CN104119475B - A kind of surface-functionalized micro-nano polymer gel particle and preparation method thereof - Google Patents

Abstract

The invention discloses a polymer gel particle, in particular a surface-functionalized micro-nano polymer gel particle and a preparation method thereof. The chemical structure of the polymer gel particles contains acid anhydride groups and pyrrolidone groups at the same time, and is connected to form a cross-linked structure through a cross-linking agent. The polymer gel particles are formed by the reaction of methylene succinic anhydride, N-vinylpyrrolidone, and a crosslinking agent, and the amount ratio between methylenesuccinic anhydride, N-vinylpyrrolidone, and the crosslinking agent is The range is: (2 ~ 4): (1 ~ 2): (1 ~ 2); preferably, the range of the amount ratio between methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent is: (2～3):(1～1.5):(1～1.5). The surface-functionalized micro-nano polymer gel particles can be used in biomedical fields such as drug carriers, targeted preparations, cancer diagnosis, hepatitis detection, protein separation, cell separation, and immune absorption.

Description

A kind of surface functionalized micro-nano polymer gel particle and preparation method thereof

technical field

The invention belongs to the field of new materials, and relates to a polymer gel particle, in particular to a surface-functionalized micro-nano polymer gel particle and a preparation method thereof.

Background technique

Polymer micro-nanoparticles have the characteristics of large specific surface area, strong adsorption, strong agglutination, and strong surface reaction ability. They are widely used in the fields of medicine and biochemistry. They can be used in clinical testing, drug delivery, and diagnosis of cancer and hepatitis. , cell labeling, identification, isolation and culture, radioimmunosolid phase carrier and immune absorption, etc.

Targeted drugs can selectively reach specific diseased tissues of the human body and slowly release active ingredients in order to maximize the efficacy of the drug, while reducing the side effects of the drug system and reducing the number of administrations. Therefore, targeted drug delivery preparations have become Important content of modern pharmacy. In order for the drug to selectively reach the target tissue to exert its medicinal effect, it is necessary to attach the drug to a carrier with guiding effect through chemical bonding or physical adsorption, encapsulation, etc., to make a "missile" drug preparation. The key to targeted drug technology lies in the selection of carrier materials.

The carrier materials that have been developed so far include inorganic materials, biological macromolecules, synthetic polymers and other materials. Inorganic materials are mainly ferrite magnetic particles, silica particles and other materials. The preparation process is relatively mature. The main problem is that there are no organic functional groups on the surface, which makes it difficult to adsorb or bond drugs or other biomolecules. Complex chemical modification, cumbersome process. Natural biomacromolecules include chitosan and its derivatives, polyamino acids, albumin, liposomes, etc. These materials have good biocompatibility and degradability, but they are mainly dissolved or dispersed in water, with loose macromolecules Molecular coils or micelles exist and cannot form solid spherical particles, so the coating rate of drugs is low, the transport efficiency is low, and there is also the problem that the surface is difficult to modify, resulting in the specificity of liposomes and other nanoparticles to tissue cells. The identification is low and the targeting is not strong. Synthetic polymer carrier materials include polyanhydrides, polyorthoesters, polyalkylcyanoacrylates, polycaprolactone, polylactic acid, polyglycolic acid and their copolymers, etc. These materials have their own characteristics and can be modified to a certain extent, but the reactivity of the functional groups is not strong, and the functional groups are relatively single, and specific follow-up reactions are required to meet the actual application requirements. The preparation process of micro-nanoparticles as ingredients is relatively complicated.

The present invention aims to propose a micro-nano polymer gel particle having both highly reactive acid anhydride groups and highly complexing pyrrolidone groups and a preparation method thereof.

Contents of the invention

The purpose of the present invention is to overcome the shortcomings of the existing micro-nano polymer particles, and provide a surface-functionalized micro-nano polymer gel particle and a preparation method thereof.

The surface of the polymer gel particles contains reactive functional groups, which are beneficial to attach specific active substances, drugs, biomolecules, tumor targeting agents, antibodies, etc. through chemical bonding, thereby realizing micro-nano polymer gel particles multifunctional.

The present invention provides following technical scheme:

A surface-functionalized micro-nano polymer gel particle, the polymer gel particle, the polymer comprising the following structural units:

Where n is 10-10000, preferably 100-1000.

