pH-Responsive Conductive Hydrogel with Amino Acid Sustained Release Function, Preparation Method and Application

Abstract

The present invention provides a pH-responsive conductive hydrogel with an amino acid slow-release function, its preparation method and application, which include the following steps: dispersing an amino acid in water and stirring to completely dissolve it to obtain a first solution; adding a templating agent to the first solution and stirring until it is fully dissolved to obtain a second solution; adding an oxidant to the second solution and stirring to mix evenly to obtain a third solution; adding a pyrrole monomer to the third solution and stirring for polymerization to obtain polypyrrole nanotubes encapsulated with amino acids; mixing the polypyrrole nanotubes encapsulated with amino acids with an amphoteric ion polymer hydrogel and stirring evenly to obtain the conductive hydrogel with an amino acid slow-release function. The polypyrrole nanotubes encapsulated with amino acids synthesized in the present invention have different ionization states of amino acids at different pH values, and by regulating the pH value of the hydrogel system, precise and effective control of the release or loading of the core material can be achieved.

Description

Technical Field

[0001] The present invention belongs to the field of intelligent hydrogels, and relates to a pH-responsive conductive hydrogel with amino acid slow-release function, a preparation method thereof, and an application thereof. Background Art

[0002] Nanogels simultaneously possess the dual characteristics of hydrogels and nanoparticles, and the nanoparticles endow them with the ability to load small molecules. The high hydrophilicity of nanogels can prolong the half-life of active ingredients in the human body, and the smaller particle size can be enriched at the tumor or other sites that need to act through the EPR effect. With its advantages such as high drug loading rate and good biocompatibility, it is considered an ideal drug delivery system. As an intelligent nanocarrier, stimulus-responsive nanogels can change their structural morphology, physical and chemical properties, etc. according to environmental changes and external stimuli. According to different trigger-response mechanisms, intelligent nanogels are divided into various types such as pH-responsive, temperature-responsive, pressure-responsive, magnetic field-responsive, etc. Compared with conventional hydrogels, intelligent nanogels have broad application prospects in the fields of controlled drug and gene release systems, biotechnology, soft robots, wearable devices, implantable biomedical sensors, etc.

[0003] When pH-responsive hydrogels are used in medical fields such as human tissue medical adhesives and implantable biomedical sensors, during the pathological changes such as human tissue healing and inflammatory reactions, they can achieve the controlled and slow release behavior of active ingredients according to different human body acid-base levels. However, the existing pH-responsive hydrogels have problems such as poor biocompatibility, high biological toxicity, uncontrollable stimulus-response mechanism, and poor mechanical properties, which restrict the application of pH-responsive hydrogels in this field. Summary of the Invention

[0004] Aiming at the problems existing in the prior art, the present invention provides a pH-responsive conductive hydrogel with amino acid slow-release function, a preparation method thereof, and an application thereof, so as to obtain a pH-responsive conductive hydrogel with good biocompatibility, precise core material controlled release, good pH-hydrogel charge response, and good mechanical properties.

[0005] The present invention is realized through the following technical solutions:

[0006] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0007] S1: Disperse amino acids in water and stir to completely dissolve them to obtain a first solution;

[0008] S2: Add a template agent to the first solution and stir until it is fully dissolved to obtain a second solution;

[0009] S3: Add an oxidizing agent to the second solution, stir and mix evenly to obtain a third solution;

[0010] S4: Add pyrrole monomer to the third solution, stir and polymerize to obtain polypyrrole nanotubes encapsulated with amino acids;

[0011] S5: Mix the polypyrrole nanotubes encapsulated with amino acids with a zwitterionic polymer hydrogel, stir evenly to obtain the conductive hydrogel with amino acid sustained-release function.

[0012] Preferably, the amino acid is any proportion combination of one or more of L-cysteine, cystine, alanine, glutamic acid, leucine, valine, proline, methionine, tryptophan, glycine, histidine or tyrosine.

[0013] Preferably, the template agent is any one of methyl orange, benzenesulfonic acid, cetyltrimethylammonium bromide, acid red G or cyclodextrin.

[0014] Preferably, when methyl orange is used as the template agent, the concentration range of methyl orange is 3 mmol / L to 5 mmol / L; when benzenesulfonic acid is used as the template agent, the concentration range of benzenesulfonic acid is 100 mmol / L to 5000 mmol / L; when cetyltrimethylammonium bromide is used as the template agent, the concentration range of cetyltrimethylammonium bromide is 800 mmol / L to 1200 mmol / L; when acid red G is used as the template agent, the concentration range of acid red G is 3 mmol / L to 5 mmol / L; when cyclodextrin is used as the template agent, the concentration range of cyclodextrin is 700 mmol / L to 1000 mmol / L.

[0015] Preferably, the oxidizing agent is FeCl 3 , Br 2 , KMnO 4 , (NH 4 ) 2 S 2 O 8 , H 2 O 2 , K 2 Cr 2 O 7 and KIO 3 Any one of them.

[0016] Preferably, the mass ratio of the pyrrole monomer to the amino acid is 1:(0.5 - 2.5).

[0017] Preferably, the molar ratio of the pyrrole monomer to the oxidizing agent is 1:(0.5 - 2.5).

