CN113603699A - Galanthamine purification production process - Google Patents
Galanthamine purification production process Download PDFInfo
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- CN113603699A CN113603699A CN202110906399.XA CN202110906399A CN113603699A CN 113603699 A CN113603699 A CN 113603699A CN 202110906399 A CN202110906399 A CN 202110906399A CN 113603699 A CN113603699 A CN 113603699A
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- chloroform
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- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 title claims abstract description 122
- 229960003980 galantamine Drugs 0.000 title claims abstract description 61
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 title claims abstract description 61
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 title claims abstract description 58
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 title claims abstract description 58
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 title claims abstract description 58
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 title claims abstract description 58
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 16
- 238000000746 purification Methods 0.000 title claims abstract description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 204
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 130
- 238000000605 extraction Methods 0.000 claims abstract description 130
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 50
- 241000319062 Lycoris radiata Species 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 34
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000741 silica gel Substances 0.000 claims abstract description 7
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 71
- 239000011259 mixed solution Substances 0.000 claims description 45
- 239000000843 powder Substances 0.000 claims description 45
- 230000002378 acidificating effect Effects 0.000 claims description 35
- 239000000047 product Substances 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000004140 cleaning Methods 0.000 claims description 25
- 239000012074 organic phase Substances 0.000 claims description 25
- 238000007599 discharging Methods 0.000 claims description 20
- 238000010992 reflux Methods 0.000 claims description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- 238000001704 evaporation Methods 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000012043 crude product Substances 0.000 claims description 10
- 230000008020 evaporation Effects 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 239000011521 glass Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 238000011068 loading method Methods 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 239000000919 ceramic Substances 0.000 claims description 8
- 229920000742 Cotton Polymers 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 238000007664 blowing Methods 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000004519 grease Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 238000005554 pickling Methods 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 5
- 239000002351 wastewater Substances 0.000 claims description 5
- 239000002994 raw material Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 229930013930 alkaloid Natural products 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- 239000012670 alkaline solution Substances 0.000 description 2
- -1 alkaloid salts Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000002745 Choline Kinase Human genes 0.000 description 1
- 108010018888 Choline kinase Proteins 0.000 description 1
- 241001111317 Chondrodendron tomentosum Species 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000234271 Galanthus Species 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 101710147108 Tyrosinase inhibitor Proteins 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000000874 microwave-assisted extraction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention relates to a galanthamine purification production process. The purification method provided by the invention is used for purifying galanthamine from lycoris radiata plants, and mainly comprises crude extraction and fine extraction, mainly used raw materials comprise lycoris radiata, methanol, chloroform, dichloromethane, chromatographic silica gel, absolute ethyl alcohol and hydrobromic acid, only equipment such as an extraction kettle and a concentration kettle is needed, the raw materials are convenient to obtain, the equipment investment is less, the operation is convenient, the separation and extraction effect on the galanthamine is good, the purity of the extracted product is high, the production cost is low, and the method is suitable for industrial and large-scale production.
Description
Technical Field
The invention relates to the technical field of galanthamine purification methods, in particular to a galanthamine purification production process.
Background
Galantamine is a tetracyclic alkaloid which is firstly separated from a plant Galanthus wooni in 1952 and belongs to a choline tyrosinase inhibitor with a reversible effect. It is characterized by easy blood brain barrier penetration and strong nerve action. Small dose of galanthamine has strong inhibition effect on the activity of choline kinase in cerebral cortex and brain, and large dose of galanthamine inhibits the activity of choline acetate enzyme in thalamus. Galantamine is used in the treatment of poliomyelitis and various neurological diseases, but is mainly used in the treatment of glaucoma and as an antidote to curare. In recent years, galantamine has attracted the interest of researchers in treating Alzheimer's disease and vascular dementia, as well as alcohol dependence and nicotine dependence.
The preparation of mixtures of galanthamine and related compounds from plant material is generally carried out by means of conventional methods for extracting alkaloids, which comprise wetting the plant material with an alkaline solution suitable for hydrolyzing the alkaloid salts contained in the biological material as free base, and extracting with a solvent in which the alkaloids are soluble. In the particular case of galanthamine-containing plants, the alkaline solution is a solution of an inorganic base such as sodium, calcium, potassium hydroxide or carbonate or ammonium hydroxide. Water miscible solvents such as methanol, ethanol and acetone or water immiscible solvents such as aliphatic or aromatic hydrocarbons or esters, e.g. ethyl acetate, can be used as extraction solvents. The extraction may be carried out at a temperature ranging from 20 ℃ to the boiling temperature of the solvent.
