CN113801134A

CN113801134A - Production process for simultaneously producing ginkgolide, ginkgetin, ginkgopolysaccharide and shikimic acid

Info

Publication number: CN113801134A
Application number: CN202111261244.1A
Authority: CN
Inventors: 凌国庆; 陈磊; 刘怀红; 储斌; 张南南; 李国学; 方威
Original assignee: Nanjing Jay Environmental Protection Technology Co ltd
Current assignee: Nanjing Jay Environmental Protection Technology Co ltd
Priority date: 2021-10-28
Filing date: 2021-10-28
Publication date: 2021-12-17
Anticipated expiration: 2041-10-28
Also published as: CN113801134B

Abstract

The invention discloses a production process for simultaneously producing bilobalide, ginkgetin, ginkgo polysaccharide and shikimic acid, which comprises the following steps: (1) filtering the ginkgo biloba extract by a ceramic membrane activated by organic acid to obtain a 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 with resin to obtain effluent liquid; desorbing to obtain desorption solution; the desorption liquid is a liquid containing ginkgetin; (3) filtering and concentrating the obtained effluent liquid by an ultrafiltration membrane to obtain trapped liquid and permeate liquid; the trapped fluid is a liquid containing ginkgo polysaccharides, and the permeate liquid is a 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 can effectively filter and remove suspended matters, colloids and macromolecular vegetable proteins 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 ginkgolide, ginkgetin, ginkgopolysaccharide and shikimic acid

Technical Field

The invention belongs to the field of natural medicine extraction, and particularly relates to a production process for simultaneously producing bilobalide, ginkgetin, ginkgo polysaccharide and shikimic acid.

Background

Folium Ginkgo is dry leaf of Ginkgo biloba L. Collected in autumn when the leaves are still green, and dried in time. Generally, the cultivation is artificial cultivation, and the cultivation areas are from north to Liaoning, from south to Guangdong, from east to Zhejiang, from west to Shaanxi, Gansu, from southwest to Sichuan, Guizhou, Yunnan and the like. Has the 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 blood stasis, obstruction of collaterals, thoracic obstruction, cardialgia, apoplexy, hemiplegia, cough with asthma due to lung deficiency, and hyperlipidemia. Ginkgo Biloba leaf Extract (GBE) is a product with rich effective components extracted from ginkgo Biloba leaves by using a proper solvent. Various preparations prepared by taking GBE as a raw material are widely applied to the fields of medicines, health-care products, food additives, functional beverages, cosmetics and the like. The product is one of the most successful cases of botanical drugs (belonging 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 protein, colloid and other impurities, and has complex components, high extraction difficulty and high cost.

Shikimic acid (shown as formula 1) is a monomer compound extracted from Chinese medicine star anise, has anti-inflammatory and analgesic effects, can be used as an intermediate of antiviral and anticancer drugs, and is an important component of a drug 'duffy' for effectively treating fatal H5N1 avian influenza virus. In addition, the early-stage research of the pharmacological research room of Beijing university of traditional Chinese medicine firstly discovers that shikimic acid has obvious antithrombotic effect and can inhibit the formation of thrombus, venous thrombosis and cerebral thrombosis. In order to clarify the antithrombotic mechanism, researchers studied the influence of shikimic acid on platelet aggregation and blood coagulation, and analyzed the relationship between the action mechanism and arachidonic acid metabolism. The results suggest that shikimic acid may exert an antithrombotic effect by affecting arachidonic acid metabolism, inhibiting platelet aggregation, and inhibiting the blood coagulation system. At present, shikimic acid is also found in folium ginkgo, the content is high, and the folium ginkgo is suitable to be used as a raw material for extracting shikimic acid.

Ginkgo polysaccharide is a polysaccharide substance extracted from semen Ginkgo, and is also called semen Ginkgo pectin. The semen Ginkgo polysaccharide is light yellow powder. Researches show that the health care function of the ginkgo biloba polysaccharide has the effects of improving immunity, reducing blood fat and blood sugar, expanding microcirculation, softening blood vessel wall, eliminating heavy metal-lead in digestive tract, resisting tumor and the like. The medicine has the following three effects: 1. immunoregulation effect: the ginkgo polysaccharide can promote the activity of splenic lymphocyte IL2 of tumor-bearing mice and CTX-injured mice, and reduce the formation of serum sIL-2R, which indicates that the ginkgo polysaccharide can promote the immune function of the tumor-bearing mice and the CTX-injured mice. 2. The anti-tumor effect is as follows: the ginkgo polysaccharide can promote the total number of T lymphocytes of a mouse in different states in vitro, can promote DCH reaction of an immunosuppressed mouse caused by Cy, and prompts that the polysaccharide can promote the cell immune function mediated by the T lymphocytes, thereby having important significance for cancer prevention and anticancer; 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 biloba polysaccharide also has good inhibition effect on human melanoma cells and HL-60 cell proliferation, and the inhibition effect has concentration-time dependence. 3. The anti-aging effect research shows that the ginkgo biloba polysaccharide can obviously improve the SOD activity of the serum of the tumor-bearing mice and reduce the MDA content, but has no obvious influence on normal mice, and the ginkgo biloba polysaccharide can promote the free radical scavenging capability of organisms in pathological states and delay the aging of the tumor-bearing mice.

Although the main components of ginkgo leaves, bilobalide, ginkgetin, ginkgo polysaccharide and shikimic acid can be used as medicines, ginkgolic acid has no definite purpose in medical clinic, and is easy to generate the side reaction of excessive expansion of capillary networks after being taken into an organism. The symptoms of flushing and sweating, numbness of the lips and blood vessel stimulation are easy to appear. Therefore, in extracting the ginkgolic acid, it is necessary to remove ginkgolic acid at the same time. At present, the domestic method for removing ginkgolic acid is mainly to extract by adding petroleum ether and separate the ginkgolic acid by utilizing the characteristic of low solubility of the ginkgolic acid in the petroleum ether; or deacidifying with resin to remove ginkgolic acid. The ginkgolic acid is removed by adopting petroleum ether extraction or deacidification resin, the production process flow is increased, the production cost is high, and the introduced impurities are removed; meanwhile, the amount of waste water is large, the pollution is serious, and the environmental protection problem is severe.

