Surface enhanced transmission polyvinyl alcohol-based hydrogel and preparation method thereof

Abstract

The application discloses a surface-enhanced transmission polyvinyl alcohol-based hydrogel and a preparation method thereof. The preparation method comprises the following steps: preparing a polyvinyl alcohol solution, adding sodium alginate into the polyvinyl alcohol solution, stirring to make the sodium alginate completely dissolved in the polyvinyl alcohol solution, preparing a mixed solution, placing the mixed solution in a mold for pre-gelation, then performing a cyclic freezing-melting crosslinking treatment, after the treatment, placing the mixed solution in an ammonium sulfate-borax solution for immersion treatment, and finally preparing the polyvinyl alcohol-based hydrogel. The polyvinyl alcohol-based hydrogel has a three-dimensional network porous structure in the inside, the pore size of the porous structure is 200nm-8um, a hole expansion structure capable of enhancing transmission is formed on the surface, the pore size of the hole expansion structure is 10um-150um, and the hole expansion structure is communicated with the porous structure. The polyvinyl alcohol-based hydrogel provided by the application has excellent ion conductivity, drug release capacity, mechanical properties and adhesion.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of preparation of polyvinyl alcohol-based multifunctional hydrogel, in particular to a surface-enhanced transmission polyvinyl alcohol-based hydrogel and a preparation method thereof. BACKGROUND

[0002] Hydrogel is a three-dimensional network polymer material system formed by cross-linking of hydrophilic polymer chains, which has good water storage and moisture retention capacity, material exchange capacity and similar properties to extracellular matrix, and has been widely used in drug delivery and release, tissue repair, medical adjuvants and tissue engineering fields. Among them, polyvinyl alcohol (PVA) has good film-forming property, mechanical property, degradability and safety, and is one of the most widely used raw materials for biomedical hydrogel. Traditional gauze soaked with medicinal liquid needs to be fixed by additional bandage, and the drug will quickly release and flow to other parts of the body, resulting in insufficient drug effect. In contrast, polyvinyl alcohol-based hydrogel can be effectively attached to the wound site and is not easy to fall off, and has the function of slow-release drug, which can promote wound healing with slow-release drug and fully play the role of drug. However, when attaching to wounds such as burns and scalds, polyvinyl alcohol-based hydrogel has a long adhesion time, which can easily cause the temperature of the wound site to rise and increase the risk of infection. Therefore, how to regulate the drug slow-release capacity of polyvinyl alcohol-based hydrogel to complete drug delivery and release within a proper time is a research with great application value in the field of biomedicine.

[0003] At present, in order to better improve the slow-release ability of polyvinyl alcohol-based hydrogel, the method of forming macroporous polyvinyl alcohol hydrogel is mainly adopted to improve the drug delivery capacity. The Chinese patent application with the application number 201810356499.8 discloses a preparation method of sponge-like macroporous polyvinyl alcohol hydrogel. After polyethylene glycol is dissolved in polyvinyl alcohol solution, the mixed solution is phase separated by reducing the temperature, then nano-hydroxyapatite is added to the mixed solution which has been phase separated to stabilize the phase separation system, the hydrogel is formed by the method of cyclic freezing / melting, polyethylene glycol and nano-hydroxyapatite are washed out, and polyvinyl alcohol hydrogel with a pore size of 30-100 μm is obtained, which has a sponge-like appearance, elasticity and three-dimensional through-porous structure. Since the macroporous structure is a structural defect for the material, under the action of external force, the macroporous structure is more likely to cause the failure of the material. The Chinese patent application with the application number 202310030838.4 discloses a supermacroporous hydrogel and its preparation method and application. The supermacroporous hydrogel is formed by crosslinking sodium alginate and polyvinyl alcohol with calcium chloride as a crosslinking agent, and has high porosity (~85%) and large pore size (100-900 μm) in the interior, and also has excellent mechanical properties. However, since the calcium ions penetrate from the outside to the inside for crosslinking, the pore size of the formed macropore is distributed in a gradient manner from large to small in the interior, and the closer to the surface position, the smaller the pore size, which is not conducive to the transportation of the drug in the hydrogel from the interior to the surface to the wound site for release. Therefore, it is of great significance to improve the drug release capacity of multifunctional hydrogel and have good mechanical properties and adhesion properties to meet the application requirements of biomedical hydrogel. SUMMARY

[0004] The purpose of the present application is to provide a surface-enhanced transmission polyvinyl alcohol-based hydrogel and a preparation method, which can improve the drug release capacity of the hydrogel and have good mechanical properties and adhesion properties.