The chemical synthesis method of alkaloid such as galanthamine in lycoris radiata has been reported, but the extraction from lycoris radiata plants is still a great important source of the substance, and the extraction method of lycoris radiata alkaloid in the prior art mainly comprises the methods of solvent extraction, ultrasonic extraction, microwave extraction, supercritical fluid extraction and the like, and the methods generally have the defects of serious environmental pollution, high production cost and the like.
Disclosure of Invention
In view of the problems in the prior art, the invention discloses a galanthamine purification production process, which comprises the following steps:
the method comprises the following steps: pulverizing dried Bulbus Lycoridis Radiatae into powder with a pulverizer to obtain Bulbus Lycoridis Radiatae powder;
step two: putting the dried lycoris radiata powder into an extraction kettle, wherein the adding amount of the lycoris radiata powder is 1/4 of the volume of the extraction kettle, and then adding methanol into the extraction kettle to soak the lycoris radiata powder, wherein the adding amount of the methanol is 10-30 cm higher than that of the soaked lycoris radiata powder;
step three: opening a valve at the bottom of the extraction kettle, putting the methanol soaked with the lycoris radiata powder in the extraction kettle into a concentration kettle, simultaneously opening a steam valve of the concentration kettle for concentration reflux, concentrating in the concentration kettle to obtain a concentrated solution, simultaneously condensing the concentrated and evaporated methanol steam through a main condenser and then returning the condensed and evaporated methanol steam into the extraction kettle again, and keeping the methanol in the extraction kettle to be always soaked with the lycoris radiata powder in the concentration reflux process, wherein the concentration reflux time is 6-10 hours;
step four: after the concentration and reflux are finished, opening a steam valve of the extraction kettle and blowing the steam valve into the extraction kettle to promote the evaporation of the methanol in the extraction kettle, condensing the methanol steam evaporated from the extraction kettle through a secondary condenser and collecting the methanol steam for later use, and discharging lycoris radiata powder residues in the extraction kettle after the methanol is evaporated;
step five: repeating the operation from the second step to the fourth step, after a certain amount of concentrated solution is collected in the concentration kettle, concentrating and evaporating the concentrated solution again to completely evaporate and discharge methanol in the concentrated solution, opening the concentration kettle, putting the concentrated solution into a container, standing overnight for 12-15 hours;
step six: removing upper-layer grease from the standing concentrated solution, and then filtering to obtain filtrate;
step seven: adding hydrochloric acid into the filtrate to adjust the pH value to 5 to obtain an acidic mixed solution, then placing the acidic mixed solution into a first extraction tower, adding chloroform, wherein the addition amount of the chloroform is three times that of the acidic mixed solution, circulating the acidic mixed solution in the first extraction tower for 10-20 minutes by using a pump, standing for layering, discharging the lower organic phase layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the first extraction tower again, and thus completing the cleaning of the acidic mixed solution by the chloroform for one time; carrying out multiple times of cleaning operation on the acidic mixed solution by using chloroform until the layered lower organic phase layer is clear, thus completing the pickling operation;
step eight: after the acid washing operation is finished, putting the water phase layer in the first extraction tower into a container to obtain acid liquor, and then recovering the chloroform in the concentration pot to the first extraction tower for later use;
step nine: adding caustic soda into the acid liquor to adjust the pH value to be alkaline to obtain alkaline mixed liquor, then putting the alkaline mixed liquor into a second extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the alkaline mixed liquor, circulating the alkaline mixed liquor in the second extraction tower for 10-20 minutes by using a pump, standing for layering, discharging the lower organic phase layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the second extraction tower again, and thus completing the cleaning of the alkaline mixed liquor by the chloroform for one time; carrying out multiple times of cleaning operation on the alkaline mixed solution by using chloroform until the layered lower organic phase layer is clear, thus finishing the alkaline cleaning operation;
