CN114057572B - Method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaf - Google Patents
Method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaf Download PDFInfo
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- CN114057572B CN114057572B CN202010767094.0A CN202010767094A CN114057572B CN 114057572 B CN114057572 B CN 114057572B CN 202010767094 A CN202010767094 A CN 202010767094A CN 114057572 B CN114057572 B CN 114057572B
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- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 title claims abstract description 106
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 title claims abstract description 106
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 title claims abstract description 106
- JXOHGGNKMLTUBP-HSUXUTPPSA-N shikimic acid Chemical compound O[C@@H]1CC(C(O)=O)=C[C@@H](O)[C@H]1O JXOHGGNKMLTUBP-HSUXUTPPSA-N 0.000 title claims abstract description 101
- JXOHGGNKMLTUBP-JKUQZMGJSA-N shikimic acid Natural products O[C@@H]1CC(C(O)=O)=C[C@H](O)[C@@H]1O JXOHGGNKMLTUBP-JKUQZMGJSA-N 0.000 title claims abstract description 101
- 241000218628 Ginkgo Species 0.000 title claims abstract description 41
- 235000011201 Ginkgo Nutrition 0.000 title claims abstract description 41
- 235000008100 Ginkgo biloba Nutrition 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 33
- 239000011347 resin Substances 0.000 claims abstract description 57
- 229920005989 resin Polymers 0.000 claims abstract description 57
- 238000000605 extraction Methods 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 11
- 238000002425 crystallisation Methods 0.000 claims abstract description 11
- 230000008025 crystallization Effects 0.000 claims abstract description 11
- 238000002386 leaching Methods 0.000 claims abstract description 8
- 238000007865 diluting Methods 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 71
- 239000003480 eluent Substances 0.000 claims description 70
- 239000000243 solution Substances 0.000 claims description 63
- 239000007788 liquid Substances 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 23
- 239000000284 extract Substances 0.000 claims description 21
- 238000005406 washing Methods 0.000 claims description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 18
- 238000001816 cooling Methods 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 239000012043 crude product Substances 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 14
- 230000005484 gravity Effects 0.000 claims description 13
- 238000011068 loading method Methods 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000001179 sorption measurement Methods 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 239000003957 anion exchange resin Substances 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 7
- 238000004064 recycling Methods 0.000 claims description 7
- -1 quinic acid radical ions Chemical class 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 3
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 claims description 3
- 239000003456 ion exchange resin Substances 0.000 claims description 3
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 6
- 241000196324 Embryophyta Species 0.000 abstract description 5
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 238000004440 column chromatography Methods 0.000 abstract description 2
- 238000005342 ion exchange Methods 0.000 abstract description 2
- 230000003287 optical effect Effects 0.000 abstract description 2
- 238000004587 chromatography analysis Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 150000003364 shikimic acids Chemical class 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 239000012535 impurity Substances 0.000 description 12
- 239000013078 crystal Substances 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 5
- 229910001626 barium chloride Inorganic materials 0.000 description 5
- 239000003463 adsorbent Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 235000021513 Cinchona Nutrition 0.000 description 3
- 241000157855 Cinchona Species 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000005837 radical ions Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- CQUUHDQRJWXDPY-UHFFFAOYSA-N 6-Hydroxykynurenic acid Chemical compound C1=C(O)C=CC2=NC(C(=O)O)=CC(O)=C21 CQUUHDQRJWXDPY-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 2
- 229960003752 oseltamivir Drugs 0.000 description 2
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 235000008227 Illicium verum Nutrition 0.000 description 1
- 240000007232 Illicium verum Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/48—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Abstract
The invention discloses a method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaves, which relates to the technical field of extraction and purification of plant active ingredients and comprises the following steps: the preparation method comprises the steps of taking ginkgo leaf as a raw material, and carrying out processes such as leaching, concentrating, diluting and centrifuging, column chromatography, extraction, concentrating, extraction, ion exchange separation, crystallization and the like to obtain shikimic acid and quinic acid with optical activity. Before shikimic acid and quinic acid are extracted and purified, shikimic acid salt and quinic acid salt are all converted into shikimic acid and quinic acid by adding acid, then a proper resin column is selected, and extraction and chromatography processes are performed, so that two high-added-value products of shikimic acid and quinic acid are obtained from ginkgo leaves simultaneously, the content of the prepared shikimic acid and quinic acid is more than 99%, and the method has great significance for deep development of ginkgo leaf resources, and has good economic benefit and practical significance.