At present, the mainstream extraction and purification methods of other ginkgo extracts such as ginkgolide and ginkgetin comprise the following steps: solvent extraction, column extraction, solvent extraction-column extraction, supercritical extraction, chromatography or column chromatography purification, etc. The following disadvantages are mainly present: (1) the consumption of organic solvent is large, the cost of raw materials is high, the organic solvent is unsafe, all electrical equipment in an extraction workshop must adopt explosion-proof grade, and the cost is greatly increased; (2) the ginkgolic acid is removed by adopting petroleum ether extraction or deacidification resin, the production process flow is increased, the production cost is high, and the introduced impurities are removed; (3) the method has the advantages of multiple steps, long route, low product purity and low yield; (4) serious pollution and serious environmental protection problem. (5) Is not suitable for large-scale production and has high unit yield cost.

At present, the extraction of shikimic acid in folium ginkgo mainly adopts a carbon dioxide supercritical extraction process, and the process adopts ultrahigh pressure to make carbon dioxide supercritical fluid contact with substances to be separated under a supercritical state, so that the substances with polarity, boiling point and molecular weight are selectively extracted in turn. Then the supercritical fluid is changed into common gas by means of decompression and temperature rise, and the extracted substances are completely or basically precipitated, thereby achieving the purpose of separation and purification. The method mainly has the following defects: (1) the carbon dioxide supercritical extraction device has high cost; (2) the energy consumption is high, and the production cost is high; (3) the process is congenital defect, and large-scale production cannot be carried out.

Therefore, there is a need for a process for producing bilobalide, ginkgetin and shikimic acid with simple and reliable process, high yield and low production cost, and which can be used for large-scale production.

Disclosure of Invention

The purpose of the invention is as follows: the invention aims to solve the technical problem of providing a production process for simultaneously producing ginkgolide, ginkgetin, ginkgo polysaccharide and shikimic acid aiming at the defects of the prior art.

The technical problem to be solved by the invention is to provide 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, ginkgo polysaccharide and shikimic acid, which comprises the following steps:

(1) filtering the ginkgo biloba extract by a ceramic membrane activated by organic acid to obtain a 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 liquid; desorbing to obtain desorption solution; the desorption liquid is a liquid containing ginkgetin;

(3) filtering and concentrating the effluent liquid obtained in the step (2) by an ultrafiltration membrane to obtain a trapped liquid and a permeate liquid; the trapped fluid is a liquid containing ginkgo polysaccharides, and the permeate liquid is a liquid containing shikimic acid.

In the step (1), the mass content of bilobalide in the ginkgo extract is 0.01-5%, the mass content of ginkgetin 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 protein, vegetable fibers, vegetable pigments, tannin, microorganisms and the like.

In the step (1), the preparation method of the ginkgo biloba extract comprises the steps of concentrating the crude extract of ginkgo biloba and carrying out solid-liquid separation. Wherein, the crude extract of ginkgo leaves is obtained by crushing ginkgo and extracting with ethanol; wherein the ethanol extraction is extraction by 60% ethanol solution; wherein the extraction times are 6 times; wherein the extraction temperature is 50-80 ℃. Wherein the concentration is an evaporative concentration, in which process ethanol can be recovered; preferably, the concentration is about 6 times by evaporation. Wherein the solid-liquid separation is centrifugation; preferably, the solid-liquid separation is centrifugation by a disk centrifuge; further preferably, the rotation speed of the centrifugation is 6000-8000 rpm.

In the step (1), the ceramic membrane after the organic acid activation is obtained by treating according to the following method: firstly, soaking a ceramic membrane in deionized water for 6-12 hours, drying and then activating by organic acid; preferably, the drying is carried out at the temperature of 80-120 ℃ for 10-12 h.

In the step (1), the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boil, and performing an activation reaction on the ceramic membrane by a vacuum vapor deposition method; preferably, the ceramic membrane is placed in an activator, a vacuum device is started, and simultaneously, the organic acid solution is heated to boiling, and the ceramic membrane is activated by the organic acid through a vacuum gas phase method.

Wherein the organic acid has a formula of C_nH_2n-2O₄The structural formula is HOOC- (CH)₂)_n-COOH; wherein n is any integer from 2 to 6; preferably, the organic acid is any one or 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 0.05-1 mol/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 0.05-0.2 mol/L.

Wherein the vacuum degree of the vacuum vapor deposition method is 10-90 kPa.

Wherein the activation time of the organic acid is 1-6 h.

Preferably, after the activation reaction is finished, cleaning and drying are carried out; further preferably, the cleaning is performed by deionized water for three times; further preferably, the drying is carried out for 4-12 h at the temperature of 80-120 ℃.

In the step (1), the ceramic membrane is a single-channel ceramic ultrafiltration membrane or a multi-channel ceramic ultrafiltration membrane, and is 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 body is 2-5 μm; preferably, the porosity of the support is 30% to 45%; more preferably, the material of the support is alumina.

Wherein the average pore diameter of the separation layer (namely the membrane layer) is 5-50 nm; preferably, the separation layer is formed by sintering titanium oxide with the particle size of 10-500 nm at 680-800 ℃.

In the step (1), the filtering temperature is 10-90 ℃, preferably 10-80 ℃, and more preferably 30-50 ℃.

In the step (1), the filtration pressure is 0.1-0.8 MPa, preferably 0.25-0.4 MPa.

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, polyamide resin is used for adsorption and desorption, the obtained desorption solution is concentrated by a nanofiltration membrane, and the obtained trapped fluid is evaporated and concentrated to obtain the ginkgolides.

