”的载体。“一碳基团”可以连接在四氢叶酸5位或10位碳原子上,主要参与嘌呤核苷酸和嘧啶核苷酸的合成与转化。尿嘧啶核苷酸转化为胸腺嘧啶核苷酸时所需的甲基即来自携有“一碳基团”的四氢叶酸所提供的甲烯基。因此,叶酸缺乏可致“一碳基团”转移障碍,胸腺嘧啶核苷酸合成困难,DNA合成受到影响,从而使细胞分裂速度减慢,仅停留在G1期,而S期及G2期相对延长。上述改变不仅会影响造血细胞(引起巨幼细胞性贫血),也会累及体细胞(尤其是消化道黏膜细胞)。叶酸缺乏可导致B1吸收障碍。叶酸对于女性的健康好处广受医学界注意,除了怀孕与哺乳期的妇女应该补充,能够用于预防直肠癌和心脏病。它也被发现能阻止自由基对染色体破坏,人类如缺乏叶酸可引起巨红细胞性贫血以及白细胞减少症。
脱氧腺苷钴胺素是维生素B12在体内主要存在形式,是一种含钴的红色化合物,需转化为甲基钴胺和辅酶B12后才具有活性。维生素B12与叶酸在DNA合成方面发挥着重要的作用。此外维生素B12在红细胞的成熟和神经系统正常维持方面也发挥着重要作用。它和叶酸的作用常互相关联。叶酸在细胞中有多种辅脢形式,有研究提示叶酸对胃肠道癌的发生有干预作用,叶酸可治疗萎缩性胃炎、改善胃粘膜病理。
酒石酸氢胆碱有促使磷脂转变、加速脂肪的运转及利胆作用;肌醇可促进细胞新陈代谢、助长发育、增进食欲。对氨基苯甲酸(PABA)实际上是叶酸的一种成分,在体内它的作用是辅酶,它与叶酸一道工作以促进蛋白质的代谢和血细胞的生成。
维生素C又称抗坏血酸,是抗氧化维生素当中的一种,它参与体内羟化反应,为形成骨骼、牙齿、结缔组织及非上皮组织细胞间粘物所必需,可维持牙齿、骨骼、血管的正常功能,增加对疾病的抵抗能力。据有关资料报道维生素C在各人群中有不同程度的缺乏。当身体出现一些小毛病时,就应该及时补充适量的维生素和矿物质来改善营养缺乏症,尤其是中老年应较为重视。维生素对许多疾病都有预防作用,而许多疾病的发生可能或多或少与维生素C的缺乏有关系,另外维生素C还能和许多其他药物联合用药治疗某些疾病。维生素C是一种抗氧化剂,保护身体免于自由基的威胁,维生素C同时也是一种辅酶。许多研究证明维生素C可以阻断致癌物N~亚硝基化合物合成,防止盐腌、渍和熏制食品含亚硝酸盐(咸肉、香肠之类也一样)中致癌物亚硝酸铵的形成,预防癌症,特别是对直肠癌和结肠癌有较好的预防作用。同时具有软化肛肠血管、增加肛肠弹性的作用。VC容易被热或氧化剂破坏,特别是光、微量重金属和荧光物质等更能促进其氧化,这使得VC在应用上受到了很大地限制。因此,维生素C的衍生物,包括VC的金属盐类、VC与各种酸形成的酯类及VC与糖类的化合物等,既能克服VC不稳定的缺点,又能更好地发挥VC的生理功能。这些衍生物包括维生素C(L-抗坏血酸)、维生素C钠(L-抗坏血酸钠)、维生素C磷酸酯镁、维生素C多磷酸酯、维生素C棕榈酸酯、维生素C硬脂酸酯、维生素C葡萄糖化合物等。
从作用机制上看,维生素B族是参与人体能量代谢的重要辅酶,而维生素C可以促进人体对维生素B族成员的吸收。复合维生素B、C通过增强人体的能量代谢,为胃肠提供更多的能量来改善胃肠动力不足所引起的功能性消化不良。这种能量代谢的增强包括协助碳水化合物和脂肪释放能量、分解氨基酸及输送含有营养素的氧及能量到整个机体。复合维生素BC将有可能成为一种新的具有较高安全性的促进胃肠系统动力的药物或保健食品,然而到目前为止还没有事实证据证明维生素B、C对胃肠系统动力的促进作用,特别是在病理状态下,维生素B、C对胃肠系统动力紊乱的治疗和调节作用。另外由于维生素B家族成员众多,并且存在相互依赖的关系,因此维生素B的成分选择和配伍,对于制备治疗或调节胃肠系统动力紊乱的药物或保健食品至关重要。
发明内容
A.发明概述
本发明涉及在有此需要之对象中促进胃肠系统动力的方法,其中所述对象患有胃肠系统疾病(即,失调症、病症、症状或者药物或手术引起的功能障碍)。该方法包括向有此需要之对象施用治疗有效量的维生素B和维生素C族组合物。本发明中所指的维生素包括其相应的类似物或衍生物,如维生素B1是指硫胺素或其类似物或衍生物;维生素B2是指核黄素或其类似物或衍生物;维生素B3是指烟酸或其类似物或衍生物;维生素B5是指泛酸或其类似物或衍生物;维生素B6是指吡哆醇或其类似物或衍生物;维生素B7是生物素或其类似物或衍生物;维生素B9是指叶酸或其类似物或衍生物;维生素B12是指氰钴胺或其类似物或衍生物;维生素C是指抗坏血酸或其类似物或衍生物;等等。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,维生素B族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
另一方面,本发明提供了一种组合物,该组合物包括有效量的维生素B族、维生素C族组合物以及药学上可接受的载体。在一个优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及药学上可接受的载体。在一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、、维生素C、酒石酸氢胆碱、肌醇以及药学上可接受的载体。在另一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及药学上可接受的载体。
