CN113543777A - 用于预防或治疗酸中毒的药物组合物 - Google Patents
用于预防或治疗酸中毒的药物组合物 Download PDFInfo
- Publication number
- CN113543777A CN113543777A CN201980090678.4A CN201980090678A CN113543777A CN 113543777 A CN113543777 A CN 113543777A CN 201980090678 A CN201980090678 A CN 201980090678A CN 113543777 A CN113543777 A CN 113543777A
- Authority
- CN
- China
- Prior art keywords
- acidosis
- acid
- pharmaceutical composition
- kynurenine
- hydroxy
- 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
- 208000010444 Acidosis Diseases 0.000 title claims abstract description 55
- 230000007950 acidosis Effects 0.000 title claims abstract description 39
- 208000026545 acidosis disease Diseases 0.000 title claims abstract description 39
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 33
- 239000002253 acid Substances 0.000 claims abstract description 14
- VCKPUUFAIGNJHC-UHFFFAOYSA-N 3-hydroxykynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC(O)=C1N VCKPUUFAIGNJHC-UHFFFAOYSA-N 0.000 claims description 48
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 claims description 44
- FLCWJWNCSHIREG-UHFFFAOYSA-N 2-(diethylamino)benzaldehyde Chemical compound CCN(CC)C1=CC=CC=C1C=O FLCWJWNCSHIREG-UHFFFAOYSA-N 0.000 claims description 41
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 39
- YYOOFJZTRCPVFD-UHFFFAOYSA-N 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O YYOOFJZTRCPVFD-UHFFFAOYSA-N 0.000 claims description 26
- 208000006443 lactic acidosis Diseases 0.000 claims description 24
- 229960002563 disulfiram Drugs 0.000 claims description 22
- 235000013305 food Nutrition 0.000 claims description 21
- RIOXQFHNBCKOKP-UHFFFAOYSA-N benomyl Chemical compound C1=CC=C2N(C(=O)NCCCC)C(NC(=O)OC)=NC2=C1 RIOXQFHNBCKOKP-UHFFFAOYSA-N 0.000 claims description 20
- MITFXPHMIHQXPI-UHFFFAOYSA-N benzoxaprofen Natural products N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 claims description 20
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 claims description 20
- -1 phospho Chemical class 0.000 claims description 19
- 150000002085 enols Chemical class 0.000 claims description 18
- 206010027417 Metabolic acidosis Diseases 0.000 claims description 16
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims description 16
- NWGYTLGTDHTPQB-UHFFFAOYSA-M sodium 2-oxopropanoate hydrate Chemical compound O.[Na+].CC(=O)C([O-])=O NWGYTLGTDHTPQB-UHFFFAOYSA-M 0.000 claims description 15
- GWYBSWWLKXEDLB-UHFFFAOYSA-N [acetyl-(4-chlorophenyl)sulfonylamino] acetate Chemical compound CC(=O)ON(C(C)=O)S(=O)(=O)C1=CC=C(Cl)C=C1 GWYBSWWLKXEDLB-UHFFFAOYSA-N 0.000 claims description 14
- ZQSIJRDFPHDXIC-UHFFFAOYSA-N Daidzein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 claims description 13
- GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 claims description 13
- KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 claims description 13
- KYQZWONCHDNPDP-QNDFHXLGSA-N daidzein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-QNDFHXLGSA-N 0.000 claims description 13
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 claims description 11
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 claims description 11
- 208000003826 Respiratory Acidosis Diseases 0.000 claims description 11
- 229960005233 cineole Drugs 0.000 claims description 11
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 10
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 10
- OZBAVEKZGSOMOJ-MIUGBVLSSA-N glycitin Chemical compound COC1=CC(C(C(C=2C=CC(O)=CC=2)=CO2)=O)=C2C=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OZBAVEKZGSOMOJ-MIUGBVLSSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 229930002330 retinoic acid Natural products 0.000 claims description 10
- 229960001727 tretinoin Drugs 0.000 claims description 10
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 claims description 9
- 229940043350 citral Drugs 0.000 claims description 9
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 claims description 9
- HGTUJZTUQFXBIH-UHFFFAOYSA-N (2,3-dimethyl-3-phenylbutan-2-yl)benzene Chemical group C=1C=CC=CC=1C(C)(C)C(C)(C)C1=CC=CC=C1 HGTUJZTUQFXBIH-UHFFFAOYSA-N 0.000 claims description 6
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 6
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 6
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 6
- 239000001488 sodium phosphate Substances 0.000 claims description 6
- XJTZHGNBKZYODI-UHFFFAOYSA-N Glycitin Natural products OCC1OC(Oc2ccc3OC=C(C(=O)c3c2CO)c4ccc(O)cc4)C(O)C(O)C1O XJTZHGNBKZYODI-UHFFFAOYSA-N 0.000 claims description 5
- DEDOPGXGGQYYMW-UHFFFAOYSA-N molinate Chemical compound CCSC(=O)N1CCCCCC1 DEDOPGXGGQYYMW-UHFFFAOYSA-N 0.000 claims description 4
- BLKAHDBNTYNLJN-UHFFFAOYSA-N 2-oxopropanoic acid;hydrate Chemical compound O.CC(=O)C(O)=O BLKAHDBNTYNLJN-UHFFFAOYSA-N 0.000 claims description 3
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 claims description 2
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 claims description 2
- 229960001779 pargyline Drugs 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 13
- 230000001603 reducing effect Effects 0.000 abstract description 11
- 230000036541 health Effects 0.000 abstract description 5
- 150000007513 acids Chemical class 0.000 abstract description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 60
- 239000004310 lactic acid Substances 0.000 description 30