[0005] In a first aspect, the present application provides a preparation method of a surface-enhanced transmission polyvinyl alcohol-based hydrogel, which comprises the following preparation steps: configuring a polyvinyl alcohol solution, adding sodium alginate to the polyvinyl alcohol solution, stirring to make the sodium alginate completely dissolved in the polyvinyl alcohol solution, preparing a mixed solution, placing the mixed solution in a mold for pre-gelation, then performing cyclic freezing-melting crosslinking treatment, after completion, soaking in an ammonium sulfate-borax solution for soaking treatment, and finally preparing a polyvinyl alcohol-based hydrogel. A three-dimensional network porous structure is formed in the interior of the polyvinyl alcohol-based hydrogel, the pore size of the porous structure is 200 nm-8 μm, an expansion structure capable of enhancing transmission is formed on the surface of the polyvinyl alcohol-based hydrogel, the pore size of the expansion structure is 10 μm-150 μm, and the expansion structure is in communication with the porous structure.

[0006] Optionally, the pore size of the porous structure is 500 nm to 8 μm; and the pore size of the expanded hole structure is 10 μm to 150 μm.

[0007] Optionally, the pore size of the porous structure is 600 nm to 8 μm; and the pore size of the expanded hole structure is 25 μm to 150 μm.

[0008] Optionally, the polyvinyl alcohol solution is prepared by adding polyvinyl alcohol into deionized water, the mass ratio of the polyvinyl alcohol and the deionized water being 5 to 15: 45 to 180, and stirring the polyvinyl alcohol and the deionized water at 50 to 95 ℃ until the polyvinyl alcohol is completely dissolved in the deionized water.

[0009] Optionally, the polyvinyl alcohol solution is prepared by adding polyvinyl alcohol into deionized water, the mass ratio of the polyvinyl alcohol and the deionized water being 5 to 15: 45 to 180, and stirring the polyvinyl alcohol and the deionized water at 50 to 95 ℃ until the polyvinyl alcohol is completely dissolved in the deionized water.

[0010] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0011] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0012] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0013] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0014] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0015] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0016] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0017] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0018] Optionally, the mixed solution is prepared by adding sodium alginate into the polyvinyl alcohol solution, the mass ratio of the sodium alginate and the polyvinyl alcohol solution being 2 to 8: 45 to 180, and stirring the sodium alginate and the polyvinyl alcohol solution at 50 to 95 ℃ until the sodium alginate is completely dissolved in the polyvinyl alcohol solution.

[0019] The surface enhanced transmission polyvinyl alcohol-based hydrogel is immersed in the ammonium sulfate-borax solution for 1-9 hours, the ammonium sulfate-borax solution has an ammonium sulfate concentration of 20-40 wt%, and a borax concentration of 0.8-1.8 wt%.

[0020] In a second aspect, the present application provides a surface enhanced transmission polyvinyl alcohol-based hydrogel, which is prepared by the above-mentioned method.

[0021] Optionally, the surface enhanced transmission polyvinyl alcohol-based hydrogel has an ionic conductivity of 10.2-13.4 mS / cm, and a drug release efficiency of 59.1%-65.9%.

[0022] Optionally, the surface enhanced transmission polyvinyl alcohol-based hydrogel has a tensile strength of 1.36-1.77 MPa, a tensile strain of 862%-1074%, and an adhesion energy of 170.3-195.5 J / m 2 .

[0023] In summary, the present application has at least one of the following beneficial effects:

[0024] 1. The present application discloses a method for preparing a surface enhanced transmission polyvinyl alcohol-based hydrogel, which is prepared by using specific raw materials and preparation processes. A three-dimensional network porous structure of polyvinyl alcohol and sodium alginate is formed in the hydrogel, and a large-aperture hole expansion structure is formed on the surface of the hydrogel. The three-dimensional network porous structure enables the polyvinyl alcohol-based hydrogel to have excellent mechanical properties, especially high tensile strength and tensile strain, and can better stretch and deform to adapt to the shape of a surface wound. Correspondingly, the porous structure in the hydrogel has a small pore size of 200 nm-8 μm. The small-pore-size porous structure can maintain the good mechanical properties of the hydrogel while enabling the hydrogel to have high drug absorption and retention capacity. The hole expansion structure on the surface of the hydrogel has a large pore size of 10 μm-150 μm. The hole expansion structure is connected with the porous structure, and the large pore size has the function of enhancing transmission, which can promote the transmission of the drug contained in the porous structure of the hydrogel to the connected surface hole expansion structure, so that the drug contained in the porous structure of the hydrogel is quickly delivered and released to the surface wound, thereby promoting wound healing. At the same time, since the surface hole expansion structure expands the contact space between the porous structure in the hydrogel and the surface of the wound, the adhesion capacity of the hydrogel can be greatly improved, so that the hydrogel has good adhesion stability and reliability while having excellent drug release capacity. In addition, the hydrogel provided by the present application also has excellent conductivity. Under the action of an electric field, the hydrogel with conductivity can realize directional release of the drug, improve the therapeutic effect of the drug, and reduce side effects.