另一方面,本发明涉及一种组合物,该组合物包括有效量的维生素B、C族组合物以及有效量的治疗和/或预防胃肠疾病的药物。在一个优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及有效量的治疗和/或预防胃肠疾病的药物。在一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇以及有效量的治疗和/或预防胃肠疾病的药物。在另一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及有效量的治疗和/或预防胃肠疾病的药物。
另一方面,本发明涉及一种组合物,该组合物包括有效量的维生素B、C族组合物以及其他有效量的维生素族化合物。在一个优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C以及其他有效量的维生素族化合物。在一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇以及其他有效量的维生素族化合物。在另一个更优选的实施方案中,该组合物包括有效量的维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇、对氨基苯甲酸以及其他有效量的维生素族化合物。所述其他维生素族化合物包括维生素A、维生素D、维生素E、维生素K等。
促进胃肠动力被用于在有此需要之对象中治疗由药物引起的胃肠功能障碍(例如,阿片类药物,如吗啡引起之肠道功能障碍或便秘)的方法中,该方法包括施用治疗有效量的维生素B、C族组合物。所述对象可正在使用阿片物质或阿片类物质进行手术后疼痛控制或慢性疼痛控制。阿片物质和阿片类物质的实例包括吗啡、可待因、羟考酮、氢可酮(hydrocodone)、美沙酮(methadone)、芬太尼(fentanyl)以及其与抗炎剂(例如对乙酰氨基酚或阿司匹林)的组合。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
促进胃肠动力可用于在有此需要之对象中治疗胃轻瘫,其通过施用治疗有效量的维生素B、C族组合物。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
在另一实施方案中,促进胃肠动力被用于在有此需要之对象中治疗胃食管反流病(gastroesophageal reflux disease,GERD)之方法中,该方法包括施用治疗有效量的维生素B、C族组合物。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。在一个具体实施方案中,所述胃食管反流病为夜间胃食管反流病。
本发明还提供了在有此需要之对象中促进胃肠动力以治疗肠易激综合征(irritable bowelsyndrome,IBS)的方法,其通过施用治疗有效量的维生素B、C族组合物来实现。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。所述肠易激综合征可为便秘型肠易激综合征或便秘/腹泻交替型肠易激综合征。
本发明还提供了在有此需要之对象中促进胃肠动力以治疗便秘的方法,其通过施用治疗有效量的维生素B、C族组合物来实现。所述便秘包括功能性(不良生活习惯、饮食习惯,老年性等无器质性病因的便秘)和药物引起的便秘。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
在一个实施方案中,促进胃肠动力被用于在有此需要之对象中治疗由手术引起或相关的胃肠功能障碍(例如手术后肠蠕动减慢)的方法中,该方法包括施用治疗有效量的维生素B、C族组合物。在一个优选实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。在一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
优选的复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、生物素、维生素C的组合物。更优选的复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇的组合物。在另一个更优选的实施方案中,复合维生素BC族组合物是包含维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6、维生素B12、叶酸、生物素、维生素C、酒石酸氢胆碱、肌醇和对氨基苯甲酸的组合物。
本发明的复合维生素BC族组合物的剂型可以为口嚼片,但不限于此,本发明组合物还可加入制备不同剂型时所需的各种常规辅料,如崩解剂、润滑剂、粘合剂、抗氧剂、络合剂等药用载体,以常规的制剂方法制成任何一种常用的口服剂型,如分散片、颗粒剂、胶囊剂、口服液等其他剂型。
