CN112079738A - Preparation method of L-carnitine catecholate - Google Patents
Preparation method of L-carnitine catecholate Download PDFInfo
- Publication number
- CN112079738A CN112079738A CN202010986694.6A CN202010986694A CN112079738A CN 112079738 A CN112079738 A CN 112079738A CN 202010986694 A CN202010986694 A CN 202010986694A CN 112079738 A CN112079738 A CN 112079738A
- Authority
- CN
- China
- Prior art keywords
- carnitine
- cooling
- steps
- temperature
- catechin
- 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
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 title claims abstract description 84
- YCIMNLLNPGFGHC-UHFFFAOYSA-L catecholate(2-) Chemical compound [O-]C1=CC=CC=C1[O-] YCIMNLLNPGFGHC-UHFFFAOYSA-L 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 89
- 238000001816 cooling Methods 0.000 claims abstract description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 44
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims abstract description 34
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims abstract description 34
- 235000005487 catechin Nutrition 0.000 claims abstract description 34
- 229950001002 cianidanol Drugs 0.000 claims abstract description 33
- 238000003756 stirring Methods 0.000 claims abstract description 25
- 238000001035 drying Methods 0.000 claims abstract description 17
- 238000005406 washing Methods 0.000 claims abstract description 16
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 14
- 238000001914 filtration Methods 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 14
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 13
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000001704 evaporation Methods 0.000 claims abstract description 3
- 239000000376 reactant Substances 0.000 claims abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 16
- 238000001291 vacuum drying Methods 0.000 claims description 15
- 239000003507 refrigerant Substances 0.000 claims description 13
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 10
- 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 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 6
- 229930003427 Vitamin E Natural products 0.000 claims description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 5
- 235000019165 vitamin E Nutrition 0.000 claims description 5
- 229940046009 vitamin E Drugs 0.000 claims description 5
- 239000011709 vitamin E Substances 0.000 claims description 5
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 4
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 4
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 4
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 3
- MRBKEAMVRSLQPH-UHFFFAOYSA-N 3-tert-butyl-4-hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1 MRBKEAMVRSLQPH-UHFFFAOYSA-N 0.000 claims description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 3
- 235000021466 carotenoid Nutrition 0.000 claims description 3
- 150000001747 carotenoids Chemical class 0.000 claims description 3
- 235000010265 sodium sulphite Nutrition 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 235000019155 vitamin A Nutrition 0.000 claims description 3
- 239000011719 vitamin A Substances 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 229940045997 vitamin a Drugs 0.000 claims description 3
- 239000003599 detergent Substances 0.000 claims description 2
- 229940001482 sodium sulfite Drugs 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000012535 impurity Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 17
- 239000003925 fat Substances 0.000 description 14
- 230000004580 weight loss Effects 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 206010016256 fatigue Diseases 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000004930 Fatty Liver Diseases 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 206010019708 Hepatic steatosis Diseases 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 208000010706 fatty liver disease Diseases 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Chemical compound C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 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 2
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 206010049771 Shock haemorrhagic Diseases 0.000 description 2
- 241001122767 Theaceae Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001765 catechin Chemical class 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000037080 exercise endurance Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229960001518 levocarnitine Drugs 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229930013915 (+)-catechin Natural products 0.000 description 1
- 235000007219 (+)-catechin Nutrition 0.000 description 1