step ten: after the alkaline washing operation is finished, discharging alkaline water in the second extraction tower, collecting and treating the alkaline water as wastewater, fully concentrating an organic phase layer in a concentration pot, recovering chloroform obtained by evaporation into the second extraction tower for later use, obtaining a concentrated crude product in the concentration pot, then adding absolute ethyl alcohol into the concentration pot to completely dissolve the concentrated crude product, obtaining an absolute ethyl alcohol solution, and pouring the absolute ethyl alcohol solution into a container for cooling;
step eleven: after the absolute ethyl alcohol solution is cooled, slowly adding hydrobromic acid while stirring to crystallize the absolute ethyl alcohol solution, stopping adding the absolute ethyl alcohol solution when the pH value of the solution is acidic, continuously stirring until a product in the absolute ethyl alcohol solution is completely crystallized and separated out, filtering and drying to obtain a crude galanthamine product;
step twelve: dissolving the crude galanthamine product with alkali water, extracting the crude galanthamine product into dichloromethane by using a separating funnel, and repeatedly extracting for three times to obtain dichloromethane mixed solution;
step thirteen: loading absorbent cotton at the bottom of a glass tube with the diameter of 200mm and the length of 1000mm, and then loading chromatographic silica gel to prepare a chromatographic column;
fourteen steps: pouring the dichloromethane mixed solution into a chromatographic column, then adding dichloromethane, collecting chromatographic liquid at the bottom of the chromatographic column, heating and distilling the chromatographic liquid in a water bath, recovering the distilled dichloromethane, distilling to obtain a solid, adding absolute ethyl alcohol into the solid for dissolving, then pouring into a glass beaker, then using hydrobromic acid to recrystallize the absolute ethyl alcohol solution, thus obtaining the galanthamine product with the concentration of about 95%, and recrystallizing to obtain the galanthamine product with the concentration of 98%.
In a preferred embodiment of the present invention, the methanol in step two is industrial methanol with a content of 90%.
As a preferable scheme of the invention, the container in the fifth step, the eighth step and the tenth step is one of a ceramic cylinder or a plastic barrel.
As a preferred scheme of the invention, the first step to the eleventh step are a crude galanthamine extraction process, and the twelfth step to the fourteenth step are a fine galanthamine extraction process.
The invention has the beneficial effects that: the purification method provided by the invention is used for purifying galanthamine from lycoris radiata plants, and mainly comprises crude extraction and fine extraction, mainly used raw materials comprise lycoris radiata, methanol, chloroform, dichloromethane, chromatographic silica gel, absolute ethyl alcohol and hydrobromic acid, only equipment such as an extraction kettle and a concentration kettle is needed, the raw materials are convenient to obtain, the equipment investment is less, the operation is convenient, the separation and extraction effect on the galanthamine is good, the purity of the extracted product is high, the production cost is low, and the method is suitable for industrial and large-scale production.
Detailed Description
Example 1
The invention relates to a galanthamine purification production process, which comprises the following steps:
preparing raw materials:
the method comprises the following steps: pulverizing dried Bulbus Lycoridis Radiatae into powder with a pulverizer to obtain Bulbus Lycoridis Radiatae powder;
the extraction process of crude galanthamine comprises the following steps:
step two: putting the dried lycoris radiata powder into an extraction kettle, wherein the adding amount of the lycoris radiata powder is 1/4 of the volume of the extraction kettle, and then adding methanol into the extraction kettle to soak the lycoris radiata powder, wherein the adding amount of the methanol is that the lycoris radiata powder is immersed and is 10 cm higher, and the used methanol is industrial methanol with the content of 90%;
step three: opening a valve at the bottom of the extraction kettle, putting the methanol soaked with the lycoris radiata powder in the extraction kettle into a concentration kettle, simultaneously opening a steam valve of the concentration kettle for concentration reflux, concentrating in the concentration kettle to obtain a concentrated solution, simultaneously condensing the concentrated and evaporated methanol steam through a main condenser and then returning the condensed and evaporated methanol steam into the extraction kettle again, and keeping the methanol in the extraction kettle to be always soaked with the lycoris radiata powder in the concentration reflux process, wherein the concentration reflux time is 6 hours;