- 235000014655 lactic acid Nutrition 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000126 substance Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000000796 flavoring agent Substances 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 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 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 5
- 229960001031 glucose Drugs 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 206010010071 Coma Diseases 0.000 description 3
- 208000008454 Hyperhidrosis Diseases 0.000 description 3
- 206010021137 Hypovolaemia Diseases 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 206010024119 Left ventricular failure Diseases 0.000 description 3
- 208000010428 Muscle Weakness Diseases 0.000 description 3
- 206010028372 Muscular weakness Diseases 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000037149 energy metabolism Effects 0.000 description 3
- 230000000870 hyperventilation Effects 0.000 description 3
- 208000000122 hyperventilation Diseases 0.000 description 3
- 230000001146 hypoxic effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 3
- 229940039790 sodium oxalate Drugs 0.000 description 3
- 230000035900 sweating Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 208000001380 Diabetic Ketoacidosis Diseases 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000006213 oxygenation reaction Methods 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- OOLBCHYXZDXLDS-UHFFFAOYSA-N 2-[4-(2,4-dichlorophenoxy)phenoxy]propanoic acid Chemical compound C1=CC(OC(C)C(O)=O)=CC=C1OC1=CC=C(Cl)C=C1Cl OOLBCHYXZDXLDS-UHFFFAOYSA-N 0.000 description 1
- VYDVAXUCDAAWPV-UHFFFAOYSA-N 4-amino-2,3-diethylbenzaldehyde Chemical compound CCC1=C(N)C=CC(C=O)=C1CC VYDVAXUCDAAWPV-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000005506 Diclofop Substances 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010049771 Shock haemorrhagic Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- UMWYYMCOBYVEPY-UHFFFAOYSA-N azanide;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2] UMWYYMCOBYVEPY-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 238000010000 carbonizing Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000012200 cell viability kit Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005428 food component Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- BACHBFVBHLGWSL-UHFFFAOYSA-N methyl 2-[4-(2,4-dichlorophenoxy)phenoxy]propanoate Chemical group C1=CC(OC(C)C(=O)OC)=CC=C1OC1=CC=C(Cl)C=C1Cl BACHBFVBHLGWSL-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 208000012268 mitochondrial disease Diseases 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- BACHBFVBHLGWSL-JTQLQIEISA-N rac-diclofop methyl Natural products C1=CC(O[C@@H](C)C(=O)OC)=CC=C1OC1=CC=C(Cl)C=C1Cl BACHBFVBHLGWSL-JTQLQIEISA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