本发明的复合维生素BC族组合物,其各组份的重量配比可有多种选择,其均对胃肠系统动力有相应的促进作用。在某些实施方案中,其可包含如下重量配比的组份:5-10份维生素B1,10-15份维生素B2,6-25份维生素B3,10-110份维生素B5,5-10份维生素B6,0.01-0.1份生物素,50-500份维生素C。在一个优选实施方案中,维生素B族组合物包含如下重量配比的组份:10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6和0.1份生物素和150份维生素C。在一个更优选的实施方案中,维生素B族组合物包含如下重量配比的组份:10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6,0.1份生物素,0.4份叶酸,250份酒石酸氢胆碱,250份肌醇和150份维生素C。在一个更优选的实施方案中,维生素B族组合物包含如下重量配比的组份:10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6,0.1份生物素,0.4份叶酸,250份酒石酸氢胆碱,0.025份维生素B12和150份维生素C。在另一个更优选的实施方案中,维生素B族组合物包含如下重量配比的组份:10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6,0.1份生物素,0.4份叶酸,250份酒石酸氢胆碱,250份肌醇,0.025份维生素B12,50份对氨基苯甲酸和150份维生素C。
B.定义
除另有定义,这里使用的所有科技术语与本发明所属技术领域的普通技术人员理解含义相同。所有专利文献、专利申请文献、公开的专利文献和其它出版物均作为参考。如本节阐述的定义与上述参考文献所述的定义不一致或相反时,以本节阐述的定义为准。
除非在上下文中明确表明,在此所用“一个”的意思是“至少一个”或“一个或多于一个”。
术语“份”,特别是涉及一个给定的量,是指正负偏差在10%以内的量。
此处所使用的术语“包含(comprises)”、“包含(comprising)”、“包括(includes)”、“包括(including)”、“含有(contains)”、“含有(containing)”及其任何变体旨在涵盖非独占性的包含物,例如包含、包括或含有一种元素或一列表的元素的过程、方法、加工产品或物质的组合物不仅包括那些元素还可能包括没有明确地列出的或该过程、方法、加工产品或物质的组合物的固有的其它元素。
此处所用的术语“维生素B族组合物”包括所有的维生素B化合物或其类似物或衍生物,如维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)和维生素B6等。
此处所用的术语“类似物”是指结构大致相同、并具有相同生物活性但可以有不同程度活性的任何两个以上分子或者是其中片段。所用术语“衍生物”是指化合物中的氢原子或原子团被其他原子或原子团取代而衍生的较复杂的化合物。
附图说明
图1:不同浓度复合VB9组份+VC对洛哌丁胺致便秘小鼠首次试验给药后墨汁在小鼠小肠内推进率(%)变化
图2:不同浓度复合VB9组份+VC对洛哌丁胺致便秘小鼠重复试验给药后墨汁在小鼠小肠内推进率(%)变化
图3:复合VB9组份+VC以及阳性对照品对2.5mg/kg洛哌丁胺致便秘小鼠给药后墨汁在小鼠小肠内推进率(%)的变化
具体实施方式
实施例1不同浓度复合维生素B9组份+维生素C对洛哌丁胺致便秘小鼠小肠推进率的影响
1.实验材料
1.1药物
复合维生素B9组分+维生素C
生产厂家:上海泽生科技开发有限公司
批号:2015.2.2
纯度:100%
性状:黄色粉末
保存条件:干燥罐避光保存
1.2试剂与仪器
1.3实验动物
种属:小鼠
品系:C57BL/6
性别和数量:雌性,40只
动物周龄:9周
体重范围:16.0-20.0g
动物来源:上海灵畅生物科技有限公司
动物合格证号:2013001803537
2.试验设计与方法
2.1.试验分组
实验动物采用随机数表法,随机分为5组,每组8只,具体分组及给药剂量见表1和表2。
表1.各组小鼠给药计量表
表2.复合维生素组各成份给药剂量表
2.2试剂配制
1)0.5%CMC-Na溶液:称取CMC-Na粉末2.0g,缓慢加入300ml超纯水,磁力搅拌至完全溶解,定容到400ml,配制成0.5%的澄清溶液,置于4℃备用。
2)1%吐温-80生理盐水:用量筒准确量取40mL生理盐水加入50mL离心管中,用移液器量取400μL吐温-80,加入离心管中,涡旋振荡混匀,室温放置备用。
3)5%墨汁:精确称取阿拉伯胶100g,加水800ml,煮沸至溶液透明,称取活性炭粉50g加入上述溶液中煮沸3次,待溶液凉后加水定容到1000ml。
4)复合VB9组份+VC高剂量组:精确称取复合VB9组份1.317g加入3片VC,研磨后加入0.5%CMC-Na 20ml,振荡混匀,形成稳定的混悬液。
5)复合VB9组份+VC中剂量组:精确称取复合VB9组份0.439g加入3片VC,研磨后加入0.5%CMC-Na 20ml,振荡混匀,形成稳定的混悬液。
6)复合VB9组份+VC低剂量组:精确称取复合VB9组份0.132g加入3片VC,研磨后加入0.5%CMC-Na 20ml,振荡混匀,形成稳定的混悬液。
7)洛哌丁胺:精确称取5.0mg洛哌丁胺,加入20mL含1.0%Tween 80的生理盐水溶液,振荡混匀后超声至少5min,现配现用。
2.3试验方法
小鼠禁食自由饮水约22~24小时后,各组按照给药剂量给药,给药体积为20ml/kg,模型组和正常组按同样剂量灌胃给予0.5%CMC-Na溶液;给药30分钟后,正常组皮下注射含1.0%Tween 80的生理盐水溶液,其他组皮下注射洛哌丁胺溶液,注射体积为10ml/kg。皮下注射30分钟后,灌胃给予墨汁,给药体积为10ml/kg[1,2,3]。
2.4观察指标
小肠墨汁推进率(%)=(墨汁推进长度/小肠总长度)×100
