Biomaterial, preparation method and application thereof, facial mask

Abstract

This invention provides a biomaterial, its preparation method, and applications, as well as a facial mask, relating to the field of biomedical materials technology. The preparation method of the biomaterial provided by this invention includes: mixing natural polysaccharide macromolecules or their sodium salts, tannic acid self-crosslinked microspheres, and water; then adding an amine compound to perform a crosslinking reaction; after the crosslinking reaction is completed, mixing with arginine to obtain the biomaterial; by mass parts, the raw materials of the biomaterial include 1-10 parts of natural polysaccharide macromolecules, 0.01-10 parts of tannic acid self-crosslinked microspheres, 200 parts of water, 0.06-0.08 parts of amine compound, and 0.01-0.1 parts of arginine. This preparation method is simple and efficient; the prepared biomaterial has good anti-inflammatory and antibacterial activity, good stability, and high safety, and can be used in the preparation of wound dressings, medical fillers, or skin care products.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a biomaterial, its preparation method and application, and a face mask. Background Technology

[0002] Natural polysaccharide compounds, such as hyaluronic acid and chondroitin sulfate, have been widely used in the biomedical field due to their excellent biocompatibility and bioactivity, including in wound dressings, medical fillers, and skincare products. How to further stabilize the bioactivity of natural polysaccharides and improve their anti-degradation properties has been a hot topic of widespread interest. Amine compounds, especially amine-containing polymers, have been widely used in antibacterial materials due to their good antibacterial properties. Meanwhile, improving the antibacterial properties and stability of natural polysaccharide materials through the combination of natural polysaccharides and amine compounds has been proven to be an effective approach. In recent years, the main strategies for combining natural polysaccharides and amine compounds include esterification reactions of amine groups with polysaccharide carboxyl groups and condensation reactions of aldehyde groups after polysaccharide oxidation with amine groups. However, these methods still have problems such as residual condensing agents and reaction products from esterification reactions, polysaccharide chain breakage caused by the use of strong oxidizing agents, and oxidant toxicity, thus limiting their further applications. Therefore, developing a novel strategy for stabilizing natural polysaccharides is of great significance.

[0003] In view of this, the present invention is proposed. Summary of the Invention

[0004] The primary objective of this invention is to provide a method for preparing biomaterials that, through the cross-linking of tannic acid self-crosslinked microspheres with amine compounds and the covalent and hydrogen bond interactions with polyhydroxy natural macromolecules, further introduces anti-inflammatory and antibacterial activities on the basis of stable natural polysaccharide macromolecules.

[0005] A second objective of this invention is to provide a biomaterial.

[0006] A third objective of this invention is to provide the application of the above-mentioned biomaterials in the preparation of wound dressings, medical filler materials, or skin care products.

[0007] The fourth objective of this invention is to provide a face mask.

[0008] To achieve the above objectives, the following technical solution is adopted:

[0009] In a first aspect, the present invention provides a method for preparing a biomaterial, comprising the following steps:

[0010] Natural polysaccharide macromolecules or their sodium salts, tannic acid self-crosslinking microspheres, and water are mixed, and then amine compounds are added to carry out a crosslinking reaction. After the crosslinking reaction is completed, the mixture is mixed with arginine to prepare the biomaterial.

[0011] The raw materials of the biomaterial, by mass fraction, include 1-10 parts of natural polysaccharide macromolecules, 0.01-10 parts of tannic acid self-crosslinked microspheres, 200 parts of water, 0.06-0.08 parts of amine compounds, and 0.01-0.1 parts of arginine.

[0012] As a further technical solution, the natural polysaccharide macromolecules include hyaluronic acid, alginic acid, chitosan, or chondroitin sulfate.

[0013] As a further technical solution, the particle size of the tannic acid self-crosslinking microspheres is 200-400 nanometers.

[0014] As a further technical solution, the preparation method of the tannic acid self-crosslinking microspheres includes: adding an oxidant to a tannic acid solution to carry out a self-crosslinking reaction, and then obtaining tannic acid self-crosslinking microspheres after separation.

[0015] As a further technical solution, the amine compound includes lysine, polylysine, or polyimide;

[0016] The molecular weights of the polylysine and polyimide are 1000-10000 Da.

[0017] As a further technical solution, the temperature of the crosslinking reaction is 5-40℃;

[0018] The cross-linking reaction takes 1-24 hours.

[0019] Secondly, the present invention provides a biomaterial prepared using the above-described preparation method.

[0020] Thirdly, the present invention provides the application of the above-mentioned biomaterials in the preparation of wound dressings, medical filler materials or skin care products.

