CN105801751A - Preparation and application of MIP (molecularly imprinted polymer) with tropane alkaloid drug specificity - Google Patents
Preparation and application of MIP (molecularly imprinted polymer) with tropane alkaloid drug specificity Download PDFInfo
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Abstract
The invention relates to the field of drug extraction, separation and purification, in particular to an MIP (molecularly imprinted polymer) with tropane alkaloid drug specificity. The MIP is mainly prepared from anisodine, methacrylic acid, trimethylolpropane trimethacrylate, 2,2'-azobis(2-methylpropionitrile) and a pore-foaming agent through a reaction, wherein the adding mole ratio of anisodine to methacrylic acid is 1:4-1:8, the adding mole ratio of trimethylolpropane trimethacrylate to methacrylic acid is 4:1-6:1, and the adding mole ratio of 2,2'-azobis(2-methylpropionitrile) to methacrylic acid is 15 mg:1 mmol-25 mg:1 mmol. Through selection of kinds and dosage of a solvent, a functional monomer, a crosslinking agent and an initiator and optimization of polymerization conditions, the MIP with better particle size distribution, physical stability and excellent adsorption is prepared, can selectively recognizing four tropane alkaloids and has good class specificity.
Description
Technical field
The present invention relates to pharmaceutical extraction and separate purification art, in particular to preparation and the application of a kind of tropane alkaloid drug specificity molecularly imprinted polymer.
Background technology
Alkaloid is the nitrogenous alkaline organic compound of class being widely present in nature, is the effective elements of the medicine in plant source, has significant physiologically active, and main manifestations is anticancer, antitumor, antiviral, antibacterial, antiinflammatory action.Generally, alkaloid kind is more, wherein tropane alkaloid is the main component that much plant source Chinese medicine plays clinical drug effect, these tropane alkaloids mainly include four classes such as hyoscyamine, scopolamine, Anisodine, Anisodamine, often coexist in plant source Chinese medicine, owing to its content is low, to such alkaloidal extraction with separate relative difficulty.At present, alkaloidal extracting method mainly has the extraction and separation technologies such as ultrasonic extraction, microwave radiation exaraction, supercritical fluid extraction, macroporous adsorbent resin technology, film extraction and separation technology, semi-bionic extraction technology.But substantial amounts of research data shows, the extract adopting said method obtained still needs to remove further impurity, just can obtain required effective ingredient.Additionally, plant source active ingredient of Chinese herbs is many, structure is complicated, add that content is low and unstability, result in its active component separation purification difficult.Separate purification at present and depend on silica gel column chromatography, macroporous adsorbent resin column chromatography, polyamide column chromatography, gel column chromatography, high performance countercurrent chromatography, preparative high performance liquid chromatography isochromatic spectrum technology.The active component high in order to obtain purity, need to extract and column chromatography repeatedly through multi-solvents, and not only solvent-oil ratio is big, environmental pollution serious, and efficiency and the response rate are also low.Therefore, find a kind of collect extracting and developing, purification integration alkaloid technology of preparing be have important practical significance.
Molecularly imprinted polymer (molecularlyimprintedpolymers, MIP) is a family macromolecule biomimetic material of engineer, and it can realize the specific recognition of pharmaceutical target molecule, enrichment and separation.MIP forms three-D space structure by the interaction of template molecule, function monomer and cross-linking agent, inside also exists in a large number and template molecule is in the molecular engram hole of the matched such as space structure, binding site, and template molecule has special identification ability and good affinity.This high molecular polymer does not only have the specific identification ability of similar enzyme and antibody, also has the chemical stability of uniqueness, the impact of the environmental factorss such as molecule distinguishability acid and alkali, alkali, heat, organic solvent.Therefore, MIP has the ability of selective extraction target molecule from complex sample, it is suitable as Solid-Phase Extraction (SPE) filler, solid-phase micro-extraction coating and chromatographic column filler etc., it is possible to achieve to the industrialization such as extracting and developing and purification and integration while target molecule.
At present, increase gradually about molecular imprinting application in the active ingredient of Chinese herbs separation purification such as flavone, alkaloid, polyphenol.The alkaloid with pharmacologically active usually has a variety of, but molecular engram is for the extraction of Chinese herbal medicine active component at present, it is all as object for single component, need to synthesize several molecularly imprinted polymer to be enriched with various active composition in batches, add active component extraction time and cost.Up to now, not yet once the technical scheme of the multiple alkaloidal molecularly imprinted polymer of Sync enrichment occurs.