-
- 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
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/13—Amines
- A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; 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
- A61K31/275—Nitriles; Isonitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- 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
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及一种用于预防或治疗酸中毒的药物组合物。该药物组合物在降低生物体内积累的酸浓度方面具有显着效果,因此有望广泛应用于医学和健康领域。
Description
技术领域
本发明涉及一种用于预防或治疗酸中毒的药物组合物。
背景技术
酸中毒是指pH值低于正常动脉血pH值7.4±0.05的状态(即氢离子浓度高的状态)。酸中毒分为“呼吸性酸中毒”和“代谢性酸中毒”,代谢性酸中毒的种类包括糖尿病酮症酸中毒、乳酸性酸中毒或水杨酸、甲醇、乙二醇等有毒物质中毒。其中,乳酸性酸中毒是指在体内产生大量乳酸并蓄积的情况下,由于酸碱平衡被破坏而发生的酸中毒,定义为乳酸超过45mg/dL并且pH值为7.25或更低的状态。在细胞中,葡萄糖在氧气存在下被代谢以产生能量。然而,在没有氧气的情况下代谢葡萄糖会产生乳酸。因此,乳酸性酸中毒多发生在机体氧减少的情况下,如缺氧休克、血容量减少、左心室衰竭等;甚至在药物和毒素(乙醇和甲醇)的影响下或在能量代谢增加的情况下(例如在肿瘤中),组织中的乳酸也会局部增加。如果乳酸性酸中毒持续,酸碱平衡被破坏,可能会出现肌肉无力、换气过度、恶心、呕吐、出汗或昏迷等症状,这些症状严重时可能导致死亡。因此,通过降低体内过度积累的乳酸浓度来维持酸碱平衡很重要。
然而,对于乳酸性酸中毒的治疗,除了提供足够的氧气外,别无选择,只能通过药物调节乳酸浓度。因此,需要开发用于预防或治疗乳酸性酸中毒的治疗剂。
因此,本发明是为解决现有技术中的上述问题而作出的,涉及一种用于预防或治疗酸中毒的药物组合物。本发明的药物组合物在降低生物体内积累的酸浓度方面具有显著效果,因此有望广泛应用于医药和健康领域。
技术问题
本发明是为解决现有技术中存在的上述问题而提出的,涉及一种用于预防或治疗酸中毒的药物组合物。
然而,本发明所要解决的技术问题不限于上述问题,本领域普通技术人员通过以下描述将清楚地理解未提及的其它问题。
问题解决方案
在下文中,参考附图来描述本文描述的各种实施例。在以下描述中,阐述了许多具体细节,例如具体配置、组成和工艺等,以提供对本发明的透彻理解。然而,某些实施例可以在没有这些特定细节中的一个或多个的情况下实施,或者与其他已知方法和配置结合实施。在其他情况下,为了避免不必要地混淆本发明,没有特别详细地描述众所周知的工艺和制造技术。在整个说明书中对“一个实施例”或“一实施例”的引用意味着结合该实施例描述的特定特征、配置、组成或特性包括在本发明的至少一个实施例中。因此,在整个说明书的不同地方出现的短语“在一个实施例中”或“一个实施例”不一定指代本发明的相同实施例。此外,在一个或多个实施例中,特定特征、配置、组成或特性可以以任何合适的方式组合。
除非在说明书中另有定义,否则本文所用的所有科学和技术术语应具有与本发明所属领域的普通技术人员通常所理解的相同的含义。
在本发明的一个实施方案中,术语“酸中毒”是指pH低于7.4±0.05的正常动脉pH的状态(即,氢离子浓度高的状态)。根据病因不同,酸中毒分为“呼吸性酸中毒”,即肺部吸氧不足或血流量减少导致组织供氧减少;和“代谢性酸中毒”,其中血液或局部组织中的乳酸量增加,而不管氧气水平的降低。呼吸性酸中毒的原因包括出血休克、心脏病发作、充血性心力衰竭、肺水肿、严重贫血等。代谢性酸中毒是由以下三种机制中的一种或多种引起的:酸负荷、碱丢失或肾酸排泄受损。酸增加的情况的实施例包括糖尿病酮症酸中毒、乳酸性酸中毒或有毒物质中毒如水杨酸、甲醇和乙二醇。
在本发明的一个实施方案中,术语“乳酸性酸中毒”是酸中毒的一种,是指在体内产生和积累大量乳酸的情况下,由于酸碱平衡被破坏而发生的酸中毒并被定义为乳酸超过45mg/dL且pH值为7.45或更低的状态。在细胞中,葡萄糖在氧气存在下被代谢以产生能量。然而,葡萄糖在没有氧气的情况下代谢会产生乳酸。因此,乳酸性酸中毒多发生在机体氧合减少的情况下,如缺氧休克、血容量减少、左心室衰竭等;甚至在药物和毒素(乙醇和甲醇)的影响下或在能量代谢增加的情况下(例如在肿瘤中),组织中的乳酸也会局部增加。如果乳酸性酸中毒持续,酸碱平衡被破坏,可能会出现肌肉无力、过度换气、恶心、呕吐、出汗或昏迷等症状,这些症状严重时可能导致死亡。因此,通过降低体内过度积累的乳酸浓度来维持酸碱平衡很重要。乳酸性酸中毒的原因包括肝病、肾病、糖尿病、白血病、获得性免疫缺陷综合征(AIDS)、糖原贮积病、药物和毒物、严重感染(全身性败血症和脑膜炎)、肿瘤、影响正常ATP产生的几种遗传代谢和线粒体疾病、肌肉萎缩症以及剧烈运动。
在本发明的一个实施方案中,术语“治疗”是指为减轻和/或改善目标疾病而实施的的行为。为了本发明的目的,治疗包括在发生酸中毒的状态下消除酸中毒的原因的行为;或在无法消除原因的情况下,通过降低产生的酸的浓度来改善酸中毒症状的行为。