[0025] 2. The application provides a preparation method of surface enhanced transmission polyvinyl alcohol-based hydrogel, which has the advantages of simple operation, strong controllability, easy control, large-scale preparation and low cost, and can be widely promoted. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 is a scanning electron microscope photograph of the surface of the polyvinyl alcohol-based hydrogel prepared in Example 1 after freeze-drying;

[0027] Figure 2 is a mechanical property comparison curve of the polyvinyl alcohol-based hydrogel prepared in Example 1, Example 2, Example 3 and Comparative Example 1;

[0028] Figure 3 is a drug release performance comparison curve of the polyvinyl alcohol-based hydrogel prepared in Example 1, Example 2, Example 3 and Comparative Example 1;

[0029] Figure 4 is a scanning electron microscope photograph of the surface of the polyvinyl alcohol-based hydrogel prepared in Comparative Example 1 after freeze-drying. DETAILED DESCRIPTION

[0030] The application provides a surface enhanced transmission polyvinyl alcohol-based hydrogel and a preparation method, in order to make the purpose, technical scheme and effect of the application more clear and explicit, the application is further described in detail below. It should be understood that the specific examples described herein are only used to explain the application and not to limit the application.

[0031] Polyvinyl alcohol (PVA) is a water-soluble polymer material made from polymeric alcoholysis of vinyl acetate, which has good film-forming property, biocompatibility and safe biodegradability. The hydrogel formed by the three-dimensional cross-linked network structure of the polyvinyl alcohol aqueous solution gelatinized by the cyclic freezing-thawing method has simple preparation method, no toxicity and good repeatability. Sodium alginate (SA) is a sodium salt of alginic acid, which is an anionic linear polysaccharide. The double network hydrogel synthesized by SA and PVA can enhance the toughness and strength of the hydrogel, and the double network hydrogel has a porous structure, which is beneficial to absorbing and retaining liquid, easily absorbing biomolecules / drugs / antibiotics, and used for drug delivery and release. The pore diameter of the pore expanding structure formed on the surface of the hydrogel is larger than that of the internal porous structure, which is beneficial to promoting the transmission of the absorbed drugs in the hydrogel to the surface, promoting drug delivery and release, while maintaining the excellent mechanical properties of the double network hydrogel. In addition, the pore expanding structure can enhance the contact between the internal network structure and the surface of the wound, and improve the adhesion performance. The application is obtained on the basis of the above research.

[0032] In some embodiments of the present application, the present application provides a method for preparing a surface-enhanced transmission polyvinyl alcohol-based hydrogel, comprising the following preparation steps: configuring a polyvinyl alcohol solution, adding sodium alginate to the polyvinyl alcohol solution, stirring to completely dissolve the sodium alginate in the polyvinyl alcohol solution, preparing a mixed solution, placing the mixed solution in a mold for pre-gelation, then performing a cyclic freezing-thawing crosslinking treatment, after completion, placing in an ammonium sulfate-borax solution for soaking treatment, and finally preparing a polyvinyl alcohol-based hydrogel. The polyvinyl alcohol-based hydrogel has a three-dimensional network porous structure formed inside, the pore size of the porous structure is 200 nm to 8 μm, the surface of the polyvinyl alcohol-based hydrogel forms an expanded hole structure capable of enhancing transmission, the pore size of the expanded hole structure is 10 μm to 150 μm, and the expanded hole structure is in communication with the porous structure. Preferably, the pore size of the porous structure is 500 nm to 8 μm; the pore size of the expanded hole structure is 10 μm to 150 μm; more preferably, the pore size of the porous structure is 600 nm to 8 μm; the pore size of the expanded hole structure is 25 μm to 150 μm.