Preferably, the above-mentioned structural units are connected into a cross-linked structure through a cross-linking agent.

The chemical structure of the polymer gel particles contains both acid anhydride groups and pyrrolidone groups.

The acid anhydride group has high reactivity and can undergo reactions such as hydrolysis, saponification, esterification, acylation, and amidation.

The pyrrolidone group has complexation reactivity, and can carry out coordination complexation with transition metals containing empty orbitals, charge-absorbing halogens, drug molecules, and the like.

The copolymerized polymer micro-nanoparticles containing acid anhydride groups and pyrrolidone groups at the same time are gel particles with a new chemical composition, and the surface of the particles and the interior of the gel network contain highly reactive acid anhydride groups and pyrrolidone groups. These functional chemical groups can undergo a series of chemical and biochemical follow-up reactions, which provide great convenience for the post-functionalization of polymer gel particles such as chemical modification, biological modification, and drug complexation. The field has broad application value.

The present invention also discloses a preparation method of surface-functionalized micro-nano polymer gel particles. The preparation method comprises the following steps:

(1) mixing reactive monomers, polymerization initiators and solvents to form a mixed reaction solution;

(2) Nitrogen and oxygen discharge are carried out to the above-mentioned mixed reaction solution, and then heated to react to form a grayish blue to milky white colloidal dispersion system;

(3) separating the product obtained in step (2), and drying the separated product.

Preferably, the method comprises the steps of:

(1) Feed reactive monomer, polymerization initiator and solvent at one time according to the set ratio, fully dissolve and mix evenly;

(2) Nitrogen and oxygen are passed through the solution prepared in step (1) for 15-30 minutes;

(3) Heat the solution system in step (2) in a constant temperature water bath, the reaction temperature is 45-120°C, the reaction time is 5-600min, and the stirring rate is 0-450rpm;

(4) After the reaction is completed, a gray-blue to milky-white colloidal dispersion system is formed, and the obtained product is separated with a high-speed centrifuge at a speed of 5000-12000rpm;

(5) washing the centrifuged product with the solvent described in step (1), centrifuging and washing again, repeating 3-5 times, to wash away the residual monomer and initiator;

(6) Put the final centrifuged product into a vacuum oven, and dry it at a temperature of 50-80° C. to a constant weight to obtain micro-nano polymer gel particles.

Wherein, the reactive monomer includes: methylene succinic anhydride, N-vinylpyrrolidone, and a crosslinking agent. Preferably, the reactive monomer consists of methylene succinic anhydride, N-vinylpyrrolidone and a crosslinking agent.

Wherein, the range of the usage ratio among methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent is: (2-4): (1-2): (1-2). Preferably, the range of the amount ratio among methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent is: (2-3):(1-1.5):(1-1.5). The inventors of the present application unexpectedly found that micro-nano polymer gel particles can be obtained when the ratio of the three is within the aforementioned range, and the particles have good sphericity and uniform particle size.

Wherein, the crosslinking agent is a molecule having more than two polymerizable structures, such molecules include but not limited to: divinylbenzene, ethylene glycol dimethacrylate, N,N'-methylenebispropylene Amide, polyethylene glycol diacrylate.

The content of the monomer accounts for 1%-50% of the total solution, preferably 5%-20%; wherein, the content of the crosslinking agent accounts for 0.1%-15% of the total amount of other monomers, preferably 1%-10%.

Wherein, the polymerization initiator is selected from thermal polymerization initiators known to those skilled in the art, such initiators include but not limited to: cumene hydroperoxide, tert-butyl hydroperoxide, diisopropyl peroxide Benzene, di-tert-butyl peroxide, lauryl peroxide, dibenzoyl peroxide, tert-butyl peroxybenzoate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, At least one of azobisisobutyronitrile and azobisisoheptanonitrile.

The content of the polymerization initiator accounts for 0.01%-0.5% of the total solution, preferably 0.01%-0.1%.