- 235000007246 (+)-epicatechin Nutrition 0.000 description 1
- PFTAWBLQPZVEMU-HIFRSBDPSA-N (-)-catechin Chemical compound C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-HIFRSBDPSA-N 0.000 description 1
- 229930013799 (-)-catechin Natural products 0.000 description 1
- 235000007331 (-)-catechin Nutrition 0.000 description 1
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 description 1
- 235000007355 (-)-epicatechin Nutrition 0.000 description 1
- 229930013783 (-)-epicatechin Natural products 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000032139 Halitosis Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HNSUOMBUJRUZHJ-UEMBJLSASA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;(e)-4-hydroxy-4-oxobut-2-enoate Chemical compound OC(=O)\C=C\C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O HNSUOMBUJRUZHJ-UEMBJLSASA-N 0.000 description 1
- JXXCENBLGFBQJM-FYZOBXCZSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;chloride Chemical compound [Cl-].C[N+](C)(C)C[C@H](O)CC(O)=O JXXCENBLGFBQJM-FYZOBXCZSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000002019 anti-mutation Effects 0.000 description 1
- 230000003471 anti-radiation Effects 0.000 description 1
- 230000037147 athletic performance Effects 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 150000005693 branched-chain amino acids Chemical class 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- CXQWRCVTCMQVQX-UHFFFAOYSA-N cis-dihydroquercetin Natural products O1C2=CC(O)=CC(O)=C2C(=O)C(O)C1C1=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-UHFFFAOYSA-N 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 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
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 235000020939 nutritional additive Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 235000020989 red meat Nutrition 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
- C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention discloses a preparation method of L-carnitine catecholate, which comprises the following steps: step one, adding a solvent into a reactor, and cooling to-5-15 ℃; step two, adding an antioxidant under the protection of nitrogen; step three, sequentially feeding L-carnitine and catechin into a reactor, wherein the L-carnitine: the mass ratio of the antioxidant is 100:1, L-carnitine: the molar ratio of the catechin is 1:0.5-1:2.0, the temperature is raised to 30-75 ℃, and the mixture is stirred until the reactants are completely dissolved; step four, closing the nitrogen, and simultaneously evaporating the solvent until the solution turns turbid under the pressure that the vacuum degree is less than-0.095 mpa; fifthly, starting nitrogen protection, stirring, cooling to room temperature, continuously cooling to-5-0 ℃, and keeping the temperature for 2 hours; and step six, filtering, washing and drying to obtain a finished product. The preparation process has the advantages of simple steps, less impurities, stable product quality and environmental protection, and the prepared L-carnitine catecholate has obviously improved hygroscopicity when being stored at room temperature, and is suitable for preparing L-carnitine salts.
Description
Technical Field
The invention belongs to the technical field of preparation of medical intermediates and nutritional additives, and particularly relates to a preparation method of L-carnitine catecholate.
Background
L-carnitine (also known as L-carnitine or transliteration carnitine) is an amino-like acid for promoting fat to be converted into energy, and red meat is a main source of the L-carnitine and has no toxic or side effect on human bodies. The main physiological function of the L-carnitine is to promote fat to be converted into energy, and the L-carnitine can reduce body fat and weight without reducing water and muscle, so that the L-carnitine is considered as the most safe weight-reducing nutritional supplement without side effect by the international obesity health organization in 2003.
The L-carnitine can promote fatty acid to pass through mitochondrial membrane for oxidation energy supply, so that during exercise, the L-carnitine can promote the combustion of fat in the body to supply energy, and meanwhile, the L-carnitine can promote the oxidation utilization of branched chain amino acid, can change the activity of respiratory enzymes in mitochondria, and can improve the oxygen oxidation energy supply capability of the organism. The appropriate administration of L-carnitine can improve the energy generation during exercise and improve the endurance level of the organism, thereby improving the athletic performance, and is particularly suitable for endurance sports.
