阅读说明：本技术 一种自粘附性聚丙烯酰胺复合水凝胶及其制备方法与应用 (Self-adhesive polyacrylamide composite hydrogel and preparation method and application thereof ) 是由 董智贤 卢淑欣 庄梓明 于 2019-10-23 设计创作，主要内容包括：本发明涉及水凝胶技术领域,尤其涉及一种自粘附性聚丙烯酰胺复合水凝胶及其制备方法与应用。本发明公开了一种自粘附性聚丙烯酰胺复合水凝胶,包括：聚丙烯酰胺水凝胶和分散在所述聚丙烯酰胺水凝胶中的负载植物多酚的层状纳米无机化合物,其中,选用生物相容性好、比表面积大的层状纳米无机化合物作为载体,负载绿色可再生、价廉易得的植物多酚,将大量酚羟基功能团引入聚丙烯酰胺水凝胶中,赋予其良好的组织粘附性,层状纳米无机化合物又可以对聚丙烯酰胺网络起到增强作用。该水凝胶对多种基材和人体皮肤表现出极好的可重复粘附性,而且具有良好的柔韧性,可伴随人体关节运动伸展回缩,不发生脱落。(The invention relates to the technical field of hydrogel, in particular to self-adhesive polyacrylamide composite hydrogel and a preparation method and application thereof. The invention discloses a self-adhesive polyacrylamide composite hydrogel, which comprises the following components: the polyacrylamide hydrogel and the layered nano inorganic compound loaded with the plant polyphenol dispersed in the polyacrylamide hydrogel are characterized in that the layered nano inorganic compound with good biocompatibility and large specific surface area is selected as a carrier to load the green, renewable, cheap and easily-obtained plant polyphenol, a large amount of phenolic hydroxyl functional groups are introduced into the polyacrylamide hydrogel, so that the polyacrylamide hydrogel is endowed with good tissue adhesion, and the layered nano inorganic compound can play a role in enhancing a polyacrylamide network. The hydrogel shows excellent repeatable adhesion to various substrates and human skin, has good flexibility, can extend and retract along with the movement of human joints, and does not fall off.)

1. A self-adhesive polyacrylamide composite hydrogel is characterized by comprising: the plant polyphenol-loaded layered nano inorganic compound is dispersed in the polyacrylamide hydrogel;

The layered nano inorganic compound is selected from zirconium phosphate, laponite, montmorillonite, kaolin, hydrotalcite or mica.

2. The self-adhesive polyacrylamide composite hydrogel according to claim 1, wherein the layered nano inorganic compound loaded with plant polyphenol is obtained by mixing and drying a plant polyphenol aqueous solution and the layered nano inorganic compound.

3. The self-adhesive polyacrylamide composite hydrogel according to claim 2, wherein the mass concentration of the plant polyphenol aqueous solution is 0.2-4%;

The mass ratio of the plant polyphenol in the plant polyphenol water solution to the layered nano inorganic compound is 0.2-2: 1.

4. The self-adhesive polyacrylamide composite hydrogel according to claim 1, wherein the plant polyphenol is selected from tannin, procyanidin, catechin, quercetin, gallic acid, ellagic acid, arbutin or curcumin.

5. the self-adhesive polyacrylamide composite hydrogel according to claim 1, wherein the zirconium phosphate is α -nano zirconium phosphate;

The thickness of the single-layer of the alpha-nano zirconium phosphate is 5-20 nanometers, and the plane size of the sheet layer is 0.4-2 micrometers.

6. A preparation method of self-adhesive polyacrylamide composite hydrogel is characterized by comprising the following steps:

Mixing an acrylamide monomer, a cross-linking agent, an initiator and a layered nano inorganic compound loaded with plant polyphenol in an ice bath, and then carrying out polymerization reaction to obtain self-adhesive polyacrylamide composite hydrogel;

the layered nano inorganic compound is selected from zirconium phosphate, laponite, montmorillonite, kaolin, hydrotalcite or mica.

7. The production method according to claim 6,

The layered nano inorganic compound loading the plant polyphenol accounts for 0.5 to 5 percent of the mass of the acrylamide monomer;

The mass of the cross-linking agent is 0.02-0.2% of that of the acrylamide monomer.

