Hydrogel material with function of supporting tissue cell growth as well as preparation method and application of hydrogel material

Abstract

The invention provides a hydrogel material with an effect of supporting tissue cell growth as well as a preparation method and application thereof, and belongs to the technical field of medicines. The hydrogel material is prepared from the following raw materials: povidone, polyvinyl alcohol, agar, boric acid, edible tannin and polyacrylic resin II. The preparation method comprises the following steps: mixing the raw materials with water to obtain a mixed solution, and then carrying out a cross-linking reaction on the mixed solution through electron beam irradiation to obtain the hydrogel material with the function of supporting tissue cell growth. The hydrogel material is applied to preparation of vascular embolism agents. The hydrogel can enable a body to generate histological reaction on the hydrogel serving as a foreign body, fibroblasts wrap the hydrogel and then grow into the hydrogel, cells migrate and proliferate to form collagenous fiber tissue of a three-dimensional network structure, and then capillary and tissue cells grow into the hydrogel to form connective tissue; meanwhile, under the action that cells swallow foreign matters, the hydrogel is digested and degraded, and finally the diseased tissues are repaired.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a hydrogel material that supports the growth of tissue cells, its preparation method, and its application. Background Technology

[0002] Currently, the types and methods for repairing tissue lesions are becoming increasingly diverse. For example, in the repair of ruptured blood vessels, clinical medicine often uses embolization to repair the vessels, that is, by occupying the space within the blood vessel lumen to form a thrombus and achieve the purpose of repair. However, a thrombus is an unstable structure, and under the influence of the fibrinolytic system and the impact of blood flow, it is prone to recanalization, leading to embolization failure. To address these issues, researchers in the field of clinical medicine have attempted to increase the fibrous component of the thrombus through various methods to enhance the embolization effect. However, because the embolic agents used contain non-degradable materials that occupy space, they hinder the ingrowth of fibroblasts, resulting in insufficient fibrosis and no tissue cell growth. Therefore, the clinical embolization effect cannot meet the treatment requirements.

[0003] Therefore, it is necessary to develop a biomaterial that can support cell ingrowth into the lesion area to form sufficient fibrosis and further tissue cell growth in order to meet the clinical requirements for stable repair of the lesion area. Summary of the Invention

[0004] The purpose of this invention is to provide a hydrogel material that supports the growth of tissue cells, its preparation method, and its application.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: One of the technical solutions of the present invention: This invention provides a hydrogel material that supports the growth of tissue cells, the hydrogel material comprising the following raw materials: polyvinyl alcohol, polyvinyl alcohol, agar, boric acid, edible tannin and polyacrylic acid resin II.

[0006] Beneficial effects: Polyvinyl alcohol, edible tannins, boric acid, and agar construct the hydrogel structure. Povidone and polyacrylic acid resin II increase the viscosity and water resistance of the hydrogel. If other similar materials are used instead, the viscosity and water resistance of the hydrogel will be changed, which will have an adverse effect on the prepared product.

[0007] Further, the mass ratio of the polyvinyl alcohol, polyvinyl alcohol, agar, boric acid, edible tannin and polyacrylic acid resin II is 1:(0.3-0.7):(0.001-0.009):(0.010-0.073):(0.050-0.069):(0.17-0.23).

[0008] Beneficial effects: Adding too much or too little hydrogel will change its viscosity and water resistance.

[0009] Furthermore, the concentration of the povidone is 7%-15%; The concentration of the polyvinyl alcohol is 4%-14%; The concentration of the agar is 0.01%-2.3%; The concentration of the boric acid is 0.1%-9.6%; The concentration of the edible tannins is 0.5%-1.5%; The concentration of the polyacrylic acid resin II is 0.3%-4.7%.

[0010] The second technical solution of the present invention: This invention provides a method for preparing a hydrogel material that supports tissue cell growth, comprising the following steps: The polyvinyl alcohol, agar, boric acid, edible tannin, polyacrylic acid resin II and water are mixed to obtain a mixture, and then cross-linked by electron beam irradiation to obtain the hydrogel material that supports the growth of tissue cells.