In view of this, the special proposition present invention.
Summary of the invention
The first object of the present invention is in that to provide a kind of tropane alkaloid drug specificity molecularly imprinted polymer, described molecularly imprinted polymer can realize specific recognition, separation, enrichment and purification that tropane alkaloid pharmaceutical target molecule is carried out, and prior art can be solved cannot the multiple alkaloidal defect of Sync enrichment.
The second object of the present invention is in that the preparation method providing a kind of described tropane alkaloid drug specificity molecularly imprinted polymer, and microsphere is had good selectivity and evident characteristics by MIP prepared by the method, and operating condition is simple, it is simple to universal.
Present invention also offers described tropane alkaloid drug specificity molecularly imprinted polymer extracting and separating the application in purification Anisodine, scopolamine, Anisodamine, atropine.
In order to realize the above-mentioned purpose of the present invention, spy by the following technical solutions:
A kind of tropane alkaloid drug specificity molecularly imprinted polymer, described molecularly imprinted polymer is with Anisodine for template molecule, with methacrylic acid for function monomer, trimethylol-propane trimethacrylate is cross-linking agent, and azodiisobutyronitrile is initiator and removes template molecule with acetonitrile for porogen reaction and obtain.
Wherein, Anisodine (ASD) itself is one of alkaloid that the present invention to be enriched with, and its cost is comparatively cheap relative to other several tropane alkaloids, and containing the easily prepared dynamical MIP of the compound of highly polar group in molecule.
The selection of function monomer has a significant impact for the absorption property of molecularly imprinted polymer, it is necessary to select according to the structure of template molecule and fundamental property.Template molecule Anisodine selected by the present invention is alkalescence, thus has selected the methacrylic acid (MAA) of acidity as function monomer according to its characteristic present invention, can the extraordinary raising compound recognition reaction to template molecule.
In order to make the imprinted polymer of generation have certain spacial framework and stable binding site, the degree of cross linking that molecularly imprinted polymer requires is significantly high.Trimethylol-propane trimethacrylate (TRIM) preferred for this invention has the higher degree of cross linking (70～90%), and has good dissolubility in pre-polymer solution.
Mostly being radical initiation reaction in molecular engram polyreaction, therefore need to add initiator initiated polymerization when reaction, the preferred azodiisobutyronitrile of the present invention (AIBN) is as initiator.Azodiisobutyronitrile is oil-soluble azo initiator, and azo-initiator stable reaction is first order reaction, it does not have side reaction, relatively good control.
The effect of the actual also act as solvents of porogen.The selection of solvent plays an important role in prepared by molecular engram, and the morphology influence of intermolecular active force and MD is very big, and plays a part porogen.The solvent being generally selected to possess following 3 conditions: 1), can dissolve template molecule and function monomer；2), big opening can be formed；3), the interaction between template molecule and function monomer is disturbed little.The solvent of the active force type selecting suitable polarity that to be typically based between microsphere and function monomer possible, the polarity of solvent is more big, and the interference of molecular recognition is also more big, and adsorption rate is more low.Acetonitrile polarity of the present invention is little, and dielectric constant is low, simultaneously that the dissolubility of several reactants is also very good.
Preferably, tropane alkaloid drug specificity molecularly imprinted polymer as above:
The mol ratio that Anisodine adds with methacrylic acid is 1:(4～8)；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is (4～6): 1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is (15～25mg): 1mmol；
The ratio of Anisodine and acetonitrile is 1mol:(400～600ml).
The present invention adopts ultraviolet spectra predicted method to screen kind and the proportioning of function monomer.After template molecule interacts with MAA, 4-vinylpridine (4-VP) and 4-vinyl benzoic acid (4-VA), wavelength there occurs change in various degree, wherein the ultraviolet spectra maximum absorption band of ASD-MAA prepolymer there occurs significant red shift (as shown in Figure 3), this is likely due to the aobvious alkalescence of template molecule, not only there is π-pi-conjugated interaction, Hyarogen-bonding with MAA, can also forming stable ionic bond, therefore the present invention selects MAA as function monomer.
Simultaneously, according to the ultraviolet spectra map analysis (as shown in Figure 4) that the different ratio (1:4,1:6,1:8) of template molecule with function monomer obtains, when the ratio of template molecule Yu function monomer is 1:4, the red shift of wavelength of polymer is the most notable, therefore determines that it is the optimal proportion of template molecule and MAA.