在本发明的一个实施方案中,术语“药物组合物”是指为了特定目的而施用的组合物。出于本发明的目的,本发明的药物组合物旨在预防或治疗酸中毒,并且可以包含涉及这种预防或治疗的化合物以及药学上可接受的载体、赋形剂或稀释剂。此外,本发明的药物组合物包含占组合物总重量0.1%至50%重量的本发明活性成分。可包含在本发明组合物中的载体、赋形剂和稀释剂的实例可包括但不限于乳糖、右旋糖、蔗糖、山梨糖醇、甘露糖醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯树胶、藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁和矿物油。
在本发明的一个实施方案中,术语“给药”是指通过任何合适的方式将本发明的组合物给予患者,并且本发明的组合物可以通过任何常用途径给药,只要该途径允许成分到达靶组织。可以是口服给药、腹腔给药、静脉内给药、肌肉给药、皮下给药、皮内给药、鼻内给药、肺内给药、直肠给药、腔内给药、腹腔内给药和鞘内给药;然而,本发明不限于此。在本发明中,有效量可以根据多种因素进行调整,包括疾病的类型、疾病的严重程度、组合物中所含活性成分和其他成分的类型和含量、制剂、患者的年龄、体重、一般健康状况、性别和饮食、给药频率、给药途径、组合物的分泌速率、治疗持续时间和同时使用的药物。对于成人,治疗药物组合物可以一次50ml至500ml的量施用于身体,其中在活性成分是化合物的情况下,剂量可以是0.1ng/kg至10mg/kg,在活性成分是单克隆抗体的情况下,剂量可以是0.1ng/kg至10mg/kg。每天给药1~12次;一天12次的,可以每2小时给药一次。此外,本发明的药物组合物可以单独给药或与本领域已知的其他疗法如化学疗法、放射疗法和手术联合给药,用于治疗靶癌干细胞。此外,本发明的药物组合物可以与设计用于增强免疫反应的其他治疗剂联合给药,例如本领域众所周知的佐剂或细胞因子(或编码细胞因子的核酸)。也可以使用其他标准递送方法,例如基因枪转移或离体治疗。在离体治疗中,例如,抗原呈递细胞(APC)、树突细胞、外周血单核细胞或骨髓细胞可以从患者或合适的供体获得并用本药物组合物离体活化,然后回输到病人中。
在本发明的一个实施方案中,“食物组合物”以各种方式用于预防或改善本发明所针对的适应症。包含本发明的组合物作为活性成分的食品组合物可以以各种食品的形式制备,例如饮料、口香糖、茶、维生素复合物、粉剂、颗粒剂、片剂、胶囊、糖果、米糕、面包等。本发明的食品组合物由对现有的毒性和副作用小的食品成分进行改良而得到的成分组分,因此在长期摄取的情况下可以放心地用于预防目的。在本发明的组合物包含在食品组合物中的情况下,本发明的组合物可以以相当于总重量的0.1%至100%的比例的量添加。在此,在以饮料的形式制备食品组合物的情况下,除了饮料包含指定比例的食品组合物之外没有特别限制,并且饮料可以含有各种调味剂或天然碳水化合物,或者与传统饮料类似的附加成分。即,天然碳水化合物的实例可包括单糖如葡萄糖、二糖如果糖、多糖如蔗糖、常规糖如糊精和环糊精,以及糖醇如木糖醇、山梨糖醇和赤藓糖醇。调味剂的实例可包括天然调味剂(奇异果甜蛋白、甜菊提取物(例如莱鲍迪甙A、甘草甜素等)和合成调味剂(糖精、阿斯巴甜等)。此外,本发明的食品组合物可以含有各种营养素、维生素、矿物质(电解质)、调味剂(例如合成调味剂和天然调味剂)、着色剂、果胶酸及其盐、藻酸及其盐、有机酸、保护胶体、增稠剂、pH调节剂、稳定剂、防腐剂、甘油、酒精、碳酸饮料中使用的碳化剂等。这些成分可以单独使用或组合使用。这些添加剂的比例通常在每100重量份本发明组合物中以0.1至100重量份范围内选择;然而,本发明不限于此。
在本发明的一个实施方案中,提供了一种用于预防或治疗酸中毒的药物组合物,其包含选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特(molinate)、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛(phenylglyoxal)、苯菌灵(benomyl)、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁(pargyline)、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸(kynurenic acid)、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸(3-hydroxy-DL-kynurenine)。
所述药物组合物优选包含选自下组的至少任意一种作为活性成分:禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
所述药物组合物更优选包含选自下组的至少任意一种作为活性成分:苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
此外,药物组合物甚至更优选包含选自下组的至少任意一种作为活性成分:二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
如上,酸中毒优选代谢性酸中毒或呼吸性酸中毒,更优选乳酸性酸中毒。然而,本发明不限于此。
在本发明的另一个实施方案中,提供了一种用于预防或改善酸中毒的食品组合物,其包含选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
所述食品组合物优选包含选自下组的至少任意一种作为活性成分:禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
所述食品组合物更优选包含选自下组的至少任意一种作为活性成分:苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
此外,食品组合物甚至更优选包含选自下组的至少任意一种作为活性成分:二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
如上,酸中毒优选代谢性酸中毒或呼吸性酸中毒,更优选乳酸性酸中毒。然而,本发明不限于此。
在本发明的又一个实施方案中,提供了一种预防或治疗酸中毒的方法,包括向有需要的受试者施用一组合物,该组合物包括选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