step four: after the concentration and reflux are finished, opening a steam valve of the extraction kettle and blowing the steam valve into the extraction kettle to promote the evaporation of the methanol in the extraction kettle, condensing the methanol steam evaporated from the extraction kettle through a secondary condenser and collecting the methanol steam for later use, and discharging lycoris radiata powder residues in the extraction kettle after the methanol is evaporated;
step five: repeating the operation from the second step to the fourth step, after collecting a certain amount of concentrated solution in the concentration kettle, concentrating and evaporating the concentrated solution again to completely evaporate and discharge methanol in the concentrated solution, opening the concentration kettle, putting the concentrated solution into a ceramic cylinder or a plastic barrel, standing overnight, and standing for 12 hours;
step six: removing upper-layer grease from the standing concentrated solution, and then filtering to obtain filtrate;
step seven: adding hydrochloric acid into the filtrate to adjust the pH value to 5 to obtain an acidic mixed solution, then placing the acidic mixed solution into a first extraction tower, adding chloroform, wherein the addition amount of the chloroform is three times that of the acidic mixed solution, circulating the acidic mixed solution in the first extraction tower for 10 minutes by using a pump, standing for layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the first extraction tower again, and thus completing the cleaning of the acidic mixed solution by the chloroform for one time; carrying out multiple times of cleaning operation on the acidic mixed solution by using chloroform until the layered lower organic phase layer is clear, thus completing the pickling operation;
step eight: after the acid washing operation is finished, putting the water phase layer in the first extraction tower into a ceramic cylinder or a plastic barrel to obtain acid liquor, and recovering chloroform in a concentration pot to the first extraction tower for later use;
step nine: adding caustic soda into the acid liquor to adjust the pH value to be alkaline to obtain alkaline mixed liquor, then putting the alkaline mixed liquor into a second extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the alkaline mixed liquor, circulating the alkaline mixed liquor in the second extraction tower for 10 minutes by using a pump, standing for layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover chloroform evaporated in the concentration process again, and sending the recovered chloroform into the second extraction tower, thereby completing the cleaning of the alkaline mixed liquor by the chloroform for one time; carrying out multiple times of cleaning operation on the alkaline mixed solution by using chloroform until the layered lower organic phase layer is clear, thus finishing the alkaline cleaning operation;
step ten: after the alkaline washing operation is finished, discharging alkaline water in the second extraction tower, collecting and treating the alkaline water as wastewater, fully concentrating an organic phase layer in a concentration pot, recovering chloroform obtained by evaporation into the second extraction tower for later use, obtaining a concentrated crude product in the concentration pot, then adding absolute ethyl alcohol into the concentration pot to completely dissolve the concentrated crude product, obtaining an absolute ethyl alcohol solution, and pouring the absolute ethyl alcohol solution into a plastic bucket for cooling;
step eleven: after the absolute ethyl alcohol solution is cooled, slowly adding hydrobromic acid while stirring to crystallize the absolute ethyl alcohol solution, stopping adding the absolute ethyl alcohol solution when the pH value of the solution is acidic, continuously stirring until a product in the absolute ethyl alcohol solution is completely crystallized and separated out, filtering and drying to obtain a crude galanthamine product;
the fine galanthamine product extraction process comprises the following steps:
step twelve: dissolving the crude galanthamine product with alkali water, extracting the crude galanthamine product into dichloromethane by using a separating funnel, and repeatedly extracting for three times to obtain dichloromethane mixed solution;
step thirteen: loading absorbent cotton at the bottom of a glass tube with the diameter of 200mm and the length of 1000mm, and then loading chromatographic silica gel to prepare a chromatographic column;
fourteen steps: pouring the dichloromethane mixed solution into a chromatographic column, then adding dichloromethane, collecting chromatographic liquid at the bottom of the chromatographic column, heating and distilling the chromatographic liquid in a water bath, recovering the distilled dichloromethane, distilling to obtain a solid, adding absolute ethyl alcohol into the solid for dissolving, then pouring into a glass beaker, then using hydrobromic acid to recrystallize the absolute ethyl alcohol solution, thus obtaining the galanthamine product with the concentration of about 95%, and recrystallizing to obtain the galanthamine product with the concentration of 98%.
