A biomass-based hyaluronic acid aerogel and its preparation method and application

Abstract

The present invention relates to the technical field of aerogel preparation, and particularly to a biomass-based hyaluronic acid aerogel, a preparation method thereof and an application. First, an aqueous solution of sodium hyaluronate is mixed with an acid solution to obtain a hydrogel; the obtained hydrogel is frozen and thawed and then immersed in a metal salt solution to obtain a hardened gel; the obtained hardened gel is immersed in an organic solvent, and the obtained organic gel is dried to obtain a biomass-based aerogel. The preparation method of the present invention is simple and reliable. The raw material sodium hyaluronate is a natural polymer, and the raw material has good biocompatibility, no harm to the environment, and is biodegradable; the aerogel prepared by the present invention has certain transparency, and has a relatively low thermal conductivity (17.6 mW / (m·K)) under environmental conditions, and has great application prospects in the field of thermal insulation. The aerogel prepared by the present invention has biocompatibility and degradability, and has great application prospects in the field of biomedicine.

Description

Technical Field

[0001] The present invention relates to the technical field of aerogel preparation, and in particular to a biomass-based hyaluronic acid aerogel and its preparation method and application. Background Art

[0002] Aerogel is an ultra-light material with a porous nano-framework, first reported by Kistler in 1931. It has outstanding advantages such as high specific surface area, low density, and low thermal conductivity. In particular, its thermal conductivity can be comparable to or even lower than that of air, showing important application potential in solving heat insulation problems. Currently, a variety of organic and inorganic aerogel materials have been discovered, such as silica aerogel, carbon aerogel, artificial and natural polymer aerogels, etc. Among them, silica aerogel has been recognized in the commercial heat insulation field due to its good heat insulation performance and mature preparation process. However, problems such as poor mechanical properties, complex synthesis process, and environmental pollution caused by the use of non-degradable materials limit the further development of aerogel materials. Therefore, the development of natural product aerogels with good biocompatibility, wide raw material sources, and natural degradability has received key attention, providing a solution to the problem of brittleness of aerogel materials and having important significance in the field of aerogel research.

[0003] Hyaluronic acid (HA) is a water-soluble polysaccharide of biological origin, widely present in human cytoplasm, playing roles such as lubricating joints and providing a cell metabolism site. It is also a natural moisturizer and has certain pharmacological effects of antibacterial, anti-inflammatory, and promoting wound healing, showing excellent biocompatibility and degradability. Currently, a large number of commercial achievements have been obtained in the biomedical field. Therefore, how to provide a transparent bio-based aerogel material with hyaluronic acid as the matrix has become an urgent technical problem in this field. Summary of the Invention

[0004] The purpose of the present invention is to provide a biomass-based hyaluronic acid aerogel and its preparation method and application to solve the problems existing in the prior art.

[0005] To achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0006] The present invention provides a preparation method of a biomass-based aerogel, comprising the following steps:

[0007] Step 1) Mix an aqueous solution of sodium hyaluronate with an acid solution to obtain a hydrogel;

[0008] Step 2) Immerse the hydrogel obtained in Step 1 in a metal salt solution after freeze-thawing to obtain a hardened gel;

[0009] Step 3) Immerse the cured glue obtained in Step 2) in an organic solvent, and after drying the obtained organic gel, a biomass-based aerogel is obtained.

[0010] Optionally, the concentration of the sodium hyaluronate aqueous solution is 10-50 mg / mL;

[0011] The acid solution includes hydrochloric acid, nitric acid or sulfuric acid, and the concentration of the acid solution is 0.1-2 mol / L.

[0012] Optionally, the volume ratio of the sodium hyaluronate aqueous solution to the acid solution is 10-100:1.

[0013] Optionally, the hydrogel is frozen and thawed 1-5 times;

[0014] The metal salt solution includes aluminum nitrate solution, calcium chloride solution or iron chloride solution;

[0015] The concentration of the metal salt solution is 0.05-1 mol / L.