The L-carnitine is supplemented to promote the activity of pyruvate dehydrogenase in cells, so that the oxidative utilization of glucose is promoted, and the fatigue generation during exercise is delayed. During exercise, the excessive production of lactic acid can increase the acidity of blood and tissue fluid, reduce the generation of ATP, cause fatigue, supplement L-carnitine can eliminate excessive lactic acid, improve exercise capacity and promote the recovery of exercise-induced fatigue. Ammonia is a product of protein degradation and also an identification of exercise-induced fatigue, and even lower levels of ammonia can be more toxic. Research finds that the L-carnitine has the protection effect of resisting ammonia toxicity, can promote urea circulation and degrade ammonia into urea, thereby eliminating the ammonia toxicity. The appropriate supplementation of L-carnitine also has a more obvious effect on chronic fatigue syndrome. L-carnitine participates in many metabolic links, and plays an important role in improving the immunity of human bodies, protecting the stability of cell membranes, improving exercise endurance and resisting fatigue. Actively correcting the deficiency of L-carnitine can promote the recovery of various metabolic disorders of patients with chronic fatigue syndrome, enhance the energy synthesis of organisms, improve the maximum exercise endurance level and play a role in resisting fatigue. Can also play a certain role in preventing and treating sub-health.
Energy is the greatest anti-aging power, and cells are fully viable with sufficient energy. The weakening of cell energy in the aging process of a human body is one of the reasons for accelerating aging, and the aging process can be delayed by properly supplementing L-carnitine. In addition, sufficient energy plays a role in protecting cells, the energy supply of the cells is insufficient when the body is aged, and the L-carnitine is supplemented, so that not only can enough energy be provided, but also the immune system can be kept strong, and the invasion of diseases can be avoided.
The heart is the most "diligent" organ of the human body and needs to pump blood continuously to sustain life. At least two thirds of the energy sources of heart cells which move continuously are from the oxidation of fat, and the L-carnitine is an indispensable key substance for the oxidation of fat, and if the L-carnitine is absent, the heart is affected firstly. L-carnitine is very important for the health of myocardial cells, and the supplement of sufficient L-carnitine is beneficial to preventing and treating various conditions of the heart, such as improving the cardiac function of people suffering from congestive heart diseases, minimizing damage after the heart diseases occur, reducing the pain of angina pectoris, and improving arrhythmia without affecting blood pressure. In addition, the L-carnitine can also improve the level of high-density lipoprotein in blood, is beneficial to clearing cholesterol in vivo, protecting blood vessels, reducing blood fat and reducing the blood pressure of patients with hypertension. A large number of animal and human experiments prove that the L-carnitine supplementation has great benefits for treating cardiovascular diseases, and the most extensive and intensive clinical research in China at present is the anti-myocardial ischemia, arrhythmia and blood fat reduction effects of the L-carnitine.
The liver, which is an important metabolic organ for lipids and fats, may cause fatty liver by eating too much fat, and may cause disorders in oxidation of long-chain fatty acids when l-carnitine is deficient in the body or methyl group is insufficiently supplied, and may also cause fatty liver by excessive accumulation of fat in the liver. Increasing or supplementing L-carnitine intake, regulating fat metabolism, promoting fat oxidation, and fundamentally eliminating redundant or accumulated fat in vivo or viscera. At present, the L-carnitine is used for preventing the occurrence of fatty liver in Switzerland, America, Japan and other countries, and the recovery can be obtained by eliminating the fat accumulated in the liver by adding the L-carnitine.
The hemorrhagic shock generator produces vasomotor dysfunction caused by endocrine disturbance in a stress state, and is closely related to the increase of free radical content in vivo and cell injury caused by ischemia and hypoxia. L-carnitine has various pharmacological actions on hemorrhagic shock.