[0021] Fourthly, the present invention provides a face mask comprising liquid A and liquid B;

[0022] Liquid A includes the aforementioned biomaterials and whitening and skin-care ingredients;

[0023] Solution B is an aqueous solution of calcium salt.

[0024] As a further technical solution, the method for preparing the face mask includes: applying liquid A to the skin surface, then spraying liquid B, and preparing the face mask after film formation.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The method for preparing biomaterials provided by this invention is simple and efficient. The prepared biomaterials have good anti-inflammatory and antibacterial activities, good stability, and high safety. They can be used in the preparation of wound dressings, medical fillers, or skin care products, and have great application prospects. Attached Figure Description

[0027] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0028] Figure 1 The antibacterial results are for the blank control, Example 1, and Comparative Example 3.

[0029] Figure 2 The biosafety results are for Example 1 (left) and Comparative Example 3 (right). Detailed Implementation

[0030] The embodiments and examples of the present invention will be described in detail below. However, those skilled in the art will understand that the following embodiments and examples are for illustrative purposes only and should not be considered as limiting the scope of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention. Unless otherwise specified, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0031] In a first aspect, the present invention provides a method for preparing a biomaterial, comprising the following steps:

[0032] Natural polysaccharide macromolecules or their sodium salts, tannic acid self-crosslinking microspheres, and water are mixed, and then amine compounds are added to carry out a crosslinking reaction. After the crosslinking reaction is completed, the mixture is mixed with arginine to prepare the biomaterial.

[0033] The raw materials for the biomaterial include natural polysaccharide macromolecules, tannic acid self-crosslinked microspheres, water, amine compounds, and arginine. Specifically, by mass fraction, the natural polysaccharide macromolecules may be, for example, but not limited to, 1 part, 2 parts, 4 parts, 6 parts, 8 parts, or 10 parts; the tannic acid self-crosslinked microspheres may be, for example, but not limited to, 0.01 parts, 0.05 parts, 0.1 parts, 0.5 parts, 1 part, 5 parts, or 10 parts; the water mass fraction is 200 parts; the amine compounds may be, for example, but not limited to, 0.06 parts, 0.07 parts, or 0.08 parts; and the arginine mass fraction may be, for example, but not limited to, 0.01 parts, 0.05 parts, or 0.1 parts.

[0034] Arginine was added after the cross-linking reaction was completed. The inventors found that adding arginine can react with the aldehyde group of the cross-linking product to improve the safety of the biomaterial. At the same time, the addition of arginine can also improve the stability of the biomaterial and enhance its repair efficacy.

[0035] The method for preparing biomaterials provided by this invention is simple and efficient. The prepared biomaterials have good anti-inflammatory and antibacterial activities, good stability, and high safety. They can be used in the preparation of wound dressings, medical fillers, or skin care products, and have great application prospects.

[0036] In some alternative embodiments, the natural polysaccharide macromolecules include, but are not limited to, hyaluronic acid, alginate, chitosan or chondroitin sulfate, or other natural polysaccharide macromolecules known to those skilled in the art.

[0037] In some alternative embodiments, the tannic acid self-crosslinking microspheres have a particle size of 200-400 nanometers.

[0038] In some optional embodiments, the method for preparing the tannic acid self-crosslinking microspheres includes: adding an oxidant to a tannic acid solution to carry out a self-crosslinking reaction, and then obtaining tannic acid self-crosslinking microspheres after separation.

[0039] In some alternative embodiments, the oxidant includes sodium periodate.

[0040] In some optional embodiments, the tannic acid self-crosslinking microspheres are prepared as follows: 45 mg of tannic acid is dissolved in 10 mL of pure water, stirred and mixed, and then 200 µL of sodium periodate solution (20 mM) is added to the solution. The mixture is reacted overnight at room temperature in the dark. After dialyzing with deionized water (MCWO=2000) and freeze-drying, the tannic acid self-crosslinking microspheres are obtained.

[0041] In some alternative embodiments, the amine compound includes, but is not limited to, lysine, polylysine, or polyimide;

[0042] The molecular weights of the polylysine and polyimide are in the range of 1000-10000 Da.

[0043] Amine compounds within the above molecular weight range can simultaneously meet the requirements of both biological activity and water solubility.

[0044] In some alternative embodiments, the temperature of the crosslinking reaction can be, for example, but not limited to, 5°C, 10°C, 20°C, 30°C, or 40°C;

[0045] The cross-linking reaction time can be, for example, but not limited to, 1h, 6h, 12h, 18h or 24h.