Wherein, the solvent is very critical for realizing the polymerization reaction of methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent in the present invention to obtain micronano polymer gel particles. Described solvent must all have good dissolving effect for methylene succinic anhydride, N-vinylpyrrolidone, linking agent and initiator, to guarantee that it is homogeneous system before reaction; And, described solvent must be for generated The macromolecular chain of the copolymer cannot be dissolved, and when the macromolecular chain reaches a certain critical length, it will precipitate out of the medium to form micro-nano polymer gel particles dispersed in the reaction solvent.

Described solvent is selected from following three classes: (a) organic acid alkyl ester: formate, ethyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isopentyl acetate, acetic acid Benzyl ester, Methyl propionate, Ethyl propionate, Butyl propionate, Methyl butyrate, Ethyl butyrate, Butyl butyrate, Isoamyl butyrate, Methyl benzoate, Ethyl benzoate, Benzene Propyl formate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate; (b) ketones: acetone, methyl ethyl ketone, pentanone, cyclohexanone; (c) alkanes: n-hexane , cyclohexane, n-heptane. Preferably, the solvent is composed of organic acid alkyl esters, ketones, and alkanes.

Preferably, the range of the usage ratio among organic acid alkyl esters, ketones and alkanes is: (5-8):(1-3):(1-2). Preferably, the range of the usage ratio among organic acid alkyl esters, ketones and alkanes is: (6-7):(1-2):(1-1.5). More preferably, the solvent consists of butyl acetate, cyclohexanone and cyclohexane.

It should be noted that this polymerization reaction system can also react normally and obtain micro-nano polymer gel particles without adding a dispersant, which is the difference between the preparation method of the present invention and the general polymer gel particle preparation method.

Wherein, the stirring rate is 0-450rpm, that is, when the stirring rate is 0, the polymer latex particles can also be reacted normally and prepared. Compared with the reaction under stirring conditions, the shape and size of the particles will be different . This is another feature of the process for preparing polymer latex particles of the present invention.

The micro-nano polymer gel particle of the present invention is characterized by a transmission electron microscope, a particle size statistical analysis by a laser particle size analyzer, and a chemical structure analysis by a Fourier transform infrared spectrum.

The micro-nano polymer gel particles prepared by the present invention can have a particle size that can be regulated by process parameters such as reaction time, monomer concentration, crosslinking agent concentration, solvent combination, etc., and the particle size range is between 10nm-10μm, preferably between Between 20nm-5μm.

The prepared micro-nano polymer gel particle has uniform particle size, its particle size distribution index is between 1.0-1.3, and the particle size distribution is relatively narrow.

The particle size of the micro-nano polymer gel prepared by the present invention is uniform, and its chemical structure analysis shows that the molecular structure of the polymer contains acid anhydride groups and pyrrolidone groups at the same time, which is a new chemical composition of surface-functionalized micro-nano polymer gel particles.

A surface-functionalized micro-nano polymer gel particle and a preparation method thereof disclosed in the above technical solution have the following advantages:

1) Design and synthesize a new chemical composition of copolymerized polymer micro-nano gel particles, which contain highly reactive anhydride groups and pyrrolidone groups on the surface of the particles and inside the gel network, which can be easily chemically modified, biologically modified, Post-functionalization such as drug complexation has broad application value in the field of biomedicine;

2) The polymerization process of particle preparation is simple, and the reaction can be carried out without dispersant and stirring, and has the characteristics of self-dispersion and self-stabilization;

3) The particle size of micro-nano polymer gel particles can be controlled by process parameters such as reaction time, monomer concentration, cross-linking agent concentration, and solvent combination;

4) The product is easily separated by centrifugation, and the reaction medium used is a low-toxic chemical and can be recycled.

The surface-functionalized micro-nano polymer gel particles provided by the invention can be used in biomedical fields such as drug carriers, targeted preparations, cancer diagnosis, hepatitis detection, protein separation, cell separation, and immune absorption.

Description of drawings

FIG. 1 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 1.

2 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 2.

3 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 3.

FIG. 4 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 4. FIG.

5 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 5.

FIG. 6 is a transmission electron micrograph of the micro-nano polymer gel particles of Example 6. FIG.

Fig. 7 is an infrared spectrogram of the chemical structure of the micro-nano polymer gel particles of the present invention.

detailed description

The technical solutions of the present invention will be described in further detail below in conjunction with the accompanying drawings and examples. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

The appearance of a surface-functionalized micro-nano polymer gel particle disclosed in the present invention is shown in Figures 1-6 of transmission electron microscope pictures. The particle size of the polymer gel particles can be regulated by process parameters, and the particle size is relatively uniform.