Example 2
The invention relates to a galanthamine purification production process, which comprises the following steps:
preparing raw materials:
the method comprises the following steps: pulverizing dried Bulbus Lycoridis Radiatae into powder with a pulverizer to obtain Bulbus Lycoridis Radiatae powder;
the extraction process of crude galanthamine comprises the following steps:
step two: putting the dried lycoris radiata powder into an extraction kettle, wherein the adding amount of the lycoris radiata powder is 1/4 of the volume of the extraction kettle, and then adding methanol into the extraction kettle to soak the lycoris radiata powder, wherein the adding amount of the methanol is that the lycoris radiata powder is immersed and is 30 cm higher, and the used methanol is industrial methanol with the content of 90%;
step three: opening a valve at the bottom of the extraction kettle, putting the methanol soaked with the lycoris radiata powder in the extraction kettle into a concentration kettle, simultaneously opening a steam valve of the concentration kettle for concentration reflux, concentrating in the concentration kettle to obtain a concentrated solution, simultaneously condensing the concentrated and evaporated methanol steam through a main condenser and then returning the condensed and evaporated methanol steam into the extraction kettle again, and keeping the methanol in the extraction kettle to be always soaked with the lycoris radiata powder in the concentration reflux process, wherein the concentration reflux time is 10 hours;
step four: after the concentration and reflux are finished, opening a steam valve of the extraction kettle and blowing the steam valve into the extraction kettle to promote the evaporation of the methanol in the extraction kettle, condensing the methanol steam evaporated from the extraction kettle through a secondary condenser and collecting the methanol steam for later use, and discharging lycoris radiata powder residues in the extraction kettle after the methanol is evaporated;
step five: repeating the operation from the second step to the fourth step, after collecting a certain amount of concentrated solution in the concentration kettle, concentrating and evaporating the concentrated solution again to completely evaporate and discharge methanol in the concentrated solution, opening the concentration kettle, putting the concentrated solution into a ceramic cylinder or a plastic barrel, standing overnight, and standing for 15 hours;
step six: removing upper-layer grease from the standing concentrated solution, and then filtering to obtain filtrate;
step seven: adding hydrochloric acid into the filtrate to adjust the pH value to 5 to obtain an acidic mixed solution, then placing the acidic mixed solution into a first extraction tower, adding chloroform, wherein the addition amount of the chloroform is three times that of the acidic mixed solution, circulating the acidic mixed solution in the first extraction tower for 20 minutes by using a pump, standing for layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the first extraction tower again, and thus completing the cleaning of the acidic mixed solution by the chloroform for one time; carrying out multiple times of cleaning operation on the acidic mixed solution by using chloroform until the layered lower organic phase layer is clear, thus completing the pickling operation;
step eight: after the acid washing operation is finished, putting the water phase layer in the first extraction tower into a ceramic cylinder or a plastic barrel to obtain acid liquor, and recovering chloroform in a concentration pot to the first extraction tower for later use;
step nine: adding caustic soda into the acid liquor to adjust the pH value to be alkaline to obtain alkaline mixed liquor, then putting the alkaline mixed liquor into a second extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the alkaline mixed liquor, circulating the alkaline mixed liquor in the second extraction tower for 20 minutes by using a pump, standing for layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover chloroform evaporated in the concentration process again, and sending the recovered chloroform into the second extraction tower, thereby completing the cleaning of the alkaline mixed liquor by the chloroform for one time; carrying out multiple times of cleaning operation on the alkaline mixed solution by using chloroform until the layered lower organic phase layer is clear, thus finishing the alkaline cleaning operation;
step ten: after the alkaline washing operation is finished, discharging alkaline water in the second extraction tower, collecting and treating the alkaline water as wastewater, fully concentrating an organic phase layer in a concentration pot, recovering chloroform obtained by evaporation into the second extraction tower for later use, obtaining a concentrated crude product in the concentration pot, then adding absolute ethyl alcohol into the concentration pot to completely dissolve the concentrated crude product, obtaining an absolute ethyl alcohol solution, and pouring the absolute ethyl alcohol solution into a plastic bucket for cooling;
step eleven: after the absolute ethyl alcohol solution is cooled, slowly adding hydrobromic acid while stirring to crystallize the absolute ethyl alcohol solution, stopping adding the absolute ethyl alcohol solution when the pH value of the solution is acidic, continuously stirring until a product in the absolute ethyl alcohol solution is completely crystallized and separated out, filtering and drying to obtain a crude galanthamine product;
the fine galanthamine product extraction process comprises the following steps:
step twelve: dissolving the crude galanthamine product with alkali water, extracting the crude galanthamine product into dichloromethane by using a separating funnel, and repeatedly extracting for three times to obtain dichloromethane mixed solution;
step thirteen: loading absorbent cotton at the bottom of a glass tube with the diameter of 200mm and the length of 1000mm, and then loading chromatographic silica gel to prepare a chromatographic column;
fourteen steps: pouring the dichloromethane mixed solution into a chromatographic column, then adding dichloromethane, collecting chromatographic liquid at the bottom of the chromatographic column, heating and distilling the chromatographic liquid in a water bath, recovering the distilled dichloromethane, distilling to obtain a solid, adding absolute ethyl alcohol into the solid for dissolving, then pouring into a glass beaker, then using hydrobromic acid to recrystallize the absolute ethyl alcohol solution, thus obtaining the galanthamine product with the concentration of about 95%, and recrystallizing to obtain the galanthamine product with the concentration of 98%.