[0018] Preferably, the mass ratio of the polypyrrole nanotubes wrapped with amino acids to the zwitterionic polymer hydrogel is (0.005 - 0.03):1.

[0019] A conductive hydrogel with amino acid sustained-release function is prepared by the above method. The shear adhesion force of the conductive hydrogel is greater than 1 KPa, the swelling ratio is greater than 1200%, and the water vapor transmission rate is greater than 2.8×10 8 g / (cm 2 ·h).

[0020] Application of the conductive hydrogel with amino acid sustained-release function prepared by the above preparation method in medical adhesives.

[0021] Compared with the prior art, the present invention has the following beneficial technical effects:

[0022] A preparation method of a conductive hydrogel with amino acid sustained-release function. During the synthesis process, the template agent effectively induces the polymerization of pyrrole monomers into polypyrrole nanotubes, and the polypyrrole nanotubes serve as the shell material. At the same time, the oxidant dopes the polypyrrole to improve its conductivity. During the synthesis of polypyrrole, polypyrrole and amino acids are combined through hydrogen bonds and electrostatic interactions, inducing the amino acids to be wrapped inside the tubular polypyrrole. Therefore, the amino acids serve as the core material. The present invention synthesizes polypyrrole nanotubes wrapped with amino acids by the template method. Amino acids have both acidic carboxyl groups and basic amino groups, and exhibit different ionization states at different pH values. The interaction mode with the positively charged polypyrrole nanotubes will also be different. The pH value will affect the loading and release of amino acids in the polypyrrole nanotubes. The zwitterionic polymer network is mainly composed of zwitterionic polymers, and each structural unit contains an equal amount of cationic and anionic groups. During the amino acid release process, charge interactions occur with amino acids with different charges, thereby affecting the charge of the entire hydrogel system. By regulating the pH value of the hydrogel system, precise and effective control of the release or loading of the core material can be achieved. The polypyrrole nanotubes have good biocompatibility. As one-dimensional linear materials, the nanotubes effectively ensure the mechanical properties of the nanomaterials.

[0023] Further, the template agent is methyl orange, benzenesulfonic acid, cetyltrimethylammonium bromide, acid red G or cyclodextrin. Such template agents are soft templates. After the reaction, they can be removed directly by washing, effectively simplifying the experimental method.

[0024] Further, effectively controlling the concentration range of the template agent effectively promotes the synthesis of polypyrrole nanotubes.

[0025] Furthermore, the mass ratio of pyrrole monomer to amino acid is 1:(0.5 - 2.5). On the one hand, the encapsulation amount of amino acid is satisfied. If the concentration of amino acid is too high, it cannot be fully encapsulated, resulting in waste of raw materials.

[0026] The present invention also provides a pH-responsive conductive hydrogel with amino acid sustained-release function. The shear adhesion force of the pH-responsive conductive hydrogel is greater than 1 KPa, and its mechanical properties are good. In addition, its swelling ratio is greater than 1200%, and its water vapor transmission rate is greater than 2.8×10 8 g / (cm 2 ·h), effectively meeting the air permeability requirements when it is used as a medical adhesive. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required in the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, so they should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0028] Figure 1 It is a schematic flow chart of synthesizing a conductive hydrogel with amino acid sustained-release function in the present invention;

[0029] Figure 2 It is a schematic structural diagram of polypyrrole nanotubes encapsulated with amino acids in the present invention;

[0030] Figure 3 It is a polypyrrole structure diagram;

[0031] Figure 4 It is a polypyrrole synthesis reaction equation;

[0032] Figure 5 It is a Fourier transform infrared spectrum diagram of polypyrrole nanotubes encapsulated with cystine and polypyrrole synthesized in Example 3;

[0033] Figure 6 It is for Figure 3 in the range of 1000 cm -1 ~1600 cm -1 local enlarged view;

[0034] Figure 7 It is the Zeta potential test results of polypyrrole nanotubes encapsulated with cystine, cystine, and polypyrrole nanotubes synthesized in Example 3 at different pH values;

[0035] Figure 8 It is a TEM diagram of polypyrrole nanotubes encapsulated with cystine synthesized in Example 3. DETAILED DESCRIPTION OF THE INVENTION

[0036] To enable those skilled in the art to understand the features and effects of the present invention, the following provides a general description and definition of the terms and phrases mentioned in the specification and claims. Unless otherwise specified, all technical and scientific terms used herein shall have the ordinary meanings understood by those skilled in the art for the present invention. In case of conflict, the definition in this specification shall prevail.

[0037] The theories or mechanisms described and disclosed herein, whether right or wrong, shall not in any way limit the scope of the present invention, that is, the content of the present invention can be implemented without being limited by any specific theory or mechanism.

[0038] In this document, all features defined in the form of numerical ranges or percentage ranges, such as numerical values, quantities, contents, and concentrations, are only for the sake of brevity and convenience. Accordingly, the description of a numerical range or percentage range should be regarded as having covered and specifically disclosed all possible sub-ranges and individual values within the range (including integers and fractions).

[0039] In this document, unless otherwise specified, the terms "comprising", "including", "containing", "having", or similar terms cover the meanings of "consisting of" and "consisting essentially of". For example, "A comprises a" covers the meanings of "A comprises a and others" and "A consists only of a".

