CN113801134B - Production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid - Google Patents

Production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid Download PDF

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CN113801134B
CN113801134B CN202111261244.1A CN202111261244A CN113801134B CN 113801134 B CN113801134 B CN 113801134B CN 202111261244 A CN202111261244 A CN 202111261244A CN 113801134 B CN113801134 B CN 113801134B
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ceramic membrane
membrane
acid
ginkgo
liquid
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CN113801134A (en
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陈磊
刘怀红
褚斌
张南南
李国学
方威
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Nanjing Jay Environmental Protection Technology Co ltd
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    • C07—ORGANIC CHEMISTRY
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    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
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    • 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
    • C07C51/47—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
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
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    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
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    • 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

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Abstract

The invention discloses a production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid, which comprises the following steps: (1) Filtering the ginkgo extract by a ceramic membrane activated by organic acid to obtain ceramic membrane filtrate, and extracting to obtain an organic phase and a water phase; the organic phase is a liquid containing bilobalide; (2) adsorbing the obtained water phase by resin to obtain effluent liquid; desorbing to obtain desorption liquid; the desorption liquid is a liquid containing ginkgo flavone; (3) Filtering and concentrating the effluent liquid by an ultrafiltration membrane to obtain trapped fluid and permeate; the trapped liquid is liquid containing ginkgo polysaccharide, and the permeate liquid is liquid containing shikimic acid. The ceramic membrane adopted by the invention can not only resist high temperature, high pressure and chemical corrosion and has long service life, but also effectively filter and remove suspended matters, colloid and macromolecular vegetable protein by adopting the ceramic membrane after activation treatment, thereby improving the product quality, reducing the turbidity and improving the yield.

Description

Production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid
Technical Field
The invention belongs to the field of natural medicine extraction, and in particular relates to a production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid.
Background
Folium Ginkgo is dry leaf of Ginkgo Ginkgo biloba L. Collected in autumn She Shanglu, and dried in time. Generally, the cultivation is performed manually, and the cultivation areas are from north to Liaoning, from south to Guangdong, from east to Zhejiang, from west to Shanxi, from Gansu to southwest to Sichuan, from Guizhou, from Yunnan, and the like. Has effects of promoting blood circulation, removing blood stasis, dredging collaterals, relieving pain, astringing lung, relieving asthma, eliminating turbid pathogen, and reducing blood lipid. Can be used for treating obstruction of collaterals by blood stasis, chest stuffiness and pain, apoplexy, hemiplegia, cough and asthma due to lung deficiency, and hyperlipidemia. The ginkgo leaf extract (Ginko Biloba Extract, GBE) is a product which takes ginkgo leaves as raw materials and adopts proper solvents to enrich the effective components of the extract. Various preparations prepared from GBE are widely applied to the fields of medicines, health products, food additives, functional beverages, cosmetics and the like. The product is one of the most successful cases of herbal medicines (belongs to traditional Chinese medicines) developed by modern science and technology. The ginkgo extract mainly contains bilobalide, ginkgetin, ginkgo polysaccharide, ginkgolic acid, shikimic acid, fat-soluble impurities, vegetable proteins, colloid and other impurities, and has the advantages of complex components, high extraction difficulty and high cost.
Shikimic acid (shown in formula 1) is a monomer compound extracted from Chinese medicinal fructus Anisi Stellati, has antiinflammatory and analgesic effects, can be used as intermediate of antiviral and anticancer drugs, and is an important component of drug "Dafei" for effectively treating deadly H5N1 type avian influenza virus. In addition, early-stage research of pharmacological research laboratory of Beijing traditional Chinese medicine university shows that shikimic acid has obvious antithrombotic effect for the first time, and can inhibit the formation of brake, venous thrombosis and cerebral thrombosis. To elucidate the antithrombotic mechanism, researchers studied the effect of shikimic acid on platelet aggregation and clotting and analyzed the relationship of its mechanism of action with arachidonic acid metabolism. As a result, shikimic acid is considered to exert an antithrombotic effect by affecting arachidonic acid metabolism, inhibiting platelet aggregation, and inhibiting the coagulation system. At present, shikimic acid is also found in ginkgo leaves, and the content is high, so that the ginkgo leaves are suitable for being used as raw materials for extracting shikimic acid.
The ginkgo polysaccharide is a polysaccharide substance extracted from ginkgo fruits, and is also called ginkgo pectin. The ginkgo polysaccharide is light yellow powder. Researches show that the gingko polysaccharide has the health-care functions of improving immunity, reducing blood fat and blood sugar, expanding microcirculation, softening vessel walls, eliminating heavy metal-lead in digestive tracts, resisting tumors and the like. The Chinese medicinal composition has the following three effects: 1. immunomodulatory effects: the ginkgo polysaccharide can promote the activity of IL2 of spleen lymphocytes of tumor-bearing mice and CTX-damaged mice, and reduce the formation of serum sIL-2R of the mice, which indicates that the ginkgo polysaccharide can promote the immune function of tumor-bearing mice and CTX-damaged mice. 2. Antitumor effect: the ginkgo polysaccharide can promote the total number of T lymphocytes of mice in different states in vitro, and can promote the DCH reaction of the immunosuppressed mice caused by Cy, so that the polysaccharide can promote the cell immune function mediated by the T lymphocytes, and has important significance for cancer prevention and resistance; the ginkgo leaf polysaccharide can inhibit the growth of S-180 solid tumor and ascites tumor, and prolong the survival time of tumor-bearing mice; the ginkgo polysaccharide also has good inhibition effect on proliferation of human melanoma cells and HL-60 cells, and the inhibition effect has concentration-time dependence. 3. The anti-aging effect research shows that the ginkgo polysaccharide can obviously improve the serum SOD activity of tumor-bearing mice and reduce the MDA content of the tumor-bearing mice, but has no obvious influence on normal mice, and the ginkgo polysaccharide can promote the free radical scavenging capability of organisms under pathological states and delay the aging of the tumor-bearing mice.
Although the main components of ginkgo leaf, bilobalide, ginkgo flavone, ginkgo polysaccharide and shikimic acid can be used as medicines, the ginkgo acid has no definite use in medical clinic, and after being taken into the organism, the ginkgo acid is easy to produce side reaction of excessive expansion of capillary networks. Can easily cause facial flush, sweat, and symptoms of lipsticks and vascular irritation. Therefore, in extracting ginkgo polysaccharide, it is necessary to simultaneously remove ginkgolic acid. At present, the method for removing ginkgolic acid in China mainly comprises the steps of adding petroleum ether for extraction, and separating the ginkgolic acid by utilizing the characteristic of low solubility of the ginkgolic acid in the petroleum ether; or removing ginkgolic acid by deacidification resin. The ginkgolic acid is removed by petroleum ether extraction or deacidification resin, so that the production process flow is increased, the production cost is high, and the introduced impurities are introduced; meanwhile, the waste water is large, the pollution is serious, and the environmental protection problem is serious.