灌胃给予墨汁20分钟后,脱颈椎处死动物,立即打开腹腔分离肠系膜,剪取上端自幽门、下端至回盲部的肠管,置于托盘上,小心不能牵扯小肠,轻轻将小肠摆成直线,测量小肠总长度,从幽门至墨汁前沿为墨汁推进长度,计算小肠墨汁推进率(%)。
2.5数据分析
试验数据均用X±S表示,采用SPSS软件进行单因素方差分析,组间比较采用LSD检验。
3.试验结果
首次试验复合维生素B对墨汁在小鼠小肠内推进距离和推进率(%)的影响见表3和说明书附图1。
表3.首次试验复合VB9组份+VC对洛哌丁胺致便秘小鼠小肠推进率的影响(X±S)
*:与模型组相比,P<0.05;**:与模型组相比,P<0.01
首次试验结果显示:与正常组相比,模型组的小肠推进率(%)显著降低(48.6±0.0VS16.1±0.0),表明小鼠便秘模型制备成功;与模型组相比,高、中、低浓度给药组的墨汁推进距离和小肠推进率(%)均显著增加(p<0.05);高中低浓度给药组在改善小鼠小肠推进率(%)方面有明显的量效关系(34.0±0.1、25.0±0.0&21.3±0.1)。
重复试验复合维生素B对墨汁在小鼠小肠内推进距离和推进率(%)的影响见表4和说明书附图2。
表4.重复试验复合VB,9组份+VC对洛哌丁胺致便秘小鼠小肠推进率的影响(X±S)
*:与模型组相比,P<0.05;**:与模型组相比,P<0.01
重复试验结果显示:与正常组相比,模型组的小肠推进率(%)显著降低(49.9±0.1VS14.0±0.0),表明小鼠便秘模型制备成功;与模型组相比,高、中浓度给药组的墨汁推进距离和小肠推进率(%)均显著增加(p<0.05);高中低浓度给药组在改善小鼠小肠推进率(%)方面有明显的量效关系(30.4±0.0、23.2±0.0&17.0±0.0)。
4.结论
供试品VB9组分+VC高、中、低剂量组均能显著改善洛哌丁胺诱导的便秘小鼠模型的小肠推进率(%),且高、中、低浓度组之间有显著的量效关系。
实施例2复合VB9组份+VC以及阳性对照品对2.5mg/kg洛哌丁胺致便秘小鼠小肠推进率的影响
1.实验材料
1.1供试品
复合VB9组分+VC
生产厂家:上海泽生科技开发有限公司
批号:20150401
纯度:100%
性状:黄色粉末
保存条件:干燥罐避光保存
1.2试剂与仪器
1.2实验动物
种属:小鼠
品系:C57BL/6
性别和数量:雄性,65只
动物周龄:8-9周
体重范围:19.0-25.0g
动物来源:上海灵畅生物科技有限公司
动物合格证号:2013001804393
2.试验设计与方法
2.1.试验分组
实验动物采用随机数表法,随机分为8组,每组8只左右,具体分组及给药剂量见表1和表2。
表1.各组小鼠给药计量表
表2.复合维生素组各成份给药剂量表
2.2试剂配制
1)0.5%CMC-Na溶液:称取CMC-Na粉末2.0g,缓慢加入300ml超纯水,磁力搅拌至完全溶解,定容到400ml,配制成0.5%的澄清溶液,置于4℃备用。
8)1%吐温-80生理盐水:用量筒准确量取40mL生理盐水加入50mL离心管中,用移液器量取400μL吐温-80,加入离心管中,涡旋振荡混匀,室温放置备用。
9)5%墨汁:精确称取阿拉伯胶100g,加水800ml,煮沸至溶液透明,称取活性炭粉50g加入上述溶液中煮沸3次,待溶液凉后加水定容到1000ml。
10)复合VB9组份+VC(x1):取1片复合VB,9组份+VC片剂,研磨后加入0.5%CMC-Na19.5ml,振荡混匀,形成稳定的混悬液。现配现用。
11)复合VB9组份+VC(x5):取5倍剂量的复合VB,9组份+VC混悬液2ml,加入0.5%CMC-Na 8ml,振荡混匀,形成稳定的混悬液。现配现用。
12)吗丁啉组:取吗丁啉1片,研磨后加入0.5%CMC-Na 32.52ml,振荡混匀,形成稳定的混悬液。现配现用。
13)枸橼酸莫沙比利组:取枸橼酸莫沙比利1片,研磨后加入0.5%CMC-Na 32.52ml,振荡混匀,形成稳定的混悬液。
14)盐酸伊托必利组:取盐酸伊托必利1片,研磨后加入0.5%CMC-Na 32.52ml,振荡混匀,形成稳定的混悬液。现配现用。
15)纳洛酮组:取注射用盐酸纳洛酮1瓶(0.8mg),加入0.5%CMC-Na 3.2ml,振荡混匀,形成澄清的溶液。现配现用。
16)洛哌丁胺:精确称取5.0mg洛哌丁胺,加入20mL含1.0%Tween 80的生理盐水溶液,振荡混匀后超声至少5min,现配现用。
2.3试验方法
小鼠禁食自由饮水约22~24小时后,各组按照给药剂量给药,给药体积为20ml/kg,模型组和正常组按同样剂量灌胃给予0.5%CMC-Na溶液;给药30分钟后,正常组皮下注射含1.0%Tween 80的生理盐水溶液,其他组皮下注射洛哌丁胺溶液,注射体积为10ml/kg。皮下注射30分钟后,灌胃给予墨汁,给药体积为10ml/kg[1,2,3]。
2.4观察指标
小肠墨汁推进率(%)=(墨汁推进长度/小肠总长度)×100
灌胃给予墨汁20分钟后,脱颈椎处死动物,立即打开腹腔分离肠系膜,剪取上端自幽门、下端至回盲部的肠管,置于托盘上,小心不能牵扯小肠,轻轻将小肠摆成直线,测量小肠总长度,从幽门至墨汁前沿为墨汁推进长度,计算小肠墨汁推进率(%)。
2.5数据分析
试验数据均用X±S表示,采用SPSS软件进行单因素方差分析,组间比较采用LSD检验。
3.试验结果
复合维生素B对墨汁在小鼠小肠内推进距离和推进率(%)的影响见表3和说明书附图3。
表3.复合VB,9组份+VC及阳性对照品对洛哌丁胺致便秘小鼠小肠推进率的影响(X±S)