[0040] In this document, for the sake of brevity, all possible combinations of all technical features in each embodiment or example are not described. Therefore, as long as there is no contradiction in the combination of these technical features, the technical features in each embodiment or example can be combined arbitrarily, and all possible combinations should be considered as within the scope described in this specification.

[0041] The present invention uses microcapsule technology to achieve the pH-responsive characteristics of the system. Microcapsule technology is a composite material technology that coats a polymer film on the surface of solid or liquid particles to form a core-shell structure. When the pH value of the system changes, the core material in the microcapsule can be encapsulated and released, and at the same time, the conductivity of the system can be adjusted. By monitoring the electrical signal, the response mechanism of the system pH value to the electrical signal of the conductive hydrogel can be realized. As a conductive polymer, polypyrrole has the characteristics of high conductivity, non-toxicity, and simple preparation. By controlling the reaction conditions, it can be prepared into various structures such as linear, hollow tubular, and granular. The present invention uses polypyrrole nanotubes as the shell material of the nanocapsule and amino acids as the core material to prepare a pH-responsive conductive hydrogel with amino acid sustained-release function. As the shell material, the tubular structure of polypyrrole can provide an effective capsule cavity, and its good conductivity is also beneficial to the construction of the entire response system. Amino acids are not only non-toxic and harmless to the human body, but also play an important role in regulating human body functions. Moreover, amino acids have both acidic carboxyl groups and basic amino groups, and have different ionization states at different pH values. The interaction mode with the positively charged polypyrrole nanotubes will also be different, and the pH value will affect the loading and release of amino acids in the polypyrrole nanotubes. Further, an amphoteric ion polymer is used as the base material of the hydrogel system. The amphoteric ion polymer network is mainly composed of amphoteric ion polymers. Each structural unit contains an equal amount of cationic and anionic groups. During the release process of amino acids, charge interactions occur with amino acids with different charges, thereby affecting the charge of the entire hydrogel system. By regulating the pH value of the hydrogel system, precise and effective control of the release or loading of the core material can be achieved. At the same time, by adjusting the conductivity of the gel system, the response mechanism of the system pH value to the electrical signal of the conductive hydrogel is realized. Polypyrrole nanotubes have good biocompatibility. As one-dimensional linear materials, the nanotubes effectively ensure the mechanical properties of the nanomaterials.

[0042] Specifically, as Figure 1 shown, a preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function in the present invention includes the following steps:

[0043] S1: Disperse amino acids in water and stir to completely dissolve them to obtain a first solution;

[0044] Among them, the amino acids are any proportion combination of one or more of L-cysteine, cystine, alanine, glutamic acid, leucine, valine, proline, methionine, tryptophan, glycine, histidine or tyrosine.

[0045] S2: Add a templating agent to the first solution and stir until it is completely dissolved to obtain a second solution;

[0046] Among them, the template agent is any one of methyl orange, benzenesulfonic acid, cetyltrimethylammonium bromide, acid red G or cyclodextrin. When methyl orange is used as the template agent, the concentration range of the methyl orange is 3 mmol / L to 5 mmol / L. When benzenesulfonic acid is used as the template agent, the concentration range of the benzenesulfonic acid is 100 mmol / L to 5000 mmol / L. When cetyltrimethylammonium bromide is used as the template agent, the concentration range of the cetyltrimethylammonium bromide is 800 mmol / L to 1200 mmol / L. When acid red G is used as the template agent, the concentration range of the acid red G is 3 mmol / L to 5 mmol / L. When cyclodextrin is used as the template agent, the concentration range of the cyclodextrin is 700 mmol / L to 1000 mmol / L.

[0047] S3: Add an oxidizing agent to the second solution, stir and mix evenly to obtain a third solution;

[0048] Among them, the oxidizing agent is FeCl 3 , Br 2 , KMnO 4 , (NH 4 ) 2 S 2 O 8 , H 2 O 2 , K 2 Cr 2 O 7 and KIO 3 Any one of them. By controlling the dosage of the oxidizing agent, polypyrrole nanotubes with different tube diameters can be synthesized.

[0049] S4: Add pyrrole monomer to the third solution, stir and polymerize, then wash the product multiple times until the pH value of the washing solution is 6 - 7, and dry the precipitate to obtain the polypyrrole nanotubes wrapped with amino acids. The average outer diameter of the polypyrrole nanotubes wrapped with amino acids is 80 - 200 nm. Before polymerization, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 80°C - 100°C, the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in the refrigerator for later use;

[0050] Among them, the mass ratio of the pyrrole monomer to the amino acid is 1:(0.5 - 2.5). The molar ratio of the pyrrole monomer to the oxidizing agent is 1:(0.5 - 2.5).

[0051] S5: Mix the polypyrrole nanotubes wrapped with amino acids with the zwitterionic polymer hydrogel, stir evenly to obtain a conductive hydrogel with amino acid slow-release function;

[0052] Among them, the mass ratio of the polypyrrole nanotubes wrapped with amino acids to the zwitterionic polymer hydrogel is (0.005 - 0.03):1.

[0053] The structural schematic diagram of the polypyrrole nanotubes wrapped with amino acids prepared in the present invention is as Figure 2 shown;

[0054] The structure diagram of the polypyrrole nanotubes in the present invention is shown in Figure 3 ;

[0055] The synthesis reaction equation of the polypyrrole nanotubes in the present invention is shown in Figure 4 .