[0011] Furthermore, the amount of water added is the total mass of the hydrogel material minus the mass of povidone, polyvinyl alcohol, agar, boric acid, edible tannin, and polyacrylic acid resin II.

[0012] Furthermore, the dose of the electron beam irradiation is 25 kGy.

[0013] The third technical solution of the present invention: The present invention also provides a hydrogel material that supports the growth of tissue cells and is used in the preparation of vascular embolization agents.

[0014] Furthermore, the application method is as follows: adding the contrast agent to the hydrogel material that supports the growth of tissue cells in the basic angiography reagent to form a mixture, and adding dextran iron to the mixture.

[0015] Furthermore, the mass ratio of the hydrogel material that supports tissue cell growth to the contrast agent is 1:(0.5-2). The mass ratio of the mixture to the dextran iron agent is 1:(0.2-3).

[0016] Furthermore, the prepared vascular embolization agent containing hydrogel material is manually injected into the blood vessel lumen through a 7Fr catheter.

[0017] The beneficial effects of this invention compared to the prior art are as follows: This invention provides a biomaterial that, during its preparation, is cross-linked by electron irradiation to form a hydrogel with a network structure. This hydrogel induces a histological response in the body to the foreign substance, with fibroblasts enveloping and ingraining the hydrogel. Supported by the hydrogel's network structure, cells migrate and proliferate, forming a three-dimensional network of collagen fibers. Subsequently, capillaries and tissue cells grow in, forming connective tissue. Simultaneously, the hydrogel is digested and degraded through phagocytosis of the foreign substance by the cells, ultimately repairing the diseased tissue through the formed connective tissue. The hydrogel preparation method provided by this invention is simple, low-cost, safe and reliable for clinical use, produces complete histological repair without foreign body residue, and can be used to prepare vascular embolization agents to achieve the closure of diseased blood vessels. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 The infrared spectrum of the hydrogel prepared in Example 3 of this invention; Figure 2 Electron microscope image of the hydrogel prepared in Example 3 of this invention; Figure 3 The wet weight change rate of the vascular embolizing agent prepared in artificial blood is shown as a broken line in an application example of the present invention. Figure 4 Histological section of the vascular embolizing agent prepared according to an application example of the present invention during animal experiments. Detailed Implementation

[0020] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0021] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0022] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0023] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0024] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0025] The water used in the following examples is purified water.

[0026] All materials used in the following examples are commercially available.

[0027] Example 1 A method for preparing a hydrogel material that supports tissue cell growth includes the following steps: A mixture of 10.9% povidone, 5.2% polyvinyl alcohol, 0.02% agar, 0.2% boric acid, 0.7% edible tannin, and 2.5% polyacrylic acid resin II in a ratio of 1:0.5:0.006:0.05:0.06:0.2 was mixed with purified water and irradiated with an electron beam at a dose of 25 kGy to obtain a hydrogel that supports the growth of tissue cells.

[0028] Example 2 A method for preparing a hydrogel material that supports tissue cell growth includes the following steps: A mixture of 13.3% povidone, 6.2% polyvinyl alcohol, 0.1% agar, 0.2% boric acid, 0.7% edible tannin, and 2.44% polyacrylic acid resin II in a ratio of 1:0.3:0.001:0.073:0.069:0.17 was mixed with purified water and irradiated with an electron beam at a dose of 25 kGy to obtain a hydrogel that supports the growth of tissue cells.

[0029] Example 3 A method for preparing a hydrogel material that supports tissue cell growth includes the following steps: A mixture of 10.9% povidone, 5.5% polyvinyl alcohol, 0.1% agar, 0.8% boric acid, 0.6% edible tannin, and 1.9% polyacrylic acid resin II in a ratio of 1:0.7:0.009:0.01:0.05:0.23 was mixed with purified water and irradiated with an electron beam at a dose of 25 kGy to obtain a hydrogel that supports the growth of tissue cells.