The main stream extraction and purification methods of other ginkgo extracts such as ginkgolide, ginkgetin and the like at present comprise the following steps: solvent extraction, column extraction, solvent extraction-column extraction, supercritical extraction, chromatography or column chromatography purification, etc. The following defects are mainly overcome: (1) The dosage of the organic solvent is large, the raw material cost is high, the organic solvent is unsafe, all electrical equipment in an extraction workshop must adopt explosion-proof grades, and the cost is greatly increased; (2) The ginkgolic acid is removed by petroleum ether extraction or deacidification resin, so that the production process flow is increased, the production cost is high, and the introduced impurities are introduced; (3) The steps are more, the route is long, the purity of the product is low, and the yield is low; (4) serious pollution and serious environmental protection problem. (5) is not suitable for large-scale production, and the unit yield cost is high.
In the existing ginkgo leaf, the shikimic acid is mainly extracted by a carbon dioxide supercritical extraction process, which adopts ultrahigh pressure, and in the supercritical state, the carbon dioxide supercritical fluid is contacted with substances to be separated, so that the substances with polarity, boiling point and molecular weight are selectively extracted in sequence. Then the supercritical fluid is changed into common gas by means of decompression and heating, and the extracted matter is completely or basically separated out, so as to achieve the aim of separation and purification. The method has the following defects: (1) the carbon dioxide supercritical extraction device has high cost; (2) high energy consumption and high production cost; (3) The process has congenital defects, and large-scale production cannot be performed.
Therefore, it is necessary to provide a production process which is simple and reliable in process, high in yield, low in production cost, and capable of producing ginkgolides, ginkgetin, ginkgolic polysaccharide and shikimic acid at the same time of mass production.
Disclosure of Invention
The invention aims to: the invention aims to solve the technical problem of providing a production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid aiming at the defects of the prior art.
The invention also solves the technical problem of providing a production process for producing ginkgo flavone.
In order to solve the first technical problem, the invention discloses a production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid, which comprises the following steps:
(1) Filtering the ginkgo extract by a ceramic membrane activated by organic acid to obtain ceramic membrane filtrate, and extracting to obtain an organic phase and a water phase; the organic phase is a liquid containing bilobalide;
(2) Adsorbing the water phase obtained in the step (1) by resin to obtain an effluent; desorbing to obtain desorption liquid; the desorption liquid is a liquid containing ginkgo flavone;
(3) Filtering and concentrating the effluent liquid obtained in the step (2) through an ultrafiltration membrane to obtain trapped fluid and permeate; the trapped liquid is liquid containing ginkgo polysaccharide, and the permeate liquid is liquid containing shikimic acid.
In the step (1), the mass content of ginkgolide in the ginkgo extract is 0.01-5%, the mass content of ginkgo flavone is 0.01-5%, the mass content of ginkgo polysaccharide is 0.01-5%, the mass content of shikimic acid is 0.01-4%, and impurities mainly comprise suspended matters, vegetable oil, vegetable proteins, vegetable fibers, vegetable pigments, tannins, microorganisms and the like.
In the step (1), the preparation method of the ginkgo biloba extract comprises the steps of concentrating and solid-liquid separating the crude ginkgo biloba extract. Wherein the crude extract of ginkgo leaf is obtained by crushing ginkgo, and extracting with ethanol; wherein the ethanol extraction is performed by 60% ethanol solution; wherein the extraction times are 6 times; wherein the extraction temperature is 50-80 ℃. Wherein the concentration is evaporative concentration, and ethanol can be recovered in the process; preferably, the concentration by evaporation is about 6 times. Wherein the solid-liquid separation is centrifugation; preferably, the solid-liquid separation is centrifugation by a disc centrifuge; further preferably, the rotational speed of the centrifugation is 6000 to 8000 revolutions per minute.
In the step (1), the ceramic membrane after the activation of the organic acid is obtained by processing according to the following method: the ceramic membrane is soaked in deionized water for 6 to 12 hours, dried and then activated by organic acid; preferably, the drying is at 80-120 ℃ for 10-12 hours.
In the step (1), the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and carrying out an activation reaction on the ceramic membrane by a vacuum vapor deposition method; preferably, the ceramic membrane is placed in an activator and the vacuum apparatus is turned on while the organic acid solution is heated to boiling, and the ceramic membrane is activated by the vacuum gas phase method using the organic acid.
Wherein the general formula of the organic acid is C n H 2n-2 O 4 The structural formula is HOOC- (CH) 2 ) n -COOH; wherein n is selected from any integer from 2 to 6; preferably, the organic acid is any one or a combination of several of succinic acid, malonic acid, glutaric acid and oxalic acid.
Wherein the solvent of the organic acid solution is an alcohol compound; preferably, the alcohol compound is methanol and/or ethanol.
Wherein the concentration of the organic acid solution is 0.05-1mol/L; preferably, the concentration of the organic acid solution is 0.05-0.4 mol/L; further preferably, the concentration of the organic acid solution is 0.05 to 0.2mol/L.
Wherein the vacuum degree of the vacuum vapor deposition method is 10-90 kPa.
Wherein the time for activating the organic acid is 1-6 hours.
Preferably, the mixture is washed and dried after the activation reaction is finished; further preferably, the cleaning is three times of deionized water cleaning; further preferably, the drying is performed at 80-120 ℃ for 4-12 hours.
In the step (1), the ceramic membrane is a single-channel ceramic ultrafiltration membrane or a multi-channel ceramic ultrafiltration membrane, preferably a multi-channel ceramic ultrafiltration membrane.
Wherein the ceramic membrane comprises a support body and a separation layer.
Wherein the average pore diameter of the support is 2-5 mu m; preferably, the porosity of the support is 30% -45%; further preferably, the material of the support is alumina.
Wherein the average pore diameter of the separation layer (i.e. the membrane layer) is 5-50 nm; preferably, the separation layer is formed by sintering titanium oxide of 10-500 nm at 680-800 ℃.
In the step (1), the temperature of the filtration is 10 to 90 ℃, preferably 10 to 80 ℃, and more preferably 30 to 50 ℃.
In the step (1), the pressure of the filtration is 0.1 to 0.8MPa, preferably 0.25 to 0.4MPa.
In the step (1), the flow rate of the filtered membrane surface is 1-6 m/s.
In the step (1), the extraction is to extract the ceramic membrane filtrate by ethyl acetate to obtain a water phase; preferably, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1.
In the step (1), the obtained organic phase is evaporated or not evaporated, and is adsorbed and desorbed by polyamide resin, the obtained desorption liquid is concentrated by a nanofiltration membrane, and the obtained trapped liquid is evaporated and concentrated to obtain the ginkgolide.
Wherein the mesh number of the polyamide resin is 20 to 80 mesh, preferably 40 to 50 mesh. Wherein the polyamide is a polymer compound formed by polymerization of an amide bond. The amide group can be adsorbed by forming hydrogen bond with compounds such as hydroxyl phenols, acids, quinones, nitro groups, etc., and the long chain fatty chain can be used as a carrier for partition chromatography. Polyamides are particularly suitable for the isolation of polyphenols such as flavonoids, quinones, phenolics, carboxyl-containing compounds and the like. .
Wherein the flow rate of the polyamide resin adsorption is 1-6 BV/h, preferably 2-4 BV/h.
Wherein the desorption is ethanol solution desorption, and desorption liquid is obtained. Wherein the concentration of the ethanol solution is 50% -75%; the flow rate of desorption is 1-4 BV/h; the dosage of the ethanol solution is 2-3 BV. The bilobalide is desorbed from the polyamide resin by ethanol desorption, so that the bilobalide with high purity and high concentration can be obtained.
Wherein, the permeate obtained by the nanofiltration membrane concentration is used for recovering ethanol.