Owing to the evident characteristics of molecularly imprinted polymer is not only relevant with function monomer interaction, the formation in its site, space is also relevant to other polymer conditions such as cross-linking agent, porogen, therefore, cross-linking agent TRIM and proportioning thereof and consumption are screened and optimized by the present invention respectively, has synthesized a series of polymer.As shown in Table 1, it is 1:5 that MIP5/10/15 represents template molecule with cross-linking agent mol ratio, and 1:10,1:15, equilibrium adsorption experiment result shows that MIP10 has maximal absorptive capacity and adsorption efficiency.Finally determine the best synthetic system of tropane alkaloid molecularly imprinted polymer.Result of the present invention shows, with Anisodine for template molecule, methacrylic acid is function monomer, trimethylol-propane trimethacrylate is cross-linking agent, acetonitrile is porogen, under the synthesis condition that ratio is 1:4:10 of template molecule, function monomer and cross-linking agent, polymer has good identification ability and characterization of adsorption.
By limiting kind and the ratio of above several main reactant, the invention provides the molecular blotting polymer microsphere that four kinds of tropane alkaloids are had simultaneously " class " specificity, selective absorption function.
The preparation method of tropane alkaloid drug specificity molecularly imprinted polymer described above, mainly comprises the steps that
1), Anisodine is dissolved in acetonitrile, adds methacrylic acid and carry out prepolymerization formation host-guest coordination compound；
2), prepolymerization add trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, after passing into inert gas shielding in the mixed solution obtained and sealing, water-bath concussion carries out polyreaction, obtains molecularly imprinted polymer；
3), by step 2) molecularly imprinted polymer of gained grinds, screening；It is eluted to by organic solution after eluent can not detect template molecule, cleans residual organic solution with methanol, after drying, obtain described tropane alkaloid drug specificity molecularly imprinted polymer.
The comparison of the different Polymer adsorption performance of table 1
The method starts from the mixed liquor of homogeneous microsphere, function monomer, cross-linking agent and initiator.Caused by initiator and produce polyreaction, obtain the particle diameter imprinted polymer in micro-nano scope uniform particle diameter.Function monomer, cross-linking agent and initiator that this polyreaction uses are solvable, but the polymer microballoon produced is insoluble and precipitate.Particle size ratio owing to obtaining is more uniform, and specific surface area is big, has more recognition site, and therefore absorption property is more excellent.
Preferably, the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as above, in step 1) in, described prepolymerized reaction condition is:
At 18～22 DEG C, ultrasonic prepolymerization 25～40min, ultrasonic frequency is 120～180Hz.
Preferably, the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as above, step 2) operation particularly as follows:
Prepolymerization adds trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, and passes into nitrogen 5～10min complete to deoxidation in the mixed solution obtained, 55～65 DEG C of water-bath concussions, 800～1200rpm polyreaction 22～26h after sealing.
Preferably, the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as above, in step 3) in, described screening was specially 700～900 mesh sieves.
Preferably, the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as above, in step 4) in, described organic solution is percentage by volume be 10～20% acetic acid methanol solution, the volume ratio of acetic acid and methanol is 3:7.
Acetic acid methanol solution is the mixed solution of acetic acid and methanol, wherein, the acetic acid methanol solution of 10% containing promising in water dissolved with 3% the acetic acid of (shared percent by volume, lower with) and 7% methanol；In like manner, the acetic acid methanol solution of 20% containing the promising methanol dissolved with the acetic acid of 6% and 14% in water.
Preferably, the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as above, in step 3) in, described drying is specially in 60～70 DEG C of vacuum drying 12～24h.
Tropane alkaloid drug specificity molecularly imprinted polymer as above is extracting and is separating the application in purification Anisodine, scopolamine, Anisodamine, atropine.
Preferably, apply as above, including following operation:
Acetone wet method is adopted to be filled in Solid-Phase Extraction void column and the tropane alkaloid medicine in sample is extracted and separates purification by described tropane alkaloid drug specificity molecularly imprinted polymer.
Solid phase extraction techniques comes across 20 century 70s, and early stage is mainly used in the research in the field such as pharmacy and clinical medicine.Similar with the principle of liquid chromatograph, utilize sample distribution ratio different between adsorbent from solvent, sample is adsorbed agent adsorption and enrichment, purification, it is achieved separate.