Description
Technical Field
The invention relates to the technical field of extraction and purification of plant active ingredients, in particular to a method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaves.
Background
Currently, active ingredients of ginkgo leaves are developed, and the main ingredients which can realize industrial production are flavonoid, terpene lactones, chlorophyll and the like. The research on shikimic acid in the last two years gradually becomes industry hot spot, but industrialization degree is not high, and the research on quinic acid is less. Literature data show that quinic acid (quinic acid) often coexist with shikimic acid in plants, and detection shows that organic acid types in ginkgo leaves are more (comprising shikimic acid, quinic acid, protocatechuic acid, 6-hydroxykynurenic acid, parahydroxybenzoic acid, gallic acid and the like), the content of shikimic acid and quinic acid is higher, and the content of shikimic acid and quinic acid is about 4%, even the content of leaves in some time periods exceeds 8%, which lays a material foundation for the development of the two organic acids. Both shikimic acid and quinic acid are optically active substances, and are used in the pharmaceutical field, for example, in the synthesis process of Oseltamivir (Oseltamivir), both of which can be used as synthesis raw materials.
At present, shikimic acid and quinic acid are mainly derived from three ways of chemical synthesis, microbial fermentation and plant extraction. Wherein, the plant extraction method is a main way for producing shikimic acid and quinic acid, and the main raw material of shikimic acid is derived from star anise, and the resource is single. The main raw material of quinic acid is derived from cinchona bark, so that the method is also called cinchona acid, the consumed raw material greatly exceeds the utilization value of generated quinic acid, and the shortage of cinchona resource also determines that the quinic acid yield is low, so that the large-scale application of quinic acid is limited.
Disclosure of Invention
Based on the technical problems in the prior art, the invention provides a method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaf, which is processed by the processes of leaching, concentrating, diluting and centrifuging, column chromatography, extracting, concentrating, extracting, ion exchange separating, crystallizing and the like, and simultaneously obtains the shikimic acid and quinic acid with optical activity, wherein the content of the prepared shikimic acid and quinic acid is more than 99 percent.
The invention provides a method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaves, which comprises the following steps:
s1, taking ginkgo leaves, crushing, adding a solvent A for leaching, and filtering to obtain an extracting solution;
s2, concentrating the extracting solution, diluting with water to adjust the specific gravity, and centrifugally separating to obtain upper column liquid;
s3, passing the upper column liquid through a resin column B, eluting with water and ethanol water solution respectively, collecting column passing effluent and water eluting liquid, and combining to obtain a combined liquid 1;
s4, concentrating the combined liquid 1 into thick paste, adding acid liquor C into the thick paste, and then adding a solvent D for extraction to obtain an extract 2;
s5, concentrating the extract 2, and then adding a solvent E for extraction to obtain an aqueous solution 3 containing shikimic acid and quinic acid;
s6, passing the aqueous solution 3 through a resin column F, washing with water, collecting column-passing effluent and water eluent, and combining to obtain a combined solution 4;
s7, passing the combined liquid 4 through a combined serial resin column G, washing in serial with water, eluting the unit serial columns of the serial resin column G by using an eluent H respectively, and collecting the unit serial columns respectively to obtain shikimic acid eluent, quinic acid eluent and eluent containing shikimic acid and quinic acid, and recycling the eluent containing shikimic acid and quinic acid to the combined liquid 4;
s8, concentrating shikimic acid eluent to a certain concentration, cooling and crystallizing to obtain a shikimic acid crude product, and recrystallizing to obtain shikimic acid;
s9, concentrating the quinic acid eluent to a certain concentration, cooling and crystallizing to obtain a quinic acid crude product, and recrystallizing to obtain quinic acid.