与模型组相比较,*P<0.05,**P<0.01,***P<0.001
试验结果显示:与正常组相比,模型组的小肠推进率(%)显著降低(60.7±12.1VS 22.8±7.9),表明小鼠便秘模型制备成功;与模型组相比,VB9组分+VC(x5)组、纳洛酮组和正常组在改善小鼠小肠推进率(%)方面有明显的量效关系(40.6±8.3、36.9±11.8&60.7±12.1),伊托必利、枸橼酸莫沙比利和吗丁啉这三种阳性药品在1倍剂量时没有显著的推进效果(26.4±7.0、20.1±5.7&19.5±3.8)。
4.结论
供试品VB9组分+VC(x5)均能显著改善洛哌丁胺诱导的便秘小鼠模型的小肠推进率(%),阳性对照品纳洛酮也具有显著的小肠推进效果,而其他三种阳性对照品伊托必利、枸橼酸莫沙比利和吗丁啉在该模型上无显著的小肠推进效果。
为了更清楚地描述和理解本发明,我们通过举例的方式详细描述了本发明,但显而易见的是,本技术领域中普通技术人员可以在不背离权利要求的精神和范围的前提下,对本发明做出适当的改变或修改。
Claims (10)
1.一种复合维生素B、C族组合物,其可用于预防和/或治疗与胃肠系统动力匮乏相关的状态或疾病。
2.根据权利要求1所述的组合物,其中所述复合维生素B、C组合物包括维生素B族组合物或其类似物或衍生物和维生素C或其类似物或衍生物。
3.根据权利要求2所述的组合物,其中所述维生素B族组合物或其类似物或衍生物选自维生素B1(硫胺素)、维生素B2(核黄素)、维生素B3(烟酸)、维生素B5(泛酸)、维生素B6和维生素B7(生物素)、维生素B9(叶酸)、维生素B12等。
4.根据权利要求2所述的组合物,其中所述维生素C或其类似物或衍生物选自维生素C(L-抗坏血酸)、维生素C钠(L-抗坏血酸钠)、维生素C磷酸酯镁、维生素C多磷酸酯、维生素C棕榈酸酯、维生素C硬脂酸酯、维生素C葡萄糖化合物等。
5.根据权利要求1或2所述的组合物,其中所述复合维生素B、C族组合物还包括酒石酸氢胆碱。
6.根据权利要求1或2所述的组合物,其中所述复合维生素BC族组合物还包括肌醇或对氨基苯甲酸。
7.根据权利要求2所述的组合物,其特征在于其包含如下重量配比的组份: 10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6,0.1份维生素B7,0.4份维生素B9,0.025份维生素B12和150份维生素C。
8.根据权利要求2所述的组合物,其特征在于其包含如下重量配比的组份:10份维生素B1,15份维生素B2,25份维生素B3,110份维生素B5,10份维生素B6,0.1份维生素B7,0.4份维生素B9,0.025份维生素B12,250份酒石酸氢胆碱和150份维生素C。
9.一种复合维生素B、C族组合物在制备治疗和/或预防与胃肠系统动力匮乏相关的胃肠状态或疾病的药物或保健食品中的用途。
10.根据权利要求9所述的用途,其中所述复合维生素B、C组合物包括维生素B族组合物或其类似物或衍生物和维生素C或其类似物或衍生物。
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510321294.2A CN106265696A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
CN202010700288.9A CN111803514A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
AU2016276482A AU2016276482A1 (en) | 2015-06-12 | 2016-06-06 | Use of composition of vitamin complex in preparing drug for stimulating gastrointestinal system motility |
US15/735,568 US10881639B2 (en) | 2015-06-12 | 2016-06-06 | Use of composition of multivitamin in preparing drug for stimulating gastrointestinal system motility |
PCT/CN2016/084938 WO2016197889A1 (zh) | 2015-06-12 | 2016-06-06 | 复合维生素组合物在制备促进胃肠系统动力的药物中的用途 |
CA2989214A CA2989214A1 (en) | 2015-06-12 | 2016-06-06 | Use of composition of multivitamin in preparing drug for stimulating gastrointestinal system motility |
JP2017564367A JP2018521031A (ja) | 2015-06-12 | 2016-06-06 | 胃腸系運動を刺激するための薬物の製造におけるマルチビタミン組成物の使用 |
EP16806787.4A EP3308787A4 (en) | 2015-06-12 | 2016-06-06 | USE OF A VITAMIN COMPLEX COMPOSITION FOR THE PREPARATION OF A MEDICAMENT FOR STIMULATING THE MOTILITY OF THE GASTROINTESTINAL SYSTEM |