Molecularly imprinted polymer technology is combined by the present invention with solid phase extraction techniques, it may be achieved selective extracting and enriching component to be measured highly sensitive, high
Compared with prior art, the invention have the benefit that
1), the present invention is by selecting solvent, function monomer, cross-linking agent, the kind of initiator and consumption, aggregation condition, prepare the molecularly imprinted polymer with better particle size distribution, physical stability, excellent absorption property, can Selective recognition four kind tropane alkaloids similar with template molecule structure, there is good " class " specificity.
2), the preparation method of tropane alkaloid medicine provided by the invention be precipitation polymerization method, the method starts from the mixed liquor of homogeneous microsphere, function monomer, cross-linking agent and initiator.Caused by initiator and produce polyreaction, obtain the particle diameter imprinted polymer in micro-nano scope uniform particle diameter.Function monomer, cross-linking agent and initiator that this polyreaction uses are solvable, but the polymer microballoon produced is insoluble and precipitate.Particle size ratio owing to obtaining is more uniform, and specific surface area is big, has more recognition site, and therefore absorption property is more excellent.
3), the molecularly imprinted polymer preparation process of the present invention is simple, cost is low, and the saturated extent of adsorption of four kinds of tropane alkaloids is big, has good extraction ability.
4), molecularly imprinted polymer provided by the invention by with solid phase extraction techniques coupling, molecularly imprinted solid phase extraction column is prepared as filler, current universal solid-phase extraction column poor selectivity can be solved, problem that matrix effect is big, the problem that in the complex matrices such as Chinese medicine, the extraction efficiency of tropane alkaloid is low can also be solved, and can simultaneously four kinds of tropane alkaloids in selective cleaning, enriched sample, the response rate to four kinds of tropane alkaloids is 70.0～96.3%.This solid-phase extraction column repeat usage is high, good separation, it is possible to remove the interference of impurity in sample, the extraction efficiency being greatly improved in sample four kinds of tropane alkaloids.
Accompanying drawing explanation
In order to be illustrated more clearly that the embodiment of the present invention or technical scheme of the prior art, the accompanying drawing used required in embodiment or description of the prior art will be briefly described below.
Fig. 1 is the scanning electron microscope diagram of the tropane alkaloid drug specificity molecularly imprinted polymer of embodiment 4 preparation；
Fig. 2 is experimental example Middle molecule imprinted polymer MIP and the non-imprinted polymer NIP adsorption effect block diagram to four kinds of tropane alkaloids；
Fig. 3 is the ultraviolet spectrogram after template molecule interacts with MAA, 4-VP and 4-VA；
The ultraviolet spectrogram that Fig. 4 is template molecule to be obtained with the different ratio of function monomer.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, it will be appreciated by those skilled in the art that the following example is merely to illustrate the present invention, and are not construed as restriction the scope of the present invention.Unreceipted actual conditions person in embodiment, conventionally the condition of condition or manufacturer's suggestion carries out.Agents useful for same or the unreceipted production firm person of instrument, be and can pass through the commercially available conventional products bought and obtain.
Embodiment 1
The preparation method of tropane alkaloid drug specificity molecularly imprinted polymer, mainly comprises the steps that
1), Anisodine is dissolved in acetonitrile, adds methacrylic acid and carry out prepolymerization formation host-guest coordination compound；
2), prepolymerization add trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, after passing into inert gas shielding in the mixed solution obtained and sealing, water-bath concussion carries out polyreaction, obtains molecularly imprinted polymer；
3), by step 2) molecularly imprinted polymer of gained grinds, screening；It is eluted to by organic solution after eluent can not detect template molecule, cleans residual organic solution with methanol, after drying, obtain described tropane alkaloid drug specificity molecularly imprinted polymer.
Wherein, the mol ratio that Anisodine and methacrylic acid add is 1:6；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is 6:1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is 15mg:1mmol；
The ratio of Anisodine and acetonitrile is 1mol:400mL.
Embodiment 2
The preparation method of tropane alkaloid drug specificity molecularly imprinted polymer, mainly comprises the steps that
1), being dissolved in acetonitrile by Anisodine, add methacrylic acid, at 18 DEG C, ultrasonic prepolymerization 40min, the condition that ultrasonic frequency is 120Hz carries out prepolymerization, forms host-guest coordination compound；
2), prepolymerization adds trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, nitrogen 5min is passed into complete to deoxidation in the mixed solution obtained, seal rear 65 DEG C of water-baths concussion, 800rpm polyreaction 22h, obtain molecularly imprinted polymer.