Wherein the mesh number of the polyamide resin is 20-80 meshes, and preferably 40-50 meshes. Wherein the polyamide is a polymer compound formed by polymerization of an amide bond. The amido group can be combined with the compounds such as hydroxyphenols, acids, quinones, nitro and the like by hydrogen bonds to be adsorbed, and the long aliphatic chain can be used as a carrier for partition chromatography. The polyamide is particularly suitable for separating polyphenol compounds, such as flavone, quinones, phenolic acids, carboxyl-containing compounds, carboxyl 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 to obtain desorption liquid. Wherein, the concentration of the ethanol solution is 50 to 75 percent; the flow rate of desorption is 1-4 BV/h; the dosage of the ethanol solution is 2-3 BV. The ginkgolides are desorbed from the polyamide resin by ethanol desorption, so that the ginkgolides with high purity and high concentration can be obtained.

And the permeate obtained by concentrating the nanofiltration membrane is used for recovering ethanol.

The nanofiltration membrane is a roll-type nanofiltration membrane, and the molecular weight cutoff is 100-800 Da, preferably 150-300 Da.

Wherein the nanofiltration concentration temperature is 10-60 ℃, and preferably 10-50 ℃.

Wherein the pressure of 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 m²(ii) in terms of/g. Wherein Van der Waals attraction between the macroporous adsorbent resin and adsorbed molecules is physically adsorbed via its large specific surface area, so that organic compounds can be eluted and separated via certain solvent according to adsorption force and molecular weight to achieve separation, purification, impurity removal, concentration, etcThe same purpose is achieved.

Wherein the flow rate of the adsorption is 1-6 BV/h, preferably 2-4 BV/h, and further preferably 2 BV/h.

Wherein, the desorption is the desorption by alcohol compounds, and preferably the desorption by ethanol.

The desorption flow rate is 1-4 BV/h, preferably 2-3 BV/h, and further preferably 2 BV/h.

Concentrating the desorption solution with a nanofiltration membrane, and evaporating the trapped fluid to obtain ginkgetin; preferably, the obtained desorption solution is concentrated by a nanofiltration membrane, the obtained permeation solution is an alcohol compound, and the alcohol compound is recycled for desorption; evaporating the trapped liquid to recover alcohol compounds for desorption, and evaporating to obtain ginkgetin.

The molecular weight cut-off of the nanofiltration membrane is 100-1000 Da, preferably 100-800 Da, more preferably 100-500 Da, and even more preferably 150-300 Da.

In the step (3), the ultrafiltration membrane is a roll-type ultrafiltration membrane, the cut-off molecular weight is 1000-20000 Da, preferably 100-15000 Da, and further preferably 1000-3000 Da.

In the step (3), the temperature for filtering and concentrating by the ultrafiltration membrane 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 ℃, and preferably 10-45 ℃.

In the step (3), the pressure of the ultrafiltration membrane is 0.5-1.5 MPa, preferably 0.8-1.2 MPa.

And (3) adsorbing and desorbing the obtained permeate liquid by anion exchange resin, and filtering and concentrating the obtained desorption liquid by a nanofiltration membrane to obtain shikimic acid.

Wherein the anion exchange resin is polyacrylic acid series weak base anion exchange resin, the average pore diameter is 1-200 μm, and the specific surface area is 100-2000 m²(ii) in terms of/g. Wherein the anion exchange resin is mainly produced by carrying weak basic groups, such as primary amino-NH 2, secondary amino-NHR or tertiary amino-NR 2, which can cleave OH-in water to be weak basic, and the positive groups of the anion exchange resin can be adsorbed and combined with anions in solution, thereby producingAnion exchange occurs and the entire other acid molecules in solution can be adsorbed, 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 adopting an acid compound, and acetic acid is preferred; the concentration of the acetic acid is 10 to 50 percent, and preferably 30 percent.

Wherein the flow rate of desorption is 1-4 BV/h; the dosage of the desorption solution is 2-3 BV.

Wherein the desorption solution is filtered and concentrated by a nanofiltration membrane, the obtained permeate liquid is recovered, and the obtained trapped fluid is shikimic acid.

The nanofiltration membrane is a roll-type nanofiltration membrane, the molecular weight cutoff is 100-1000 Da, preferably 100-800 Da, more preferably 100-500 Da, and even more preferably 150-300 Da.

In order to solve the second technical problem, the invention discloses a production process for producing ginkgetin, which comprises the following steps:

(i) filtering the ginkgo biloba extract by a ceramic membrane activated by organic acid to obtain a ceramic membrane filtrate, and extracting to obtain a water phase;

(ii) and (e) adsorbing the water phase obtained in the step (i) by using resin, and desorbing to obtain desorption liquid which is liquid containing ginkgetin.

In the step (i), the preparation method of the ginkgo biloba extract comprises the steps of concentrating the crude extract of ginkgo biloba leaves and carrying out solid-liquid separation. Wherein, the crude extract of ginkgo leaves is obtained by crushing ginkgo and extracting with ethanol; wherein the ethanol extraction is extraction by 60% ethanol solution; wherein the extraction times are 6 times; wherein the extraction temperature is 50-80 ℃. Wherein the concentration is an evaporative concentration, in which process ethanol can be recovered; preferably, the concentration is about 6 times by evaporation. Wherein the solid-liquid separation is centrifugation; preferably, the solid-liquid separation is centrifugation by a disk centrifuge; further preferably, the rotation speed of the centrifugation is 6000-8000 rpm.

In the step (i), the ceramic membrane after the organic acid activation is obtained by treating according to the following method: soaking a ceramic membrane in deionized water for 6-12 hours, drying, and activating by organic acid; preferably, the drying is carried out at the temperature of 80-120 ℃ for 10-12 h.

In the step (i), the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boil, and performing an activation reaction on the ceramic membrane by a vacuum vapor deposition method; preferably, the ceramic membrane is placed in an activator, a vacuum device is started, and simultaneously, the organic acid solution is heated to boiling, and the ceramic membrane is activated by the organic acid through a vacuum gas phase method.

Wherein the vacuum degree of the vacuum vapor deposition method is 10-90 kPa.

Wherein the activation time of the organic acid is 1-6 h.

In 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.