In the invention S3, the upper column liquid passes through a resin column B, water and ethanol water solutions with different concentrations are respectively used for eluting, column passing effluent liquid and water eluting liquid are collected and combined to obtain a combined liquid 1; collecting ethanol eluate with corresponding concentration for preparing folium Ginkgo extract.
In the invention S7, the combined liquid 4 can be added into equal volume of water for dilution, the mixture is passed through a combined serial resin column G and is washed in serial with water, then the relatively concentrated resin columns for adsorbing shikimic acid and quinic acid are eluted by using an eluent H respectively, the eluents containing shikimic acid and quinic acid are collected respectively, and the eluents eluted by using the eluent H for the resin columns for cross adsorption of shikimic acid and quinic acid in the combined columns are recycled to the combined liquid 4.
Preferably, in S4, the acid liquid C is at least one of sulfuric acid and hydrochloric acid; preferably, the acid C is added in the thick paste according to H + Calculated as 1.5 to 3 times of molar equivalent of quinic acid radical ions.
Preferably, the resin column B is a macroporous adsorption resin column; preferably, the resin column F is a macroporous adsorbent resin column; preferably, the resin column G is a basic anion exchange resin column, and preferably, the resin G is one of D380 and HPD-130 type basic anion resins.
Preferably, the combined tandem resin column G is composed of 10 identical resin columns, the resin aspect ratio being 1:1.5 to 3.5 percent, and the column loading amount of the resin is 60 to 70 percent of the column volume.
In the invention S7, the basic anion exchange resin column G works according to the following principle: when the combined solution 4 passes through a resin column G (basic anion exchange resin column) consisting of 10 columns connected in series, the combined solution 4 is adsorbed by the ion exchange resin according to the priority order of the rear impurity (certain acidic substance), quinic acid, shikimic acid and the front impurity (certain acidic substance), and the acid radical ions adsorb OH on the resin column G - And the exchange is carried out, thereby achieving the aim of purification and separation. The method comprises the steps of separating and purifying by using water as a mobile phase to remove the front impurities, concentrating the rear impurities in a first column, concentrating the cross part of the rear impurities and part of quinic acid in a second column, concentrating quinic acid in a third column and a fourth column, concentrating the cross part of quinic acid and shikimic acid in a fifth column and a sixth column, concentrating shikimic acid in a seventh column and an eighth column, and concentrating part of shikimic acid and the front impurities in a ninth column and a tenth column. Eluting with eluent H, and eluting the organic acid radical ion by the acid radical ion in the eluent H, and eluting with H in the eluent H + Combining to generate organic acid, eluting three columns and four columns in series, and collecting eluent containing quinic acid; eluting the seven columns and the eight columns in series, and collecting eluent containing shikimic acid; eluting the second column, the fifth column and the sixth column, collecting eluent containing shikimic acid and quinic acid, and recycling the eluent to the combined solution 4; the first column is directly regenerated by alkali liquor, and the regenerated liquor decontaminates the water treatment station; the ninth and tenth columns were used as starting columns for the next round of treatment of the pool 4. In the eluting process, detecting whether the eluting solution contains acid radical ions in the eluent H, if so, indicating that all organic acid radical ions adsorbed by the resin are exchanged and eluted, and stopping collecting the eluting solution.
Preferably, the solvent A is a mixed solution of an organic solvent and water, wherein the organic solvent is at least one of acetone, ethanol and methanol, and the volume fraction of the organic solvent is 50-80%; preferably, the solvent D is a mixed solution of an organic solvent and water, wherein the organic solvent is at least one of acetone and isopropanol, and the volume fraction of the organic solvent is 70-95%; preferably, the solvent E is at least one of diethyl ether, ethyl acetate and methyl acetate.
Preferably, in S2, water is added for dilution and adjustment to the specific gravity of 1.02-1.05 g/ml; preferably, in S4, the specific gravity of the thick paste is 1.18-1.24 g/ml.
In the present invention, specific gravity means: the ratio of the weight of the substance to the weight of pure water in volume at 4 ℃, i.e. the relative density when the reference is water.