3), by step 2) the molecularly imprinted polymer grinding of gained, excessively 700 mesh sieves, acetic acid methanol solution (volume ratio of acetic acid and methanol is 3:7) with 10% is eluted to after can not detecting template molecule in eluent, clean residual organic solution with methanol, be drying to obtain described tropane alkaloid drug specificity molecularly imprinted polymer.
Wherein, the mol ratio that Anisodine and methacrylic acid add is 1:8；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is 4:1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is 25mg:1mmol；
The ratio of Anisodine and acetonitrile is 1mol:400mL.
Embodiment 3
The preparation method of tropane alkaloid drug specificity molecularly imprinted polymer, mainly comprises the steps that
1), being dissolved in acetonitrile by Anisodine, add methacrylic acid, at 22 DEG C, ultrasonic prepolymerization 25min, the condition that ultrasonic frequency is 180Hz carries out prepolymerization, forms host-guest coordination compound；
2), prepolymerization adds trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, nitrogen 10min is passed into complete to deoxidation in the mixed solution obtained, seal rear 55 DEG C of water-baths concussion, 1200rpm polyreaction 26h, obtain molecularly imprinted polymer.
3), by step 2) the molecularly imprinted polymer grinding of gained, excessively 900 mesh sieves, acetic acid methanol solution (volume ratio of acetic acid and methanol is 3:7) with 20% is eluted to after can not detecting template molecule in eluent, clean residual organic solution with methanol, be drying to obtain described tropane alkaloid drug specificity molecularly imprinted polymer.
Wherein, the mol ratio that Anisodine and methacrylic acid add is 1:6；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is 5:1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is 20mg:1mmol；
The ratio of Anisodine and acetonitrile is 1mol:600mL.
Embodiment 4
The preparation method of tropane alkaloid drug specificity molecularly imprinted polymer, mainly comprises the steps that
Taking a certain amount of template molecule Anisodine and the mixing of function monomer methacrylic acid is dissolved in a certain amount of acetonitrile, at 20 DEG C, ultrasonic prepolymerization 30min, the condition that ultrasonic frequency is 150Hz carries out prepolymerization.Prepolymerization adds trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing.Logical nitrogen deoxidation 10min, sealed flask, at 60 DEG C, constant temperature water bath vibration polymerization 24h, rotating speed 1000rpm, obtains white suspension liquid.
By the polymer abrasive obtained after centrifugal, cross 800 mesh sieves, the elution template molecule of the acetic acid methanol solution (volume ratio of acetic acid and methanol is 3:7) with 15%, detect to supernatant without template molecule.5h is washed to remove acetic acid and the complete material of unreacted with methanol.At 70 DEG C, vacuum drying 12h, standby.
Wherein, the mol ratio that Anisodine and methacrylic acid add is 1:4；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is 5:1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is 20mg:1mmol；
The ratio of Anisodine and acetonitrile is 1mol:500mL.
The electron scanning micrograph of tropane alkaloid drug specificity molecularly imprinted polymer prepared by the present embodiment is as shown in Figure 1, as can be seen from Figure 1: molecularly imprinted polymer is circular microsphere, rough surface and rule, its particle diameter is mainly distributed on 3～4 microns, is suitable for Solid-Phase Extraction material.
Application examples
The MIP weighing 100mg is dissolved in 1mL acetone filling SPE post, uses sieve plate compacting.Successively with the pre-drip washing of 1mL acetonitrile, each 2mL activation of first alcohol and water before loading.It is 50 μ g/mL containing four kinds of alkaloidal standard solution loadings by 1mL concentration, adopts 1～3mL saturated normal hexane acetonitrile solution that solid-phase extraction column is carried out drip washing, with 2～5mL15～30% acetic acid methanol solution, solid-phase extraction column is carried out eluting.Collect eluent, be dissolved in after drying up in 1mL methanol, measure with HPLC.
According to the method described above with the molecularly imprinted solid phase extraction column of the present invention four kinds of tropane alkaloid medicines in Chinese medicine Tangut Przewalskia fruit being purified, are enriched with, response rate result is as shown in table 1.
Wherein ASD is Anisodine (Anisodine), SPM be scopolamine (Scopolamine), ASM be Anisodamine (Anisodamine), ATP is atropine (Atropinol).
Four kinds of alkaloid measurement results and the response rate (n=3) in table 2 Tangut Przewalskia fruit
Experimental example
The adsorption effect of four kinds of tropane alkaloid mixed standard solutions is detected by tropane alkaloid drug specificity molecularly imprinted polymer (MIP) and non-imprinted polymer (NIP).