BR112017026834-5A BR112017026834A2 (zh) | 2015-06-12 | 2016-06-06 | [Use of the inventive name established by ISA under Rule 37.2] The use of a complex vitamin composition for the preparation of a medicament for promoting gastrointestinal motility |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510321294.2A CN106265696A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010700288.9A Division CN111803514A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106265696A true CN106265696A (zh) | 2017-01-04 |
Family
ID=57502901
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010700288.9A Pending CN111803514A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
CN201510321294.2A Pending CN106265696A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010700288.9A Pending CN111803514A (zh) | 2015-06-12 | 2015-06-12 | 使用复合维生素b、c组合物促进胃肠系统动力的方法 |
Country Status (8)
Country | Link |
---|---|
US (1) | US10881639B2 (zh) |
EP (1) | EP3308787A4 (zh) |
JP (1) | JP2018521031A (zh) |
CN (2) | CN111803514A (zh) |
AU (1) | AU2016276482A1 (zh) |
BR (1) | BR112017026834A2 (zh) |
CA (1) | CA2989214A1 (zh) |
WO (1) | WO2016197889A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108079008A (zh) * | 2016-11-23 | 2018-05-29 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物 |
CN108567792A (zh) * | 2017-03-07 | 2018-09-25 | 上海泽生科技开发股份有限公司 | 一种治疗阿尔茨海默病的复合维生素组合物 |
WO2019206107A1 (zh) * | 2018-04-28 | 2019-10-31 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物及其制备方法 |
CN113194749A (zh) * | 2018-12-11 | 2021-07-30 | 帝斯曼知识产权资产管理有限公司 | 核黄素的有益于肠道健康的用途 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3801498A1 (en) * | 2018-06-08 | 2021-04-14 | DSM IP Assets B.V. | Methods and compositions to support the growth or maintenance of oxygen-sensitive bacteria in the gastrointestinal tract |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104337813A (zh) * | 2013-07-23 | 2015-02-11 | 上海泽生科技开发有限公司 | 使用维生素b组合物促进胃肠系统动力的方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999064022A1 (en) * | 1998-06-10 | 1999-12-16 | Crum Albert B | Prophylactic and therapeutic nutritional supplement for creation/maintenance of health-protective intestinal microflora and enhancement of the immune system |