Wherein the nanofiltration membrane is a roll nanofiltration membrane, the molecular weight cut-off is 100-800 Da, and preferably 150-300 Da.
Wherein the temperature of the nanofiltration concentration is 10-60 ℃, preferably 10-50 ℃.
Wherein the pressure of the nanofiltration concentration is 0.5-4.0 MPa, preferably 1.0-3.0 MPa.
In the step (2), the resin is macroporous adsorption resin; the macroporous adsorption resin is styrene type or acrylic acid macroporous adsorption resin, the average pore diameter is 1-200 mu m, and the specific surface area is 100-2000 m 2 And/g. The macroporous adsorption resin and adsorbed molecules are subjected to physical adsorption through the huge specific surface to work, so that organic compounds can be eluted and separated through a certain solvent according to adsorption force and molecular weight thereof to achieve different purposes of separation, purification, impurity removal, concentration and the like.
Wherein the flow rate of the adsorption is 1-6 BV/h, preferably 2-4 BV/h, and more preferably 2BV/h.
Wherein the desorption is desorption with an alcohol compound, preferably ethanol.
Wherein the flow rate of desorption is 1-4 BV/h, preferably 2-3 BV/h, and more preferably 2BV/h.
In the step (2), the obtained desorption liquid is concentrated by a nanofiltration membrane, and the obtained trapped liquid is evaporated to obtain ginkgetin; preferably, the obtained desorption liquid is concentrated by a nanofiltration membrane, and the obtained permeate liquid is an alcohol compound and is recovered for desorption; evaporating the obtained trapped fluid to recover alcohol compound for desorption, and evaporating to obtain ginkgetin.
Wherein the molecular weight cut-off of the nanofiltration membrane is 100-1000 Da, preferably 100-800 Da, more preferably 100-500 Da, even more preferably 150-300 Da.
In the step (3), the ultrafiltration membrane is a roll ultrafiltration membrane, the molecular weight cut-off is 1000-20000 Da, preferably 100-15000 Da, and more preferably 1000-3000 Da.
In the step (3), the temperature of the ultrafiltration membrane filtration concentration is 10-60 ℃ and the pressure is 0.8-4 MPa.
In the step (3), the filtering temperature of the ultrafiltration membrane is 10-60 ℃, preferably 10-45 ℃.
In the step (3), the pressure of the ultrafiltration membrane filtration is 0.5-1.5 MPa, preferably 0.8-1.2 MPa.
In the step (3), the obtained permeate is adsorbed and desorbed by anion exchange resin, and the obtained desorption liquid is filtered and concentrated by a nanofiltration membrane to obtain shikimic acid.
Wherein the anion exchange resin is polyacrylic acid weak base anion exchange resin, the average pore diameter is 1-200 mu m, and the specific surface area is 100-2000 m 2 And/g. Wherein the anion exchange resin is mainly weak alkaline by carrying weak alkaline groups such as primary amino-NH 2, secondary amino-NHR or tertiary amino-NR 2, which can understand OH-in water, and positive groups can be combined with anion adsorption in solution, thereby generating anion exchange effect, and adsorbing all other acid molecules in solution, such as shikimic acid.
Wherein the flow rate of the adsorption is 1-6 BV/h, preferably 2-4 BV/h.
Wherein the desorption is performed by using an acid compound, preferably acetic acid; the concentration of the acetic acid is 10% -50%, preferably 30%.
Wherein the flow rate of desorption is 1-4 BV/h; the dosage of the desorption solution is 2-3 BV.
Wherein the obtained desorption liquid is filtered and concentrated by a nanofiltration membrane, the obtained permeate liquid is recovered, and the obtained trapped liquid is shikimic acid.
Wherein the nanofiltration membrane is a roll nanofiltration membrane, the molecular weight cut-off is 100-1000 Da, preferably 100-800 Da, more preferably 100-500 Da, even more preferably 150-300 Da.
Wherein the temperature of the nanofiltration concentration is 10-60 ℃, preferably 10-50 ℃.
Wherein the pressure of the nanofiltration concentration is 0.5-4.0 MPa, preferably 1.0-3.0 MPa.
In order to solve the second technical problem, the invention discloses a production process for producing ginkgo flavone, which comprises the following steps:
(i) Filtering the ginkgo extract by a ceramic membrane activated by organic acid to obtain ceramic membrane filtrate, and extracting to obtain a water phase;
(ii) Adsorbing and desorbing the water phase obtained in the step (i) through resin, wherein the obtained desorption liquid is a ginkgo flavone-containing liquid.
In the step (1), the mass content of ginkgolide in the ginkgo extract is 0.01-5%, the mass content of ginkgo flavone is 0.01-5%, the mass content of ginkgo polysaccharide is 0.01-5%, the mass content of shikimic acid is 0.01-4%, and impurities mainly comprise suspended matters, vegetable oil, vegetable proteins, vegetable fibers, vegetable pigments, tannins, microorganisms and the like.
In the step (i), the preparation method of the ginkgo biloba extract comprises the steps of concentrating and solid-liquid separating the crude ginkgo biloba extract. Wherein the crude extract of ginkgo leaf is obtained by crushing ginkgo, and extracting with ethanol; wherein the ethanol extraction is performed by 60% ethanol solution; wherein the extraction times are 6 times; wherein the extraction temperature is 50-80 ℃. Wherein the concentration is evaporative concentration, and ethanol can be recovered in the process; preferably, the concentration by evaporation is about 6 times. Wherein the solid-liquid separation is centrifugation; preferably, the solid-liquid separation is centrifugation by a disc centrifuge; further preferably, the rotational speed of the centrifugation is 6000 to 8000 revolutions per minute.
In the step (i), the ceramic membrane after the activation of the organic acid is obtained by the following method: firstly, soaking a ceramic membrane in deionized water for 6-12 hours, and then activating the ceramic membrane by organic acid after drying; preferably, the drying is at 80-120 ℃ for 10-12 hours.
In the step (i), the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and carrying out an activation reaction on the ceramic membrane by a vacuum vapor deposition method; preferably, the ceramic membrane is placed in an activator and the vacuum apparatus is turned on while the organic acid solution is heated to boiling, and the ceramic membrane is activated by the vacuum gas phase method using the organic acid.
Wherein the general formula of the organic acid is C n H 2n-2 O 4 The structural formula is HOOC- (CH) 2 ) n -COOH; wherein n is selected from any integer from 2 to 6; preferably, the organic acid is any one or a combination of several of succinic acid, malonic acid, glutaric acid and oxalic acid.
Wherein the solvent of the organic acid solution is an alcohol compound; preferably, the alcohol compound is methanol and/or ethanol.
Wherein the concentration of the organic acid solution is 0.05-1mol/L; preferably, the concentration of the organic acid solution is 0.05-0.4 mol/L; further preferably, the concentration of the organic acid solution is 0.05 to 0.2mol/L.
Wherein the vacuum degree of the vacuum vapor deposition method is 10-90 kPa.
Wherein the time for activating the organic acid is 1-6 hours.
Preferably, the mixture is washed and dried after the activation reaction is finished; further preferably, the cleaning is three times of deionized water cleaning; further preferably, the drying is performed at 80-120 ℃ for 4-12 hours.