Preferably, the eluent H is 3-5% sulfuric acid or hydrochloric acid aqueous solution.
Preferably, in S3, the column loading amount of the column loading liquid is 3-5 BV, and the water washing amount is 1-1.5 BV; preferably, in S6, the column loading amount of the aqueous solution 3 is 4-6 BV, and the water washing amount is 1-3 BV; preferably, in S7, the upper column amount of the combined liquid 4 is calculated according to 30-50 g shikimic acid/L ion exchange resin, and the water consumption of water washing is 2-3 BV.
Preferably, in S1, the leaching temperature is 25-70 ℃, the extraction times are 3-4 times, and the weight-volume ratio g/mL of ginkgo leaf and solvent A during each extraction is 1: 4-6 times; preferably, in S4, the extraction temperature is 20-50 ℃, the extraction is carried out for 3-6 times, and the volume ratio of the thick paste to the solvent D in each extraction is 1:3 to 6; preferably, in S5, the extraction temperature is 20-50 ℃, the extraction is carried out for 3-6 times, and the volume ratio of feed liquid to solvent E is 1 during each extraction: 1 to 2.
Preferably, in S8, the shikimic acid eluent is concentrated to a concentration of more than 0.35g/ml, preferably, the recrystallization concentration of shikimic acid is 0.5-0.6 g/ml; preferably, the quinic acid stripping solution is concentrated to a concentration of more than 0.55g/ml, and the quinic acid recrystallization concentration is 0.6-0.7 g/ml; preferably, in S8 and S9, the crystallization temperature is 5-15 ℃ and the crystallization time is 8-72 h.
Compared with the prior art, the invention has the following beneficial effects:
1. in the experimental process, the applicant finds that part of shikimic acid (accounting for 30% of the total shikimic acid) in ginkgo leaves exists in the form of shikimate, and quinic acid basically exists in the form of quinic acid salt, so that shikimic acid and quinic acid cannot be well separated and purified by an organic solvent extraction method or a resin adsorption method.
2. The applicant provides a method for extracting shikimic acid and quinic acid from folium ginkgo based on economic consideration of industrial production, and further exploits comprehensive utilization of folium ginkgo resources; the extraction rate, selectivity and separation effect of each operation step on shikimic acid and quinic acid are good, the purity content of the obtained product is high, the yield is high, the content of the obtained shikimic acid and quinic acid is more than 99%, the method is suitable for industrial production, the used organic solvent can be repeatedly recovered and reused, and the resin can be repeatedly used after regeneration, so that the method has little influence on the environment; the invention has simple operation and small equipment investment;
3. the invention enriches the market output of shikimic acid and quinic acid based on the higher content of shikimic acid and quinic acid in ginkgo leaves, lays a material foundation for large-scale application of shikimic acid and quinic acid, and lays an economic foundation for popularization and application of pharmaceutical preparations synthesized based on shikimic acid and quinic acid as raw materials in the follow-up process.
Detailed Description
The technical scheme of the invention is described in detail through specific embodiments.
Example 1
A method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo comprises the following steps:
step 1: taking 1000g of ginkgo leaf, crushing, adding 4000ml of 50% ethanol, stirring and leaching at 25 ℃, separating an extracting solution and ginkgo leaf residues, extracting for 4 times, and combining filtrate to obtain 15000ml of extracting solution;
step 2: collecting extractive solution, concentrating, recovering ethanol, cooling, diluting with water to adjust the specific gravity of water to 1.02, centrifuging to remove insoluble impurities to obtain 4500ml of upper column solution;
step 3: loading the extractive solution into 1000ml macroporous adsorbent resin column B, washing with 1000ml water, and eluting with ethanol of different concentrations to obtain folium Ginkgo extract. Collecting the effluent liquid after passing through the column and the water washing liquid to obtain a combined liquid 1, wherein the volume of the combined liquid is 5500ml;
step 4: collecting the mixed solution 1, concentrating into thick paste with specific gravity of 1.18g/ml, detecting quinic acid content in the thick paste to 70.5mg/ml, adding 7.2ml98% concentrated sulfuric acid into the thick paste, and stirring. Then 3000ml of 95% acetone solution was added to the thick paste, extraction was performed 3 times at 20℃and the extracts were combined to obtain extract 2, the volume of which was 9200ml.