The chemical structure of a surface-functionalized micro-nano polymer gel particle disclosed in the present invention is shown in the infrared spectrum diagram in FIG. 7 . The vicinity of 1779cm ^-1 and 1850cm ^-1 is the characteristic absorption of the anhydride group, and the vicinity of 1666cm ^-1 is the vibration absorption of the carbonyl (C=O) in the pyrrolidone ring. This absorption peak is very broad due to the resonance of the CN bond, and the wave number span At 30-35cm ^-1 . Infrared spectrum shows that the molecular structure of the micro-nano polymer gel particle of the present invention contains both acid anhydride groups and pyrrolidone groups, and is a surface-functionalized micro-nano polymer gel particle with a new chemical composition.

The preparation method of micro-nano polymer gel particles: Feed the reaction monomer, polymerization initiator, and solvent into the reactor equipped with nitrogen conduit, condenser, stirrer, and thermometer at one time according to the set ratio, fully dissolve and mix evenly ; Nitrogen and oxygen exhaust for 15-30min; heat the solution system in a constant temperature water bath, the temperature is 45-120°C, the time is 5-600min, the stirring rate is 0-450rpm; after the reaction is completed, the obtained product is separated by a high-speed centrifuge, The rotation speed is 5000-12000rpm; the centrifuged product is washed with a solvent, centrifuged and washed again, and repeated 3-5 times; the final centrifuged product is placed in a vacuum oven and dried at 60°C until it reaches a constant weight.

Wherein, the reactive monomer includes: methylene succinic anhydride, N-vinylpyrrolidone, and a crosslinking agent. Preferably, the reactive monomer consists of methylene succinic anhydride, N-vinylpyrrolidone and a crosslinking agent.

Wherein, the range of the usage ratio among methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent is: (2-4): (1-2): (1-2). Preferably, the range of the amount ratio among methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent is: (2-3):(1-1.5):(1-1.5). The inventors of the present application unexpectedly found that micro-nano polymer gel particles can be obtained when the ratio of the three is within the aforementioned range, and the particles have good sphericity and uniform particle size.

Wherein, the crosslinking agent is a molecule having more than two polymerizable structures, such molecules include but not limited to: divinylbenzene, ethylene glycol dimethacrylate, N,N'-methylenebispropylene Amide, polyethylene glycol diacrylate.

The content of the monomer accounts for 1%-50% of the total solution, preferably 5%-20%; wherein, the content of the crosslinking agent accounts for 0.1%-15% of the total amount of other monomers, preferably 1%-10%.

Wherein, the polymerization initiator is selected from thermal polymerization initiators known to those skilled in the art, such initiators include but not limited to: cumene hydroperoxide, tert-butyl hydroperoxide, diisopropyl peroxide Benzene, di-tert-butyl peroxide, lauryl peroxide, dibenzoyl peroxide, tert-butyl peroxybenzoate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, At least one of azobisisobutyronitrile and azobisisoheptanonitrile.

The content of the polymerization initiator accounts for 0.01%-0.5% of the total solution, preferably 0.01%-0.1%.

Wherein, the solvent is very critical for realizing the polymerization reaction of methylene succinic anhydride, N-vinylpyrrolidone and crosslinking agent in the present invention to obtain micronano polymer gel particles. Described solvent must all have good dissolving effect for methylene succinic anhydride, N-vinylpyrrolidone, linking agent and initiator, to guarantee that it is homogeneous system before reaction; And, described solvent must be for generated The macromolecular chain of the copolymer cannot be dissolved, and when the macromolecular chain reaches a certain critical length, it will precipitate out of the medium to form micro-nano polymer gel particles dispersed in the reaction solvent.