In the step (i), the ceramic membrane is a single-channel ceramic ultrafiltration membrane or a multi-channel ceramic ultrafiltration membrane, preferably a multi-channel ceramic ultrafiltration membrane.
Wherein the ceramic membrane comprises a support body and a separation layer.
Wherein the average pore diameter of the support is 2-5 mu m; preferably, the porosity of the support is 30% -45%; further preferably, the material of the support is alumina.
Wherein the average pore diameter of the separation layer (i.e. the membrane layer) is 5-50 nm; preferably, the separation layer is formed by sintering titanium oxide of 10-500 nm at 680-800 ℃.
In the step (i), the temperature of the filtration is 10 to 90 ℃, preferably 10 to 80 ℃, and more preferably 30 to 50 ℃.
In step (i), the filtration pressure is 0.1 to 0.8MPa, preferably 0.25 to 0.4MPa.
In the step (i), the flow rate of the filtered membrane surface is 1-6 m/s.
In the step (i), the extraction is to extract the ceramic membrane filtrate by ethyl acetate to obtain a water phase; preferably, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1.
In step (ii), the resin is a macroporous adsorbent resin; the macroporous adsorption resin is styrene type or acrylic acid macroporous adsorption resin, the average pore diameter is 1-200 mu m, and the specific surface area is 100-2000 m 2 And/g. The macroporous adsorption resin and adsorbed molecules are subjected to physical adsorption through the huge specific surface to work, so that organic compounds can be eluted and separated through a certain solvent according to adsorption force and molecular weight thereof to achieve different purposes of separation, purification, impurity removal, concentration and the like.
Wherein the flow rate of the adsorption is 1-6 BV/h, preferably 2-4 BV/h.
Wherein the desorption is desorption with an alcohol compound, preferably ethanol.
Wherein the flow rate of desorption is 1-4 BV/h, preferably 2-3 BV/h.
In the step (ii), the obtained desorption liquid is concentrated by a nanofiltration membrane, and the obtained trapped liquid is evaporated to obtain ginkgetin; preferably, the obtained desorption liquid is concentrated by a nanofiltration membrane, and the obtained permeate liquid is an alcohol compound and is recovered for desorption; evaporating the obtained trapped fluid to recover alcohol compound for desorption to obtain ginkgetin.
Wherein the molecular weight cut-off of the nanofiltration membrane is 100-1000 Da, preferably 100-800 Da, more preferably 100-500 Da, even more preferably 150-300 Da.
In the present invention, the ethanol solution and the acetic acid solution refer to mass ratios unless otherwise specified.
The beneficial effects are that: compared with the prior art, the invention has the following advantages:
1. the ceramic membrane adopted by the invention can not only resist high temperature, high pressure and chemical corrosion and has long service life, but also effectively filter and remove suspended matters, colloid and macromolecular vegetable protein by adopting the ceramic membrane after activation treatment, thereby improving the product quality, reducing the turbidity and improving the yield.
2. The invention adopts the ceramic membrane filtration ginkgo extraction centrifugate after the activation treatment, can remove more than 99.9 percent of ginkgolic acid in one step, reduces the procedures of petroleum ether extraction added in the traditional process, and reduces the production cost. In addition, 99.8% of vegetable oily impurities can be removed, the quality of filtrate is high, the feeding load of polyamide resin in the subsequent working section is reduced, and the consumption of ethyl acetate is reduced.
3. The extraction process adopts nanofiltration membrane to pre-concentrate the polyamide resin desorption liquid, so that the ethanol evaporation capacity can be reduced by more than 80 percent. The membrane concentration can concentrate ginkgolide at low temperature, reduce the loss of ginkgolide due to degradation during high temperature evaporation, improve the yield of ginkgolide, reduce the production energy consumption, and reduce the production cost.
4. The macroporous adsorption resin distillate is filtered and concentrated, so that the ginkgo polysaccharide and shikimic acid can be effectively separated, and the purity of the ginkgo polysaccharide is higher; and meanwhile, the ginkgo polysaccharide is concentrated, so that the evaporation capacity can be reduced, and the energy consumption can be reduced.
5. The extraction process of the invention adopts nanofiltration membrane to concentrate weak base anion exchange resin vinegar acidolysis liquid absorption, which can reduce the acetic acid evaporation capacity by more than 90 percent. The membrane concentration can concentrate shikimic acid at low temperature, so that the loss of shikimic acid caused by degradation during high-temperature evaporation is reduced, the yield of shikimic acid is improved, and meanwhile, the nanofiltration membrane filtrate is acetic acid, and can be directly recycled for resin desorption of the next batch, so that the production energy consumption and the production cost are reduced;
6. the extraction process adopts membrane separation equipment and ion exchange resin equipment, reduces the occupied area of the equipment and reduces the capital cost. The process performs a great amount of optimization work on the parameters of new equipment and the traditional process, obtains the optimal production process parameters, ensures the efficient and energy-saving operation of production, and simultaneously has higher quality of products. Compared with the traditional production process, the production process has the advantages of saving energy, high automation degree, saving labor cost by 60 percent and remarkable economic benefit.
Drawings
The foregoing and/or other advantages of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings and detailed description.
FIG. 1 is a schematic diagram of a process flow for simultaneously producing bilobalide, ginkgetin, ginkgo polysaccharide and shikimic acid.
FIG. 2 is a diagram of the ceramic membrane filtrate obtained in example 3; wherein A is ceramic membrane filtrate after 2 hours of filtration; and B is the ceramic membrane filtrate just after filtration.
FIG. 3 is a graph of the ceramic membrane filtrate obtained in comparative example 1; wherein A is the ceramic membrane filtrate just after filtration; and B is ceramic membrane filtrate after 2 hours of filtration.
FIG. 4 is a graph of the ceramic membrane filtrate obtained in example 7; wherein A is the ceramic membrane filtrate just after filtration; and B is ceramic membrane filtrate after 2 hours of filtration.
FIG. 5 is a graph of the ceramic membrane filtrate obtained in comparative example 2; wherein A is the ceramic membrane filtrate just after filtration; and B is ceramic membrane filtrate after 2 hours of filtration.
Detailed Description
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, are commercially available.
The content of ginkgo polysaccharide, the content of shikimic acid and the content of impurities in the following examples are all mass contents unless specified.
The macroporous resin in the following examples is Eimeria brand D751, the macroporous adsorbent resin is styrene, the average pore diameter of the resin is 40 μm, and the specific surface area is 120m 2 /g。
The weakly basic anion exchange resin described in the following examples is Eimer brand LK17, a polyacrylic acid weak base anion exchange resin having an average pore size of 50 μm and a specific surface area of 100m 2 /g。
In the examples which follow, the polyamide resins used have the formula [ NH- (CH) 2 ) 5 -CO] n From epsilon-hexoseAmide.
In the following examples, the support is made of alumina unless otherwise specified.
In the following examples, unless otherwise specified, "turbidity after filtration by ceramic membrane" means turbidity after filtration for 2 hours.
In the following examples, the content of bilobalide and impurities is mass percent.