[0056] The preparation method of the pH-responsive conductive hydrogel with amino acid slow-release function in the present invention has easy-to-control reaction conditions and a simple reaction process. The polypyrrole nanotubes wrapped with amino acids, as the core component, can be compounded with various types of zwitterionic polymer hydrogels. In specific usage scenarios, the preparation scheme of the zwitterionic polymer can be modularly optimized according to the usage target. This scheme has a wide range of applications and high application value.

[0057] The shear adhesion force of the conductive hydrogel with amino acid slow-release function prepared in the present invention is greater than 1 KPa, the swelling ratio is greater than 1200%, and the water vapor transmission rate is greater than 2.8×10 8 g / (cm 2 ·h). The present invention designs and synthesizes a pH-responsive intelligent zwitterionic polymer conductive hydrogel, the core component of which is a pH-responsive polypyrrole nanocapsule. Among them, polypyrrole is used as the shell material, which not only enhances the conductivity of the hydrogel as a conductive polymer nano-additive, but also serves as a nano-container to load amino acids. Amino acids are widely sourced, environmentally friendly, and biocompatible. By utilizing the structural characteristics of amino acids with amino and carboxyl groups, the goal of loading and releasing amino acids in the polypyrrole nanotubes under different pH conditions is achieved, realizing pH responsiveness and controllable slow release of amino acids. Further compounding with the zwitterionic polymer hydrogel constructs a pH-responsive conductive hydrogel with amino acid slow-release function. This pH-responsive intelligent zwitterionic polymer conductive hydrogel has excellent properties such as good pH responsiveness, controllable conductivity, monitorable response mechanism, and good biocompatibility, and can be applied to electronic skin, tissue adhesives, drug delivery carriers, wound dressings, soft robots, etc., with wide application value.

[0058] The preparation method of the zwitterionic polymer hydrogel used in the present invention is as follows:

[0059] In an ice-water bath at 0 °C, lithium magnesium silicate was uniformly dispersed in deionized water to obtain a first reaction solution; [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), N-[tris(hydroxymethyl)methyl]acrylamide (THMA), ammonium persulfate, and 4-cyano-4-(phenylthiocarbamothioyl) pentanoic acid were added to the first reaction solution and stirred evenly to obtain a second reaction solution; the second reaction solution was sealed and reacted at 20-40 °C for 24 h to obtain the zwitterionic polymer hydrogel.

[0060] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0061] Conventional instrument equipment in the art is used in the following embodiments. For the experimental methods without specific conditions noted in the following embodiments, they are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. Various raw materials are used in the following embodiments. Unless otherwise stated, commercially available products are used, and their specifications are conventional specifications in the art. In the specification of the present invention and the following embodiments, unless otherwise specified, "%" represents weight percentage, "parts" represents weight parts, and the ratio represents weight ratio.

[0062] Example 1

[0063] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0064] S1: Take 0.55 g of cystine and disperse it in 300 mL of deionized water, and stir at room temperature for 30 min to completely dissolve it.

[0065] S2: Take 300 mg of methyl orange and dissolve it in 300 mL of the above solution, and stir at room temperature for 5 h until completely dissolved. After dissolution, the solution becomes clear peach red;

[0066] S3: Slowly add 2.22 g of ferric chloride hexahydrate to the solution obtained in S2, and deep red flocculent precipitates immediately appear in the solution. Stir and mix evenly;

[0067] S4: Continue to stir rapidly for 50 min, then add 1.1 g of pyrrole monomer, observe that the solution turns black-green, and polymerize at room temperature (25 °C) for 24 h by in-situ polymerization to obtain polypyrrole nanotubes wrapped with cystine. The average outer diameter of the polypyrrole nanotubes wrapped with cystine is 80 nm. Filter by suction, and wash the product repeatedly with deionized water and absolute ethanol to remove the template, unreacted pyrrole monomer and Fecl3 ·6H 2 O until the pH value is neutral, then dry for later use. Before use, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 80 °C and the pressure is 0.08 MPa.

[0068] S5: Take 0.6 g of the product obtained above and add it to 70 g of the zwitterionic polymer hydrogel prepared according to the scheme in the present invention, stir and mix evenly to obtain a conductive hydrogel with amino acid sustained-release function.

[0069] Example 2

[0070] A preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function, comprising the following steps:

[0071] S1: Take 0.55 g of cystine and disperse it in 490 mL of water, stir at room temperature for 30 min to completely dissolve it.

[0072] S2: Take 300 mg of methyl orange and dissolve it in 300 mL of the above solution, stir at room temperature for 5 h until completely dissolved, and the solution becomes clear peach red after dissolution;

[0073] S3: Slowly add 2.22 g of ferric chloride hexahydrate to the solution obtained in S2, and dark red flocculent precipitates immediately appear in the solution, stir and mix evenly;

[0074] S4: Continue to stir rapidly for 50 min, then add 1.1 g of pyrrole monomer, observe that the solution turns black-green, polymerize at room temperature (25 °C) for 24 h by in-situ polymerization to obtain polypyrrole nanotubes encapsulated with cystine, and the average outer diameter of the polypyrrole nanotubes encapsulated with cystine is 90 nm. Filter by suction, and repeatedly wash the product with deionized water and absolute ethanol to remove the template, unreacted pyrrole monomer and Fecl 3 ·6H 2 O until the pH value is neutral, then dry for later use. Before use, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 80 °C and the pressure is 0.08 MPa.