Catechin, also known as Catechin and Catechin (Caredhieacid), is a phenolic active substance extracted from natural plants such as tea. The relative molecular mass of catechin is 290.28; white needle-shaped crystals (water-acetic acid), melting point 212-216 ℃; dissolving in hot water, ethanol, glacial acetic acid, and acetone, slightly dissolving in cold water and diethyl ether, and hardly dissolving in benzene, chloroform and petroleum ether. Catechin is an important component of tea, and has effects of preventing and treating cardiovascular diseases, and preventing cancer. The D-catechuic acid has the functions of reducing the permeability of capillary vessels, stopping diarrhea, stopping bleeding, resisting virus, killing fungi, inhibiting ACE, preventing gastric ulcer and the like. Catechin is natural oil antioxidant, and has antioxidant activity even better than vitamin E. And can scavenge free radicals produced by human body to protect cell membrane. Has effects in scavenging free radicals, and thus can be used for delaying aging. In addition, clinical trials have shown that catechins significantly reduce plaque and alleviate periodontal disease. Catechins can inhibit pathogenic bacteria (such as botulinum), and has no harm to beneficial bacteria (such as lactobacillus), so that it has intestinal function regulating effect. Can inhibit pathogenic bacteria causing human dermatosis, and has good therapeutic effect on eczema. Catechin can remove odor of methyl mercaptan, so it can remove halitosis of smoker, and reduce odor of pig, chicken and human excrement (because catechin can resist bacteria producing malodor in human intestinal tract). There are also studies showing that catechin has also effects of inhibiting blood pressure (lowering diastolic and systolic pressures) and blood glucose (inhibiting glycolytic enzymes), lowering cholesterol and Low Density Lipoprotein (LDL) in blood, and increasing the amount of High Density Lipoprotein (HDL) (used in Japan as cholesterol), anti-radiation and ultraviolet (made into cosmetics for preventing ultraviolet in the United states), anti-mutation (proven in microorganisms, but no human experimental report).
Through retrieval, products such as L-carnitine taurine, L-carnitine fumaric acid, L-carnitine hydrochloric acid and the like exist in the market, and the L-carnitine catechin is not reported. Therefore, a preparation method which has simple process steps, stable product quality and environmental friendliness is needed.
Disclosure of Invention
The invention provides a preparation method of L-carnitine catecholate, which is mainly characterized by simple preparation process steps, stable product quality and environmental protection, and the moisture absorption of the prepared L-carnitine catecholate is obviously improved when the prepared L-carnitine catecholate is stored at room temperature.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a preparation method of L-carnitine catecholate comprises the following steps:
step one, adding a solvent into a reactor, and cooling to-5-15 ℃;
step two, adding an antioxidant under the protection of nitrogen;
step three, sequentially feeding L-carnitine and catechin into a reactor, wherein the L-carnitine: the mass ratio of the antioxidant is 100:1, L-carnitine: the molar ratio of the catechin is 1:0.5-1:2.0, the temperature is raised to 30-75 ℃, and the mixture is stirred until the reactants are completely dissolved;
step four, closing the nitrogen, and simultaneously evaporating the solvent until the solution turns turbid under the pressure that the vacuum degree is less than-0.095 mpa;
fifthly, starting nitrogen protection, stirring, cooling to room temperature, continuously cooling to-5-0 ℃, and keeping the temperature for 2 hours;
and step six, filtering, washing and drying to obtain a finished product.
Further, the solvent in the first step is one of ethanol, isopropanol, methanol, acetone or ethyl acetate.
Further, the antioxidant in the second step is one of sodium metabisulfite, sodium sulfite, vitamin A, vitamin C, vitamin E, carotenoid, antioxidant dismutase and butyl hydroxy anisol.
Further, l-carnitine in step three: the catechin molar ratio is 1: 1.
Further, the temperature in the third step is 30-45 ℃.
Further, the temperature reduction in the fifth step is cooling by a refrigerant.
Furthermore, the detergent for washing in the sixth step and the solvent in the first step are the same substance.
Further, the drying in the sixth step is vacuum drying, and the vacuum drying temperature is 30-60 ℃.
The above catechin is also called catechin, and its molecule has two chiral carbon atoms, four stereoisomers: (+) -catechin, (-) -catechin, (+) -epicatechin, (-) -epicatechin.