[0033] In some embodiments of the present application, the polyvinyl alcohol solution is configured, comprising:

[0034] The polyvinyl alcohol is added to the deionized water, the mass ratio of the polyvinyl alcohol to the deionized water is 5 to 15: 45 to 180, and the polyvinyl alcohol is completely dissolved in the deionized water by stirring at 50 to 95°C to prepare the polyvinyl alcohol solution. The stirring speed is 50 to 500 rpm / min. Preferably, the mass ratio of the polyvinyl alcohol to the deionized water is 8 to 12: 70 to 110; preferably, the polyvinyl alcohol is completely dissolved in the deionized water by stirring at 80 to 95°C.

[0035] In some embodiments of the present application, the sodium alginate is added to the polyvinyl alcohol solution, and the mixed solution is prepared by stirring to completely dissolve the sodium alginate in the polyvinyl alcohol solution, comprising:

[0036] The sodium alginate is added to the polyvinyl alcohol solution, the mass ratio of the sodium alginate to the polyvinyl alcohol solution is 2 to 8: 45 to 180, and the mixed solution is prepared by stirring at 50 to 95°C, and the stirring speed is 50 to 500 rpm / min. Preferably, the mass ratio of the sodium alginate to the polyvinyl alcohol solution is 4 to 6: 80 to 100; preferably, the stirring is performed at 80 to 95°C.

[0037] In some embodiments of the present application, the mixed solution is placed in a mold for pre-gelation, comprising:

[0038] The mixed solution is placed in a mold and left for 0.5 to 5 h. Preferably, it is left for 0.5 to 3 h.

[0039] In some embodiments of the present application, the cyclic freezing-thawing crosslinking treatment is performed, comprising:

[0040] The freezing temperature is -90℃ to -60℃, the freezing time is 6 to 10 hours, the thawing temperature is 50 to 70℃, and the thawing time is 10 minutes to 60 minutes.

[0041] In some embodiments of the present application, the cyclic freezing-thawing crosslinking is performed, comprising:

[0042] The freezing temperature is -85℃ to -75℃, the freezing time is 7 to 9 hours, the thawing temperature is 60 to 70℃, and the thawing time is 15 minutes to 35 minutes.

[0043] In some embodiments of the present application, the immersion treatment in the ammonium sulfate-borax solution is performed, comprising:

[0044] The immersion treatment in the ammonium sulfate-borax solution is performed for 1 to 9 hours, the ammonium sulfate concentration of the ammonium sulfate-borax solution is 20 to 40 wt%, and the borax concentration is 0.8 to 1.8 wt%. Preferably, the ammonium sulfate concentration is 25 to 35 wt%, and preferably, the borax concentration is 1.0 to 1.6 wt%.

[0045] In some embodiments of the present application, the surface-enhanced transport polyvinyl alcohol-based hydrogel has an ionic conductivity of 10.2 to 13.4 mS / cm and a drug release efficiency of 59.1% to 65.9%. Preferably, the ionic conductivity is 12.5 to 13.4 mS / cm, and the drug release efficiency is 65.2% to 65.9%.

[0046] In some embodiments of the present application, the surface-enhanced transport polyvinyl alcohol-based hydrogel has a tensile strength of 1.36 to 1.77 MPa, a tensile strain of 862% to 1074%, and an adhesion energy of 170.3 to 195.5 J / m 2 . Preferably, the tensile strength is 1.65 to 1.77 MPa, the tensile strain is 944% to 1074%, and the adhesion energy is 170.3 to 195.5 J / m 2 .

[0047] The present application is further described in detail below in conjunction with specific examples and comparative examples. In the specific examples of the present application, the raw materials are all commercially available unless otherwise specified.

[0048] Example 1

[0049] The present embodiment provides a surface-enhanced transport polyvinyl alcohol-based hydrogel and a preparation method, comprising the following steps:

[0050] S1. Preparation of polyvinyl alcohol solution: polyvinyl alcohol (G108396 polyvinyl alcohol, pharmaceutical grade, gel strength ~ 240g Bloom, Shanghai Aldrin Biochemical Technology Co., Ltd.) and deionized water were weighed according to the mass ratio, and the mass ratio of polyvinyl alcohol and deionized water was 10:90. The polyvinyl alcohol was added to the deionized water, and the polyvinyl alcohol was completely dissolved in the deionized water under the condition of 90℃ water bath stirring for 4h, the stirring speed was 250rpm / min, and the polyvinyl alcohol solution was prepared;