如上,酸中毒优选代谢性酸中毒或呼吸性酸中毒,更优选乳酸性酸中毒。然而,本发明不限于此。
在本发明的又一个实施方案中,提供了一种用于预防或治疗酸中毒的方法中的组合物,该组合物包含选自下组的至少任意一种作为活性成分:CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
如上,酸中毒优选代谢性酸中毒或呼吸性酸中毒,更优选乳酸性酸中毒。然而,本发明不限于此。
在下文中,将逐步详细地描述本发明。
发明的有益效果
本发明涉及一种用于预防或治疗酸中毒的药物组合物。该药物组合物在降低生物体内积累的酸浓度方面具有显著效果,因此有望广泛应用于医学和健康领域。
附图简要说明
图1示出了根据本发明的一个实施例,通过评估用于酸中毒治疗的候选物质的酸中毒降低效果。
发明详述
测试本发明筛选的用于治疗乳酸性酸中毒的候选物质是否具有降低乳酸浓度的作用。结果发现,所有候选物质都具有降低乳酸浓度的作用。更具体地,在与使用与候选物质相同浓度的阳性对照(50μM草酸钠)比较的情况下,发现由柠檬醛、CVT-10216、氰胺和视黄酸组成的组具有约5%的乳酸浓度降低作用;禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺和苯甲酰甲醛组成的组具有约10%的乳酸浓度降低作用;由苯菌灵、顺式二氨基二氯铂、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸组成的组具有约15%的降乳酸作用;由二乙氨基苯甲醛、双硫仑和3-羟基-DL-犬尿氨酸组成的组具有约20%的乳酸浓度降低作用。
在下文中,将通过实施例更详细地描述本发明。这些实施例仅用于更详细地描述本发明,对于本领域技术人员来说显而易见的是,根据本发明的要旨,本发明的范围不受这些实施例的限制。
实施例1:筛选用于酸中毒治疗的候选物质
通过筛选各种候选物质以开发治疗酸中毒的物质,本发明人发现了如下表1所示的物质。
表1
实施例2:测试酸中毒治疗候选物质降酸效果
测试表1所示的候选物质的乳酸浓度降低效果。
为此,首先在37℃和5%CO2环境下,将获自美国典型培养物保藏中心(ATCC)的A549癌细胞(腺癌人肺泡基底上皮细胞,Cat#CCL-185)接种在含有10%胎牛血清和1%抗生素-抗真菌剂的RPMI1640培养基中培养中,,每3天进行一次传代。当糖酵解在缺氧状态下被激活时,会大量产生乳酸。癌细胞的细胞非常密集,在消耗能量的活动中非常活跃,因此已知会大量产生乳酸。
将细胞以3×105个细胞/孔的浓度接种于24孔板中,孵育过夜。然后,用溶解在二甲基亚砜(DMSO)中的如表1所示的每种候选物质(浓度为50μM)处理每块板。进一步进行孵育24小时。对于候选物质的阴性对照,不进行任何处理;对于阳性对照,以相同浓度(50μM)或高10倍的浓度(50mM)进行草酸钠处理,草酸钠通常被已知为乳酸性酸中毒的治疗剂。随后,将50μl用DPBS稀释得到的细胞培养液与50μl乳酸检测反应缓冲液(Promega,Madison,WI,USA)混合,加入96孔板。使反应在室温下进行1小时。然后,用分光光度计(SynergyHTXMulti-Reader,BioTek)测量发光。同时,用细胞活力分析试剂盒(CellCountingKit-8)测定每个样品中的细胞数,并进行计算,从而可以将每个样品的乳酸测量值与相同细胞数的阴性对照中的乳酸测量值进行比较。所有实验均重复3次,平均值如图1所示。
实验结果发现,本发明筛选出的所有用于治疗乳酸性酸中毒的候选物质均具有降低乳酸浓度的作用,只是程度不同。更具体地,在与使用与候选物质相同浓度的阳性对照(50μM草酸钠)比较的情况下,发现由柠檬醛、CVT-10216、氰胺和视黄酸组成的组具有约5%的乳酸浓度降低作用;由禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺和苯甲酰甲醛组成的组具有约10%的乳酸浓度降低作用;由苯菌灵、顺式二氨基二氯铂、氯丙酰胺、黄豆苷、优降宁(pargyline)、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸具有约15%的降乳酸作用;由二乙氨基苯甲醛、双硫仑和3-羟基-DL-犬尿氨酸组成的组具有约20%的乳酸浓度降低作用。
虽然已经对本发明的具体部分进行了详细的描述,但是对于本领域技术人员来说,这样的具体描述只是一个优选实施例是显而易见的,本发明的范围并不限于此。因此,本发明的实质范围将由所附权利要求及其等同物来限定。
工业适用性
乳酸性酸中毒多发生在机体氧合减少的情况下,如缺氧休克、血容量减少、左心室衰竭等;甚至在药物和毒素(乙醇和甲醇)的影响下或在能量代谢增加的情况下(例如在肿瘤中),组织中的乳酸也会局部增加。如果乳酸性酸中毒持续,酸碱平衡被破坏,可能会出现肌肉无力、过度换气、恶心、呕吐、出汗或昏迷等症状,这些症状严重时可能导致死亡。因此,通过降低体内过度积累的乳酸浓度来维持酸碱平衡很重要。
本发明的药物组合物在降低生物体内积累的酸浓度方面具有显著效果,因此有望广泛应用于医药和健康领域。
Claims (18)
1.一种用于预防或治疗酸中毒的药物组合物,所述药物组合物包含选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸、或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特(molinate)、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛(phenylglyoxal)、苯菌灵(benomyl)、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁(pargyline)、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸(kynurenic acid)、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸(3-hydroxy-DL-kynurenine)。