[0016] Optionally, the soaking time in Step 2) is 5-10 h.

[0017] Optionally, the organic solvent includes one or more of ethanol solution, methanol solution and isopropanol solution;

[0018] The volume concentration of the organic solvent is 70-100%.

[0019] Optionally, the number of soakings in Step 3) is 1-5 times, the time is 5-10 h, and the organic solvent needs to be replaced each time of soaking.

[0020] Optionally, the drying method in Step 3) is supercritical carbon dioxide drying.

[0021] The present invention also provides a biomass-based aerogel prepared by the above preparation method.

[0022] The present invention also provides the application of the above bio-based aerogel in heat preservation and heat insulation or biomedicine.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The preparation method of the present invention is simple and reliable, and the raw material sodium hyaluronate is a natural polymer, which has good biocompatibility, no toxicity to the environment, and can be biodegradable;

[0025] (2) The present invention can form a sodium hyaluronate hydrogel by adding a hydrochloric acid solution;

[0026] (3) The mechanical properties of the hydrogel of the present invention can be further enhanced by soaking in an aluminum nitrate solution.

[0027] (4) The aerogel prepared by the present invention has a certain transparency and a relatively low thermal conductivity (17.6 mW / (m·K)) at room temperature, and has great application prospects in the field of thermal insulation.

[0028] (5) The aerogel prepared by the present invention has biocompatibility and degradability, and has great application prospects in the field of biomedicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is a physical diagram of the transparent aerogel material prepared by the present invention;

[0030] Figure 2 is a scanning electron microscope image of the HA-2 aerogel prepared by the present invention;

[0031] Figure 3 is the nitrogen adsorption isotherm and pore size distribution diagram of the HA-3 aerogel;

[0032] Figure 4 is the thermal conductivity diagram of the HA-1 to HA-4 aerogels;

[0033] Figure 5 is the compressive stress-strain curve diagram of the HA-1 to HA-4 aerogels;

[0034] Figure 6 is the test diagram of the adhesion and hemostasis performance of the HA-2 aerogel on pig liver. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0035] Now, various exemplary embodiments of the present invention will 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, characteristics, and implementation embodiments of the present invention.

[0036] It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0037] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although this invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of this invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to those documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0038] Without departing from the scope or spirit of this invention, various improvements and changes can be made to the specific embodiments of the specification of this invention, which are obvious to those skilled in the art. Other embodiments obtained from the specification of this invention are obvious to those skilled in the art. The specification and examples of this application are merely exemplary.

[0039] Regarding "comprising", "including", "having", "containing", etc. used herein, they are all open-ended terms, meaning including but not limited to.

[0040] As used in this invention, "room temperature" and "normal temperature" are both calculated as 25 ± 2 °C unless otherwise specified.

[0041] This invention provides a method for preparing a biomass-based aerogel, comprising the following steps:

[0042] Step 1) Mix an aqueous sodium hyaluronate solution with an acid solution to obtain a hydrogel;

[0043] Step 2) Immerse the hydrogel obtained in Step 1) in a metal salt solution after freeze-thawing to obtain a hardened gel;

[0044] Step 3) Immerse the hardened gel obtained in Step 2) in an organic solvent, and the obtained organic gel is dried to obtain a biomass-based aerogel.

[0045] In this invention, the aqueous sodium hyaluronate solution is prepared by mixing sodium hyaluronate and water, and the sodium hyaluronate solution is a homogeneous and transparent solution.

[0046] In this invention, the concentration of the aqueous sodium hyaluronate solution is 10 - 50 mg / mL, preferably 15 - 45 mg / mL, more preferably 20 - 40 mg / mL, and even more preferably 25 - 30 mg / mL;

[0047] The acid solution contains hydrochloric acid, sulfuric acid or nitric acid, and is used to adjust the pH of the aqueous sodium hyaluronate solution to obtain a hydrogel;

[0048] The concentration of the acid solution is 0.1 - 2 mol / L, preferably 0.4 - 1.8 mol / L, more preferably 0.6 - 1.5 mol / L, and even more preferably 1 - 1.2 mol / L.