In the step (i), the filtering temperature is 10-90 ℃, preferably 10-80 ℃, and more preferably 30-50 ℃.

In the step (i), the filtration pressure is 0.1-0.8 MPa, preferably 0.25-0.4 MPa.

In the step (i), the flow velocity of the filtered membrane surface is 1-6 m/s.

In the step (i), the ceramic membrane filtrate is extracted 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 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 m²(ii) in terms of/g. The Van der Waals attraction between the macroporous adsorption resin and the adsorbed molecules performs physical adsorption through the huge specific surface of the macroporous adsorption resin, so that organic compounds can be eluted and separated by a certain solvent according to the adsorption force and the molecular weight of the organic compounds, and different purposes such as separation, purification, impurity removal, concentration and the like are achieved.

Wherein the flow rate of the adsorption is 1-6 BV/h, preferably 2-4 BV/h.

Wherein the flow rate of desorption is 1-4 BV/h, preferably 2-3 BV/h.

In the step (ii), concentrating the desorption solution by using a nanofiltration membrane, and evaporating the trapped fluid to obtain ginkgetin; preferably, the obtained desorption solution is concentrated by a nanofiltration membrane, the obtained permeation solution is an alcohol compound, and the alcohol compound is recycled for desorption; evaporating the trapped liquid to recover alcohol compounds for desorption to obtain ginkgetin.

In the present invention, the ethanol solution and the acetic acid solution are, unless otherwise specified, all in terms of mass ratio.

Has the advantages 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 can effectively filter and remove suspended matters, colloids and macromolecular vegetable proteins by adopting the ceramic membrane after activation treatment, thereby improving the product quality, reducing the turbidity and improving the yield.

2. The method adopts the ceramic membrane after the activation treatment to filter the gingko to extract the centrifugate, can remove more than 99.9 percent of ginkgoic acid by one step, reduces the working procedure of adding petroleum ether for extraction in the traditional process, and reduces the production cost. In addition, 99.8% of vegetable oily impurities can be removed, the quality of the filtrate is high, the feeding load of polyamide resin in the subsequent working section is reduced, and the using amount of ethyl acetate is reduced.

3. The extraction process adopts a nanofiltration membrane to pre-concentrate the polyamide resin desorption solution, and can reduce the ethanol evaporation capacity by more than 80 percent. The membrane concentration can concentrate the ginkgolide at low temperature, reduce the loss of the ginkgolide caused by degradation during high-temperature evaporation, improve the yield of the ginkgolide, reduce the production energy consumption and reduce the production cost.

4. According to the invention, the macroporous adsorption resin distillate is filtered and concentrated, so that the ginkgo polysaccharide and the shikimic acid can be effectively separated, and the purity of the ginkgo polysaccharide is higher; meanwhile, the ginkgo biloba polysaccharide is concentrated, so that the evaporation capacity can be reduced, and the energy consumption can be reduced.

5. The extraction process adopts a nanofiltration membrane to concentrate weak base anion exchange resin acetic acid desorption solution, and can reduce the evaporation capacity of acetic acid by more than 90 percent. The membrane concentration can concentrate shikimic acid at low temperature, reduce the loss caused by the degradation of shikimic acid during high-temperature evaporation, improve the yield of shikimic acid, and simultaneously, the nanofiltration membrane filtrate is acetic acid, can be directly reused for resin desorption of the next batch, and reduce the production energy consumption and the production cost;

6. the extraction process of the invention adopts membrane separation equipment and ion exchange resin equipment, thus reducing the floor area of the equipment and lowering the capital cost. The process carries out a large amount of optimization work on the parameters of new equipment and the traditional process to obtain the optimal production process parameters, ensures the efficient and energy-saving operation of production, and simultaneously has higher product quality. The production process is energy-saving, has high automation degree compared with the traditional production process, can save 60 percent of labor cost, and has remarkable economic benefit.

Drawings

The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.

FIG. 1 is a schematic diagram of a process for simultaneously producing bilobalide, ginkgetin, ginkgo polysaccharide and shikimic acid according to the present invention.

FIG. 2 is a graph of the ceramic membrane filtrate obtained in example 3; wherein A is ceramic membrane filtrate after 2 hours of filtration; b is the ceramic membrane filtrate which is just filtered.

FIG. 3 is a graph of the ceramic membrane filtrate obtained in comparative example 1; wherein, A is ceramic membrane filtrate which is just filtered; b is the 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 ceramic membrane filtrate which is just filtered; b is the 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 ceramic membrane filtrate which is just filtered; b is the 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 are commercially available, unless otherwise specified.

The ginkgo polysaccharide content, the shikimic acid content and the impurity content in the following examples are all mass contents unless otherwise specified.

In the following examples, the macroporous resin was Eimeria brand D751, the macroporous adsorbent resin was of styrene type, the average pore diameter of the resin was 40 μm, and the specific surface area was 120m²/g。

The weakly basic anion exchange resin described in the following examples is Eimeria brand LK17, a polyacrylic acid series weakly basic anion exchange resin having an average pore size of 50 μm and a specific surface area of 100m²/g。

In the following examples, the polyamide resins used have the formula [ NH- (CH)₂)₅-CO]_nIs prepared from epsilon-caprolactam.

In the following examples, the support is made of alumina unless otherwise specified.

In the following examples, unless otherwise specified, the term "turbidity after the ceramic membrane filtrate was generated" means turbidity after 2 hours of filtration.

In the following examples, the bilobalide and the impurity content are all mass percentages.