[0051] S2. Preparation of mixed solution: sodium alginate powder and the above polyvinyl alcohol solution were weighed according to the mass ratio, and the mass ratio of sodium alginate powder (S100128, Shanghai Aldrin Biochemical Technology Co., Ltd.) and the above polyvinyl alcohol solution was 5:90. The sodium alginate powder was added to the polyvinyl alcohol solution, and the sodium alginate powder was completely dissolved in the polyvinyl alcohol solution under the condition of 90℃ water bath stirring for 3h, the stirring speed was 250rpm / min, and the mixed solution was prepared;

[0052] S3. Preparation of hydrogel: the prepared mixed solution was poured into the mold and pre-gelled for 1.5h, and then cross-linked by 3 cycles of freezing-thawing, the freezing temperature was-80℃, the freezing time was 8h, the thawing temperature was 60℃, and the thawing time was 20min. After completion, it was immersed in an ammonium sulfate-borax solution for 6h, the concentration of ammonium sulfate in the solution was 30wt%, and the concentration of borax in the solution was 1.2wt%, and finally the polyvinyl alcohol-based hydrogel was prepared.

[0053] Microstructure test:

[0054] The microstructure of the polyvinyl alcohol-based hydrogel was characterized by scanning electron microscope (SEM). Figure 1 is the scanning electron microscope image of the surface of the polyvinyl alcohol-based hydrogel prepared by freezing drying in step S3 of example 1, from Figure 1 It can be seen from the figure that the polyvinyl alcohol-based hydrogel has a three-dimensional network porous structure, the pore size of the porous structure is 500nm-5μm, the surface of the polyvinyl alcohol-based hydrogel has an enlarged hole structure for enhancing transmission, the pore size of the enlarged hole structure is 15μm-120μm, and the enlarged hole structure is connected with the porous structure.

[0055] Mechanical property test:

[0056] A universal mechanical testing machine was used to test the tensile properties of the polyvinyl alcohol-based hydrogel. The polyvinyl alcohol-based hydrogel prepared in step S3 of Example 1 was cut to prepare a tensile sample (the size of the sample was 12*4*2 mm), and the tensile rate was 100 mm / min. The tensile stress and strain were calculated according to the initial cross-sectional area and initial length of the sample. The tensile stress-strain curve of the polyvinyl alcohol-based hydrogel of Example 1 is shown in Figure 2 , the tensile strength of the polyvinyl alcohol-based hydrogel of Example 1 was 1.65 MPa, and the tensile strain was 1074%. It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 1 has excellent mechanical properties.

[0057] Ion conductivity test:

[0058] An electrochemical workstation was used to test the conductivity of the polyvinyl alcohol-based hydrogel. The polyvinyl alcohol-based hydrogel prepared in step S3 of Example 1 was cut to prepare a conductivity test sample (the size of the sample was 12*4*2 mm), and the test sample was connected to the test port of the electrochemical workstation. The electrical signal transmitted out can be used to calculate the ion conductivity of the test sample, and the calculation formula is: δ = L / RS, δ is the ion conductivity; L is the length of the test sample, S is the cross-sectional area of the test sample; R is the resistance. The ion conductivity of the polyvinyl alcohol-based hydrogel of Example 1 was 12.5 mS / cm. It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 1 has excellent conductivity.

[0059] Adhesion test:

[0060] A universal mechanical testing machine was used to test the adhesion of the polyvinyl alcohol-based hydrogel. The polyvinyl alcohol-based hydrogel prepared in step S3 of Example 1 was cut to prepare an adhesion sample, and the size was 70 mm x 20 mm. A layer of chitosan adhesive was uniformly coated on the range of 45 mm from one end (the coating amount was 0.5 μL / mm 2 ), and then immediately covered with a frozen pig skin strip with a size of 70 mm x 20 mm (average thickness 2.8 mm). After pressing for 1 h, the pig skin sample was soaked in a near-neutral phosphate buffered saline solution (PBS buffer) for 2 h to balance the pH. The non-adhesion side of the hydrogel and the pig skin sample was adhered to a rigid polyester film using 502 strong glue, and the free end of the rigid polyester film adhered with the hydrogel and the pig skin was clamped with a clamp for peeling, and the peeling rate was 24 mm / min. The force and displacement during peeling were recorded. The adhesion energy was defined as the work done by the adherend per unit area, and the calculation formula was E is the adhesive energy, F and x are the force and displacement in the peeling test, L is the maximum displacement when the hydrogel is completely separated from the pigskin, and S is the adhesive area (45 mm x 20 mm) coated with the chitosan adhesive. The adhesive energy of the polyvinyl alcohol-based hydrogel of Example 1 is measured to be 195.5 J / m2. 2 It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 1 has excellent adhesive properties.