[0075] S5: Take 0.6 g of the product obtained above and add it to 70 g of the zwitterionic polymer hydrogel prepared according to the scheme in the present invention, stir and mix evenly to obtain a conductive hydrogel with amino acid sustained-release function.

[0076] Example 3

[0077] A preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function, comprising the following steps:

[0078] S1: Dissolve 0.55 g of cystine in 490 mL of water, stir at room temperature for 30 min to completely dissolve it.

[0079] S2: Dissolve 300 mg of methyl orange in 300 mL of the above solution, stir at room temperature for 5 h until completely dissolved, and the solution turns into a clear peach red after dissolution;

[0080] S3: Slowly add 6.65 g of ferric chloride hexahydrate to the solution obtained in S2, and dark red flocculent precipitates immediately appear in the solution. Stir and mix evenly;

[0081] S4: Continue to stir rapidly for 50 min, then add 1.1 g of pyrrole monomer. Observe that the solution turns black-green, and polymerize at room temperature (25 °C) for 24 h by in-situ polymerization method to obtain polypyrrole nanotubes encapsulated with cystine, as Figure 8 shown. The average outer diameter of the polypyrrole nanotubes encapsulated with cystine is 100 nm. Filter by suction, and repeatedly wash the product with deionized water and absolute ethanol to remove the template, unreacted pyrrole monomer and Fecl 3 ·6H 2 O until the pH value is neutral, and dry for standby. Before use, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 80 °C and the pressure is 0.08 MPa.

[0082] S5: Take 0.6 g of the product obtained above and add it to 70 g of the zwitterionic polymer hydrogel prepared according to the scheme in the present invention, stir and mix evenly to prepare a conductive hydrogel with amino acid slow-release function.

[0083] Perform infrared spectrum test on the cystine@polypyrrole nanotube capsules synthesized in this example. The test results are shown in Figure 5 and Figure 6 . Figure 6 In, the infrared spectra of polypyrrole and cystine@polypyrrole both show the characteristic peaks of polypyrrole. The in-plane bending vibration absorption peaks of the C-H bonds on the pyrrole ring are at 1168 cm -1 and 1035 cm -1 . The C-N stretching vibration peak is at 1299 cm -1 . The characteristic stretching vibration peaks of C=C and =C-N in the polypyrrole ring are at 1542 cm -1 and 1460 cm -1 . These signal peaks prove that polypyrrole is successfully prepared. Figure 5 In, in addition to the characteristic absorption peaks of polypyrrole, cystine@polypyrrole shows the stretching vibration absorption peak of -NH in L-Cys at 3452 cm -1 , and at 1668 cm -1The stretching vibration absorption peak of the carbonyl group in L-Cys appears, proving the successful complexation of L-Cys and PNT.

[0084] Furthermore, in order to verify the pH-responsive characteristics of the conductive hydrogel with amino acid slow-release function, in this example, the Zeta potentials of cystine (L-Cys), polypyrrole nanotubes (PNT), and polypyrrole nanotubes coated with cystine (L-Cys@PNT) at different pH values were measured. The results are as Figure 7 shown. Cystine has two dissociable groups, a carboxyl group and an amino group. It carries a positive charge under acidic conditions and a negative charge under alkaline conditions, and its isoelectric point is pH = 5.02. As can be seen from the figure, the Zeta potential of cystine changes from positive to negative with the increase of pH value. The Zeta potential of polypyrrole nanotubes is always positive within the pH value change range, and its Zeta potential value increases with the increase of pH value. The Zeta potential of polypyrrole nanotubes coated with cystine changes from positive to negative with the increase of pH value. As shown in the figure, compared with the Zeta potential value of cystine, the Zeta potential value of polypyrrole nanotubes coated with cystine has changed significantly, indicating that cystine has adsorbed on the polypyrrole nanotubes, changing the charge-carrying situation of cystine. It can also be seen from the figure that when the pH value is less than 5, both cystine and polypyrrole nanotubes carry positive charges, and their charge polarities are the same, resulting in poor adsorption. When the pH value is greater than 5, cystine carries a negative charge and polypyrrole nanotubes carry a positive charge, and their charge polarities are opposite, resulting in strong adsorption. Therefore, different pH value conditions can regulate the loading and release of polypyrrole nanotubes on cystine.

[0085] Example 4

[0086] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0087] S1: Take 1.65 g of histidine and disperse it in 490 mL of water, and stir at room temperature for 30 min to completely dissolve it.

[0088] S2: Take 300 mg of methyl orange and dissolve it in 300 mL of the above solution, and stir at room temperature for 5 h until completely dissolved. After dissolution, the solution becomes a clear peach red;

[0089] S3: Slowly add 6.65 g of ferric chloride hexahydrate to the solution obtained in S2, and deep red flocculent precipitates immediately appear in the solution. Stir and mix evenly;

[0090] S4: Continue rapid stirring for 50 min, then add 1.1 g of pyrrole monomer. Observe that the solution turns blackish green, and polymerize it at room temperature (25 °C) for 24 h by in-situ polymerization to obtain polypyrrole nanotubes encapsulated with histidine. The average outer diameter of the polypyrrole nanotubes encapsulated with histidine is 150 nm. Perform suction filtration, and repeatedly wash the product with deionized water and absolute ethanol to remove the template, unreacted pyrrole monomer and Fecl 3 ·6H 2 O until the pH value is neutral, and dry it for standby. Before use, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 90 °C and the pressure is 0.08 MPa.