Example 3
The invention relates to a galanthamine purification production process, which comprises the following steps:
preparing raw materials:
the method comprises the following steps: pulverizing dried Bulbus Lycoridis Radiatae into powder with a pulverizer to obtain Bulbus Lycoridis Radiatae powder;
the extraction process of crude galanthamine comprises the following steps:
step two: putting the dried lycoris radiata powder into an extraction kettle, wherein the adding amount of the lycoris radiata powder is 1/4 of the volume of the extraction kettle, and then adding methanol into the extraction kettle to soak the lycoris radiata powder, wherein the adding amount of the methanol is that the lycoris radiata powder is immersed and is 20 cm higher, and the used methanol is industrial methanol with the content of 90%;
step three: opening a valve at the bottom of the extraction kettle, putting the methanol soaked with the lycoris radiata powder in the extraction kettle into a concentration kettle, simultaneously opening a steam valve of the concentration kettle for concentration reflux, concentrating in the concentration kettle to obtain a concentrated solution, simultaneously condensing the concentrated and evaporated methanol steam through a main condenser and then returning the condensed and evaporated methanol steam into the extraction kettle again, keeping the methanol in the extraction kettle to be always soaked with the lycoris radiata powder in the concentration reflux process, and preferably selecting the concentration reflux time to be 8 hours;
step four: after the concentration and reflux are finished, opening a steam valve of the extraction kettle and blowing the steam valve into the extraction kettle to promote the evaporation of the methanol in the extraction kettle, condensing the methanol steam evaporated from the extraction kettle through a secondary condenser and collecting the methanol steam for later use, and discharging lycoris radiata powder residues in the extraction kettle after the methanol is evaporated;
step five: repeating the operation of the second step to the fourth step, so that after a certain amount of concentrated solution is collected in the concentration kettle, concentrating and evaporating the concentrated solution again to completely evaporate and discharge methanol in the concentrated solution, opening the concentration kettle, putting the concentrated solution into a ceramic cylinder or a plastic barrel, and standing overnight for preferably 13 hours;
step six: removing upper-layer grease from the standing concentrated solution, and then filtering to obtain filtrate;
step seven: adding hydrochloric acid into the filtrate to adjust the pH value to 5 to obtain an acidic mixed solution, then placing the acidic mixed solution into a first extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the acidic mixed solution, circulating the acidic mixed solution in the first extraction tower by using a pump for preferably 15 minutes, standing for layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the first extraction tower again, and thus completing the cleaning of the acidic mixed solution by the chloroform for one time; carrying out multiple times of cleaning operation on the acidic mixed solution by using chloroform until the layered lower organic phase layer is clear, thus completing the pickling operation;
step eight: after the acid washing operation is finished, putting the water phase layer in the first extraction tower into a ceramic cylinder or a plastic barrel to obtain acid liquor, and recovering chloroform in a concentration pot to the first extraction tower for later use;
step nine: adding caustic soda into the acid liquor to adjust the pH value to be alkaline to obtain alkaline mixed liquor, then putting the alkaline mixed liquor into a second extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the alkaline mixed liquor, circulating the alkaline mixed liquor in the second extraction tower by using a pump for preferably 15 minutes, then standing and layering, discharging an organic phase layer at the lower layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover chloroform evaporated in the concentration process again and sending the chloroform into the second extraction tower, thereby completing the cleaning of the alkaline mixed liquor by the chloroform for one time; carrying out multiple times of cleaning operation on the alkaline mixed solution by using chloroform until the layered lower organic phase layer is clear, thus finishing the alkaline cleaning operation;
step ten: after the alkaline washing operation is finished, discharging alkaline water in the second extraction tower, collecting and treating the alkaline water as wastewater, fully concentrating an organic phase layer in a concentration pot, recovering chloroform obtained by evaporation into the second extraction tower for later use, obtaining a concentrated crude product in the concentration pot, then adding absolute ethyl alcohol into the concentration pot to completely dissolve the concentrated crude product, obtaining an absolute ethyl alcohol solution, and pouring the absolute ethyl alcohol solution into a plastic bucket for cooling;