Example 1: extracting the ginkgo polysaccharides and shikimic acid according to the flow chart shown in figure 1:

(1) crushing ginkgo leaves to 20 meshes, leaching the ginkgo leaves by using a 60% ethanol solution at 50-80 ℃, and extracting for 6 times to obtain a crude extract of the ginkgo leaves;

(2) evaporating and concentrating the crude extract obtained in the step (1) for 6 times to obtain a concentrated solution of ginkgo leaf extract, and simultaneously recovering ethanol;

(3) centrifuging the concentrated ginkgo leaf extract solution obtained in the step (2) at 6000rpm/min for 10min by using a disk centrifuge to obtain ginkgo leaf extract centrifugate;

(4) filtering and clarifying the gingko extracting centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate, wherein the content of gingko polysaccharide is 0.47%, the content of shikimic acid is 0.82%, and the content of impurities is 0.56%;

wherein, before the activation modification of the ceramic ultrafiltration membrane, the aperture of the support body is 3 μm, and the porosity is 30%; the aperture of the separation layer is 50 nm; the separation layer is formed by firing titanium oxide with the particle size of 100nm at 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 flow rate of the membrane surface is 5 m/s;

(5) extracting the ceramic membrane filtrate obtained in the step (4) by ethyl acetate to respectively obtain a water phase and an organic phase; 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 obtained in the step (6) by a roll-type ultrafiltration membrane (the molecular weight cutoff is 1000Da) at 60 ℃ and 1.0MPa to obtain a cutoff liquid, namely the ginkgo biloba extract, and collecting the filtrate of the ultrafiltration membrane;

(8) adsorbing the ultrafiltration membrane permeate obtained in the step (7) by weak base anion exchange resin at the adsorption flow rate of 2 BV/h; the adsorption multiple is 6 times; desorbing with 30% acetic acid solution at a flow rate of 2BV/h and a consumption of 2 BV.

(9) Concentrating the desorption solution obtained in the step (8) into a roll type nanofiltration membrane (the molecular weight cut-off is 800Da) through the nanofiltration membrane at the temperature of 60 ℃ and the pressure of 0.8 MPa; and evaporating, crystallizing and drying the concentrated solution of the nanofiltration membrane to obtain shikimic acid.

In the step (4), the activation process of the ceramic membrane comprises the following steps:

(a) soaking the ceramic membrane in deionized water for 12h, and drying at 100 ℃ for 10 h;

(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 boil, and carrying out activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;

(c) and (c) washing the ceramic membrane obtained in the step (b) with deionized water for three times, and drying for 10 hours at 100 ℃.

The ceramic membrane has the advantages that the aperture 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 ginkgoic acid in filtrate is high, the filtrate of the ceramic membrane is turbid after occurrence, and the turbidity is 12 NTU; the ultrafiltration membrane has smaller molecular weight and smaller flux, the loss of the ginkgo polysaccharide is less, but the content of impurities is higher; the nanofiltration membrane has higher molecular weight cut-off, lower pressure, lower flux and larger shikimic acid loss.

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 the ceramic membrane filtrate is better, and the turbidity is 2.3 NTU.

Example 2: extracting the ginkgo polysaccharides and shikimic acid according to the flow chart shown in figure 1:

(4) filtering and clarifying the gingko extracting centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate, wherein the content of gingko polysaccharide is 0.48%, the content of shikimic acid is 0.85%, and the content of impurities is 0.53%;

wherein, before the activation modification of the ceramic ultrafiltration membrane, the aperture of the support body is 3 μm, and the porosity is 30%; the aperture of the separation layer is 20 nm; the separation layer is formed by firing titanium oxide with the particle size of 30nm at high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating ethanol solution with succinic acid as an activating agent;

wherein the filtering temperature is 20 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4.5 m/s;

(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 obtained in the step (6) by a roll-type ultrafiltration membrane (the molecular weight cutoff is 5000Da) at 20 ℃ and 0.8MPa to obtain a cutoff liquid, namely the ginkgo biloba extract, and collecting the filtrate of the ultrafiltration membrane;

(8) adsorbing the ultrafiltration membrane permeate obtained in the step (7) by weak base anion exchange resin at the adsorption flow rate of 3 BV/h; the adsorption multiple is 5 BV; desorbing with 30% acetic acid solution at a flow rate of 3BV/h and a consumption of 3 BV.

(9) Concentrating the desorption solution obtained in the step (8) through a nanofiltration membrane to form a roll type nanofiltration membrane (the molecular weight cut-off is 100Da) at 20 ℃ and 2.0 MPa; and evaporating, crystallizing and drying the concentrated solution of the nanofiltration membrane to obtain shikimic acid.

(b) placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating a 0.2mol/L succinic acid solution in a round-bottom flask to boil, and carrying out activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;

The ceramic membrane has the advantages that the aperture is small, the temperature and the pressure are low, the flux of the ceramic membrane is low, but the content of ginkgolic acid in filtrate is low, and the phenomenon of rear turbidity cannot be caused; the ultrafiltration membrane has larger molecular weight, larger flux, larger loss of the gingko polysaccharide, but lower impurity content; the nanofiltration membrane has low molecular weight cut-off, high pressure required to operate, low flux, small shikimic acid loss, but acetic acid cut-off and low shikimic acid purity.

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 the ceramic membrane filtrate is good, and the turbidity is 1.1 NTU.

Example 3: extracting the ginkgo polysaccharides and shikimic acid according to the flow chart shown in figure 1:

(4) filtering and clarifying the gingko extraction centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate shown in a figure 2, wherein the content of gingko polysaccharide is 0.45%, the content of shikimic acid is 0.81%, and the content of impurities is 0.58%; turbidity of a was 3.0 NTU; turbidity of B was 1.0 NTU;

wherein, before the activation modification of the ceramic ultrafiltration membrane (multi-channel ceramic ultrafiltration membrane), the aperture of the support body is 3 μm, and the porosity is 30%; the aperture of the separation layer is 30 nm; the separation layer is formed by firing titanium oxide with the particle size of 50nm at high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with oxalic acid as an activating agent;

wherein the filtering temperature is 40 ℃, the pressure is 0.35MPa, and the membrane surface flow rate is 4 m/s;

(7) filtering the effluent obtained in the step (6) by a roll-type ultrafiltration membrane (the cut-off molecular weight is 1500Da) at 40 ℃ and 1.0MPa to obtain a cut-off solution which is the ginkgo biloba extract, and collecting the filtrate of the ultrafiltration membrane;

(8) adsorbing the ultrafiltration membrane permeate obtained in the step (7) by weak base anion exchange resin, wherein the adsorption flow rate is 3BV/h, and the adsorption multiple is 6 BV; desorbing with 30% acetic acid solution at a flow rate of 3 BV/h; the dosage of the acetic acid solution is 2 BV.