[0061] Drug release test:

[0062] 2 mg of the antibacterial drug ciprofloxacin is fully dissolved in 20 mL of deionized water, and the polyvinyl alcohol-based hydrogel sample (the size of the sample is 5 cm*10 cm) prepared in the final step S3 of Example 1 is immersed in the ciprofloxacin solution. After the polyvinyl alcohol-based hydrogel sample completely absorbs the solution, it is placed in a dialysis bag (MW: 3500) and 7 mL of a phosphate buffer solution with a pH of 7.4 is added. The dialysis bag is placed in a conical flask containing 50 mL of the phosphate buffer solution, and is incubated at 37°C with constant shaking (frequency of 100 rpm). Samples are taken at 10, 30, 40, 80, 90, 150 and 160 min, and the absorbance is measured. The cumulative drug release amount is calculated according to the formula A=ε*c*l, where A is the absorbance, ε is the molar absorption coefficient, c is the concentration of the solute in the solution (mol / L), and l is the thickness of the solution (cm). As shown in Figure 3 It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 1 has excellent drug release capacity.

[0063] Example 2

[0064] This example provides a preparation method of a polyvinyl alcohol-based hydrogel, which comprises the following steps:

[0065] S1. Prepare a polyvinyl alcohol solution: according to the mass ratio, weigh polyvinyl alcohol (G108396 polyvinyl alcohol, pharmaceutical grade, gel strength ~ 240 g Bloom, Shanghai Aladdin Biochemical Technology Co., Ltd.) and deionized water, and the mass ratio of polyvinyl alcohol to deionized water is 10:90. The polyvinyl alcohol is added to the deionized water, and the polyvinyl alcohol is completely dissolved in the deionized water under the condition of a 90°C water bath and stirring at a speed of 250 rpm / min for 4 h, to prepare a polyvinyl alcohol solution;

[0066] S2. Preparation of mixed solution: Sodium alginate powder (S100128, Shanghai Aldrich Biochemical Technology Co., Ltd.) and the above polyvinyl alcohol solution were weighed according to the mass ratio of 5:90, and the sodium alginate powder was added into the polyvinyl alcohol solution. The sodium alginate powder was completely dissolved in the polyvinyl alcohol solution under the condition of water bath at 90°C for 3h with stirring at a speed of 250rpm / min, and a mixed solution was prepared;

[0067] S3. Preparation of hydrogel: The mixed solution was poured into a mold and pre-gelled for 1.5h, and then subjected to three cycles of freezing-melting crosslinking treatment, with a freezing temperature of-80°C, a freezing time of 8h, and a melting temperature of 70°C, a melting time of 20min. After completion, the hydrogel was immersed in an ammonium sulfate-borax solution for 6h, with an ammonium sulfate concentration of 30wt% and a borax concentration of 1.2wt%.

[0068] The polyvinyl alcohol-based hydrogel prepared in step S3 of Example 2 was tested by using the same characterization test method as in Example 1. It was found that the polyvinyl alcohol-based hydrogel prepared in step S3 of Example 2 had the same microstructure as the polyvinyl alcohol-based hydrogel prepared in Example 1, with a three-dimensional network porous structure inside and an enhanced transmission flared hole structure on the surface. The pore size of the porous structure was 600nm-8μm, the pore size of the flared hole structure was 25μm-150μm, and the flared hole structure was connected with the porous structure. The tensile strength of the polyvinyl alcohol-based hydrogel of Example 2 was 1.77MPa, the tensile strain was 944%, the ion conductivity was 13.4mS / cm, the adhesion energy was 170.3J / m 2 , and the drug release efficiency was 65.9% at 160min. It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 2 has excellent mechanical properties, ion conductivity, adhesion properties and drug release properties.