Example 1: extraction of ginkgo polysaccharide and shikimic acid according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering and clarifying the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain ceramic membrane filtrate, wherein the content of ginkgo biloba polysaccharide is 0.47%, the content of shikimic acid is 0.82%, and the content of impurities is 0.56%;
wherein, before the ceramic ultrafiltration membrane is activated and modified, the pore diameter of the support is 3 mu m, and the porosity is 30%; the pore diameter of the separation layer is 50nm; the separating layer is formed by firing titanium oxide with the grain diameter of 100nm at the high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with malonic acid as an activating agent;
wherein the temperature of the filtration is 80 ℃, the pressure is 0.6MPa, and the membrane surface flow rate is 5m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1;
(6) Adsorbing the water phase obtained in the step (5) by macroporous resin (the flow rate is 6BV/h, and the adsorption multiple is 3 times), and collecting effluent liquid;
(7) Filtering the effluent liquid obtained in the step (6) by a roll-type ultrafiltration membrane (with a molecular weight cut-off of 1000 Da) at 60 ℃ and under 1.0MPa to obtain a cut-off liquid which is ginkgo polysaccharide, and collecting an ultrafiltration membrane filtrate;
(8) Adsorbing the ultrafiltration membrane permeate in the step (7) by weak-base anion exchange resin, wherein the adsorption flow rate is 2BV/h; the adsorption multiple is 6 times; the desorption is carried out by adopting acetic acid solution with the concentration of 30 percent, the flow rate of the desorption is 2BV/h, and the consumption of the acetic acid solution is 2BV.
(9) Concentrating the desorption solution obtained in the step (8) at 60 ℃ and 0.8MPa by using a nanofiltration membrane which is a coiled nanofiltration membrane (the molecular weight cut-off is 800 Da); evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain shikimic acid.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L malonic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The pore diameter of the ceramic membrane is large, the temperature and the pressure are high, the flux of the ceramic membrane is high, but the content of ginkgolic acid in filtrate is high, the ceramic membrane filtrate is subjected to post-turbidity, and the turbidity is 12NTU; the ultrafiltration membrane has smaller molecular weight, smaller flux and smaller loss of ginkgo polysaccharide, but higher impurity content; the nanofiltration membrane has higher molecular weight cut-off, lower pressure and lower flux, and simultaneously the loss of shikimic acid is larger.
The yield of the finally obtained ginkgo polysaccharide is 95.6 percent, and the purity is 93.5 percent; the yield of shikimic acid is 81.2%, the purity is 99.5%, the removal rate of ginkgolic acid is 96.5%, the quality of ceramic membrane filtrate is good, and the turbidity is 2.3NTU.
Example 2: extraction of ginkgo polysaccharide and shikimic acid according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering and clarifying the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain ceramic membrane filtrate, wherein the content of ginkgo biloba polysaccharide is 0.48%, the content of shikimic acid is 0.85%, and the content of impurities is 0.53%;
wherein, before the ceramic ultrafiltration membrane is activated and modified, the pore diameter of the support is 3 mu m, and the porosity is 30%; the aperture of the separation layer is 20nm; the separating layer is formed by firing titanium oxide with the particle size of 30nm at the high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with succinic acid as an activating agent;
Wherein the temperature of the filtration is 20 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4.5m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1;
(6) Adsorbing the water phase obtained in the step (5) by macroporous resin (the flow rate is 2BV/h, and the adsorption multiple is 3 times), and collecting effluent liquid;
(7) Filtering the effluent liquid obtained in the step (6) by a roll-type ultrafiltration membrane (with a molecular weight cut-off of 5000 Da) at 20 ℃ and 0.8MPa to obtain a cut-off liquid which is ginkgo polysaccharide, and collecting an ultrafiltration membrane filtrate;
(8) Adsorbing the ultrafiltration membrane permeate in the step (7) by weak-base anion exchange resin, wherein the adsorption flow rate is 3BV/h; the adsorption multiple is 5BV; the desorption is carried out by adopting acetic acid solution with the concentration of 30 percent, the flow rate of the desorption is 3BV/h, and the consumption of the acetic acid solution is 3BV.
(9) Concentrating the desorption solution obtained in the step (8) at 20 ℃ and 2.0MPa by using a nanofiltration membrane which is a coiled nanofiltration membrane (the molecular weight cut-off is 100 Da); evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain shikimic acid.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L succinic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The ceramic membrane of the embodiment has smaller pore diameter, lower temperature and pressure and lower flux of the ceramic membrane, but the content of ginkgolic acid in filtrate is low, and the phenomenon of rear turbidity cannot occur; the ultrafiltration membrane has larger molecular weight, larger flux, larger loss of ginkgo polysaccharide, but lower impurity content; the nanofiltration membrane has lower molecular weight cut-off, higher pressure required to operate, lower flux and low loss of shikimic acid, but acetic acid cut-off exists, and the purity of shikimic acid is not high.
The yield of the finally obtained ginkgo polysaccharide is 83.5 percent, and the purity is 97.7 percent; the yield of shikimic acid is 99.2%, the purity is 94.1%, the removal rate of ginkgolic acid is 99.8%, the quality of ceramic membrane filtrate is good, and the turbidity is 1.1NTU.
Example 3: extraction of ginkgo polysaccharide and shikimic acid according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane to obtain ceramic membrane filtrate shown in the figure 2, wherein the content of ginkgo biloba polysaccharide is 0.45%, the content of shikimic acid is 0.81%, and the content of impurities is 0.58%; the turbidity of A is 3.0NTU; b has a turbidity of 1.0NTU;
wherein, before the ceramic ultrafiltration membrane (multi-channel ceramic ultrafiltration membrane) is activated and modified, the pore diameter of the support body is 3 mu m, and the porosity is 30%; the pore diameter of the separation layer is 30nm; the separating layer is formed by firing titanium oxide with the particle size of 50nm at the high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with oxalic acid as an activating agent;
wherein the temperature of the filtration is 40 ℃, the pressure is 0.35MPa, and the membrane surface flow rate is 4m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1;
(6) Adsorbing the water phase obtained in the step (5) by macroporous resin (the flow rate is 2BV/h, and the adsorption multiple is 3 times), and collecting effluent liquid;
(7) Filtering the effluent liquid obtained in the step (6) by a roll-type ultrafiltration membrane (with a molecular weight cut-off of 1500 Da) at 40 ℃ and 1.0MPa to obtain a cut-off liquid which is ginkgo polysaccharide, and collecting an ultrafiltration membrane filtrate;
(8) Adsorbing the ultrafiltration membrane permeate in the step (7) by weak-alkaline anion exchange resin, wherein the adsorption flow rate is 3BV/h, and the adsorption multiple is 6BV; desorbing by adopting acetic acid solution with the concentration of 30 percent, wherein the flow rate of the desorption is 3BV/h; the amount of acetic acid solution was 2BV.
(9) Concentrating the desorption solution obtained in the step (8) at 40 ℃ and 1.5MPa by using a nanofiltration membrane which is a coiled nanofiltration membrane (the molecular weight cut-off is 150 Da); evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain shikimic acid.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L oxalic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The ceramic membrane of the embodiment has proper aperture and moderate temperature and pressure, can ensure that the flux of the ceramic membrane is higher, and simultaneously ensures that the content of ginkgolic acid in filtrate is lower, and does not generate post-turbidity; the ultrafiltration membrane has moderate molecular weight, larger flux, higher yield of ginkgo polysaccharide and lower impurity content; the molecular weight cut-off of the nanofiltration membrane is moderate, the pressure required to run is larger, the flux is smaller, but the loss of shikimic acid is small, acetic acid cut-off is avoided, and the purity of shikimic acid is higher.