8. The method according to claim 6, wherein the polymerization reaction is carried out at a temperature of 25 to 30 ℃ for 4 to 24 hours.

9. the method of claim 6, wherein the cross-linking agent is selected from the group consisting of N, N' -methylenebisacrylamide or ethylene glycol dimethacrylate;

The initiator is a redox initiator.

10. use of the self-adhesive polyacrylamide composite hydrogel according to any one of claims 1 to 5 or the self-adhesive polyacrylamide composite hydrogel prepared by the preparation method according to any one of claims 6 to 9 in skin repair, wound dressing, wound closure or wearable devices.

Technical Field

The invention relates to the technical field of hydrogel, in particular to self-adhesive polyacrylamide composite hydrogel and a preparation method and application thereof.

background

the hydrogel is a three-dimensional network structure material formed by hydrophilic macromolecules or polymers through covalent bonds, hydrogen bonds, van der waals force and other actions in a crosslinking mode, has the advantages of soft property, high water content, good biocompatibility, easiness in forming, controllable shape and size and the like, and has wide application prospects in the fields of three-dimensional tissue engineering substrates, drug carriers, biological composite materials, wearable equipment and the like. Most of the traditional polymer hydrogels are lack of tissue adhesion, and the development of self-adhesion hydrogel has more practical value in the fields of wearable bioelectronic equipment and artificial skin.

The preparation of hydrogels from adhesive in recent years has been inspired by mussels and was achieved by the introduction of dopamine in the hydrogel system. The byssus secretory protein of marine mussel organisms can realize high-strength and high-toughness adhesion on almost all substrate materials and is not influenced by water or a humid environment, and researches show that high-content levodopa (DOPA) and lysine in the adhesive protein secreted by the mussels are sources of strong adhesion force of the adhesive protein. The molecular structure of Polydopamine (PDA) is similar to that of mussel adhesive protein, and based on phenolic hydroxyl chemical reaction, the polydopamine can interact with a substrate covalently and/or non-covalently according to the surface properties of different substrates, so that the polydopamine can be adhered to the surface of the substrate. Therefore, researchers have tried to modify biocompatible materials including sodium alginate, gelatin, chitosan, hyaluronic acid, polyethyleneimine, polyethylene glycol, etc. with dopamine to prepare self-adhesive hydrogels; researchers also adopt dopamine modified carbon materials such as carbon nanotubes, graphene, carbon nanofibers and the like or mineral fillers such as clay, hydrotalcite and the like, and then compound the carbon materials with polyacrylic acid, polyacrylamide and the like to prepare the self-adhesive hydrogel.

The existing mussel-like hydrogel is mainly adhered to other substrates through three action mechanisms, namely, one action mechanism is to form an adhesive layer on the surface of the substrate through the non-covalent bond interaction of poly-dopamine phenolic hydroxyl and metal ions, such as chelation with metal ions such as Fe ³⁺, Ca ²⁺ and Mg ²⁺, the other action mechanism is to perform in-situ oxidation or crosslinking on dopamine, such as quinone-based crosslinking by using oxidized dopamine phenolic hydroxyl of sodium periodate or tyrosinase and the like and form covalent bonds with the substrate, the other action mechanism is to perform Michael addition reaction or Schiff base reaction on dopamine and amino groups, sulfydryl and the like on the surface of the substrate and form covalent bonds, the oxidation or crosslinking is generally performed in situ, the viscosity of the hydrogel is determined by the curing time, and the viscosity of the hydrogel is not longer after curing, so the existing mussel-like hydrogel is usually disposable and cannot be repeatedly used for multiple times, in addition, the dopamine is expensive and scarce in price and is not suitable for industrial large-scale production, and the color of the poly-dopamine is black, so that the appearance of hydrogel products is influenced.

Disclosure of Invention

The invention provides self-adhesive polyacrylamide composite hydrogel and a preparation method and application thereof, and solves the problems that dopamine used as a raw material for preparing existing mussel-like hydrogel is expensive and scarce in source; the color of the polydopamine is black, so that the appearance of the hydrogel product is influenced; the hydrogel is usually disposable, and cannot be reused for many times.