The preparation method of matched group non-molecularly imprinted polymer (NIP) microsphere, with embodiment 4, is distinctive in that, is added without template molecule Anisodine in preparation process.
Weigh 5mg molecularly imprinted polymer MIP and non-imprinted polymer NIP in 10mL test tube, it is separately added into four kinds of tropane alkaloid mixed standard solution 2ml of finite concentration, vibration absorption 5h is carried out under room temperature, take supernatant after centrifugal and cross 0.45 μm of filter membrane, measure solution equilibria concentration after it adsorbs, calculate its equilibrium adsorption capacity.
MIP and the NIP of this experimental example is to the adsorption effect of four kinds of tropane alkaloid mixed standard solutions as shown in Figure 2.The adsorbance of four kinds of tropane alkaloid mixed standard solutions is above NIP by MIP as can be seen from Figure 2, illustrates that the absorption of four kinds of tropane alkaloids of concentration is belonged to class specific adsorption by MIP；Simultaneously it can also be seen that the absorption property of analog is had the certain difference, each analyte adsorption rate order on MIP to be by MIP by imprinted polymer: ASM > ATP > SPM > ASD.
This result purifies for this molecularly imprinted polymer as the filler of Solid-Phase Extraction, is enriched with four kinds of tropane alkaloids offer foundations.
Although illustrate and describing the present invention with specific embodiment, however it will be appreciated that may be made that when without departing substantially from the spirit and scope of the present invention many other change and amendment.It is, therefore, intended that include all such changes and modifications belonging in the scope of the invention in the following claims.
Claims (10)
1. a tropane alkaloid drug specificity molecularly imprinted polymer, it is characterized in that, described molecularly imprinted polymer is with Anisodine for template molecule, with methacrylic acid for function monomer, trimethylol-propane trimethacrylate is cross-linking agent, and azodiisobutyronitrile is initiator and removes template molecule with acetonitrile for porogen reaction and obtain.
2. tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 1, it is characterised in that:
The mol ratio that Anisodine adds with methacrylic acid is 1:(4～8)；
The mol ratio that trimethylol-propane trimethacrylate adds with methacrylic acid is (4～6): 1；
The ratio that azodiisobutyronitrile adds with methacrylic acid is (15～25mg): 1mmol；
The ratio of Anisodine and acetonitrile is 1mol:(400～600ml).
3. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer described in claim 1 or 2, it is characterised in that mainly comprise the steps that
1), Anisodine is dissolved in acetonitrile, adds methacrylic acid and carry out prepolymerization, form host-guest coordination compound；
2), prepolymerization add trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, after passing into inert gas shielding in the mixed solution obtained and sealing, water-bath concussion carries out polyreaction, obtains molecularly imprinted polymer；
3), by step 2) molecularly imprinted polymer of gained grinds, screening；It is eluted to by organic solution after eluent can not detect template molecule, cleans residual organic solution with methanol, after drying, obtain described tropane alkaloid drug specificity molecularly imprinted polymer.
4. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 3, it is characterised in that in step 1) in, described prepolymerized reaction condition is:
At 18～22 DEG C, ultrasonic prepolymerization 25～40min, ultrasonic frequency is 120～180Hz.
5. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 3, it is characterised in that step 2) operation particularly as follows:
Prepolymerization adds trimethylol-propane trimethacrylate and azodiisobutyronitrile after completing, and passes into nitrogen 5～10min complete to deoxidation in the mixed solution obtained, 55～65 DEG C of water-bath concussions, 800～1200rpm polyreaction 22～26h after sealing.
6. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 3, it is characterised in that in step 3) in, described screening was specially 700～900 mesh sieves.
7. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 3, it is characterized in that, in step 3) in, described organic solution is percentage by volume be 10～20% acetic acid methanol solution, the volume ratio of acetic acid and methanol is 3:7.
8. the preparation method of tropane alkaloid drug specificity molecularly imprinted polymer as claimed in claim 3, it is characterised in that in step 3) in, described drying is specially in 60～70 DEG C of vacuum drying 12～24h.
9. the tropane alkaloid drug specificity molecularly imprinted polymer described in claim 1 or 2 is extracting and is separating the application in purification Anisodine, scopolamine, Anisodamine or atropine.
10. apply as claimed in claim 9, it is characterised in that include following operation:
Acetone wet method is adopted to be filled in Solid-Phase Extraction void column and the tropane alkaloid medicine in sample is extracted and separates purification by described tropane alkaloid drug specificity molecularly imprinted polymer.
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