[0046] Secondly, the present invention provides a biomaterial prepared using the above-described preparation method.

[0047] The prepared biomaterials have good anti-inflammatory and antibacterial activities, good stability, and high safety. They can be used to prepare wound dressings, medical fillers, or skin care products, and have great application prospects.

[0048] Thirdly, the present invention provides the application of the above-mentioned biomaterials in the preparation of wound dressings, medical filler materials or skin care products.

[0049] Fourthly, the present invention provides a face mask comprising liquid A and liquid B;

[0050] Liquid A includes the aforementioned biomaterials and whitening and skin-care ingredients;

[0051] Solution B is an aqueous solution of calcium salt.

[0052] In some alternative embodiments, the skin-whitening ingredients include salicylic acid, vitamin C, asiaticoside, arbutin, kojic acid, niacinamide, or vitamin B derivatives.

[0053] In some optional embodiments, the amount of the whitening skin care ingredient is 0.5-3 g / mL.

[0054] In some alternative embodiments, the concentration of calcium salt in solution B is 0.5-1.5 g / mL.

[0055] In some optional embodiments, the method for preparing the face mask includes: applying liquid A to the skin surface, then spraying liquid B, and forming a film to obtain the face mask.

[0056] This mask effectively avoids the problems of existing masks not covering the face completely, having blind spots, and the mask size not matching the face shape.

[0057] The present invention will be further illustrated below with specific embodiments and comparative examples. However, it should be understood that these embodiments are merely for the purpose of more detailed illustration and should not be construed as limiting the present invention in any way.

[0058] Unless otherwise specified, in the following examples and Comparative Example 1, the preparation method of tannic acid self-crosslinked microspheres was as follows: 45 mg of tannic acid was dissolved in 10 mL of pure water, and after stirring and mixing, 200 µL of sodium periodate solution (20 mM) was added to the solution. The reaction was carried out overnight at room temperature in the dark. After dialyzing with deionized water (MCWO=2000) and freeze-drying, tannic acid self-crosslinked microspheres were obtained. The particle size of the tannic acid self-crosslinked microspheres was 200-400 nm.

[0059] Example 1

[0060] (1) At room temperature, 5g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0061] (2) Add 0.08 g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution, stir for 1 hour, then add 0.08 g of polylysine (molecular weight 3000), continue stirring for 24 hours, then add 0.02 g of arginine, stir and mix to prepare the target biomaterial.

[0062] Example 2

[0063] (1) At room temperature, 6g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0064] (2) Add 0.06g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution, stir for 10 hours, then add 0.06g of polylysine (molecular weight 3000), stir for 24 hours, then add 0.01g of arginine, stir and mix to prepare the target biomaterial.

[0065] Example 3

[0066] (1) At room temperature, 6g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0067] (2) Add 0.1g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution. After reacting for 1 hour, add 0.06g of polylysine (molecular weight 5000). After stirring for 10 hours, add 0.04g of arginine. After stirring and mixing, the target biomaterial is prepared.

[0068] Example 4

[0069] (1) At room temperature, 6g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0070] (2) Add 0.1g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution. After reacting for 1 hour, add 0.06g of polyimide (molecular weight 2000). After stirring for 10 hours, add 0.04g of arginine. After stirring and mixing, the target biomaterial is prepared.

[0071] Example 5

[0072] (1) At room temperature, 1g of chondroitin sulfate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of chondroitin sulfate;

[0073] (2) Add 0.08 g of tannic acid self-crosslinked microspheres to the chondroitin sulfate solution prepared in (1) above, stir for 10 hours, then add 0.08 g of polylysine (molecular weight 3000), stir for 24 hours, then add 0.02 g of arginine, stir and mix to prepare the target biomaterial.

[0074] Example 6

[0075] (1) At room temperature, 1g of acidified chitosan was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0076] (2) Add 0.08 g of tannic acid self-crosslinking microspheres to the sodium hyaluronate solution prepared in (1) above, stir for 1 hour, then add 0.08 g of polylysine (molecular weight 3000), stir for another 10 hours, then add 0.02 g of arginine, stir and mix to prepare the target biomaterial.

[0077] Example 7

[0078] (1) At room temperature, 10g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0079] (2) Add 0.01g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution, stir for 1 hour, then add 0.07g of polylysine (molecular weight 1000), continue stirring for 24 hours, then add 0.02g of arginine, stir and mix to prepare the target biomaterial.