(9) Concentrating the desorption solution obtained in the step (8) through a nanofiltration membrane to form a roll type nanofiltration membrane (the molecular weight cutoff is 150Da) at 40 ℃ and 1.5 MPa; and evaporating, crystallizing and drying the concentrated solution of the nanofiltration membrane to obtain shikimic acid.

(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 boil, and carrying out activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;

The ceramic membrane has proper aperture and moderate temperature and pressure, can ensure high flux of the ceramic membrane and lower content of ginkgolic acid in filtrate, and does not generate rear turbidity; the ultrafiltration membrane has moderate molecular weight, larger flux, higher yield of the ginkgo polysaccharide and lower impurity content; the nanofiltration membrane has moderate molecular weight cut-off, large operating pressure and small flux, but the shikimic acid has small loss, no acetic acid cut-off and high shikimic acid purity.

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: extracting the ginkgo polysaccharides and shikimic acid according to the flow chart shown in figure 1:

(4) filtering and clarifying the gingko extracting centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate, wherein the content of gingko polysaccharide is 0.46%, the content of shikimic acid is 0.84%, and the content of impurities is 0.53%;

wherein, before the activation modification of the ceramic ultrafiltration membrane, the aperture of the support body is 3 μm, and the porosity is 30%; the aperture of the separation layer is 10 nm; the separation layer is formed by firing titanium oxide with the particle size of 20nm at high temperature of 680 ℃; the ceramic ultrafiltration membrane is obtained by activating an ethanol solution with glutaric acid as an activating agent;

wherein the filtering temperature is 60 ℃, the pressure is 0.8MPa, and the membrane surface flow rate is 4 m/s;

(7) filtering the effluent obtained in the step (6) by a roll-type ultrafiltration membrane (the cut-off molecular weight is 3000Da) at 40 ℃ and 0.6MPa to obtain a cut-off solution which is the ginkgo biloba extract, and collecting the filtrate of the ultrafiltration membrane;

(8) adsorbing the ultrafiltration membrane permeate obtained in the step (7) by weak base anion exchange resin at the flow rate of 4 BV/h; the adsorption multiple is 2 BV; desorbing with 30% acetic acid solution at a flow rate of 2BV/h and a consumption of 2 BV.

(b) placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating a 0.2mol/L glutaric acid solution in a round-bottom flask to boil, and carrying out activation reaction for 3 hours, wherein the vacuum degree is 10 kPa;

The ceramic membrane has the advantages of small aperture, high temperature and pressure, high energy consumption, extremely low ginkgolic acid content in filtrate and no rear turbidity; the ultrafiltration membrane has moderate molecular weight, larger flux, higher yield of the ginkgo polysaccharide and lower impurity content; the nanofiltration membrane has moderate molecular weight cut-off, large operating pressure and high flux, but the shikimic acid has small loss, no acetic acid cut-off and high shikimic acid purity.

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 the ceramic membrane filtrate is good, and the turbidity is 1.0 NTU.

Comparative example 1

In the same manner as in example 3, only the ceramic membrane was replaced with an unactivated ceramic membrane, and the obtained ceramic membrane filtrate is shown in fig. 3, wherein after being filtered by the unactivated ceramic membrane, the obtained ceramic membrane filtrate contains 0.41% of ginkgo biloba polysaccharides, 0.65% of shikimic acid, and 3.5% of impurities; wherein, the turbidity of A is 12.5 NTU; the turbidity of B was 75.0 NTU.

The yield of the finally obtained ginkgo biloba 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 filtrate has poor quality, and the turbidity is 75NTU after the turbidity phenomenon occurs after 2 hours.

Example 5: the extraction of bilobalide is performed according to the scheme shown in figure 1:

(4) filtering and clarifying the gingko extracting centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate;

wherein the filtering temperature is 20 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4 m/s;

(6) adsorbing the organic phase obtained in the step (5) by 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 solution, wherein the flow rate of the ethanol is 4BV/h, and the using amount of the ethanol is 3 BV;

(7) concentrating the desorption solution obtained in the step (6) at 20 ℃ and 0.5MPa through a roll-type ultrafiltration membrane (the molecular weight cutoff is 800 Da);

(8) and (4) evaporating, crystallizing and drying the nanofiltration membrane concentrated solution in the step (7) to obtain the ginkgolides.

The ceramic membrane has the advantages of large aperture, low temperature and pressure, high flux, and high ginkgolic acid content in the filtrate; the nanofiltration membrane has higher molecular weight cut-off, lower pressure, lower flux and larger loss of ginkgolides.

The yield of the finally obtained ginkgolides is 75.6 percent, the purity of the ginkgolides is 93.6 percent, the removal rate of ginkgolic acid is 98.6 percent, and the turbidity of the ceramic membrane filtrate is 12NTU after the turbidity phenomenon occurs.

Example 6: the extraction of bilobalide is performed according to the scheme shown in figure 1:

(1) crushing ginkgo leaves to 5 meshes, leaching the ginkgo leaves by using a 60% ethanol solution at 50-80 ℃, and extracting for 6 times to obtain a crude extract of the ginkgo leaves;

(3) centrifuging the concentrated ginkgo leaf extract solution obtained in the step (2) for 10min by a 6000rpm/min disc centrifuge to obtain ginkgo leaf extract centrifugate;

wherein, before the activation modification of the ceramic membrane ultrafiltration membrane, the aperture of the support body is 2 μm, and the porosity is 30%; the aperture of the separation layer is 20 nm; the separation 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 ethanol solution with succinic acid as an activating agent;

wherein the filtering temperature is 60 ℃, the pressure is 0.2MPa, and the membrane surface flow rate is 4 m/s;

(6) adsorbing the organic phase obtained in the step (5) by 20-mesh polyamide resin (the flow rate is 1BV/h, the adsorption multiple is 1 time), desorbing by 75% ethanol to obtain desorption solution, wherein the flow rate of the ethanol is 1BV/h, and the using amount of the ethanol is 2 BV;

(7) concentrating the desorption solution obtained in the step (6) at 60 ℃ and 4.0MPa through a nanofiltration membrane to form a roll type ultrafiltration membrane (the molecular weight cutoff is 100 Da);

(b) placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating a 0.05mol/L succinic acid solution in a round-bottom flask to boil, and carrying out activation reaction for 5 hours, wherein the vacuum degree is 90 kPa;

(c) and (c) washing the ceramic membrane obtained in the step (b) with deionized water for three times, and drying for 4 hours at 100 ℃.