The yield of the finally obtained ginkgo polysaccharide is 95.7 percent, and the purity is 99.3 percent; the yield of shikimic acid is 98.2%, the purity is 99.1%, and the removal rate of ginkgolic acid is 99.7%.
Example 4: extraction of ginkgo polysaccharide and shikimic acid according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering and clarifying the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain ceramic membrane filtrate, wherein the content of ginkgo biloba polysaccharide is 0.46%, the content of shikimic acid is 0.84%, and the content of impurities is 0.53%;
wherein, before the ceramic ultrafiltration membrane is activated and modified, the pore diameter of the support is 3 mu m, and the porosity is 30%; the aperture of the separation layer is 10nm; the separating layer is formed by firing titanium oxide with the particle size of 20nm at 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with glutaric acid as an activating agent;
wherein the temperature of the filtration is 60 ℃, the pressure is 0.8MPa, and the membrane surface flow rate is 4m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1;
(6) Adsorbing the water phase obtained in the step (5) by macroporous resin (the flow rate is 2BV/h, and the adsorption multiple is 3 times), and collecting effluent liquid;
(7) Filtering the effluent liquid obtained in the step (6) by a roll-type ultrafiltration membrane (with a molecular weight cut-off of 3000 Da) at 40 ℃ and 0.6MPa to obtain a cut-off liquid which is ginkgo polysaccharide, and collecting an ultrafiltration membrane filtrate;
(8) Adsorbing the ultrafiltration membrane permeate in the step (7) by weak-base anion exchange resin, wherein the adsorption flow rate is 4BV/h; the adsorption multiple is 2BV; the desorption is carried out by adopting acetic acid solution with the concentration of 30 percent, the flow rate of the desorption is 2BV/h, and the consumption of the acetic acid solution is 2BV.
(9) Concentrating the desorption solution obtained in the step (8) at 40 ℃ and 1.5MPa by using a nanofiltration membrane which is a coiled nanofiltration membrane (the molecular weight cut-off is 150 Da); evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain shikimic acid.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device with the vacuum degree of 10kPa, heating 0.2mol/L glutaric acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The ceramic membrane of the embodiment has small pore diameter, higher temperature and pressure, higher energy consumption, extremely low content of ginkgolic acid in filtrate and no post-turbidity phenomenon; the ultrafiltration membrane has moderate molecular weight, larger flux, higher yield of ginkgo polysaccharide and lower impurity content; the nanofiltration membrane has moderate molecular weight cut-off, higher pressure and flux which are required to be operated, but the loss of shikimic acid is small, acetic acid cut-off is avoided, and the purity of shikimic acid is higher.
The yield of the finally obtained ginkgo polysaccharide is 94.3 percent, and the purity is 97.8 percent; the yield of shikimic acid is 97.9%, the purity is 99.2%, the removal rate of ginkgolic acid is 99.9%, the quality of ceramic membrane filtrate is good, and the turbidity is 1.0NTU.
Comparative example 1
As in example 3, the ceramic membrane was replaced with an unactivated ceramic membrane alone, and the obtained ceramic membrane filtrate was shown in fig. 3, wherein the content of ginkgo polysaccharide in the obtained ceramic membrane filtrate was 0.41%, the content of shikimic acid was 0.65%, and the impurity content was 3.5% after filtration through the unactivated ceramic membrane; wherein, the turbidity of A is 12.5NTU; the turbidity of B was 75.0NTU.
The yield of the finally obtained ginkgo polysaccharide is 78.5 percent, and the purity is 83.2 percent; the yield of shikimic acid is 81.3%, the purity is 86.4%, and the removal rate of ginkgolic acid is 43%. The ceramic membrane filter liquid has poor quality, and the turbidity of the ceramic membrane filter liquid after 2 hours is 75NTU.
Example 5: extraction of bilobalide according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using a ceramic ultrafiltration membrane after activation and modification to obtain ceramic membrane filtrate;
wherein, before the ceramic ultrafiltration membrane is activated and modified, the pore diameter of the support is 3 mu m, and the porosity is 30%; the pore diameter of the separation layer is 50nm; the separating layer is formed by firing titanium oxide with the grain diameter of 100nm at the high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with malonic acid as an activating agent;
wherein the temperature of the filtration is 20 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1: 3-1: 1, a step of;
(6) Adsorbing the organic phase obtained in the step (5) by using 80-mesh polyamide resin (the flow rate is 6BV/h, the adsorption multiple is 3 times), and desorbing by using 50% ethanol solution to obtain desorption liquid, wherein the flow rate of ethanol is 4BV/h, and the ethanol consumption is 3BV;
(7) Concentrating the desorption solution obtained in the step (6) at 20 ℃ and 0.5MPa by using a coiled ultrafiltration membrane (the molecular weight cut-off is 800 Da);
(8) Evaporating, crystallizing and drying the nanofiltration membrane concentrate in the step (7) to obtain the ginkgolide.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L malonic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The pore diameter of the ceramic membrane is large, the temperature and the pressure are low, the flux of the ceramic membrane is high, but the content of ginkgolic acid in filtrate is high; the nanofiltration membrane has higher molecular weight cut-off, lower pressure and lower flux, and simultaneously the loss of ginkgolide is larger.
The yield of the finally obtained ginkgolide is 75.6%, the purity of the ginkgolide is 93.6%, the removal rate of ginkgolic acid is 98.6%, the ceramic membrane filtrate is turbid after the occurrence of the phenomenon, and the turbidity is 12NTU.
Example 6: extraction of bilobalide according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 5 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using a ceramic ultrafiltration membrane after activation and modification to obtain ceramic membrane filtrate;
wherein, before the ceramic membrane ultrafiltration membrane is activated and modified, the pore diameter of a support is 2 mu m, and the porosity is 30 percent; the aperture of the separation layer is 20nm; the separating layer is formed by firing titanium oxide with the particle size of 30nm at the high temperature of 750 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with succinic acid as an activating agent;
wherein the temperature of the filtration is 60 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1: 3-1: 1, a step of;
(6) Adsorbing the organic phase obtained in the step (5) by using polyamide resin with 20 meshes (the flow rate is 1BV/h, the adsorption multiple is 1 time), and desorbing by using 75% ethanol to obtain desorption liquid, wherein the flow rate of the ethanol is 1BV/h, and the ethanol consumption is 2BV;
(7) Concentrating the desorption solution obtained in the step (6) at 60 ℃ and 4.0MPa by using a nanofiltration membrane as a coiled ultrafiltration membrane (the molecular weight cut-off is 100 Da);
(8) Evaporating, crystallizing and drying the nanofiltration membrane concentrate in the step (7) to obtain the ginkgolide.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.05mol/L succinic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 5 hours, wherein the vacuum degree is 90 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 4 hours.
The ceramic membrane of the embodiment has smaller pore diameter, lower pressure, higher temperature and lower ceramic membrane flux, good filtrate quality and very low ginkgolic acid content below 1 ppm; the molecular weight cut-off of the nanofiltration membrane is very low and the pressure is high. The nanofiltration membrane has lower filtration flux, but the yield of bilobalide in the step is high.
The yield of the finally obtained ginkgolide is 97.8%, the purity of the ginkgolide is 99.2%, the removal rate of ginkgolic acid is 99.9%, the quality of ceramic membrane filtrate is good, and the turbidity is 4.5NTU.