[0091] S5: Take 0.6 g of the above-obtained product and add it to 70 g of the zwitterionic polymer hydrogel prepared according to the scheme in the present invention, stir and mix evenly to obtain a conductive hydrogel with amino acid sustained-release function.

[0092] Example 5

[0093] A preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function, comprising the following steps:

[0094] S1: Take 1.65 g of histidine and disperse it in 490 mL of water, stir at room temperature for 30 min to completely dissolve it.

[0095] S2: Take 300 mg of methyl orange and dissolve it in 300 mL of the above solution, stir at room temperature for 5 h until completely dissolved, and the solution turns clear peach red after dissolution;

[0096] S3: Slowly add 6.65 g of ferric chloride hexahydrate to the solution obtained in S2, and dark red flocculent precipitates immediately appear in the solution, stir and mix evenly;

[0097] S4: Continue rapid stirring for 50 min, then add 1.1 g of pyrrole monomer. Observe that the solution turns blackish green, and polymerize it at room temperature (25 °C) for 24 h by in-situ polymerization to obtain polypyrrole nanotubes encapsulated with histidine. The average outer diameter of the polypyrrole nanotubes encapsulated with histidine is 170 nm. Perform suction filtration, and repeatedly wash the product with deionized water and absolute ethanol to remove the template, unreacted pyrrole monomer and Fecl 3 ·6H 2 O until the pH value is neutral, and dry it for standby. Before use, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 90 °C and the pressure is 0.08 MPa.

[0098] S5: Take 0.6 g of the above-obtained product and add it to 70 g of the zwitterionic polymer hydrogel prepared according to the scheme in the present invention, stir and mix evenly to obtain a conductive hydrogel with amino acid sustained-release function.

[0099] Example 6

[0100] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0101] S1: Disperse L-cysteine in water and stir to completely dissolve it to obtain a first solution;

[0102] S2: Add methyl orange to the first solution and stir until it is fully dissolved to obtain a second solution, wherein the concentration of methyl orange is 3 mmol / L;

[0103] S3: Add FeCl 3 , stir and mix evenly to obtain a third solution;

[0104] S4: Before polymerization, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 80 °C and the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in a refrigerator for later use; add the pyrrole monomer to the third solution, stir and polymerize, and then wash the product multiple times until the pH value of the washing solution is 6-7. Dry the precipitate to obtain polypyrrole nanotubes wrapped with L-cysteine; wherein, the mass ratio of the pyrrole monomer to L-cysteine is 1:0.5. The molar ratio of the pyrrole monomer to FeCl 3 is 1:0.5, and the average outer diameter of the polypyrrole nanotubes wrapped with L-cysteine is 200 nm.

[0105] S5: Mix the polypyrrole nanotubes wrapped with amino acids with the zwitterionic polymer hydrogel and stir evenly. Among them, the mass ratio of the polypyrrole nanotubes wrapped with amino acids to the zwitterionic polymer hydrogel is 0.005:1 to obtain a conductive hydrogel with amino acid slow-release function;

[0106] The conductive hydrogel with amino acid slow-release function prepared by the present invention has a shear adhesion force of 1.3 KPa, a swelling ratio of 1200%, and a water vapor transmission rate of 2.8×10 8 g / (cm 2 ·h).

[0107] Example 7

[0108] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0109] S1: Disperse alanine in water and stir to completely dissolve it to obtain a first solution;

[0110] S2: Add benzenesulfonic acid to the first solution and stir until it is fully dissolved to obtain a second solution, where the concentration of benzenesulfonic acid is 100 mmol / L;

[0111] S3: Add Br 2 to the second solution and stir to mix evenly to obtain a third solution;

[0112] S4: Before polymerization, the pyrrole monomer is purified by vacuum distillation. During the vacuum distillation process, the temperature is 90 °C and the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in a refrigerator for later use; add the pyrrole monomer to the third solution, stir and polymerize, and then wash the product multiple times until the pH value of the washing solution is 6 - 7. Dry the precipitate to obtain polypyrrole nanotubes wrapped with amino acids; among them, the mass ratio of the pyrrole monomer to alanine is 1:0.9. The molar ratio of the pyrrole monomer to Br 2 is 1:1, and the average outer diameter of the prepared polypyrrole nanotubes wrapped with amino acids is 95 nm.

[0113] S5: Mix the polypyrrole nanotubes wrapped with amino acids with an amphoteric ion polymer hydrogel and stir evenly. Among them, the mass ratio of the polypyrrole nanotubes wrapped with amino acids to the amphoteric ion polymer hydrogel is 0.01:1 to obtain a conductive hydrogel with an amino acid slow-release function;

[0114] The conductive hydrogel with an amino acid slow-release function prepared by the present invention has a shear adhesion force of 1.5 KPa, a swelling ratio of 1220%, and a water vapor transmission rate of 2.9×10 8 g / (cm 2 ·h).