Step 5: collecting extract 2, concentrating, recovering solvent to complete, concentrating, removing impurities with 320ml ethyl acetate, extracting at 50deg.C for 6 times, separating the lower layer, and removing small amount of ethyl acetate to obtain water solution 3 containing shikimic acid and quinic acid, and volume of water solution 3 is 310ml.
Step 6: the aqueous solution 3 is passed through a 60ml macroporous adsorption resin column F, washed with water by 60ml, and the column passing solution and the water washing solution are collected to obtain a combined solution 4 with the volume of 370ml.
Step 7: the combined solution 4 is taken and diluted by adding 500ml of water, and the shikimic acid content is detected to be 47.9mg/ml and the quinic acid content is detected to be 44.2mg/ml. The resin is washed with 2000ml of water in series by 10 series combined resin columns (the resin is D380 type alkaline anion exchange resin, the resin column loading amount is 100 ml/column) with the diameter of 5cm and the height of 7.5 cm. And (3) eluting the three columns and the four columns in series by using 5% sulfuric acid aqueous solution of an eluent, and when the using amount of the eluent is 420ml, titrating the eluent by using a barium chloride solution to generate white precipitation, stopping eluting and collecting the quinic acid eluent. And (3) eluting seven columns and eight columns in series by using 5% sulfuric acid aqueous solution of an eluent, titrating the eluent by using a barium chloride solution to generate white precipitate when the using amount of the eluent is 490ml, stopping eluting, and collecting shikimic acid eluent. Eluting the eluent obtained by the second column, the fifth column and the sixth column by using 5% sulfuric acid aqueous solution of eluent, and recycling the eluent to the combined solution 4 for reuse to prepare shikimic acid and quinic acid.
Step 8: concentrating shikimic acid eluate to a concentration of 0.35g/ml, and cooling toCrystallizing at 5deg.C for 72 hr under stirring, and filtering to obtain shikimic acid crude product. Dissolving shikimic acid crude product with water under heating, controlling shikimic acid concentration to 0.5g/ml, cooling to 5deg.C, stirring for crystallization for 72 hr, filtering the crystal, drying the filter cake (pressure of-0.095 MPa, drying temperature of 60deg.C, drying time of 5 hr), obtaining shikimic acid 7.8g with content of 99.6%,
step 9: concentrating the quinic acid eluent to the concentration of 0.55g/ml, cooling to 5 ℃, stirring and crystallizing for 72 hours, and filtering the crystal to obtain a quinic acid crude product. Dissolving quinic acid crude product with water under heating, controlling quinic acid concentration to 0.6g/ml, cooling to 5deg.C, stirring for crystallization for 72 hr, filtering the crystal, drying the filter cake (pressure at-0.095 MPa, drying temperature at 60deg.C, drying time at 5 hr) to obtain quinic acid 5.6g with content of 99.5%,
example 2
A method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo comprises the following steps:
step 1: pulverizing folium Ginkgo 1000g, adding 70% methanol 6000ml, extracting under stirring at 70deg.C, separating extractive solution and folium Ginkgo residue, extracting for 3 times, and mixing filtrates to obtain extractive solution 17000ml;
step 2: taking the extracting solution, concentrating and recycling methanol until the extracting solution is completely cooled, adding water to dilute and adjust the specific gravity of the water solution to be 1.05, and centrifugally separating to remove insoluble impurities to obtain 3000ml of upper column liquid;
step 3: loading the extractive solution into 1000ml macroporous adsorbent resin column B, washing with 1500ml water, and eluting with ethanol of different concentrations to obtain folium Ginkgo extract. Collecting the effluent liquid after passing through the column and the water washing liquid to obtain a combined liquid 1, wherein the volume of the combined liquid is 4500ml;
step 4: collecting the mixed solution 1, concentrating into soft extract with specific gravity of 1.24g/ml, detecting quinic acid content in the soft extract to be 116.7mg/ml, adding 14.5ml98% concentrated sulfuric acid into the soft extract, and stirring. Then, 1200ml of 70% acetone solution was added to the thick paste, the mixture was extracted 6 times at 50℃to obtain extract 2, the volume of which was 7300ml.