As the invention adopts the invention, compared with the prior art, the invention has the technical progress that: according to the invention, the L-carnitine and the catechin are subjected to thermal dissolution under the action of protective gas according to a certain proportion, then the solvent is removed at low temperature, the L-carnitine catecholate is slowly separated out, and further solid-liquid separation and drying processes are carried out to finally obtain the crystalline L-carnitine catecholate, wherein the moisture absorption of the L-carnitine catecholate is obviously improved when the L-carnitine catecholate is stored at room temperature.
In conclusion, the preparation process has the advantages of simple steps, less impurities, stable product quality and environmental friendliness, and the prepared L-carnitine catecholate has obviously improved hygroscopicity when stored at room temperature, and is suitable for preparing L-carnitine salts.
Detailed Description
The following description is given in conjunction with preferred embodiments of the present invention. It should be understood that the preferred embodiments described herein are for purposes of illustration and explanation only and are not intended to limit the present invention.
Example 1
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 434.7g of ethanol was added to a three-necked flask, and the temperature was reduced to 15 ℃.
(2) 99.9% nitrogen gas was introduced below the ethanol liquid level, stirring was started, and after 5 minutes of introduction, 1.6g of vitamin C was slowly added.
(3) 161g of L-carnitine and 290.21g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 45 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the ethanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-5 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 48.3g of ethanol is added into another three-neck flask, and the temperature is reduced to-5 ℃.
(7) Filtering, washing with-5 deg.C ethanol, vacuum drying at 43 deg.C, and cooling when drying weight loss reaches 0.3% to obtain the final product.
Example 2
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 434.7g of isopropyl alcohol was added to a three-necked flask, and the temperature was lowered to 10 ℃.
(2) 99.9% nitrogen was introduced below the isopropyl alcohol level, stirring was started, and after 5 minutes of introduction, 1.6g of vitamin A was slowly added.
(3) 161g of L-carnitine and 290.1g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 40 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the isopropanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-4 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) To another three-necked flask, 48.3g of isopropyl alcohol was added and the temperature was lowered to-4 ℃.
(7) Filtering, washing with-4 deg.C isopropanol, vacuum drying at 45 deg.C, and cooling when drying weight loss reaches 0.3%.
Example 3
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 434.7g of ethanol was added to a three-necked flask, and the temperature was lowered to 5 ℃.
(2) 99.9% nitrogen was introduced below the ethanol level, stirring was started, and after 5 minutes of introduction, 1.6g of butylated hydroxyanisole was slowly added.
(3) 161g of L-carnitine and 290.1g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 50 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the ethanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-3 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 48.3g of ethanol is added into another three-neck flask, and the temperature is reduced to-3 ℃.
(7) Filtering, washing with-3 deg.C ethanol, vacuum drying at 50 deg.C, and cooling when drying weight loss reaches 0.3%.
Example 4
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 869.4g of acetone was added to a three-necked flask, and the temperature was lowered to 5 ℃.
(2) 99.9% nitrogen was passed below the level of the acetone, stirring was started, and after 5 minutes of aeration, 3.2g of carotenoid was slowly added.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 30 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the acetone was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-5 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of acetone was added to another three-necked flask and the temperature was reduced to-5 ℃.
(7) Filtering, washing with acetone at-5 deg.C, vacuum drying at 38 deg.C, and cooling when drying weight loss reaches 0.3%.
Example 5
A preparation method of L-carnitine catecholate comprises the following steps:
(1) ethyl acetate 869.4 was added to the three-necked flask and the temperature was reduced to-5 ℃.
(2) Introducing 99.9% nitrogen below the liquid level of ethyl acetate, stirring, introducing the nitrogen for 5 minutes, and slowly adding 3.2g of vitamin E.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 55 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the ethyl acetate was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-2 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of ethyl acetate was added to another three-necked flask, and the temperature was lowered to-2 ℃.
(7) Filtering, washing with-2 deg.C ethyl acetate, vacuum drying at 60 deg.C, and cooling when drying weight loss reaches 0.3% to obtain the final product.