The ceramic membrane of the embodiment has smaller aperture, lower pressure, higher temperature, lower ceramic membrane flux, good filtrate quality and low ginkgolic acid content which is below 1 ppm; the nanofiltration membrane has low molecular weight cut-off and high pressure. The nanofiltration membrane has low filtration flux, but the yield of the ginkgolides in the step is high.

The yield of the finally obtained ginkgolide is 97.8 percent, the purity of the ginkgolide is 99.2 percent, the removal rate of ginkgoic acid is 99.9 percent, the quality of the ceramic membrane filtrate is good, and the turbidity is 4.5 NTU.

Example 7: the extraction of bilobalide is performed according to the scheme shown in figure 1:

(1) crushing ginkgo leaves to 40 meshes, leaching the ginkgo leaves by using a 60% ethanol solution at 50-80 ℃, and extracting for 6 times to obtain a crude extract of the ginkgo leaves;

(3) centrifuging the concentrated solution of ginkgo leaf extract obtained in the step (2) for 10min by a disc centrifuge at 8000rpm/min to obtain ginkgo leaf extract centrifugate;

(4) filtering and clarifying the gingko extraction centrifugate obtained in the step (3) by using an activated and modified ceramic ultrafiltration membrane, and removing impurities to obtain a ceramic membrane filtrate shown in a figure 4; wherein, the turbidity of A is 1.0 NTU; the turbidity of B was 2.0 NTU.

Before the activation modification of the ceramic membrane ultrafiltration membrane, the pore diameter of a support body is 2 mu m, and the porosity is 35%; the aperture of the separation layer is 30 nm; the separation 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 flow rate of the membrane surface is 4.5 m/s;

(6) adsorbing the organic phase obtained in the step (5) by 40-mesh polyamide resin (the flow rate is 3BV/h, the adsorption multiple is 4 times), desorbing by 75% ethanol to obtain desorption solution, wherein the flow rate of the ethanol is 1BV/h, and the using amount of the ethanol is 3 BV;

(7) concentrating the desorption solution obtained in the step (6) at 30 ℃ and 2.5MPa through a roll-type ultrafiltration membrane (the molecular weight cutoff is 150 Da);

(a) soaking the ceramic membrane in deionized water for 10h, and drying at 100 ℃ for 12 h;

(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 boil, and carrying out activation reaction for 6 hours, wherein the vacuum degree is 20 kPa;

(c) and (c) washing the ceramic membrane obtained in the step (b) with deionized water for three times, and drying at 100 ℃ for 12 hours.

The ceramic membrane has moderate aperture, temperature and pressure, high and stable flux, good filtrate quality, high ginkgolic acid removal rate up to 99.9%, and low content below 0.5ppm by detection; the nanofiltration membrane has moderate filtering pressure, larger flux and high yield of the ginkgolide, and is more suitable for industrial production.

The yield of the finally obtained ginkgolide is 98.3 percent, the purity of the ginkgolide is 99.5 percent, the removal rate of ginkgoic acid is 99.9 percent, the quality of the ceramic membrane filtrate is good, and the turbidity is 1.0 NTU.

Example 8: the extraction of bilobalide is performed according to the scheme shown in figure 1:

(1) crushing ginkgo leaves to 30 meshes, leaching the ginkgo leaves by using a 60% ethanol solution at 50-80 ℃, and extracting for 6 times to obtain a crude extract of the ginkgo leaves;

(3) centrifuging the concentrated solution of folium Ginkgo extract obtained in step (2) by a disk centrifuge at 6000rpm/min for 10min to obtain semen Ginkgo extract centrifugate;

before the activation modification of the ceramic membrane ultrafiltration membrane, the pore diameter of a support body is 2 mu m, and the porosity is 35%; the aperture of the separation layer is 5 nm; the separation 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 filtering temperature is 60 ℃, the pressure is 0.8MPa, and the membrane surface flow rate is 5 m/s;

(6) adsorbing the organic phase obtained in the step (5) by 40-mesh polyamide resin (the flow rate is 2BV/h, the adsorption multiple is 4 times), desorbing by 60% ethanol to obtain desorption solution, wherein the flow rate of the ethanol is 2BV/h, and the using amount of the ethanol is 2 BV;

(7) concentrating the desorption solution obtained in the step (6) at 30 ℃ and 2.5MPa through a nanofiltration membrane to form a roll type ultrafiltration membrane (the molecular weight cutoff is 150 Da);

(a) soaking the ceramic membrane in deionized water for 12h, and drying at 100 ℃ for 12 h;

(b) placing the ceramic membrane obtained in the step (a) in an activator, starting a vacuum device, heating a 0.1mol/L glutaric acid solution in a round-bottom flask to boil, and carrying out activation reaction for 2 hours, wherein the vacuum degree is 30 kPa;

The ceramic membrane has small pore size and high filtering temperature, the filtering pressure liquid to be maintained is high, the filtrate is filtered and clarified, but the phenomenon of back 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 low, the intercepted molecular weight of the nanofiltration membrane is proper, the pressure is moderate, the flux is high, and the yield of the ginkgolides is high.