Step 5: collecting extract 2, concentrating, recovering solvent to complete, concentrating to obtain volume of 330ml, extracting with 660ml diethyl ether for removing impurities, extracting at 20deg.C for 3 times, separating the lower layer, removing small amount of diethyl ether from the water solution to obtain water solution 3 containing shikimic acid and quinic acid, and collecting the volume of 320ml.
Step 6: the aqueous solution 3 is passed through a 60ml macroporous adsorption resin column F, washed with water 180ml, and the column passing solution and the water washing solution are collected to obtain a combined solution 4 with the volume of 500ml.
Step 7: the combined solution 4 is taken and diluted by adding 370ml of water, and the shikimic acid content is detected to be 48.6mg/ml and the quinic acid content is detected to be 43.2mg/ml. The resin is washed with 2000ml of water in series by 10 series combined resin columns (the resin is D380 type alkaline anion exchange resin, the resin column loading amount is 100 ml/column) with the diameter of 5cm and the height of 7.5 cm. And (3) eluting the three columns and the four columns in series by using a sulfuric acid aqueous solution with 3% of an eluent, titrating the eluent by using a barium chloride solution to generate white precipitate when the using amount of the eluent is 650ml, stopping eluting, and collecting the quinic acid eluent. And (3) eluting the seven columns and the eight columns in series by using a sulfuric acid water solution with 3% of an eluent, titrating the eluent by using a barium chloride solution to generate white precipitate when the using amount of the eluent is 680ml, stopping eluting, and collecting the shikimic acid eluent. Eluting the eluent obtained by the second column, the fifth column and the sixth column by using a sulfuric acid water solution with 3% of eluent, and recycling the eluent to the combined solution for 4 applications to prepare shikimic acid and quinic acid.
Step 8: concentrating the shikimic acid eluent to the concentration of 0.52g/ml, cooling to 10 ℃, stirring and crystallizing for 8 hours, and filtering the crystallized product to obtain the shikimic acid crude product. Dissolving shikimic acid crude product with water under heating, controlling shikimic acid concentration to 0.6g/ml, cooling to 10deg.C, stirring for crystallization for 8 hr, filtering to obtain crystal, drying filter cake (pressure of-0.095 MPa, drying temperature of 60deg.C, drying time of 5 hr), obtaining shikimic acid 7.2g with content of 99.3%,
step 9: concentrating the quinic acid eluent to the concentration of 0.60g/ml, cooling to 10 ℃, stirring and crystallizing for 8 hours, and filtering the crystal to obtain a quinic acid crude product. Dissolving quinic acid crude product with water under heating, controlling quinic acid concentration to 0.70g/ml, cooling to 10deg.C, stirring for crystallization for 8 hr, filtering to obtain crystal, drying filter cake (pressure at-0.095 MPa, drying temperature at 60deg.C, drying time at 5 hr) to obtain quinic acid 6.1g with content of 99.2%,
example 3
A method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo comprises the following steps:
step 1: taking 1000g of ginkgo leaf, crushing, adding 5000ml of 80% acetone, stirring and leaching at 50 ℃, separating an extracting solution and ginkgo leaf residues, extracting for 3 times, and combining filtrate to obtain 14000ml of extracting solution;
step 2: collecting extractive solution, concentrating, recovering acetone to completion, cooling, diluting with water to adjust the specific gravity of water solution to 1.03, centrifuging to remove insoluble impurities to obtain 4000ml of upper column solution;
step 3: loading the extractive solution into 1000ml macroporous adsorbent resin column B, washing with 1000ml water, and eluting with ethanol of different concentrations to obtain folium Ginkgo extract. Collecting the effluent liquid after passing through the column and the water washing liquid to obtain a combined liquid 1, wherein the volume of the combined liquid is 5000ml;
step 4: collecting the mixed solution 1, concentrating into soft extract with specific gravity of 1.22g/ml 400ml, detecting quinic acid content in the soft extract to 88.5mg/ml, adding 23.2ml36% hydrochloric acid into the soft extract, and stirring. 2000ml of 80% isopropyl alcohol solution was added to the thick paste, the mixture was extracted 4 times at 35℃to obtain extract 2, the volume of which was 8200ml.