[0115] Example 8

[0116] A preparation method of a pH-responsive conductive hydrogel with an amino acid slow-release function, comprising the following steps:

[0117] S1: Disperse glutamic acid in water and stir until it is completely dissolved to obtain a first solution;

[0118] S2: Add cetyltrimethylammonium bromide to the first solution and stir until it is fully dissolved to obtain a second solution, where the concentration of cetyltrimethylammonium bromide is 800 mmol / L;

[0119] S3: Add KMnO 4 to the second solution and stir to mix evenly to obtain a third solution;

[0120] S4: The pyrrole monomer is purified by vacuum distillation before polymerization. During the vacuum distillation process, the temperature is 100 °C and the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in a refrigerator for later use. Pyrrole monomer is added to the third solution, and after stirring and polymerization, the product is washed multiple times until the pH value of the washing liquid is 6 - 7. The precipitate is dried to obtain polypyrrole nanotubes encapsulated with amino acids. Among them, the mass ratio of pyrrole monomer to glutamic acid is 1:1.5. The molar ratio of pyrrole monomer to KMnO 4 is 1:1, and the average outer diameter of the prepared polypyrrole nanotubes encapsulated with amino acids is 100 nm.

[0121] S5: The polypyrrole nanotubes encapsulated with amino acids are mixed with zwitterionic polymer hydrogel and stirred evenly. Among them, the mass ratio of polypyrrole nanotubes encapsulated with amino acids to zwitterionic polymer hydrogel is 0.015:1 to obtain a conductive hydrogel with amino acid slow-release function.

[0122] The conductive hydrogel with amino acid slow-release function prepared by the present invention has a shear adhesion force of 1.7 KPa, a swelling ratio of 1250%, and a water vapor transmission rate of 3.1×10 8 g / (cm 2 ·h).

[0123] Example 9

[0124] A preparation method of a pH-responsive conductive hydrogel with amino acid slow-release function, comprising the following steps:

[0125] S1: Valine is dispersed in water and stirred to completely dissolve to obtain a first solution.

[0126] S2: Acid red G is added to the first solution and stirred until fully dissolved to obtain a second solution, where the concentration of acid red G is 3 mmol / L.

[0127] S3: (NH 4 ) 2 S 2 O 8 is added and stirred and mixed evenly to obtain a third solution.

[0128] S4: The pyrrole monomer is purified by vacuum distillation before polymerization. During the vacuum distillation process, the temperature is 100 °C and the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in a refrigerator for later use. Pyrrole monomer is added to the third solution, and after stirring and polymerization, the product is washed multiple times until the pH value of the washing solution is 6-7. The precipitate is dried to obtain polypyrrole nanotubes wrapped with amino acids. Among them, the mass ratio of pyrrole monomer to glutamic acid is 1:2. The molar ratio of pyrrole monomer to (NH 4 ) 2 S 2 O 8 is 1:1.5, and the average outer diameter of the prepared polypyrrole nanotubes wrapped with amino acids is 120 nm.

[0129] S5: The polypyrrole nanotubes wrapped with amino acids are mixed with an amphoteric ion polymer hydrogel and stirred evenly. Among them, the mass ratio of the polypyrrole nanotubes wrapped with amino acids to the amphoteric ion polymer hydrogel is 0.03:1 to obtain a conductive hydrogel with amino acid sustained-release function.

[0130] The conductive hydrogel with amino acid sustained-release function prepared by the present invention has a shear adhesion force of 1.9 KPa, a swelling ratio of 1260%, and a water vapor transmission rate of 3.2×10 8 g / (cm 2 ·h).

[0131] Example 10

[0132] A preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function, comprising the following steps:

[0133] S1: Proline is dispersed in water and stirred until it is completely dissolved to obtain a first solution;

[0134] S2: Cyclodextrin is added to the first solution and stirred until it is fully dissolved to obtain a second solution, where the concentration of cyclodextrin is 700 mmol / L;

[0135] S3: H 2 O 2 is added to the second solution and stirred and mixed evenly to obtain a third solution;

[0136] S4: The pyrrole monomer is purified by vacuum distillation before polymerization. During the vacuum distillation process, the temperature is 100 °C and the pressure is 0.08 Mpa. The purified pyrrole monomer is immediately sealed in a brown airtight bottle and refrigerated in a refrigerator for later use; Pyrrole monomer is added to the third solution, and after stirring and polymerization, the product is washed multiple times until the pH value of the washing solution is 6-7, and the precipitate is dried to obtain polypyrrole nanotubes coated with amino acids; Among them, the mass ratio of pyrrole monomer to glutamic acid is 1:2.5. The molar ratio of pyrrole monomer to H 2 O 2 is 1:2.5, and the average outer diameter of the polypyrrole nanotubes coated with amino acids prepared is 140 nm.

[0137] S5: The polypyrrole nanotubes coated with amino acids are mixed with zwitterionic polymer hydrogel and stirred evenly. Among them, the mass ratio of polypyrrole nanotubes coated with amino acids to zwitterionic polymer hydrogel is 0.03:1 to obtain a conductive hydrogel with amino acid slow-release function;

[0138] The conductive hydrogel with amino acid slow-release function prepared by the present invention has a shear adhesion force of 1.9 KPa, a swelling ratio of 1260%, and a water vapor transmission rate of 3.2×10 8 g / (cm 2 ·h).