The specific technical scheme is as follows:

The invention provides a self-adhesive polyacrylamide composite hydrogel, which comprises the following components: the plant polyphenol-loaded layered nano inorganic compound is dispersed in the polyacrylamide hydrogel.

The plant polyphenol is a natural polyphenol substance which is widely present in plants, mainly exists in peels, roots, leaves and fruits of the plants, is rich in natural reserves, and is characterized in that the structure of the plant polyphenol has a large number of phenolic hydroxyl groups, and the structure of the plant polyphenol mainly contains ortho-phenolic hydroxyl groups of pyrogallol and catechol structures. A large number of phenolic hydroxyl groups in the plant polyphenol can play a role in complexing and crosslinking through various chemical bonds such as hydrogen bonds, ionic bonds, hydrophobic association and the like and intermolecular actions, and can also endow the hydrogel material with good adhesion to various substrate surfaces.

In the present invention, the plant polyphenol is selected from tannin, procyanidin, catechin, quercetin, gallic acid, ellagic acid, arbutin or curcumin.

the structural formula of the tannin is shown as a formula (I),

the tannin is also called tannin, tannic acid, gallotannic acid, tannin, larch tannin extract and the like, is yellow or light brown light amorphous powder or flake, has the molecular formula of C ₇₆ H ₅₂ O ₄₆, the molecular weight of 1701 and the water solubility of 250g/L (20 ℃), has pharmacological functions of oxidation resistance, inflammation diminishing, sterilization, astringency, hemostasis and the like, has obvious inhibiting effect on various pathogenic bacteria such as escherichia coli, cholera bacteria, staphylococcus aureus and the like, can be used for cosmetics and medical ointment for treating eczema, bedsore, hemorrhoid and the like, is a very mature industrial product, has low price and wide source, and has high hydroxyl ratio, so the plant polyphenol is preferably the tannin.

The layered nano inorganic compound is selected from zirconium phosphate, laponite, montmorillonite, kaolin, hydrotalcite or mica, and is preferably zirconium phosphate.

In the invention, the nano zirconium phosphate is alpha-nano zirconium phosphate (alpha-ZrP) and has a typical layered structure, the thickness of a single layer is 5-20 nanometers, and the plane size of the layer is 0.4-2 micrometers. In the alpha-ZrP laminated structure, the-POH group faces to the surface of the laminated plate, water molecules are positioned in a cavity of the crystal structure and form hydrogen bonds with P-OH, the acting force between layers is Van der Waals force, and the size of interlayer spacing can be changed by embedding, pillaring or bonding an organic group with a certain size. The alpha-ZrP has good biocompatibility, is insoluble in water and most organic solvents, can resist strong acid and certain alkalinity, and has high mechanical strength and chemical stability; the nano-sheet layer has large specific surface area and high charge density, and is easy to firmly combine with particles with opposite charges.

In the invention, the preferred zirconium phosphate is alpha-nano zirconium phosphate, belongs to a cationic nano layered compound, and has a single-layer thickness of 5-20 nm and a sheet plane size of 0.4-2 microns. The alpha-nano zirconium phosphate not only has the characteristics of other layered compounds, but also has unique properties: the alpha-nano zirconium phosphate has the advantages of good biocompatibility, simple preparation method, good crystal form, narrow particle size distribution, insolubility in water and most organic solvents, good acid and alkali resistance and thermal stability, stable layered structure, large specific surface area and surface charge density, and ion exchange capacity of 600mmol/100g which is 6 times of that of clay. More importantly, zirconium ions in the alpha-nano zirconium phosphate can also form a complex with the plant polyphenol ortho-position phenolic hydroxyl, so that a large amount of free phenolic hydroxyl of the plant polyphenol can be kept from being oxidized in the in-situ polymerization process of acrylamide, and the polymerization inhibition effect of the plant polyphenol phenolic hydroxyl on the polymerization reaction of the acrylamide monomer can be weakened. During the storage and use process, the plant polyphenol loaded by the nano zirconium phosphate can be gradually released, so that the polyacrylamide hydrogel has good repeatable adhesion to the surfaces of various substrates.

the invention uses alpha-nano zirconium phosphate (alpha-ZrP) to load plant polyphenol, and the plant polyphenol can be adsorbed on the surface and the interlayer of the alpha-ZrP through chemical adsorption, hydrogen bond, electric double layer electrostatic force and the like. The plant polyphenol adsorbed on the surface of the zirconium phosphate contains a large amount of hydroxyl, so that the hydrophilicity of the nano zirconium phosphate can be greatly improved, the nano zirconium phosphate can be stably dispersed in an aqueous solution for a long time, and the nano zirconium phosphate is prevented from settling in the polymerization process of acrylamide.