[0049] In the present invention, the volume ratio of the sodium hyaluronate aqueous solution to the acid solution is 10 - 100:1, preferably 20 - 90:1, more preferably 30 - 80:1, and even more preferably 50 - 60:1.

[0050] In the present invention, the hydrogel is frozen and thawed 1 - 5 times, preferably 2 - 4 times, and most preferably 3 times to promote the hardening of hyaluronic acid;

[0051] In the present invention, the freezing method of the hydrogel includes but is not limited to freezing in a refrigerator, and the freezing temperature is -15 to -30 °C, preferably -18 to -25 °C, more preferably -20 to -22 °C; the freezing time is 6 - 24 h, preferably 10 - 20 h, more preferably 12 - 15 h.

[0052] In the present invention, the hydrogel is thawed at room temperature, and the thawing time is 6 - 24 h, preferably 10 - 20 h, more preferably 12 - 15 h.

[0053] In the present invention, the metal salt solution includes but is not limited to an aluminum nitrate solution, a calcium chloride solution, or an iron chloride solution, preferably an aluminum nitrate solution or a calcium chloride solution, and more preferably an aluminum nitrate solution;

[0054] The concentration of the metal salt solution is 0.05 - 1 mol / L, preferably 0.08 - 0.8 mol / L, more preferably 0.1 - 0.5 mol / L, and even more preferably 0.3 - 0.4 mol / L.

[0055] In the present invention, the soaking time in step 2) is 5 - 10 h, preferably 6 - 9 h, more preferably 7 - 8 h.

[0056] In the present invention, the organic solvent includes one or more of an ethanol solution, a methanol solution, and an isopropanol solution, preferably one or more of an ethanol solution and a methanol solution;

[0057] The volume concentration of the organic solvent is 70 - 100%, preferably 80 - 90%.

[0058] In the present invention, the number of soakings in step 3) is 1 - 5 times, preferably 2 - 4 times, more preferably 3 times, the time is 5 - 10 h, preferably 6 - 9 h, more preferably 7 - 8 h, and the organic solvent needs to be replaced each time of soaking.

[0059] In the present invention, the medium in the gel is converted from water to an organic solvent by soaking in the organic solvent. The organic solvent can be miscible with liquid carbon dioxide. Therefore, in the further supercritical drying process, liquid carbon dioxide can enter the gel network better. Soaking with organic solvents of different concentrations can gradually and slowly reduce the polarity of the medium in the gel, minimizing the change in the gel structure caused by the change of the medium.

[0060] In the present invention, the drying in step 3) preferably includes drying by the supercritical liquid carbon dioxide drying method, which can maximize the retention of the original structure of the gel and improve the optical transparency of the aerogel sample. Those skilled in the art can perform it according to the conventional operation of the supercritical liquid carbon dioxide drying method.

[0061] The present invention also provides a biomass-based aerogel prepared by the above preparation method.

[0062] In the present invention, the microscopic morphology of the bio-based aerogel material is a nano-porous structure formed by the interweaving of nanofibers. The diameter of the nanofibers is 10-100 nanometers, the average pore diameter of the nano-pores is 10-60 nanometers, and the specific surface area of the material is 200-600 m 2 / g. In the present invention, the thermal conductivity of the bio-based aerogel material is 17-25 mW / (m·K).

[0063] The present invention also provides the application of the above bio-based aerogel in thermal insulation or biomedicine.