Step 5: concentrating the extract 2, recovering solvent to complete, concentrating to a volume of 350ml, extracting with 350ml methyl acetate for removing impurities, extracting at 35deg.C for 5 times, and separating the lower layer to remove small amount of methyl acetate in the water solution to obtain water solution 3 containing shikimic acid and quinic acid with a volume of 340ml.
Step 6: the aqueous solution 3 is passed through a 60ml macroporous adsorption resin column F, washed with water by 120ml, and the column passing solution and the water washing solution are collected to obtain a combined solution 4 with the volume of 440ml.
Step 7: taking the combined liquid 4, adding 440ml of water for dilution, and detecting that the shikimic acid content is 40.9mg/ml and the quinic acid content is 36.4mg/ml. The resin was washed with 3000ml of water in series by 10 series-packed resin columns (HPD-130 type basic anion exchange resin, resin loading of 100 ml/column) having a diameter of 5cm and a height of 7.5 cm. And (3) eluting the three columns and the four columns in series by using 5% hydrochloric acid aqueous solution of an eluent, and when the using amount of the eluent is 440ml, titrating the eluent by using a silver nitrate solution to generate white precipitation, stopping eluting and collecting the quinic acid eluent. And (3) eluting seven columns and eight columns in series by using 5% hydrochloric acid aqueous solution of an eluent, titrating the eluent by using a barium chloride solution to generate white precipitate when the using amount of the eluent is 480ml, stopping eluting, and collecting shikimic acid eluent. Eluting the eluent obtained by the second column, the fifth column and the sixth column by using 5% hydrochloric acid aqueous solution of eluent, and recycling the eluent to the combined solution 4 for reuse to prepare shikimic acid and quinic acid.
Step 8: concentrating the shikimic acid eluent to the concentration of 0.45g/ml, cooling to 15 ℃, stirring and crystallizing for 36 hours, and filtering the crystallized product to obtain the shikimic acid crude product. Dissolving shikimic acid crude product with water under heating, controlling shikimic acid concentration to 0.55g/ml, cooling to 15deg.C, stirring for crystallization for 36 hr, filtering the crystal, drying the filter cake (pressure at-0.095 MPa, drying temperature at 60deg.C, drying time at 5 hr) to obtain shikimic acid 7.5g with content of 99.5%,
step 9: concentrating the quinic acid eluent to the concentration of 0.58g/ml, cooling to 15 ℃, stirring and crystallizing for 36 hours, and filtering the crystals to obtain a quinic acid crude product. Dissolving quinic acid crude product with water under heating, controlling quinic acid concentration to 0.65g/ml, cooling to 10deg.C, stirring for crystallization for 36 hr, filtering the crystal, drying the filter cake (pressure at-0.095 MPa, drying temperature at 60deg.C, drying time at 5 hr) to obtain quinic acid 5.8g with content of 99.4%,
the foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (9)
1. A method for simultaneously extracting shikimic acid and quinic acid from ginkgo leaf, which is characterized by comprising the following steps:
s1, taking ginkgo leaves, crushing, adding a solvent A for leaching, and filtering to obtain an extracting solution;
s2, concentrating the extracting solution, diluting with water to adjust the specific gravity, and centrifugally separating to obtain upper column liquid;
s3, passing the upper column liquid through a resin column B, eluting with water and ethanol water solution respectively, collecting column passing effluent and water eluting liquid, and combining to obtain a combined liquid 1;
s4, concentrating the combined liquid 1 into thick paste, adding acid liquor C into the thick paste, and then adding a solvent D for extraction to obtain an extract 2;
s5, concentrating the extract 2, and then adding a solvent E for extraction to obtain an aqueous solution 3 containing shikimic acid and quinic acid;
s6, passing the aqueous solution 3 through a resin column F, washing with water, collecting column-passing effluent and water eluent, and combining to obtain a combined solution 4;