[0139] Example 11

[0140] The difference from Example 6 is that the amino acid is methionine, the concentration of the template agent methyl orange is 4 mmol / L, and the oxidant is K 2 Cr 2 O 7 .

[0141] Example 12

[0142] The difference from Example 6 is that the concentration of the template agent methyl orange is 5 mmol / L.

[0143] Example 13

[0144] The difference from Example 7 is that the amino acid is tryptophan, the concentration of the template agent benzenesulfonic acid is 120 mmol / L, and the oxidant is KIO 3 .

[0145] Example 14

[0146] The difference from Example 7 is that the concentration of the template agent benzenesulfonic acid is 500 mmol / L.

[0147] Example 15

[0148] The difference from Example 7 is that the concentration of the template agent benzenesulfonic acid is 1000 mmol / L.

[0149] Example 16

[0150] The difference from Example 7 is that the amino acid is glycine and the concentration of the template agent benzenesulfonic acid is 2000 mmol / L.

[0151] Example 17

[0152] The difference from Example 7 is that the concentration of the template agent benzenesulfonic acid is 3000 mmol / L.

[0153] Example 18

[0154] The difference from Example 7 is that the amino acid is tyrosine and the concentration of the template agent benzenesulfonic acid is 5000 mmol / L.

[0155] Example 19

[0156] The difference from Example 8 is that the amino acid is a mixture of tyrosine and glycine, and the concentration of the template agent cetyltrimethylammonium bromide is 1000 mmol / L.

[0157] Example 20

[0158] The difference from Example 8 is that the amino acid is a mixture of cystine, alanine and glycine, and the concentration of the template agent cetyltrimethylammonium bromide is 1200 mmol / L.

[0159] Example 21

[0160] The difference from Example 9 is that the amino acid is a mixture of glutamic acid and leucine, and the concentration of the template agent acid red G is 4 mmol / L.

[0161] Example 22

[0162] The difference from Example 9 is that the amino acid is a mixture of tryptophan and glycine, and the concentration of the template agent acid red G is 5 mmol / L.

[0163] Example 23

[0164] The difference from Example 10 is that the amino acid is L-cysteine and the concentration of the template agent cyclodextrin is 800 mmol / L.

[0165] Example 24

[0166] The difference from Example 10 is that the amino acid is cystine and the concentration of the template agent cyclodextrin is 1000 mmol / L.

[0167] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

[0168] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. Preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function, Characterized in that, It includes the following steps: S1: Disperse amino acids in water and stir to completely dissolve them to obtain a first solution; S2: Add a template agent to the first solution and stir until it is fully dissolved to obtain a second solution; S3: Add an oxidant to the second solution and stir to mix evenly to obtain a third solution; S4: Add pyrrole monomers to the third solution and stir to polymerize to obtain polypyrrole nanotubes wrapped with amino acids; S5: Mix the polypyrrole nanotubes wrapped with amino acids with a zwitterionic polymer hydrogel and stir evenly to obtain the conductive hydrogel with amino acid sustained-release function.

2. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The amino acid is one or more of L-cysteine, cystine, alanine, glutamic acid, leucine, valine, proline, methionine, tryptophan, glycine, histidine or tyrosine in any proportion combination.

3. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The template agent is any one of methyl orange, benzenesulfonic acid, cetyltrimethylammonium bromide, acid red G or cyclodextrin.

4. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 3, Characterized in that, When methyl orange is used as the template agent, the concentration range of methyl orange is 3 mmol / L to 5 mmol / L; when benzenesulfonic acid is used as the template agent, the concentration range of benzenesulfonic acid is 100 mmol / L to 5000 mmol / L; when cetyltrimethylammonium bromide is used as the template agent, the concentration range of cetyltrimethylammonium bromide is 800 mmol / L to 1200 mmol / L; when acid red G is used as the template agent, the concentration range of acid red G is 3 mmol / L to 5 mmol / L; when cyclodextrin is used as the template agent, the concentration range of cyclodextrin is 700 mmol / L to 1000 mmol / L.

5. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The oxidant is FeCl 3 , Br 2 , KMnO 4 , (NH 4 ) 2 S 2 O 8 , H 2 O 2 , K 2 Cr 2 O 7 and KIO 3 Any one of them.

6. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The mass ratio of the pyrrole monomer to the amino acid is 1:(0.5 - 2.5).

7. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The molar ratio of the pyrrole monomer to the oxidant is 1:(0.5 - 2.5).

8. The preparation method of a pH-responsive conductive hydrogel with amino acid sustained-release function according to claim 1, Characterized in that, The mass ratio of the polypyrrole nanotubes wrapped with amino acids to the zwitterionic polymer hydrogel is (0.005 - 0.03):

1.

9. A conductive hydrogel with an amino acid sustained-release function, characterized in that Prepared by the method according to any one of claims 1 to 8, the shear adhesion force of the conductive hydrogel is greater than 1 KPa, the swelling ratio is greater than 1200%, and the water vapor transmission rate is greater than 2.8×10 8 g / (cm 2 ·h).

10. Application of the conductive hydrogel with an amino acid sustained-release function prepared by the preparation method according to any one of claims 1 - 8 in a medical adhesive.

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