The yield of the finally obtained ginkgolide is 94.3 percent, the purity of the ginkgolide is 99.1 percent, the removal rate of ginkgoic acid is 97.3 percent, the quality of the ceramic membrane filtrate is good, and the turbidity is 2.7 NTU.

Example 9: the extraction of bilobalide is performed according to the scheme shown in figure 1:

before the activation modification of the ceramic membrane ultrafiltration membrane, the pore diameter of a support body is 2 mu m, and the porosity is 35%; the aperture of the separation layer is 10 nm; the separation 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 filtering temperature is 30 ℃, the pressure is 0.6MPa, and the membrane surface flow rate is 3 m/s;

(6) adsorbing the organic phase obtained in the step (5) by 30-mesh polyamide resin (the flow rate is 3BV/h, the adsorption multiple is 3 times), desorbing by 70% ethanol to obtain desorption solution, wherein the flow rate of the ethanol is 2BV/h, and the using amount of the ethanol is 2 BV;

(7) concentrating the desorption solution obtained in the step (6) at 40 ℃ and 2.0MPa through a roll-type ultrafiltration membrane (the molecular weight cutoff is 300 Da);

(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 boil, and carrying out activation reaction for 4 hours, wherein the vacuum degree is 50 kPa;

The ceramic membrane has small aperture, moderate filtering temperature and relatively high pressure, and can ensure effective filtering and clarification. The ceramic membrane flux is low, the operation energy consumption is higher, but the filtrate quality is good, the rear turbidity phenomenon cannot be generated, and the content of ginkgoic acid is very low and is below 1 ppm; the nanofiltration membrane has slightly larger molecular weight cut-off and large flux, and the yield of the ginkgolides is slightly reduced compared with that of the embodiment 3.

The yield of the finally obtained ginkgolide is 92.9 percent, the purity of the ginkgolide is 98.5 percent, the removal rate of ginkgoic acid is 99.7 percent, the quality of the ceramic membrane filtrate is good, and the turbidity is 1.8 NTU.

Comparative example 2

As in example 7, only the ceramic membrane was replaced with an unactivated ceramic membrane and the resulting ceramic membrane filtrate is shown in fig. 5; wherein, the turbidity of A is 10.0 NTU; the turbidity of B was 78.0 NTU.

The yield of the finally obtained ginkgolides is 75%, the purity of the ginkgolides is 86%, the removal rate of ginkgolic acid is 43%, the quality of the ceramic membrane filtrate is poor, and the turbidity of the ceramic membrane filtrate after 2 hours is 78NTU (turbidity removal) phenomenon.

Example 10: extracting ginkgetin according to the flow chart shown in figure 1

(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 a ceramic membrane filtrate shown in figure 2, wherein the content of ginkgetin is 2.56%, and the content of impurities is 0.58%; turbidity of a was 3.0 NTU; turbidity of B was 1.0 NTU;

(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), desorbing by using ethanol, wherein the desorption flow rate is 3BV/h, and the using amount of an ethanol solution is 3 BV;

(7) concentrating the desorption solution obtained in the step (6) at 20 ℃ and 2.0MPa through a nanofiltration membrane (roll-type nanofiltration membrane with the molecular weight cutoff of 100 Da); and evaporating, crystallizing and drying the nanofiltration membrane concentrated solution to obtain the ginkgetin.

The ceramic membrane has proper aperture and moderate temperature and pressure, can ensure high flux of the ceramic membrane and lower content of ginkgolic acid in filtrate, and does not generate rear turbidity; the nanofiltration membrane has moderate molecular weight cut-off, large operating pressure and small flux, but the ginkgo flavone has small loss, no ethanol cut-off and high purity.

The yield of the finally obtained ginkgetin 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 is shown in fig. 3, wherein after being filtered by the unactivated ceramic membrane, the obtained ceramic membrane filtrate contains 2.47% of ginkgetin and 3.5% of impurities; the final yield of ginkgetin is 78.9%, the purity is 85.7%, and the removal rate of ginkgolic acid is 43%. The ceramic membrane filtrate has poor quality, and the turbidity is 75NTU after the turbidity phenomenon occurs after 2 hours.

The present invention provides a method and a concept for a process for simultaneously producing bilobalide, ginkgetin, ginko polysaccharide and shikimic acid, and a method and a way for implementing the technical scheme are numerous, and the above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, a plurality of improvements and modifications can be made without departing from the principle of the present invention, and the improvements and modifications should be regarded as the protection scope of the present invention. All the components not specified in the present embodiment can be realized by the prior art.

Claims

1. A production process for simultaneously producing ginkgolides, ginkgetin, ginkgopolysaccharides and shikimic acid is characterized by comprising the following steps:

2. The process according to claim 1, wherein in step (1), the ceramic membrane after the activation with organic acid is obtained by treating the ceramic membrane as follows: soaking the ceramic membrane in deionized water for 6-12 h, drying and activating by organic acid.

3. The production process according to claim 2, wherein the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and performing an activation reaction on the ceramic membrane by a vacuum vapor deposition method.

4. The production process according to claim 3, wherein the solvent of the organic acid solution is an alcohol compound; the concentration of the organic acid solution is 0.05-1 mol/L.

5. The production process according to claim 3, wherein the time of the activation reaction is 1 to 6 hours.

6. The production process according to any one of claims 1 to 3, wherein the ceramic membrane support has an average pore size of 2 to 5 μm; the average pore diameter of the separation layer of the ceramic membrane is 5-50 nm.

7. The production 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 6 m/s.

8. A process for preparing ginkgetin includes such steps as activating the liquid extract of gingko, filtering by ceramic membrane to obtain filtrate, extracting, adsorbing by resin, and desorbing to obtain the liquid containing ginkgetin.

9. The production process according to claim 8, wherein the organic acid is activated by placing the ceramic membrane in a closed container, heating the organic acid solution to boiling, and performing an activation reaction on the ceramic membrane by a vacuum vapor deposition method.

10. The production process according to claim 9, wherein the solvent of the organic acid solution is an alcohol compound; the concentration of the organic acid solution is 0.05-1 mol/L.