s7, passing the combined liquid 4 through a combined serial resin column G, washing in serial with water, eluting the unit serial columns of the serial resin column G by using an eluent H respectively, and collecting the unit serial columns respectively to obtain shikimic acid eluent, quinic acid eluent and eluent containing shikimic acid and quinic acid, and recycling the eluent containing shikimic acid and quinic acid to the combined liquid 4;
s8, concentrating shikimic acid eluent to a certain concentration, cooling and crystallizing to obtain a shikimic acid crude product, and recrystallizing to obtain shikimic acid;
s9, concentrating the quinic acid eluent to a certain concentration, cooling and crystallizing to obtain a quinic acid crude product, and recrystallizing to obtain quinic acid;
the solvent A is a mixed solution of an organic solvent and water, wherein the organic solvent is at least one of acetone, ethanol and methanol; the resin column B is a macroporous adsorption resin column; the acid liquor C is at least one of sulfuric acid and hydrochloric acid; the solvent D is a mixed solution of an organic solvent and water, wherein the organic solvent is at least one of acetone and isopropanol; the solvent E is at least one of diethyl ether, ethyl acetate and methyl acetate; the resin column F is a macroporous adsorption resin column; the resin column G is an alkaline anion exchange resin column; the eluent H is 3-5% sulfuric acid or hydrochloric acid aqueous solution.
2. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein in S4, the acid C is added in the thick paste according to H + Calculated as 1.5 to 3 times of molar equivalent of quinic acid radical ions.
3. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1 or 2, wherein the resin G is one of D380 and HPD-130 basic anion resins.
4. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein the combined serial resin column G is composed of 10 identical resin columns with a resin diameter-to-height ratio of 1:1.5 to 3.5 percent, and the column loading amount of the resin is 60 to 70 percent of the column volume.
5. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein the volume fraction of organic solvent in solvent A is 50-80%; the volume fraction of the organic solvent in the solvent D is 70-95%.
6. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein in S2, water is added to dilute and adjust the specific gravity to 1.02-1.05 g/ml; s4, the specific gravity of the thick paste is 1.18-1.24 g/ml.
7. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to any one of claims 1-6, wherein in S3, the upper column amount of the upper column liquid is 3-5 BV, and the water amount of water washing is 1-1.5 BV; s6, the column loading amount of the aqueous solution 3 is 4-6 BV, and the water washing amount is 1-3 BV; in S7, the column loading amount of the combined liquid 4 is calculated according to 30-50 g shikimic acid/L ion exchange resin, and the water consumption of water washing is 2-3 BV.
8. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein in S1, the leaching temperature is 25-70deg.C, the extraction times are 3-4 times, and the weight-volume ratio g/mL of folium Ginkgo and solvent A is 1: 4-6 times; in S4, the extraction temperature is 20-50 ℃, the extraction is carried out for 3-6 times, and the volume ratio of the thick paste to the solvent D during each extraction is 1:3 to 6; in S5, the extraction temperature is 20-50 ℃, the extraction is carried out for 3-6 times, and the volume ratio of feed liquid to solvent E is 1 during each extraction: 1 to 2.
9. The method for simultaneously extracting shikimic acid and quinic acid from folium Ginkgo according to claim 1, wherein in S8, the shikimic acid eluent is concentrated to a concentration of more than 0.35g/ml, and the recrystallization concentration of shikimic acid is 0.5-0.6 g/ml; concentrating quinic acid stripping liquid to a concentration of more than 0.55g/ml, wherein the recrystallization concentration of quinic acid is 0.6-0.7 g/ml; in S8 and S9, the crystallization temperature is 5-15 ℃ and the crystallization time is 8-72 h.
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| CN111233658A (en) * | 2020-02-27 | 2020-06-05 | 陕西嘉禾生物科技股份有限公司 | Method for extracting shikimic acid and quinic acid from folium ginkgo |
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