Example 6
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 869.4g of acetone was added to a three-necked flask and the temperature was reduced to 0 ℃.
(2) Introducing 99.9% nitrogen below the acetone liquid level, stirring, introducing the nitrogen for 5 minutes, and slowly adding 3.2g of antioxidant dismutase.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 60 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the acetone was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-1 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of acetone was added to another three-necked flask and the temperature was reduced to-1 ℃.
(7) Filtering, washing with acetone at-1 deg.C, vacuum drying at 55 deg.C, and cooling and storing when drying weight loss reaches 0.3%.
Example 7
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 1835.4g of methanol was charged into a three-necked flask, and the temperature was lowered to 5 ℃.
(2) 99.9% nitrogen was introduced below the methanol level, stirring was started, and after 5 minutes of aeration, 3.2g of sodium metabisulfite was slowly added.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 35 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the methanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-5 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of methanol was added to another three-necked flask and the temperature was lowered to-5 ℃.
(7) Filtering, washing with methanol at-5 deg.C, vacuum drying at 38 deg.C, and cooling when drying weight loss reaches 0.3%.
Example 8
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 1835.4g of isopropanol was added to a three-necked flask and the temperature was reduced to-3 ℃.
(2) 999.9% nitrogen was introduced below the level of isopropyl alcohol, stirring was started, and after 5 minutes of introduction, 3.2g of sodium sulfite was slowly added.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 65 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the isopropanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) And starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to 0 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) Into another three-necked flask, 96.6g of isopropyl alcohol was added, and the temperature was lowered to 0 ℃.
(7) Filtering, washing with 0 deg.C isopropanol, vacuum drying at 60 deg.C, and cooling when drying weight loss reaches 0.3% to obtain the final product.
Example 9
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 1835g of ethyl acetate is added to the three-neck flask and the temperature is reduced to 12 ℃.
(2) Introducing 99.9% nitrogen below the liquid level of ethyl acetate, stirring, introducing the nitrogen for 5 minutes, and slowly adding 3.2g of antioxidant dismutase.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 70 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the ethyl acetate was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-5 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of ethyl acetate was added to another three-necked flask, and the temperature was lowered to-5 ℃.
(7) Filtering, washing with-5 deg.C ethyl acetate, vacuum drying at 40 deg.C, and cooling when drying weight loss reaches 0.3% to obtain the final product.
Example 10
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 434.7g of methanol was charged into a three-necked flask, and the temperature was lowered to 8 ℃.
(2) 99.9% nitrogen was introduced below the methanol level, stirring was started, and after 5 minutes of aeration, 1.6g of vitamin E was slowly added.
(3) 161g of L-carnitine and 290.21g of catechin are sequentially fed into a three-neck flask, the temperature is increased to 75 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the methanol was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) Starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to-3 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) Into another three-necked flask, 48.3g of methanol was charged and the temperature was lowered to-3 ℃.
(7) Filtering, washing with methanol at-3 deg.C, vacuum drying at 30 deg.C, and cooling and storing when drying weight loss reaches 0.3%.
Example 11
A preparation method of L-carnitine catecholate comprises the following steps:
(1) 869.4g of acetone was added to a three-necked flask, and the temperature was lowered to 6 ℃.
(2) 99.9% nitrogen was introduced below the acetone level, stirring was started, and after 5 minutes of introduction, 3.2g of sodium metabisulfite was slowly added.
(3) 322g of L-carnitine and 580.4g of catechin are sequentially fed into a three-neck flask, the temperature is raised to 45 ℃, and the mixture is stirred until the product is completely dissolved.
(4) The nitrogen was turned off while the acetone was evaporated to a cloudy solution at a vacuum of less than 0.095 mpa.
(5) And starting nitrogen protection, stirring and cooling to room temperature, then continuously cooling to 0 ℃ by using a refrigerant, and preserving heat for 2 hours.