2.根据权利要求1的药物组合物,其特征在于,所述药物组合物包含选自下组的至少任意一种作为活性成分:禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
3.根据权利要求2的药物组合物,其特征在于,所述药物组合物包含选自下组的至少任意一种作为活性成分:苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
4.根据权利要求3的药物组合物,其特征在于,药物组合物包含选自下组的至少任意一种作为活性成分:二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
5.根据权利要求1的药物组合物,其特征在于,所述酸中毒是代谢性酸中毒或呼吸性酸中毒。
6.根据权利要求5的药物组合物,其特征在于,所述代谢性酸中毒是乳酸性酸中毒。
7.一种用于预防或治疗酸中毒的食品组合物,所述食品组合物包含选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
8.根据权利要求7的食品组合物,其特征在于,所述食品组合物包含选自下组的至少任意一种作为活性成分:禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸中。
9.根据权利要求8的食品组合物,其特征在于,所述食品组合物包含选自下组的至少任意一种作为活性成分:苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
10.根据权利要求9的食品组合物,其特征在于,食品组合物包含选自下组的至少任意一种作为活性成分:二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
11.根据权利要求7的食品组合物,其特征在于,所述酸中毒是代谢性酸中毒或呼吸性酸中毒。
12.根据权利要求11的食品组合物,其特征在于,所述代谢性酸中毒是乳酸性酸中毒。
13.一种预防或治疗酸中毒的方法,包括向有需要的受试者施用一组合物,该组合物包括选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
14.根据权利要求13的方法,其特征在于,所述酸中毒是代谢性酸中毒或呼吸性酸中毒。
15.根据权利要求14的方法,其特征在于,所述代谢性酸中毒是乳酸性酸中毒。
16.一种用于预防或治疗酸中毒的方法中的组合物,所述组合物包含选自下组的至少任意一种作为活性成分:柠檬醛、CVT-10216(3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-1-苯并吡喃-7-基]氧基]甲基]苯甲酸,或3-[[[3-[4-[(甲磺酰基)氨基]苯基]-4-氧代-4H-色烯-7-基]氧基]甲基]苯甲酸)、氰胺、视黄酸、禾草特、N-乙酰基-N-乙酰氧基-4-氯苯磺酰胺、苯甲酰甲醛、苯菌灵、顺式二氨基二氯铂(CDDP)、氯丙酰胺、黄豆苷、优降宁、磷酸(烯醇)丙酮酸单钠盐水合物、犬尿喹啉酸、二乙氨基苯甲醛(DEAB)、双硫仑和3-羟基-DL-犬尿氨酸。
17.根据权利要求16的药物组合物,其特征在于,所述酸中毒是代谢性酸中毒或呼吸性酸中毒。
18.根据权利要求17的药物组合物,其特征在于,所述代谢性酸中毒是乳酸性酸中毒。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2018-0151767 | 2018-11-30 | ||
KR1020180151767A KR102011815B1 (ko) | 2018-11-30 | 2018-11-30 | 산증의 예방 또는 치료용 약학조성물 |
KR10-2019-0098083 | 2018-11-30 | ||
KR1020190098083A KR102088689B1 (ko) | 2018-11-30 | 2019-08-12 | 산증의 예방 또는 치료용 약학조성물 |
PCT/KR2019/016720 WO2020111866A1 (ko) | 2018-11-30 | 2019-11-29 | 산증의 예방 또는 치료용 약학조성물 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113543777A true CN113543777A (zh) | 2021-10-22 |
Family
ID=70859708
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201980090678.4A Pending CN113543777A (zh) | 2018-11-30 | 2019-11-29 | 用于预防或治疗酸中毒的药物组合物 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20220105053A1 (zh) |
JP (1) | JP2022509875A (zh) |
CN (1) | CN113543777A (zh) |
WO (1) | WO2020111866A1 (zh) |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL109762A0 (en) * | 1993-06-18 | 1994-08-26 | Allergan Inc | Method for treating hypoxia-associated ocular complications |
GB0303676D0 (en) * | 2003-02-18 | 2003-03-19 | Quest Int | Improvements in or relating to flavour compositions |
EP2958592A1 (en) * | 2013-02-22 | 2015-12-30 | F. Hoffmann-La Roche AG | Methods of treating cancer and preventing drug resistance |