Described solvent is selected from following three classes: (a) organic acid alkyl ester: formate, ethyl acetate, butyl acetate, isobutyl acetate, sec-butyl acetate, pentyl acetate, isopentyl acetate, acetic acid Benzyl ester, Methyl propionate, Ethyl propionate, Butyl propionate, Methyl butyrate, Ethyl butyrate, Butyl butyrate, Isoamyl butyrate, Methyl benzoate, Ethyl benzoate, Benzene Propyl formate, butyl benzoate, isoamyl benzoate, methyl phenylacetate, ethyl phenylacetate; (b) ketones: acetone, methyl ethyl ketone, pentanone, cyclohexanone; (c) alkanes: n-hexane , cyclohexane, n-heptane. Preferably, the solvent is composed of organic acid alkyl esters, ketones, and alkanes.

Preferably, the range of the usage ratio among organic acid alkyl esters, ketones and alkanes is: (5-8):(1-3):(1-2). Preferably, the range of the usage ratio among organic acid alkyl esters, ketones and alkanes is: (6-7):(1-2):(1-1.5). More preferably, the solvent consists of butyl acetate, cyclohexanone and cyclohexane.

It should be noted that this polymerization reaction system can also react normally and obtain micro-nano polymer gel particles without adding a dispersant, which is the difference between the preparation method of the present invention and the general polymer gel particle preparation method.

Wherein, the stirring rate is 0-450rpm, that is, when the stirring rate is 0, the polymer latex particles can also be reacted normally and prepared. Compared with the reaction under stirring conditions, the shape and size of the particles will be different . This is another feature of the process for preparing polymer latex particles of the present invention.

The micro-nano polymer gel particles obtained under different preparation conditions were observed with HITACHIH-800 transmission electron microscope. Disperse and dilute the product after centrifugation and washing with a solvent, vibrate ultrasonically for 15 minutes, then use a dropper to draw a small amount of sample and drop it on the copper grid of the electron microscope, and let it dry naturally. The copper mesh has been covered with polyvinyl butyral support film, and the surface has been sprayed with carbon.

The particle size and particle size distribution of the polymer gel particles were measured with a MalvemMastersize2000 laser particle size analyzer. Disperse and dilute the product after centrifugation and washing with a solvent (the dilution rate is more than 1000 times), fully vibrate in an ultrasonic generator to disperse the particles, and then carry out instrumental analysis. The data statistical analysis method is as follows:

${\mathrm{<span\; class="notranslate">\; d</span>}}_{\mathrm{<span\; class="notranslate">\; no</span>}}<span\; class="notranslate">\; =</span>\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{\mathrm{<span\; class="notranslate">\; no</span>}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; d</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; /</span>\mathrm{<span\; class="notranslate">\; no</span>}$

${\mathrm{<span\; class="notranslate">\; d</span>}}_{\mathrm{<span\; class="notranslate">\; w</span>}}<span\; class="notranslate">\; =</span>\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{\mathrm{<span\; class="notranslate">\; no</span>}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; d</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}^{\mathrm{<span\; class="notranslate">\; 4</span>}}<span\; class="notranslate">\; /</span>\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{\mathrm{<span\; class="notranslate">\; no</span>}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; d</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}^{\mathrm{<span\; class="notranslate">\; 3</span>}}$

PDI＝ _dw / _dn

In the formula, d _i - single microsphere particle size; d _n - microsphere number average particle size; d _w - microsphere weight average particle size; n - sample volume; PDI - particle size distribution index.

The chemical structure of micro-nano polymer gel particles was determined by ThermoNicolet Nexus670 Fourier transform infrared spectrometer.

Example 1

Methylene succinic anhydride 0.65g, N-vinylpyrrolidone 0.25g, divinylbenzene 0.3g, dibenzoyl peroxide 0.01g, butyl acetate 72mL, cyclohexanone 12mL, n-hexane 15mL, add to 250mL Fully dissolve in a three-necked flask; pass nitrogen and oxygen for 20 minutes; heat the solution system in a constant temperature water bath to initiate polymerization reaction, keep the temperature at 85°C, and complete the reaction for 8 hours. The product was separated with a centrifuge at 5000 rpm, washed with butyl acetate, centrifuged again and washed three times; the final centrifuged product was placed in a vacuum oven and dried at 60°C until it reached a constant weight.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 1 . The average particle diameter of the particles is 76nm, and the particle size distribution index is 1.05, which is close to monodispersity.