[0064] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0065] Example 1

[0066] Add 200 mg of sodium hyaluronate to 20 mL of deionized water, and then let it stand for 1 day until all the sodium hyaluronate is dissolved to obtain a uniform and transparent solution. Add 1 mL of 0.3 M HCl solution to the above solution and stir quickly to obtain a HA hydrogel. Then, the hydrogel is frozen at -20 °C in the refrigerator for 12 h and thawed at room temperature for 12 h, and the freezing and thawing cycles are repeated 5 times. Then, the frozen and thawed hydrogel is soaked in a mixed solution of Al(NO3)3, water and methanol. The concentration of Al(NO3)3 dissolved in water is 0.1 M, and the ratio of methanol to water is 1:1. Soak for 8 h. Then, the soaked hydrogel is soaked twice in an ethanol aqueous solution with concentrations of 70% and 90% respectively, and then soaked three times in absolute ethanol to remove water, 8 h each time, and the solution is replaced each time. The obtained alcogel is treated by the supercritical liquid carbon dioxide drying method to obtain the final aerogel sample (HA-1).

[0067] Example 2

[0068] 300 mg of sodium hyaluronate was added to 20 mL of deionized water, and then left standing for 1 day until the sodium hyaluronate was completely dissolved to obtain a homogeneous transparent solution. 1 mL of 0.5 M HCl solution was added to the above solution and stirred rapidly to homogeneity to obtain an HA hydrogel. Then, the hydrogel was left standing in a refrigerator at -20 °C for 12 h for freezing, and left standing at room temperature for 12 h for thawing. The freezing and thawing cycles were repeated 3 times. Then, the frozen and thawed hydrogel was centrifuged and immersed in a mixed solution of Al(NO3)3, water and methanol. The concentration of Al(NO3)3 in water was 0.1 M, and the ratio of methanol to water was 1:1. The immersion time was 8 h. Then, the immersed hydrogel was immersed 2 times in an aqueous methanol solution with concentrations of 70% and 90% respectively, and then immersed 3 times in anhydrous methanol to remove water, and then immersed 2 times in anhydrous isopropanol, 8 h each time, and the solution was replaced each time. The obtained alcogel was treated by supercritical liquid carbon dioxide drying method to obtain the final aerogel sample (HA-2).

[0069] Example 3

[0070] 400 mg of sodium hyaluronate was added to 20 mL of deionized water, and then left standing for 1 day until the sodium hyaluronate was completely dissolved to obtain a homogeneous transparent solution. 1.2 mL of 0.5 M HCl solution was added to the above solution and stirred rapidly to homogeneity to obtain an HA hydrogel. Then, the hydrogel was left standing in a refrigerator at -20 °C for 12 h for freezing, and left standing at room temperature for 12 h for thawing. The freezing and thawing cycles were repeated 3 times. Then, the frozen and thawed hydrogel was centrifuged and immersed in a mixed solution of Al(NO3)3, water and methanol. The concentration of Al(NO3)3 in water was 0.1 M, and the ratio of methanol to water was 1:1. The immersion time was 8 h. Then, the immersed hydrogel was immersed 2 times in an aqueous methanol solution with concentrations of 70% and 90% respectively, and then immersed 3 times in anhydrous methanol to remove water, 8 h each time, and the solution was replaced each time. The obtained alcogel was treated by supercritical liquid carbon dioxide drying method to obtain the final aerogel sample (HA-3).

[0071] Example 4

[0072] Add 600 mg of sodium hyaluronate to 20 mL of deionized water, and then let it stand for 1 day until the sodium hyaluronate is completely dissolved to obtain a homogeneous transparent solution. Add 1 mL of 1 M HCl solution to the above solution and stir evenly quickly to obtain an HA hydrogel. Then freeze the hydrogel at -20 °C in the refrigerator for 12 h and thaw it at room temperature for 12 h. Repeat the freeze-thaw cycle 3 times. Then, after centrifuging the freeze-thawed hydrogel, soak it in a mixed solution of Al(NO3)3, water, and methanol. The concentration of Al(NO3)3 dissolved in water is 0.1 M, and the ratio of methanol to water is 3:7. Soak for 8 h. Then soak the soaked hydrogel twice in an ethanol aqueous solution with concentrations of 70% and 90% respectively, then soak it three times in absolute ethanol to remove moisture, and then soak it twice in absolute isopropanol, 8 h each time, and change the solution each time. Treat the obtained alcogel by supercritical liquid carbon dioxide drying method to obtain the final aerogel sample (HA-4).