US20080213395A1 (en) * | 2004-10-14 | 2008-09-04 | Adventures Plus Pty Ltd | Method for the Treatment of Gastrointestinal and Other Disorders with an Admixture of Vitamins |
CN103327986B (zh) * | 2010-07-22 | 2018-05-25 | 雷文制药有限公司 | 包含使用磁偶极子稳定化溶液的治疗或改善疾病并增强表现的方法 |
CN104256652A (zh) * | 2014-10-08 | 2015-01-07 | 李明刚 | 一种口服复合维生素纳米脂质体 |
-
2015
- 2015-06-12 CN CN202010700288.9A patent/CN111803514A/zh active Pending
- 2015-06-12 CN CN201510321294.2A patent/CN106265696A/zh active Pending
-
2016
- 2016-06-06 US US15/735,568 patent/US10881639B2/en active Active
- 2016-06-06 EP EP16806787.4A patent/EP3308787A4/en not_active Withdrawn
- 2016-06-06 JP JP2017564367A patent/JP2018521031A/ja active Pending
- 2016-06-06 BR BR112017026834-5A patent/BR112017026834A2/zh not_active Application Discontinuation
- 2016-06-06 CA CA2989214A patent/CA2989214A1/en not_active Abandoned
- 2016-06-06 WO PCT/CN2016/084938 patent/WO2016197889A1/zh active Application Filing
- 2016-06-06 AU AU2016276482A patent/AU2016276482A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104337813A (zh) * | 2013-07-23 | 2015-02-11 | 上海泽生科技开发有限公司 | 使用维生素b组合物促进胃肠系统动力的方法 |
Non-Patent Citations (2)
Title |
---|
李定国等: "《常用药物用药兵法》", 30 November 2014, 武汉:湖北科学技术出版社 * |
艾齐等: "《不可不知的食疗常识》", 31 July 2012, 哈尔滨:黑龙江科学技术出版社 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108079008A (zh) * | 2016-11-23 | 2018-05-29 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物 |
WO2018095209A1 (zh) * | 2016-11-23 | 2018-05-31 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物 |
CN110022882A (zh) * | 2016-11-23 | 2019-07-16 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物 |
US11351171B2 (en) | 2016-11-23 | 2022-06-07 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Composite vitamin composition promoting gastrointestinal system motility |
US11759463B2 (en) | 2016-11-23 | 2023-09-19 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Composite vitamin composition promoting gastrointestinal system motility |
CN108567792A (zh) * | 2017-03-07 | 2018-09-25 | 上海泽生科技开发股份有限公司 | 一种治疗阿尔茨海默病的复合维生素组合物 |
CN110520135A (zh) * | 2017-03-07 | 2019-11-29 | 上海泽生科技开发股份有限公司 | 维生素组合物在制备用于预防、治疗或延迟阿尔茨海默病的药物中的用途 |
WO2019206107A1 (zh) * | 2018-04-28 | 2019-10-31 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物及其制备方法 |
CN113194749A (zh) * | 2018-12-11 | 2021-07-30 | 帝斯曼知识产权资产管理有限公司 | 核黄素的有益于肠道健康的用途 |