[0030] The infrared spectrum of the prepared hydrogel material is shown below. Figure 1 As shown, through Figure 1 The characteristic peaks indicate that the hydrogel material prepared in Example 3 contains a large number of groups that can form hydrogen bonds, such as OH (3442.91 cm⁻¹). -1 ), and also has a large number of structures dominated by CC chains (2949.17cm) -1 ), and carbonyl groups that can also participate in the formation of hydrogen bonds (1655.70cm). -1 These characteristic peaks in the infrared spectra are consistent with the chemical structures of polyvinyl chloride and polyvinyl alcohol.

[0031] Electron microscope images of the prepared hydrogel materials are as follows: Figure 2 As shown, through Figure 2 It can be seen that the microstructure of the hydrogel material prepared in Example 3 is a network structure, and the center value of the mesh diameter is about 100 μm.

[0032] Comparative Example 1 A method for preparing a hydrogel material includes the following steps: The difference from Example 3 is that the concentration of povidone is 10.9%, the concentration of polyvinyl alcohol is 5.5%, the concentration of agar is 0.1%, the concentration of boric acid is 0.8%, the concentration of edible tannin is 0.6%, and the concentration of polyacrylic acid resin II is 0%. The remaining steps and preparation conditions were the same as in Example 3. The hydrolysis resistance of the hydrogel material prepared in Comparative Example 1 was reduced, and it was significantly less effective than the hydrolysis resistance of the hydrogel material prepared in Example 3 of this invention.

[0033] Comparative Example 2 A method for preparing a hydrogel material includes the following steps: The difference from Example 3 is that the concentration of povidone is 5%, the concentration of polyvinyl alcohol is 5.5%, the concentration of agar is 0.1%, the concentration of boric acid is 0.8%, the concentration of edible tannin is 0.6%, and the concentration of polyacrylic acid resin II is 1.9%. The remaining steps and preparation conditions were the same as in Example 3. The viscosity and hydrolysis resistance of the hydrogel material prepared in Comparative Example 1 were reduced, and were significantly inferior to the viscosity and hydrolysis resistance of the hydrogel material prepared in Example 3 of this invention.

[0034] Application examples The hydrogel material with tissue cell growth support function prepared in Example 3 was mixed with angiography basic reagent at a mass ratio of 1:0.6 to form a mixture. Dextran iron was added to the mixture at a mass ratio of 1:1 to prepare a vascular embolization agent.

[0035] Performance verification: 1. Viscosity test of hydrogel materials The viscosity of the hydrogel material prepared in Example 3 was tested according to the method specified in Part 7.3 of GB / T 2794-2022 "Determination of Viscosity of Adhesives", and the viscosity measurement value was 370 Pa.s.

[0036] 2. Water content test of hydrogel materials The water content of the hydrogel material prepared in Example 3 was tested according to the method specified in T / CIRA 13-2020 "Technical Specification for Preparation of Medical Hydrogels by Radiation Method", and the measured water content was 85%.

[0037] 3. Biological evaluation of hydrogel materials According to the evaluation items and test methods specified in GB / T 16886.1-2022 "Biological evaluation of medical devices - Part 1: Evaluation and testing in the risk management process", tests were conducted on hemolysis, acute systemic toxicity, cytotoxicity, skin sensitization, intradermal reaction, genotoxicity, implantation test, and sub-chronic systemic toxicity test. The test results showed that all items met the requirements for biological evaluation of implantable medical devices.

[0038] 4. Wet weight change test of vascular embolization agent Artificial blood was prepared according to the method proposed in YY / T 0700 "Test Method for Blood and Body Fluid Penetration Resistance of Protective Clothing Materials for Blood and Body Fluid Protective Equipment". 2 mL of the vascular embolizing agent prepared in the application example was injected into 5 mL of the artificial blood solution and immersed at 20 ℃. The wet weight of the sample was measured at 30, 60, 90, and 120 days, and the wet weight change rate was calculated. The results are as follows. Figure 3 As shown, by Figure 3 It can be seen that the sample exhibits relatively stable hydrolysis resistance over a period of 120 days.