(6) 96.6g of acetone was added to another three-necked flask and the temperature was reduced to 0 ℃.
(7) Filtering, washing with 0 deg.C acetone, vacuum drying at 35 deg.C, and cooling and storing when drying weight loss reaches 0.3%.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the claims of the present invention.
Claims (8)
1. A preparation method of L-carnitine catecholate is characterized by comprising the following steps: the method comprises the following steps:
step one, adding a solvent into a reactor, and cooling to-5-15 ℃;
step two, adding an antioxidant under the protection of nitrogen;
step three, sequentially feeding L-carnitine and catechin into a reactor, wherein the L-carnitine: the mass ratio of the antioxidant is 100:1, L-carnitine: the molar ratio of the catechin is 1:0.5-1:2.0, the temperature is raised to 30-75 ℃, and the mixture is stirred until the reactants are completely dissolved;
step four, closing the nitrogen, and simultaneously evaporating the solvent until the solution turns turbid under the pressure that the vacuum degree is less than-0.095 mpa;
fifthly, starting nitrogen protection, stirring, cooling to room temperature, continuously cooling to-5-0 ℃, and keeping the temperature for 2 hours;
and step six, filtering, washing and drying to obtain a finished product.
2. The method of claim 1, wherein the method comprises the steps of: the solvent in the step one is one of ethanol, isopropanol, methanol, acetone or ethyl acetate.
3. The method of claim 1, wherein the method comprises the steps of: and in the second step, the antioxidant is one of sodium metabisulfite, sodium sulfite, vitamin A, vitamin C, vitamin E, carotenoid, antioxidant dismutase and butyl hydroxy anisol.
4. The method of claim 1, wherein the method comprises the steps of: the L-carnitine in step three: the catechin molar ratio is 1: 1.
5. The method of claim 1, wherein the method comprises the steps of: the temperature in the third step is 30-45 ℃.
6. The method of claim 1, wherein the method comprises the steps of: and step five, cooling is cooling by a refrigerant.
7. The method of claim 1, wherein the method comprises the steps of: the detergent for washing in the sixth step and the solvent in the first step are the same substances.
8. The method of claim 1, wherein the method comprises the steps of: and the drying in the sixth step is vacuum drying, and the vacuum drying temperature is 30-60 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010986694.6A CN112079738A (en) | 2020-09-18 | 2020-09-18 | Preparation method of L-carnitine catecholate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010986694.6A CN112079738A (en) | 2020-09-18 | 2020-09-18 | Preparation method of L-carnitine catecholate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112079738A true CN112079738A (en) | 2020-12-15 |
Family
ID=73738166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010986694.6A Pending CN112079738A (en) | 2020-09-18 | 2020-09-18 | Preparation method of L-carnitine catecholate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112079738A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101774934A (en) * | 2009-12-31 | 2010-07-14 | 湖北海力化工科技有限公司 | Method for synthesizing lauroyl L-carnitine hydrochloride |
| CN101817759A (en) * | 2010-05-12 | 2010-09-01 | 天津天成制药有限公司 | Preparation method of L-carnitine nitrate |
| CN102911067A (en) * | 2011-08-04 | 2013-02-06 | 广州市奥海生物科技有限公司 | L-carnitine pyruvate, and preparation method and application thereof |
| CN102911068A (en) * | 2011-08-04 | 2013-02-06 | 广州市奥海生物科技有限公司 | L-carnitine L-malate, and preparation method and application thereof |
| CN104276986A (en) * | 2013-07-12 | 2015-01-14 | 辽宁科硕营养科技有限公司 | Method for preparing taurine L-carnitine |