step eleven: after the absolute ethyl alcohol solution is cooled, slowly adding hydrobromic acid while stirring to crystallize the absolute ethyl alcohol solution, stopping adding the absolute ethyl alcohol solution when the pH value of the solution is acidic, continuously stirring until a product in the absolute ethyl alcohol solution is completely crystallized and separated out, filtering and drying to obtain a crude galanthamine product;
the fine galanthamine product extraction process comprises the following steps:
step twelve: dissolving the crude galanthamine product with alkali water, extracting the crude galanthamine product into dichloromethane by using a separating funnel, and repeatedly extracting for three times to obtain dichloromethane mixed solution;
step thirteen: loading absorbent cotton at the bottom of a glass tube with the diameter of 200mm and the length of 1000mm, and then loading chromatographic silica gel to prepare a chromatographic column;
fourteen steps: pouring the dichloromethane mixed solution into a chromatographic column, then adding dichloromethane, collecting chromatographic liquid at the bottom of the chromatographic column, heating and distilling the chromatographic liquid in a water bath, recovering the distilled dichloromethane, distilling to obtain a solid, adding absolute ethyl alcohol into the solid for dissolving, then pouring into a glass beaker, then using hydrobromic acid to recrystallize the absolute ethyl alcohol solution, thus obtaining the galanthamine product with the concentration of about 95%, and recrystallizing to obtain the galanthamine product with the concentration of 98%.
Components not described in detail herein are prior art.
Although the present invention has been described in detail with reference to the specific embodiments, the present invention is not limited to the above embodiments, and various changes and modifications without inventive changes may be made within the knowledge of those skilled in the art without departing from the spirit of the present invention. .
Claims (5)
1. The galanthamine purification production process is characterized by comprising the following steps:
the method comprises the following steps: pulverizing dried Bulbus Lycoridis Radiatae into powder with a pulverizer to obtain Bulbus Lycoridis Radiatae powder;
step two: putting the dried lycoris radiata powder into an extraction kettle, wherein the adding amount of the lycoris radiata powder is 1/4 of the volume of the extraction kettle, and then adding methanol into the extraction kettle to soak the lycoris radiata powder, wherein the adding amount of the methanol is 10-30 cm higher than that of the soaked lycoris radiata powder;
step three: opening a valve at the bottom of the extraction kettle, putting the methanol soaked with the lycoris radiata powder in the extraction kettle into a concentration kettle, simultaneously opening a steam valve of the concentration kettle for concentration reflux, concentrating in the concentration kettle to obtain a concentrated solution, simultaneously condensing the concentrated and evaporated methanol steam through a main condenser and then returning the condensed and evaporated methanol steam into the extraction kettle again, and keeping the methanol in the extraction kettle to be always soaked with the lycoris radiata powder in the concentration reflux process, wherein the concentration reflux time is 6-10 hours;
step four: after the concentration and reflux are finished, opening a steam valve of the extraction kettle and blowing the steam valve into the extraction kettle to promote the evaporation of the methanol in the extraction kettle, condensing the methanol steam evaporated from the extraction kettle through a secondary condenser and collecting the methanol steam for later use, and discharging lycoris radiata powder residues in the extraction kettle after the methanol is evaporated;
step five: repeating the operation from the second step to the fourth step, after a certain amount of concentrated solution is collected in the concentration kettle, concentrating and evaporating the concentrated solution again to completely evaporate and discharge methanol in the concentrated solution, opening the concentration kettle, putting the concentrated solution into a container, standing overnight for 12-15 hours;
step six: removing upper-layer grease from the standing concentrated solution, and then filtering to obtain filtrate;