[0039] 5. Animal experiments Laboratory animals: New Zealand rabbits, 3-3.5kg, 8 males.

[0040] Experimental groups: Five main observation points were set up at 2 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks, with 1 animal at 2 weeks, 2 animals at 4 weeks, 1 animal at 6 weeks, 1 animal at 8 weeks, and 3 animals at 12 weeks.

[0041] Experimental procedure: After successful anesthesia, 0.3 mL of the vascular embolizing agent prepared in the application example was injected via puncture of one femoral artery. As planned, the animal was euthanized on the same day at the observation point, and samples were collected. Gross dissection was performed to observe the arterial embolism, and histopathological section staining was performed to observe cell regeneration.

[0042] Experimental Results: No complications occurred during the experiment, and all arteries were successfully embolized. Histopathological sections stained with MSB showed the following results. Figure 4 As shown, by Figure 4 It can be seen that at 2 weeks, the embolic agent is fully mixed with blood components, and the embolic agent and red blood cells occupy most of the lumen. Fibroblasts begin to grow into the lumen from the vessel wall. At 6 weeks, collagen fibers are arranged regularly and almost fill the blood vessel lumen. The embolic agent has degraded. At 12 weeks, capillaries and tissue cells grow into the collagen fibers to form connective tissue and close the blood vessel lumen.

[0043] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A hydrogel material that supports tissue cell growth, characterized in that, The hydrogel material comprises the following raw materials: povidone, polyvinyl alcohol, agar, boric acid, edible tannin and polyacrylic acid resin II.

2. The hydrogel material having a support tissue cell growth effect according to claim 1, wherein, The mass ratio of the povidone, polyvinyl alcohol, agar, boric acid, edible tannin and polyacrylic acid resin II is 1: (0.3-0.7): (0.001-0.009): (0.010-0.073): (0.050-0.069): (0.17-0.23).

3. The hydrogel material having a support tissue cell growth effect according to claim 1, wherein, The concentration of the povidone is 7%-15%; The concentration of the polyvinyl alcohol is 4%-14%; The concentration of the agar is 0.01%-2.3%; The concentration of the boric acid is 0.1%-9.6%; The concentration of the edible tannin is 0.5%-1.5%; The concentration of the polyacrylic acid resin II is 0.3%-4.7%.

4. A method for producing the hydrogel material having a support tissue cell growth effect according to any one of claims 1 to 3, characterized by, The method comprises the following steps: The povidone, polyvinyl alcohol, agar, boric acid, edible tannin, polyacrylic acid resin II and water are mixed to obtain a mixed solution, and then the mixed solution is subjected to cross-linking reaction by electron beam irradiation to obtain the hydrogel material with the function of supporting tissue cell growth.

5. The method for preparing the hydrogel material with tissue cell growth support function according to claim 4, characterized in that, The dose of the electron beam irradiation is 25 kGy.

6. The hydrogel material with the function of supporting tissue cell growth according to any one of claims 1-3 is applied to prepare a vascular embolism agent.

7. Use according to claim 6, characterized in that, The application method is: adding an angiography agent into the hydrogel material with the function of supporting tissue cell growth according to any one of claims 1-3 to obtain a mixed solution, and then adding an iron dextran agent into the mixed solution.

8. Use according to claim 7, characterized in that, The mass ratio of the hydrogel material with the function of supporting tissue cell growth to the angiography base agent is 1: (0.5-2); The mass ratio of the mixed solution to the iron dextran agent is 1: (0.2-3).

9. The application according to claim 6, characterized in that, The prepared vascular embolism agent containing the hydrogel material is manually injected into a vascular cavity through a 7Fr catheter.

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