Example 7: extraction of bilobalide according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 40 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disc centrifuge at 8000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane to obtain ceramic membrane filtrate shown in figure 4; wherein, the turbidity of A is 1.0NTU; the turbidity of B was 2.0NTU.
Wherein, before the ceramic membrane ultrafiltration membrane is activated and modified, the pore diameter of a support is 2 mu m, and the porosity is 35%; the pore diameter of the separation layer is 30nm; the separating layer is formed by firing titanium oxide with the particle size of 50nm at the high temperature of 700 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with oxalic acid as an activating agent;
wherein the temperature of the filtration is 40 ℃, the pressure is 0.35MPa, and the membrane surface flow rate is 4.5m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1: 3-1: 1, a step of;
(6) Adsorbing the organic phase obtained in the step (5) by using 40-mesh polyamide resin (the flow rate is 3BV/h, the adsorption multiple is 4 times), and desorbing by using 75% ethanol to obtain desorption liquid, wherein the flow rate of the ethanol is 1BV/h, and the ethanol consumption is 3BV;
(7) Concentrating the desorption solution obtained in the step (6) at 30 ℃ and 2.5MPa through a coiled ultrafiltration membrane (the molecular weight cut-off is 150 Da);
(8) Evaporating, crystallizing and drying the nanofiltration membrane concentrate in the step (7) to obtain the ginkgolide.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 10 hours, and drying at 100 ℃ for 12 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L oxalic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 6 hours, wherein the vacuum degree is 20 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 12 hours.
The ceramic membrane of the embodiment has moderate aperture, temperature and pressure, high and stable ceramic membrane flux, good filtrate quality, high ginkgolic acid removal rate up to 99.9 percent, and low content of the ginkgolic acid under 0.5ppm through detection; the nanofiltration membrane has moderate filtration pressure and large flux, and simultaneously, the yield of the ginkgolide is high, so that the method is suitable for industrial production.
The yield of the finally obtained ginkgolide is 98.3%, the purity of the ginkgolide is 99.5%, the removal rate of ginkgolic acid is 99.9%, the quality of ceramic membrane filtrate is good, and the turbidity is 1.0NTU.
Example 8: extraction of bilobalide according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 30 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using a ceramic ultrafiltration membrane after activation and modification to obtain ceramic membrane filtrate;
wherein, before the ceramic membrane ultrafiltration membrane is activated and modified, the pore diameter of a support is 2 mu m, and the porosity is 35%; the aperture of the separation layer is 5nm; the separating layer is formed by firing titanium oxide with the particle size of 10nm at the high temperature of 800 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with glutaric acid as an activating agent;
Wherein the temperature of the filtration is 60 ℃, the pressure is 0.8MPa, and the membrane surface flow rate is 5m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1: 3-1: 1, a step of;
(6) Adsorbing the organic phase obtained in the step (5) by using 40-mesh polyamide resin (the flow rate is 2BV/h, the adsorption multiple is 4 times), and desorbing by using 60% ethanol to obtain desorption liquid, wherein the flow rate of the ethanol is 2BV/h, and the ethanol consumption is 2BV;
(7) Concentrating the desorption solution obtained in the step (6) at 30 ℃ and 2.5MPa by using a nanofiltration membrane as a coiled ultrafiltration membrane (the molecular weight cut-off is 150 Da);
(8) Evaporating, crystallizing and drying the nanofiltration membrane concentrate in the step (7) to obtain the ginkgolide.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 12 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating the glutaric acid solution with the vacuum degree of 30kPa and the concentration of 0.1mol/L in a round bottom flask to boiling, and performing an activation reaction for 2 hours;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The aperture of the ceramic membrane of the embodiment is small, the filtering temperature is high, the filtering pressure liquid to be maintained is high, the filtrate is filtered and clarified, but the phenomenon of rear turbidity can occur, the energy consumption is high, and a part of products can be intercepted by the ceramic membrane. The flux of the ceramic membrane is lower, the molecular weight cut-off of the nanofiltration membrane is proper, the pressure is moderate, the flux is higher, and the yield of the ginkgolide is high.
The yield of the finally obtained ginkgolide is 94.3%, the purity of the ginkgolide is 99.1%, the removal rate of ginkgolic acid is 97.3%, the quality of ceramic membrane filtrate is good, and the turbidity is 2.7NTU.
Example 9: extraction of bilobalide according to the flow chart shown in figure 1:
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering, clarifying and removing impurities from the ginkgo biloba extract centrifugate obtained in the step (3) by using a ceramic ultrafiltration membrane after activation and modification to obtain ceramic membrane filtrate;
wherein, before the ceramic membrane ultrafiltration membrane is activated and modified, the pore diameter of a support is 2 mu m, and the porosity is 35%; the aperture of the separation layer is 10nm; the separating layer is formed by firing titanium oxide with the particle size of 20nm at the high temperature of 800 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with malonic acid as an activating agent;
Wherein the temperature of the filtration is 30 ℃, the pressure is 0.6MPa, and the membrane surface flow rate is 3m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1: 3-1: 1, a step of;
(6) Adsorbing the organic phase obtained in the step (5) by using 30-mesh polyamide resin (the flow rate is 3BV/h, the adsorption multiple is 3 times), and desorbing by using 70% ethanol to obtain desorption liquid, wherein the flow rate of the ethanol is 2BV/h, and the ethanol consumption is 2BV;
(7) Concentrating the desorption solution obtained in the step (6) at 40 ℃ and 2.0MPa through a coiled ultrafiltration membrane (the molecular weight cut-off is 300 Da);
(8) Evaporating, crystallizing and drying the nanofiltration membrane concentrate in the step (7) to obtain the ginkgolide.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.05mol/L malonic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 4 hours, wherein the vacuum degree is 50 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The ceramic membrane of the embodiment has smaller pore diameter, moderate filtering temperature and relatively higher pressure, and can ensure effective filtering and clarification. The flux of the ceramic membrane is lower, the operation energy consumption is higher, the quality of the filtrate is good, the phenomenon of rear turbidity cannot occur, and the content of ginkgolic acid is very low and is below 1 ppm; the molecular weight cut-off of the nanofiltration membrane is slightly larger, the flux is large, and the yield of ginkgolide is slightly reduced compared with that of the example 3.
The yield of the finally obtained ginkgolide is 92.9%, the purity of the ginkgolide is 98.5%, the removal rate of ginkgolic acid is 99.7%, the quality of ceramic membrane filtrate is good, and the turbidity is 1.8NTU.
Comparative example 2
As in example 7, only the ceramic membrane was replaced with an unactivated ceramic membrane, and the resulting ceramic membrane filtrate was as shown in fig. 5; wherein, the turbidity of A is 10.0NTU; the turbidity of B was 78.0NTU.
The yield of the obtained ginkgolide is 75%, the purity of the ginkgolide is 86%, the removal rate of ginkgolic acid is 43%, the quality of ceramic membrane filtrate is poor, and the turbidity of the ceramic membrane filtrate after 2 hours is 78NTU.