Example 2

Other conditions were the same as in Example 1, except that the amounts of methylene succinic anhydride, N-vinylpyrrolidone, and divinylbenzene were 1.5 g, 0.8 g, and 1.2 g, respectively.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 2 . The average particle size of the particles is 115nm, and the particle size distribution index is 1.03, which is close to monodispersity, indicating that the particle size of the polymer gel particles increases with the increase of the monomer concentration.

Example 3

Other conditions are the same as in Example 1, except that the monomers used are: methylene succinic anhydride, N-vinylpyrrolidone, polyethylene glycol diacrylate, and the consumption of the three monomers is respectively 2.6g, 1.25g, 1.5g.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 3 . The average particle size of the particles is 212nm, and the particle size distribution index is 1.06, which is close to monodispersity, indicating that polymer gel particles can still be obtained by changing the type of crosslinking agent, and as the monomer concentration increases, the polymer gel particles particle size increases.

Example 4

The type and amount of the monomers used are the same as in Example 3, except that the mixed solvent used consists of: 70 mL of butyl acetate, 12 mL of cyclohexanone, and 10 mL of n-hexane.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 4 . The average particle size of the particles is 370nm, and the particle size distribution index is 1.05, which is close to monodispersity, indicating that the polymer gel can be adjusted by changing the type and proportion of the reaction solvent while the type and amount of the monomer remain unchanged. particle size.

Example 5

The type and amount of the monomers used are the same as in Example 3, except that the mixed solvent used consists of 65 mL of butyl acetate, 20 mL of cyclohexanone, and 10 mL of n-hexane.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 5 . The average particle size of the particles is 565nm, and the particle size distribution index is 1.13, indicating that with the increase of the amount of ketone solvent, the sphericity of the particles becomes worse, and there is adhesion between the particles.

Example 6

The type and amount of the monomers used are the same as in Example 3, except that the mixed solvent used consists of 65 mL of butyl acetate, 12 mL of cyclohexanone, and 20 mL of n-hexane.

The transmission electron micrograph of the obtained micro-nano polymer gel particles is shown in FIG. 6 . The average particle size of the particles is 768nm, and the particle size distribution index is 1.24, indicating that with the increase of the amount of alkane solvent, the sphericity of the particles becomes worse, and there is adhesion between the particles.

Comparative example 1

Other conditions are the same as in Example 1, except that the monomer does not contain the crosslinking agent divinylbenzene. The results showed that the obtained reaction product was a polymer colloidal substance, and the polymer gel particles could not be obtained, which indicated that the crosslinking agent was very important for the formation of the polymer gel particles.

Comparative example 2

Other conditions were the same as in Example 1, except that the amounts of methylene succinic anhydride, N-vinylpyrrolidone, and divinylbenzene were 2.6 g, 1.25 g, and 0.2 g, respectively. The results showed that: the obtained reaction product contained polymer colloidal substances, and there were a small amount of polymer gel particles but adhered to each other, indicating that the amount of cross-linking agent was very important for the formation of complete polymer gel particles.

Comparative example 3

Other conditions were the same as in Example 1, except that the mixed solvent used consisted of: 80 mL of cyclohexanone, 15 mL of n-hexane, and no butyl acetate. The results showed that the obtained reaction product was a polymer colloidal substance, and polymer gel particles could not be obtained. It shows that the solvent type and ratio are very important to the formation of polymer gel particles.

Comparative example 4

Other conditions were the same as in Example 1, except that the mixed solvent used consisted of: 65 mL of butyl acetate, 30 mL of cyclohexanone, and no n-hexane. The results show that the obtained reaction product contains polymer colloidal substances, and there are a small amount of polymer gel particles but adhere to each other, indicating that the solvent type and ratio are very important for the formation of complete polymer gel particles.

Comparative example 5

Other conditions were the same as in Example 1, except that the mixed solvent used consisted of: 65 mL of butyl acetate, 30 mL of n-hexane, and no cyclohexanone. The results show that the obtained reaction product contains polymer colloidal substances, and there are a small amount of polymer gel particles, but the sphericity is not good, and the particle size is uneven, indicating that the solvent type and ratio are very important for the formation of complete polymer gel particles .