Also Published As
Publication number | Publication date |
---|---|
CN111803514A (zh) | 2020-10-23 |
AU2016276482A1 (en) | 2018-01-18 |
EP3308787A1 (en) | 2018-04-18 |
WO2016197889A1 (zh) | 2016-12-15 |
JP2018521031A (ja) | 2018-08-02 |
BR112017026834A2 (zh) | 2018-08-14 |
EP3308787A4 (en) | 2019-01-16 |
CA2989214A1 (en) | 2016-12-15 |
US10881639B2 (en) | 2021-01-05 |
US20180353469A1 (en) | 2018-12-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106265696A (zh) | 使用复合维生素b、c组合物促进胃肠系统动力的方法 | |
US11759463B2 (en) | Composite vitamin composition promoting gastrointestinal system motility | |
CN104337813A (zh) | 使用维生素b组合物促进胃肠系统动力的方法 | |
CN106902104A (zh) | 用于治疗神经外伤的方法 | |
EP3395341A1 (en) | Composition for treating motor neuron diseases and use thereof | |
JP5032310B2 (ja) | 疲労回復のための医薬 | |
CN110403945B (zh) | 促进胃肠系统动力的复合维生素组合物及其制备方法 | |
CN107595874A (zh) | 一种含有丁苯酞的药物组合物及其在制备治疗脑血管病药物中的应用 | |
CN117045652B (zh) | 犬尿喹啉酸在制备缓解和/或治疗神经性贪食症的药物中的应用 | |
CN115581699A (zh) | 促进胃肠系统动力的复合维生素组合物及其制备方法 | |
CN102648915B (zh) | 一种治疗或预防神经病理性疼痛的药物组合物 | |
CN103656161B (zh) | 一种中药组合物及其制备方法和用途 | |
Yadav | Pharmacology & Toxicology | |
CN107595875A (zh) | 含有丁苯酞的组合物及其在治疗脑血管病药物中的应用 | |
EP3389666A1 (en) | Compositions comprising 3'-o-glucuronide epicatechin and methods of making and using such compositions | |
Waleed et al. | A Case Report on Charcot Marie Tooth Disease, and the Role of Vitamin C in this Disease | |
CN1259974C (zh) | 非阿片类药物组合的戒毒药 | |
TR2023000876A2 (tr) | Transvers mi̇yeli̇t hastaliğinin i̇laç tedavi̇si̇nde kullanilmak üzere geli̇şti̇ri̇len kompozi̇syon | |
CN113209069A (zh) | 二甲基甘氨酸在制备降血糖药物中的应用 | |
EA006963B1 (ru) | Адаптогенный лекарственный препарат для перорального применения | |
JPH05132423A (ja) | 覚醒の増加および維持をもたらす医薬組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
CB02 | Change of applicant information | ||
CB02 | Change of applicant information |
Address after: 201203 Shanghai Curie road in Pudong New Area Zhangjiang hi tech Park No. 68 Applicant after: ZENSUN (SHANGHAI) SCIENCE & TECHNOLOGY, Co.,Ltd. Address before: 201203 Shanghai Curie road in Pudong New Area Zhangjiang hi tech Park No. 68 Applicant before: ZENSUN (SHANGHAI) SCIENCE & TECHNOLOGY Ltd. |
|
SE01 | Entry into force of request for 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: 20170104 |