[0069] Example 3

[0070] This example provides a preparation method of a polyvinyl alcohol-based hydrogel, which comprises the following steps:

[0071] S1. Preparation of polyvinyl alcohol solution: Polyvinyl alcohol (G108396 polyvinyl alcohol, pharmaceutical grade, gel strength ~ 240g Bloom, Shanghai Aldrich Biochemical Technology Co., Ltd.) and deionized water were weighed according to the mass ratio of 10:90, and the polyvinyl alcohol was added into the deionized water. The polyvinyl alcohol was completely dissolved in the deionized water under the condition of water bath at 90°C for 4h with stirring at a speed of 250rpm / min, and a polyvinyl alcohol solution was prepared;

[0072] S2. Preparation of mixed solution: Sodium alginate powder (S100128, Shanghai Aldrich Biochemical Technology Co., Ltd.) and the above polyvinyl alcohol solution were weighed according to the mass ratio of 5:90, and the sodium alginate powder was added to the polyvinyl alcohol solution. The sodium alginate powder was completely dissolved in the polyvinyl alcohol solution under the condition of water bath at 90°C for 3h, and the stirring speed was 250rpm / min. A mixed solution was prepared;

[0073] S3. Preparation of hydrogel: The mixed solution was poured into the mold and pre-gelled for 1.5h, and then subjected to three cycles of freezing-thawing crosslinking treatment, with freezing temperature of-80°C, freezing time of 8h, and thawing temperature of 50°C, thawing time of 20min. After completion, it was immersed in an ammonium sulfate-borax solution for 6h, with ammonium sulfate concentration of 30wt% and borax concentration of 1.2wt% in the solution.

[0074] The polyvinyl alcohol-based hydrogel prepared in step S3 of Example 3 was tested by the same characterization test method as Example 1. It was found that the polyvinyl alcohol-based hydrogel prepared in step S3 of Example 3 had the same microstructure as the polyvinyl alcohol-based hydrogel prepared in Example 1, with a three-dimensional network porous structure inside and an enhanced transmission flared structure on the surface. The pore size of the porous structure was 200nm-3μm, the pore size of the flared structure was 10μm-75μm, and the flared structure was connected with the porous structure. The tensile strength of the polyvinyl alcohol-based hydrogel of Example 3 was 1.36MPa, the tensile strain was 862%, the ionic conductivity was 10.2mS / cm, the adhesion energy was 180.5J / m 2 , and the drug release efficiency was 59.1% at 160min. It can be seen that the polyvinyl alcohol-based hydrogel prepared in Example 3 has excellent mechanical properties, ionic conductivity, adhesion properties and drug release properties.

[0075] Comparative Example 1

[0076] This comparative example provides a preparation of a polyvinyl alcohol hydrogel, including the following steps:

[0077] S1. Preparation of polyvinyl alcohol solution: Polyvinyl alcohol (G108396 polyvinyl alcohol, pharmaceutical grade, gel strength ~ 240g Bloom, Shanghai Aldrich Biochemical Technology Co., Ltd.) and deionized water were weighed according to the mass ratio of 10:90, and the polyvinyl alcohol was added to the deionized water. The polyvinyl alcohol was completely dissolved in the deionized water under the condition of water bath at 90°C for 4h, and the stirring speed was 250rpm / min. A polyvinyl alcohol solution was prepared;

[0078] S2. Preparation of the mixed solution: according to the mass ratio, sodium alginate powder (S100128, Shanghai Aldrich Biochemical Technology Co., Ltd.) and the polyvinyl alcohol solution described above were weighed in a mass ratio of 5:90, and the sodium alginate powder was added to the polyvinyl alcohol solution. The mixture was stirred at 90°C for 3h to completely dissolve the sodium alginate powder in the polyvinyl alcohol solution, and the stirring speed was 250rpm / min, thereby preparing the mixed solution;

[0079] S3. Preparation of the hydrogel: the mixed solution was poured into the mold and pre-gelled for 1.5h, and then subjected to three cycles of freezing-thawing crosslinking treatment, with a freezing temperature of-80°C, a freezing time of 8h, and a thawing temperature of 20°C, a thawing time of 6h. After completion, the hydrogel was immersed in an ammonium sulfate-borax solution for 6h, with an ammonium sulfate concentration of 30wt% and a borax concentration of 1.2wt%.

[0080] The polyvinyl alcohol-based hydrogel prepared in step S3 of Comparative Example 1 was tested using the same characterization test method as in Example 1. Figure 4 The scanning electron microscope image of the surface of the polyvinyl alcohol-based hydrogel prepared in Comparative Example 1 after freeze-drying is shown in FIG. 2. Figure 4 As can be seen from FIG. 2, the polyvinyl alcohol-based hydrogel prepared in Comparative Example 1 has substantially no pore structure on the surface. The tensile strength of the polyvinyl alcohol-based hydrogel prepared in Comparative Example 1 was measured to be 1.86MPa, the tensile strain was 602%, the ion conductivity was 6.6mS / cm, the adhesion energy was 120.2J / m 2 , and the drug release efficiency at 160min was 38.3%. It can be seen that the mechanical properties, conductive properties, adhesion properties, and drug release properties of the polyvinyl alcohol-based hydrogel prepared in Comparative Example 1 are significantly inferior to those of Example 1.