It should be pointed out that the specific embodiments described above can enable those skilled in the art to understand the innovative invention more comprehensively, but it does not limit the innovative invention in any way. Therefore, although this specification has described the innovative invention in detail through the embodiments, those skilled in the art should understand that all technical solutions and improvements thereof that do not depart from the spirit and scope of the innovative invention should be included in the Among the protection scope of this innovative invention patent.

Claims (5)

1. a surface-functionalized micro-nano polymer gel particle, the chemical constitution of described polymer gel particle comprises following construction unit:

Wherein, n=10-10000;

Said structure unit is connected as cross-linked structure by cross-linking agent;

The chemical constitution of described polymer gel particle contains anhydride group and pyrrolidone group simultaneously;

Described anhydride group has high reaction activity, it is possible to be hydrolyzed, saponification, esterification, acidylate, amidation process;

Described pyrrolidone group has complex reaction activity, it is possible to carry out ligand complex with the transition metal containing unoccupied orbital, the halogen of suction electricity, drug molecule;

Further, described polymer gel particle is prepared by following step:

(1) in the disposable reaction monomers that feeds intake of setting ratio, polymerization initiator and solvent, fully dissolve, mix homogeneously;

(2) step (1) joined solution is carried out logical nitrogen deoxygenation, time 15-30min;

(3) solution system of step (2) is placed in water bath with thermostatic control and heats, reaction temperature 45-120 DEG C, response time 5-600min, stir speed (S.S.) 0-450rpm;

(4) after completion of the reaction, form ash blue to opalescent colloidal dispersion, the product high speed centrifuge obtained is separated, rotating speed 5000-12000rpm;

(5) with step (1) described solvent, centrifugal product being washed, recentrifuge separates, washing, repeats 3-5 time, to wash most residual monomer and initiator;

(6) final centrifugal product is put into vacuum drying oven, dry to constant weight at 50 DEG C of-80 DEG C of temperature, obtain micro-nano polymer gel particle;

Reaction monomers described in above-mentioned steps is itaconic anhydride and NVP and crosslinkers monomers, and the amount ratio between described itaconic anhydride, NVP, crosslinkers monomers three ranges for: (2～4): (1～2): (1～2); Described solvent is combined by organic acid alkylester did, ketone, alkanes, and the amount ratio between organic acid alkylester did, ketone, alkanes three ranges for: (5～8): (1～3): (1～2).

2. a preparation method for the surface-functionalized micro-nano polymer gel particle described in claim 1, described method comprises the steps of

(1) in the disposable reaction monomers that feeds intake of setting ratio, polymerization initiator and solvent, fully dissolve, mix homogeneously;

(2) step (1) joined solution is carried out logical nitrogen deoxygenation, time 15-30min;

(3) solution system of step (2) is placed in water bath with thermostatic control and heats, reaction temperature 45-120 DEG C, response time 5-600min, stir speed (S.S.) 0-450rpm;

(4) after completion of the reaction, form ash blue to opalescent colloidal dispersion, the product high speed centrifuge obtained is separated, rotating speed 5000-12000rpm;

(5) with step (1) described solvent, centrifugal product being washed, recentrifuge separates, washing, repeats 3-5 time, to wash most residual monomer and initiator;

(6) final centrifugal product is put into vacuum drying oven, dry to constant weight at 50 DEG C of-80 DEG C of temperature, obtain micro-nano polymer gel particle;

Reaction monomers described in above-mentioned steps is itaconic anhydride and NVP and crosslinkers monomers, and the amount ratio between described itaconic anhydride, NVP, crosslinkers monomers three ranges for: (2～4): (1～2): (1～2); Described solvent is combined by organic acid alkylester did, ketone, alkanes, and the amount ratio between organic acid alkylester did, ketone, alkanes three ranges for: (5～8): (1～3): (1～2).

3. method as claimed in claim 2, the amount ratio between itaconic anhydride, NVP, crosslinkers monomers three ranges for: (2～3): (1～1.5): (1～1.5).

4. method as claimed in claim 2 or claim 3, described crosslinkers monomers is the molecule with two or more polymerizable structure, is chosen in particular from divinylbenzene, Ethylene glycol dimethacrylate, N, N '-methylene-bisacrylamide or polyethyleneglycol diacrylate.

5. method as claimed in claim 2 or claim 3, the particle size range of the micro-nano polymer gel particle obtained is between 10nm-10 μm.