[0073] Perform thermal conductivity test, scanning electron microscope test, surface area test, pore size test, and compression test on the aerogels obtained in the above 4 examples. The specific results are shown in the attached drawings and Table 1. It can be seen from the results that by using this method, a transparent heat-insulating aerogel material can be obtained, and the thermal conductivity of the aerogel first decreases and then increases with the increase of the concentration of the sodium hyaluronate solution. Among them, the HA-2 aerogel has the lowest thermal conductivity, which is 17.6 mW / (m·K). Therefore, the aerogel prepared by the present invention also has great application prospects in the field of thermal insulation.

[0074] Figure 1 is a physical photo of the aerogel prepared in the embodiment of the present invention. It can be seen that the aerogel prepared by the present invention is transparent and has potential in the thermal insulation application of optical windows and the visualization treatment of biomedicine.

[0075] Figure 2 The electron microscope image shows that the HA aerogel is composed of nanofibers tightly wound together, with a fine nanostructure, and the diameter of the nanofibers is about 20 nm.

[0076] Figure 3 It can be seen that the specific surface area of the aerogel is about 500 m 2 g -1 or so, and the average pore size is 10 - 40 nm, further proving that the aerogel belongs to mesoporous materials and has a fine nanostructure.

[0077] Figure 4The thermal conductivity of the aerogel was measured. It can be seen that as the concentration of the sodium hyaluronate solution increases, the thermal conductivity of the aerogel first decreases and then increases, showing a "U"-shaped trend. Among them, the thermal conductivity of HA-2 is the lowest (17.6 mW / (m·K)). Therefore, the aerogel prepared by the present invention also has great application prospects in the field of thermal insulation.

[0078] Table 1 Performance test table of the aerogel prepared in the examples

[0079]

[0080] The above examples were repeated multiple times, and the obtained results were similar, indicating that the preparation method of this method has good repeatability.

[0081] Figure 5 The compression stress-strain curve of the aerogel was measured, and the elastic modulus was calculated by fitting a straight line to the curve at 5-10% strain. The slope is the value of the elastic modulus.

[0082] Figure 6 The adhesion and hemostatic properties of the HA-2 aerogel on pig liver were tested. It can be seen that due to strong water absorption, the HA aerogel has strong adhesion, and the HA aerogel is mainly composed of hyaluronic acid, with excellent biocompatibility and degradability, and also has potential applications in the biomedical field.

[0083] The above are only the preferred embodiments of the present invention. It should be pointed out 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.

Claims

1. A method for preparing a biomass-based aerogel, characterized in that: The preparation method is as follows: 300 mg of sodium hyaluronate is added to 20 mL of deionized water, and then allowed to stand for 1 day until the sodium hyaluronate is completely dissolved to obtain a transparent solution; 1 mL of 0.5 M HCl solution is added to the transparent solution and stirred evenly to obtain a hydrogel; the hydrogel is then allowed to stand for 12 hours in a refrigerator at -20°C for freezing, and allowed to stand for 12 hours at room temperature for thawing, and the freezing and thawing cycles are repeated 3 times; the frozen and thawed hydrogel is then centrifuged and immersed in a mixed solution of Al(NO3)3, water and methanol, wherein the concentration of Al(NO3)3 dissolved in water is 0.1 M, and the ratio of methanol to water is 1:1, and the immersion is performed for 8 hours; the immersed hydrogel is then immersed in a methanol aqueous solution for 2 times, wherein the volume concentrations of the methanol aqueous solution are 70% and 90% respectively, and then immersed in anhydrous methanol for 3 times to remove moisture, and then immersed in anhydrous isopropanol for 2 times, each time for 8 hours, and the solution is replaced each time to obtain an alcohol gel; the alcohol gel is treated by a supercritical liquid carbon dioxide drying method to obtain an aerogel.

2. The biomass-based aerogel prepared by the preparation method according to claim 1.

3. Use of the biomass-based aerogel according to claim 2 in thermal insulation or preparation of biomedicine.

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