| CN109096129A (en) * | 2018-09-30 | 2018-12-28 | 东北制药集团股份有限公司 | A kind of preparation method of L-carnitine-L-tartrate |
-
2020
- 2020-09-18 CN CN202010986694.6A patent/CN112079738A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101774934A (en) * | 2009-12-31 | 2010-07-14 | 湖北海力化工科技有限公司 | Method for synthesizing lauroyl L-carnitine hydrochloride |
| CN101817759A (en) * | 2010-05-12 | 2010-09-01 | 天津天成制药有限公司 | Preparation method of L-carnitine nitrate |
| CN102911067A (en) * | 2011-08-04 | 2013-02-06 | 广州市奥海生物科技有限公司 | L-carnitine pyruvate, and preparation method and application thereof |
| CN102911068A (en) * | 2011-08-04 | 2013-02-06 | 广州市奥海生物科技有限公司 | L-carnitine L-malate, and preparation method and application thereof |
| CN104276986A (en) * | 2013-07-12 | 2015-01-14 | 辽宁科硕营养科技有限公司 | Method for preparing taurine L-carnitine |
| CN109096129A (en) * | 2018-09-30 | 2018-12-28 | 东北制药集团股份有限公司 | A kind of preparation method of L-carnitine-L-tartrate |
Non-Patent Citations (2)
| Title |
|---|
| 李全 等: "左旋肉毒碱盐酸盐新的合成方法（II）", 《中国药物化学杂志》 * |
| 韦丽娜 等: "六堡茶中的表没食子儿茶素没食子", 《化学工程与装备》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4342952B2 (en) | Natural phenolic products and their derivatives for protection against neurodegenerative diseases | |
| AU2002224848B2 (en) | Supplement to be enterally administered for parenteral nutrition or partial enteral/oral nutrition of the critically ill, the chronically ill and people with malnutrition | |
| FI79523C (en) | Process for the preparation of novel, therapeutically valuable salts of 3-hydroxybutyric acid | |
| US4808574A (en) | Composition inhibiting pathological addiction to alcohol | |
| WO2000004895A2 (en) | Nutritional and therapeutic uses of 3-hydroxyalkanoate oligomers | |
| EP2143434A1 (en) | Composition for promoting ketone compound formation | |
| WO2011078204A1 (en) | Prophylactic or therapeutic agent for hyperlipemia, and anti-fatigue agent | |
| US5710143A (en) | Anti-obesity agents | |
| CN111990463A (en) | Bovine colostrum composite powder | |
| CN112079738A (en) | Preparation method of L-carnitine catecholate | |
| KR20030029994A (en) | Creatine ester pronutrient compounds and formulations | |
| WO2019088482A1 (en) | Composition for ameliorating circulatory system diseases, comprising tea extract with varied ingredient content | |
| JP4814501B2 (en) | Antioxidant function improver | |
| KR102447966B1 (en) | Composition for preventing, improving or treating muscular disorder or muscular damage comprising deer antler fermented by lactic acid bacteria as an active ingredient | |
| CN108477437A (en) | squid protein beverage and preparation method thereof | |
| US20170079953A1 (en) | Melatonin and its use in preventing postoperative complications | |
| FR3050455A1 (en) | POLYCAFEOYLQUINIC ACID AMIDE DERIVATIVES, PROCESS FOR PREPARATION AND USES | |
| JP2008231080A (en) | Promoter for leptin secretion from adipocyte | |
| EP1615908A1 (en) | Basic salt of thioctic acid with l-carnitine | |
| EP4327810A1 (en) | Lipid decrease promoter | |
| CN109010330B (en) | Use of genistein for reducing N-glycolylneuraminic acid in the back-mouth animals | |
| CA2598786C (en) | Composition and method for increasing the anabolic state of muscle cells | |
| US7645794B2 (en) | Composition and method for increasing the anabolic state of muscle cells | |
| AU2007358961A1 (en) | Composition and method for increasing the anabolic state of muscle cells | |
| JPH02503792A (en) | Pharmaceutical composition for treating adrenoleukodystrophy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| 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 |
Application publication date: 20201215 |
|
| RJ01 | Rejection of invention patent application after publication |