In the invention, the plane size and the specific surface area of the alpha-nano zirconium phosphate sheet layer are large, so that the adsorption, chain growth and termination of an acrylamide monomer active center on the surface of the alpha-nano zirconium phosphate sheet layer are facilitated, the polyacrylamide macromolecular chains are used as a multifunctional physical cross-linking agent among polyacrylamide macromolecular chains, and the polyacrylamide macromolecular chains are adsorbed on the surface of the alpha-nano zirconium phosphate sheet layer to form a special organic-inorganic network structure, so that the hydrogel has excellent mechanical properties. The polyacrylamide and alpha-nano zirconium phosphate nano composite hydrogel can only be prepared by in-situ polymerization and cannot be obtained by simply and physically blending a polymer and alpha-nano zirconium phosphate.

In the invention, the layered nano inorganic compound loaded with the plant polyphenol is preferably obtained by mixing and drying a plant polyphenol aqueous solution and the layered nano inorganic compound. Wherein the mass concentration of the plant polyphenol water solution is 0.2-4%, preferably 1-3%, more preferably 1%, 2% or 3%; the mass ratio of the plant polyphenol in the plant polyphenol water solution to the layered nano inorganic compound is (0.2-2): 1, preferably (0.5-1): 1 is more preferably 0.5: 1. 1.5: 1 or 1: 1; the mixing is preferably carried out using stirring; the stirring and mixing time is preferably 6-24 h, more preferably 6h, 12h or 24 h; after the mixing, centrifuging to take the precipitate and drying; the drying is preferably vacuum drying; the temperature of the vacuum drying is preferably 60 ℃, and the time is preferably 4-24 h; in the embodiment of the invention, the thickness of the single-chip layer of the plant polyphenol modified nano zirconium phosphate obtained after drying is 5-20 nanometers, and the plane size of the chip layer is 0.4-2 micrometers.

The invention also provides a preparation method of the self-adhesive polyacrylamide composite hydrogel, which comprises the following steps:

Mixing acrylamide monomer, cross-linking agent, initiator and layered nano inorganic compound loaded with plant polyphenol in ice bath, and then carrying out polymerization reaction to obtain the self-adhesive polyacrylamide composite hydrogel.

According to the invention, an acrylamide monomer, a cross-linking agent, an initiator and a layered nano inorganic compound loaded with plant polyphenol are mixed in an ice bath, wherein the temperature of the ice bath is preferably 0-5 ℃, more preferably 3 ℃, the mixing is preferably performed by adopting magnetic stirring, the rotating speed of the magnetic stirring is preferably 500-1000 rpm, more preferably 500-800 rpm, further preferably 500 rpm, and the time is preferably 0.5-2 h, more preferably 1 h;

After the mixing, the method further comprises the following steps: removing the ice bath and the magnetons, performing ultrasonic defoaming on the mixed solution, and then pouring the mixed solution into a mold for polymerization reaction; the polymerization reaction leads an acrylamide monomer to be polymerized in situ to form polyacrylamide, and simultaneously, the layered nano inorganic compound loaded with plant polyphenol is physically dispersed in the polyacrylamide to obtain the self-adhesive polyacrylamide composite hydrogel; the polymerization reaction temperature is 25-30 ℃, the time is 4-24 hours, preferably 25 ℃ and 12 hours.

In the invention, the cross-linking agent is selected from N, N '-methylene bisacrylamide or ethylene glycol dimethacrylate, preferably N, N' -methylene bisacrylamide;

The initiator is preferably a redox initiator;

The redox initiator includes: an oxidizing agent and a reducing agent; the oxidant comprises persulfate, chlorate or ammonium cerium nitrate; the reducing agent comprises N, N, N ', N' -tetramethyl ethylenediamine, sodium sulfite or thiourea.