Example 10: extraction of ginkgo flavone according to the flow chart shown in figure 1
(1) Crushing ginkgo leaves to 20 meshes, leaching with 60% ethanol solution at 50-80 ℃ for 6 times to obtain crude ginkgo leaf extract;
(2) Evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain ginkgo leaf extract concentrate, and recovering ethanol;
(3) Centrifuging the ginkgo leaf extract concentrate obtained in the step (2) for 10min by a disk centrifuge at 6000rpm/min to obtain ginkgo leaf extract centrifugate;
(4) Filtering and clarifying the ginkgo biloba extract centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain ceramic membrane filtrate shown in the figure 2, wherein the ginkgo flavone content is 2.56%, and the impurity content is 0.58%; the turbidity of A is 3.0NTU; b has a turbidity of 1.0NTU;
Wherein, before the ceramic ultrafiltration membrane (multi-channel ceramic ultrafiltration membrane) is activated and modified, the pore diameter of the support body is 3 mu m, and the porosity is 30%; the pore diameter of the separation layer is 30nm; the separating layer is formed by firing titanium oxide with the particle size of 50nm at the high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with oxalic acid as an activating agent;
wherein the temperature of the filtration is 40 ℃, the pressure is 0.35MPa, and the membrane surface flow rate is 4m/s;
(5) Extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to obtain a water phase and an organic phase respectively; wherein, the volume ratio of the ethyl acetate to the ceramic membrane filtrate is 1:3-1:1;
(6) Adsorbing the water phase obtained in the step (5) by macroporous resin (the flow rate is 2BV/h, the adsorption multiple is 3 times), and then desorbing by ethanol, wherein the flow rate of desorption is 3BV/h, and the dosage of ethanol solution is 3BV;
(7) Concentrating the desorption solution obtained in the step (6) at 20 ℃ and 2.0MPa through a nanofiltration membrane (a coiled nanofiltration membrane with a molecular weight cutoff of 100 Da); evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain ginkgo flavone.
In the step (4), the activation process of the ceramic membrane is as follows:
(a) Soaking the ceramic membrane in deionized water for 12 hours, and drying at 100 ℃ for 10 hours;
(b) Placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating 0.2mol/L oxalic acid solution in a round-bottom flask to boiling, and performing an activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;
(c) And (3) cleaning the ceramic membrane obtained in the step (b) with deionized water three times, and drying at 100 ℃ for 10 hours.
The ceramic membrane of the embodiment has proper aperture and moderate temperature and pressure, can ensure that the flux of the ceramic membrane is higher, and simultaneously ensures that the content of ginkgolic acid in filtrate is lower, and does not generate post-turbidity; the nanofiltration membrane has moderate interception molecular weight, larger pressure required to run and smaller flux, but the loss of ginkgo flavone is small, no ethanol is intercepted, and the purity of the ginkgo flavone is higher.
The final yield of ginkgo flavone is 97.6%, the purity is 98.7%, and the removal rate of ginkgolic acid is 99.7%.
Comparative example 3:
in the same manner as in example 10, only the ceramic membrane was replaced with an unactivated ceramic membrane, and the obtained ceramic membrane filtrate was shown in FIG. 3, wherein the ginkgo flavone content in the obtained ceramic membrane filtrate was 2.47% and the impurity content was 3.5% after filtration through the unactivated ceramic membrane; the final yield of ginkgo flavone is 78.9%, the purity is 85.7%, and the removal rate of ginkgolic acid is 43%. The ceramic membrane filter liquid has poor quality, and the turbidity of the ceramic membrane filter liquid after 2 hours is 75NTU.
The invention provides a method and a thinking of a production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid, and the method and the way for realizing the technical scheme are numerous, the above is only a preferred embodiment of the invention, and it should be pointed out that a plurality of improvements and modifications can be made by those skilled in the art without departing from the principle of the invention, and the improvements and the modifications are also considered as the protection scope of the invention. The components not explicitly described in this embodiment can be implemented by using the prior art.

Claims (7)

1. A production process for simultaneously producing bilobalide, ginkgetin, ginkgolic polysaccharide and shikimic acid is characterized by comprising the following steps:
(1) Filtering the ginkgo extract by a ceramic membrane activated by organic acid to obtain ceramic membrane filtrate, and extracting to obtain an organic phase and a water phase; the organic phase is a liquid containing bilobalide;
(2) Adsorbing the water phase obtained in the step (1) by resin to obtain an effluent; desorbing to obtain desorption liquid; the desorption liquid is a liquid containing ginkgo flavone;
(3) Filtering and concentrating the effluent liquid obtained in the step (2) through an ultrafiltration membrane to obtain trapped fluid and permeate; the trapped liquid is liquid containing ginkgo polysaccharide, and the permeate liquid is liquid containing shikimic acid;
In the step (1), the ginkgo extract is obtained by crushing, extracting with ethanol, concentrating and separating solid from liquid;
in the step (1), the ceramic membrane after the activation of the organic acid is obtained by processing according to the following method: firstly, soaking a ceramic membrane in deionized water for 6-12 hours, and then activating the ceramic membrane by organic acid after drying; the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and carrying out an activation reaction on the ceramic membrane by a vacuum vapor deposition method;
the average pore diameter of the support body of the ceramic membrane is 2-5 mu m; the average pore diameter of the separation layer of the ceramic membrane is 5-50 nm;
the organic acid is any one or a combination of several of succinic acid, malonic acid, glutaric acid and oxalic acid; the vacuum degree of the vacuum vapor deposition method is 10-90 kPa;
in the step (2), the resin is polyamide resin;
in the step (3), the ultrafiltration membrane is a roll ultrafiltration membrane, and the molecular weight cut-off is 1000-20000 Da.
2. The production process according to claim 1, wherein the solvent of the organic acid solution is an alcohol compound; the concentration of the organic acid solution is 0.05-1mol/L.
3. The production process according to claim 1, wherein the time of the activation reaction is 1 to 6 hours.
4. The process according to claim 1, wherein the filtration temperature is 10 to 90 ℃, the pressure is 0.1 to 0.8MPa, and the membrane surface flow rate is 1 to 6m/s.
5. A production process for producing ginkgo flavone is characterized in that ginkgo extract is filtered by a ceramic membrane activated by organic acid to obtain ceramic membrane filtrate, the ceramic membrane filtrate is extracted, an obtained water phase is adsorbed and desorbed by resin, and the obtained desorption liquid is a liquid containing ginkgo flavone;
the ceramic membrane after the activation of the organic acid is obtained by processing according to the following method: firstly, soaking a ceramic membrane in deionized water for 6-12 hours, and then activating the ceramic membrane by organic acid after drying; the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and carrying out an activation reaction on the ceramic membrane by a vacuum vapor deposition method; the average pore diameter of the support body of the ceramic membrane is 2-5 mu m; the average pore diameter of the separation layer of the ceramic membrane is 5-50 nm; the organic acid is any one or a combination of several of succinic acid, malonic acid, glutaric acid and oxalic acid; the vacuum degree of the vacuum vapor deposition method is 10-90 kPa;
the resin is polyamide resin.
6. The process according to claim 5, wherein the organic acid is activated by placing the ceramic film in a closed container, heating the organic acid solution to boiling, and performing an activation reaction on the ceramic film by a vacuum vapor deposition method.
7. The process according to claim 5, wherein the solvent of the organic acid solution is an alcohol compound; the concentration of the organic acid solution is 0.05-1mol/L.
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CN103588785A (en) * 2013-11-28 2014-02-19 上海信谊百路达药业有限公司 Refining method for ginkgolide A and ginkgolide B
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