WO2018097734A1 (en) * | 2016-11-23 | 2018-05-31 | Bohne Askøy As | Prevention and/or treatment of hyperlactataemia |
KR102011815B1 (ko) * | 2018-11-30 | 2019-08-19 | 주식회사 하임바이오 | 산증의 예방 또는 치료용 약학조성물 |
-
2019
- 2019-11-29 CN CN201980090678.4A patent/CN113543777A/zh active Pending
- 2019-11-29 JP JP2021531387A patent/JP2022509875A/ja active Pending
- 2019-11-29 WO PCT/KR2019/016720 patent/WO2020111866A1/ko active Application Filing
- 2019-11-29 US US17/429,575 patent/US20220105053A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
US20220105053A1 (en) | 2022-04-07 |
JP2022509875A (ja) | 2022-01-24 |
WO2020111866A1 (ko) | 2020-06-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102299934B1 (ko) | 숙취해소에 뛰어나며 알코올에 의한 간 손상을 예방 또는 치료용 조성물 | |
US9700572B2 (en) | Anti-cancer agent | |
KR102227117B1 (ko) | 2,3,5-치환된 싸이오펜 화합물의 유방암 예방, 개선 또는 치료 용도 | |
WO2018145664A1 (zh) | 提高耐力表现的抗疲劳组合物 | |
ES2865477T3 (es) | Composiciones y métodos para la prevención y/o tratamiento de la deficiencia de vitamina B12 | |
US20100210589A1 (en) | Method for improving hepatic function | |
US10016476B2 (en) | Nutrient combinations for affecting an aging process | |
KR102011815B1 (ko) | 산증의 예방 또는 치료용 약학조성물 | |
US20230117757A1 (en) | Coenzyme q production accelerator and method for accelerating coenzyme q production | |
NO20001717L (no) | Serotonin-inneholdende formulering for oral administrering og anvendelse av samme | |
US20220125745A1 (en) | Pharmaceutical composition for co-administration of acidosis-inducing drug | |
CN113543777A (zh) | 用于预防或治疗酸中毒的药物组合物 | |
CN103202824A (zh) | 松醇类物质在制药或保健品中的应用 | |
KR102088689B1 (ko) | 산증의 예방 또는 치료용 약학조성물 | |
KR102209386B1 (ko) | 호모해링토닌을 유효성분으로 함유하는 대사질환 예방 또는 치료용 약학조성물 | |
JP2010512382A (ja) | シコニン系化合物を含む糖尿病予防及び治療のための医薬組成物、並びにその用途 | |
EP3043788B1 (en) | D-glyceric acid or dl-glyceric acid for use in the treatment of degeneration diseases related to aging | |
CN113382727A (zh) | 与引起酸中毒的药物联合给药的药物组合物 | |
CN103355665B (zh) | 一种用于辅助降血糖的组合物 | |
US20200306231A1 (en) | Oral hypoglycemic agents as food additives and supplements | |
KR100583876B1 (ko) | 당뇨병 환자의 식이를 위한 참다래 추출물을 함유하는건강기능식품 | |
CN103393707B (zh) | 一种治疗糖尿病的药物组合物及其制备方法 | |
US20230270733A1 (en) | Preventive, relief or therapeutic use of 2,3,5-substituted thiophene compound against gastrointestinal stromal tumor | |
CN100584381C (zh) | 含有磺脲类抗糖尿病药物和b族维生素的药物组合物 | |
DE102006014420A1 (de) | Mittel zur Verminderung des verwertbaren Kaloriengehalts der Nahrung und zur therapeutischen Gewichtsabnahme, insbesondere zur Anwendung bei Adipositas (Fettsucht) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20211022 |
|
WD01 | Invention patent application deemed withdrawn after publication |