In the present invention, the redox initiator is preferably: ammonium persulfate/N, N '-tetramethylethylenediamine, potassium persulfate/N, N' -tetramethylethylenediamine, ammonium persulfate/sodium sulfite, potassium persulfate/sodium sulfite, sodium chlorate/sodium sulfite, or ceric ammonium nitrate/thiourea.

The weight of the layered nano inorganic compound loaded with the plant polyphenol is 0.5-5 percent of that of the acrylamide monomer, and more preferably 1.45 percent; the mass of the cross-linking agent is 0.02-0.2% of the mass of the monomer, more preferably 0.029-0.058%, and further preferably 0.029%, 0.042% or 0.058%; in the redox initiator, the mass of the oxidizing agent is 0.1% to 0.5%, more preferably 0.23% to 0.3%, and still more preferably 0.3% or 0.23% of the mass of the monomer, and the mass of the reducing agent is 0.5% to 5% o, preferably 1.5% o or 3% o of the mass of the monomer.

The invention also provides application of the self-adhesive polyacrylamide composite hydrogel and the self-adhesive polyacrylamide composite hydrogel prepared by the preparation method in skin repair, wound dressing, wound suture or wearable equipment.

According to the technical scheme, the invention has the following advantages:

The invention provides a self-adhesive polyacrylamide composite hydrogel, which comprises the following components: the plant polyphenol-loaded layered nano inorganic compound is dispersed in the polyacrylamide hydrogel; the layered nano inorganic compound is selected from zirconium phosphate, laponite, montmorillonite, kaolin, hydrotalcite or mica.

According to the invention, a layered nano inorganic compound with good biocompatibility and large specific surface area is selected as a carrier, green, renewable, cheap and easily available plant polyphenol is used as a modifier, and is compounded with polyacrylamide in situ to prepare the hydrogel with self-adhesion, a large amount of phenolic hydroxyl groups of the plant polyphenol endows the hydrogel with super-strong adhesion, and the layered nano inorganic compound can also play a role in enhancing a polyacrylamide network. The polyacrylamide composite hydrogel is transparent, has self-adhesion performance, shows excellent repeatable adhesion (repeatable adhesion-stripping for more than 20 times) to various substrates such as skin, metal, glass, plastic, rubber and the like, has tensile strength of 170KPa and tensile deformation of more than 1700%, and has good flexibility. The polyacrylamide composite gel hydrogel has good adhesion to human skin, can stretch and contract along with human joint movement, cannot be peeled off or damaged in the joint movement process, is very easy to peel off from the skin after use, and has no pain, gel residue and stimulation to the skin in the peeling process.

the preparation method of the self-adhesive polyacrylamide composite hydrogel provided by the invention is simple and feasible, has wide raw material sources and low price, and is easy to realize industrial production.

Drawings

in order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without inventive exercise.

FIG. 1 is a scanning electron microscope image (20000 times magnified) of tannin-loaded alpha-nano zirconium phosphate provided in example 1 of the present invention;

FIG. 2 is an X-ray diffraction diagram of tannin-loaded alpha-nano zirconium phosphate and alpha-nano zirconium phosphate raw materials provided in example 1 of the present invention;

FIG. 3 is a scanning electron micrograph of a freeze-dried sample of the self-adhesive polyacrylamide composite hydrogel provided in example 1 of the present invention ((a) magnified 2000 times and (b) magnified 5000 times);

Fig. 4 is an experimental diagram of various substrates adhered by the self-adhesive polyacrylamide composite hydrogel provided in embodiment 1 of the present invention, wherein the substrates from left to right are a PMMA plate, a silicone rubber sheet, a titanium alloy back plate for a mobile phone, a glass screen for a mobile phone, and a hook in sequence;

Fig. 5 is an experimental graph of the adhesion of the self-adhesive polyacrylamide composite hydrogel to human skin provided in embodiment 1 of the present invention.

Detailed Description

In order to make the objects, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it should be apparent that the embodiments described below are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.