[0081] It should be understood that the application of the present application is not limited to the above examples, and those of ordinary skill in the art can make improvements or changes according to the above description, and all such improvements and changes shall fall within the scope of the claims appended to the present application. In addition, unless specifically described or necessary for sequential steps, the order of the above steps is not limited to the above list, and can be changed or rearranged according to the desired design.

Claims

1. A method of preparing a surface enhanced transmission polyvinyl alcohol-based hydrogel, characterized by, The preparation method comprises the following steps: preparing a polyvinyl alcohol solution, adding sodium alginate into the polyvinyl alcohol solution, stirring to completely dissolve the sodium alginate in the polyvinyl alcohol solution, preparing a mixed solution, pre-gelatinizing the mixed solution in a mold, then performing a cyclic freezing-thawing crosslinking treatment, and finally preparing a polyvinyl alcohol-based hydrogel after soaking in an ammonium sulfate-borax solution. The cyclic freezing-thawing crosslinking treatment comprises the following steps: The freezing temperature is-90℃ to-60℃, the freezing time is 6 to 10 hours, the thawing temperature is 50 to 70℃, and the thawing time is 10 to 60 minutes.

2. The method for preparing the surface-enhanced transport polyvinyl alcohol-based hydrogel according to claim 1, characterized in that, The polyvinyl alcohol solution is prepared by the following steps: The polyvinyl alcohol is added into deionized water, the mass ratio of the polyvinyl alcohol to the deionized water is 5 to 15:45 to 180, and the polyvinyl alcohol is completely dissolved in the deionized water by stirring at 50 to 95℃, so as to prepare the polyvinyl alcohol solution, and the stirring speed is 50 to 500 rpm.

3. The method for preparing the surface-enhanced transport polyvinyl alcohol-based hydrogel according to claim 1, characterized in that, The mixed solution is prepared by the following steps: The sodium alginate is added into the polyvinyl alcohol solution, the mass ratio of the sodium alginate to the polyvinyl alcohol solution is 2 to 8:45 to 180, and the mixed solution is prepared by stirring at 50 to 95℃, and the stirring speed is 50 to 500 rpm.

4. The method for preparing the surface-enhanced transport polyvinyl alcohol-based hydrogel according to claim 1, characterized in that, The mixed solution is pre-gelatinized in the mold by the following steps: The mixed solution is placed in the mold and left for 0.5 to 5 hours.

5. The method for preparing the surface-enhanced transport polyvinyl alcohol-based hydrogel according to claim 1, characterized in that, The cyclic freezing-thawing crosslinking treatment comprises the following steps: The freezing temperature is-85℃ to-75℃, the freezing time is 7 to 9 hours, the thawing temperature is 60 to 70℃, and the thawing time is 15 to 35 minutes.

6. The method for preparing the surface-enhanced transport polyvinyl alcohol-based hydrogel according to any one of claims 1 to 5, characterized in that, The soaking treatment in the ammonium sulfate-borax solution comprises the following steps: The soaking treatment in the ammonium sulfate-borax solution is performed for 1 to 9 hours, the ammonium sulfate concentration of the ammonium sulfate-borax solution is 20 to 40 wt%, and the borax concentration is 0.8 to 1.8 wt%. 7.A surface-enhanced transmission polyvinyl alcohol-based hydrogel prepared by the surface-enhanced transmission polyvinyl alcohol-based hydrogel preparation method in any one of claims 1 to 6. 8.The surface-enhanced transmission polyvinyl alcohol-based hydrogel in claim 7, wherein the ion conductivity of the surface-enhanced transmission polyvinyl alcohol-based hydrogel is 10.2 to 13.4 mS / cm, and the drug release efficiency is 59.1% to 65.9%.

9. The surface enhanced transport polyvinyl alcohol-based hydrogel according to claim 7 or 8, having a tensile strength of 1.36 ~ 1.77 MPa, a tensile strain of 862% ~ 1074%, and an adhesion energy of 170.3 ~ 195.5 J / m 2 .

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