step seven: adding hydrochloric acid into the filtrate to adjust the pH value to 5 to obtain an acidic mixed solution, then placing the acidic mixed solution into a first extraction tower, adding chloroform, wherein the addition amount of the chloroform is three times that of the acidic mixed solution, circulating the acidic mixed solution in the first extraction tower for 10-20 minutes by using a pump, standing for layering, discharging the lower organic phase layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the first extraction tower again, and thus completing the cleaning of the acidic mixed solution by the chloroform for one time; carrying out multiple times of cleaning operation on the acidic mixed solution by using chloroform until the layered lower organic phase layer is clear, thus completing the pickling operation;
step eight: after the acid washing operation is finished, putting the water phase layer in the first extraction tower into a container to obtain acid liquor, and then recovering the chloroform in the concentration pot to the first extraction tower for later use;
step nine: adding caustic soda into the acid liquor to adjust the pH value to be alkaline to obtain alkaline mixed liquor, then putting the alkaline mixed liquor into a second extraction tower, adding chloroform, wherein the adding amount of the chloroform is three times that of the alkaline mixed liquor, circulating the alkaline mixed liquor in the second extraction tower for 10-20 minutes by using a pump, standing for layering, discharging the lower organic phase layer into a concentration pot after layering, then opening a steam valve of the concentration pot to recover and send the chloroform evaporated in the concentration process into the second extraction tower again, and thus completing the cleaning of the alkaline mixed liquor by the chloroform for one time; carrying out multiple times of cleaning operation on the alkaline mixed solution by using chloroform until the layered lower organic phase layer is clear, thus finishing the alkaline cleaning operation;
step ten: after the alkaline washing operation is finished, discharging alkaline water in the second extraction tower, collecting and treating the alkaline water as wastewater, fully concentrating an organic phase layer in a concentration pot, recovering chloroform obtained by evaporation into the second extraction tower for later use, obtaining a concentrated crude product in the concentration pot, then adding absolute ethyl alcohol into the concentration pot to completely dissolve the concentrated crude product, obtaining an absolute ethyl alcohol solution, and pouring the absolute ethyl alcohol solution into a container for cooling;
step eleven: after the absolute ethyl alcohol solution is cooled, slowly adding hydrobromic acid while stirring to crystallize the absolute ethyl alcohol solution, stopping adding the absolute ethyl alcohol solution when the pH value of the solution is acidic, continuously stirring until a product in the absolute ethyl alcohol solution is completely crystallized and separated out, filtering and drying to obtain a crude galanthamine product;
step twelve: dissolving the crude galanthamine product with alkali water, extracting the crude galanthamine product into dichloromethane by using a separating funnel, and repeatedly extracting for three times to obtain dichloromethane mixed solution;
step thirteen: loading absorbent cotton at the bottom of a glass tube with the diameter of 200mm and the length of 1000mm, and then loading chromatographic silica gel to prepare a chromatographic column;
fourteen steps: pouring the dichloromethane mixed solution into a chromatographic column, then adding dichloromethane, collecting chromatographic liquid at the bottom of the chromatographic column, heating and distilling the chromatographic liquid in a water bath, recovering the distilled dichloromethane, distilling to obtain a solid, adding absolute ethyl alcohol into the solid for dissolving, then pouring into a glass beaker, then using hydrobromic acid to recrystallize the absolute ethyl alcohol solution, thus obtaining the galanthamine product with the concentration of about 95%, and recrystallizing to obtain the galanthamine product with the concentration of 98%.
2. The process for the purification production of galanthamine according to claim 1, wherein: and step two, the methanol is industrial methanol with the content of 90 percent.
3. The process for the purification production of galanthamine according to claim 1, wherein: in the fifth step, the eighth step and the tenth step, the container is one of a ceramic cylinder or a plastic barrel.
4. The process for the purification production of galanthamine according to claim 1, wherein: step one to step eleven are processes for extracting crude galanthamine.
5. The process for the purification production of galanthamine according to claim 1, wherein: the twelfth step to the fourteenth step are processes for extracting a fine galanthamine product.
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