[0080] Example 8

[0081] (1) At room temperature, 10g of sodium hyaluronate was dissolved in 200mL of deionized water and stirred to obtain an aqueous solution of sodium hyaluronate;

[0082] (2) Add 10g of tannic acid self-crosslinking microspheres to the above sodium hyaluronate solution, stir for 1 hour, then add 0.07g of polylysine (molecular weight 10000), continue stirring for 24 hours, then add 0.1g of arginine, stir and mix to prepare the target biomaterial.

[0083] Comparative Example 1

[0084] The difference from Example 1 is that the tannic acid self-crosslinking microspheres are replaced with an equal amount of tannic acid.

[0085] Comparative Example 2

[0086] The difference from Example 1 is that the tannic acid self-crosslinking microspheres are replaced with an equal amount of tea polyphenols.

[0087] Comparative Example 3

[0088] The difference from Example 1 is that arginine is not added.

[0089] Experimental Example 1

[0090] The stability (the prepared materials were left to stand for 7 days and the presence of precipitation) and antibacterial properties of the biological materials provided in the examples and comparative examples were tested respectively (the number of colonies was counted by a plate antibacterial test: Staphylococcus aureus was diluted with PBS to 10 μL / mL). 6 Then, 180 μL of bacterial suspension and 20 μL of sample were respectively pipetted into well plates and incubated at 37°C for 6-8 h. 50 μL of each sample was then plated. After further incubation at 37°C for 12 h, the number of colonies was observed. The results are shown in Table 1 and 2. Figure 1 As shown.

[0091] Table 1. Target material properties and antibacterial performance of different formulations

[0092] .

[0093] As can be seen, the materials of Examples 1-8 of the present invention have better stability and higher antibacterial properties than Comparative Examples 1-2. The poor stability of Comparative Examples 1-2 may be due to localized excessive cross-linking.

[0094] Experimental Example 2

[0095] The materials provided in Example 1 and Comparative Example 3 were subjected to biosafety experiments, and the experimental steps are as follows:

[0096] Cytotoxicity of the materials was assessed using the CCK-8 assay. Samples were freeze-dried and sterilized, then prepared into initial concentrations using complete culture medium. The complete culture medium served as a blank control. Mouse fibroblasts (L929) were seeded at a density of 10,000 cells per well in 96-well plates, with 200 μL of culture medium added to each well. After 24 hours of culture, the culture medium was replaced with 200 μL of either the sample group or the blank control, with six replicates per group. After 24 and 48 hours of incubation, the original culture medium was discarded and replaced with 100 μL of CCK-8 solution (10%, v / v). Incubation was continued for 1 hour, and the absorbance at 450 nm was measured using a microplate reader to calculate the cytotoxicity values. Results are shown below. Figure 2 As shown, the material in Example 1 of this invention exhibits higher safety than that in Comparative Example 3. This may be because arginine can react with the aldehyde groups in the material, thereby enhancing its safety.

[0097] Example 9

[0098] A face mask comprising liquid A and liquid B;

[0099] Liquid A includes the biomaterials and skin-whitening ingredients (salicylic acid, content of 0.1%) provided in Example 1.

[0100] Solution B is a 1% aqueous solution of calcium chloride.

[0101] Instructions for use: Apply liquid A to the skin surface, then spray on liquid B. After the film forms, the mask is prepared.

[0102] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a biomaterial, characterized in that, Includes the following steps: Natural polysaccharide macromolecules or their sodium salts, tannic acid self-crosslinking microspheres, and water are mixed, and then amine compounds are added to carry out a crosslinking reaction. After the crosslinking reaction is completed, the mixture is mixed with arginine to prepare the biomaterial. The raw materials of the biomaterial, by mass fraction, include 1-10 parts of natural polysaccharide macromolecules, 0.01-10 parts of tannic acid self-crosslinked microspheres, 200 parts of water, 0.06-0.08 parts of amine compounds, and 0.01-0.1 parts of arginine; The method for preparing the tannic acid self-crosslinking microspheres includes: adding an oxidant to a tannic acid solution to carry out a self-crosslinking reaction, and then obtaining tannic acid self-crosslinking microspheres after separation; The natural polysaccharide macromolecules include hyaluronic acid, alginic acid, chitosan, or chondroitin sulfate; The amine compounds include lysine, polylysine, or polyimide; The particle size of the tannic acid self-crosslinked microspheres is 200-400 nanometers.

2. The preparation method according to claim 1, characterized in that, The molecular weights of the polylysine and polyimide are 1000-10000 Da.

3. The preparation method according to claim 1, characterized in that, The temperature for the crosslinking reaction is 5-40℃; The cross-linking reaction takes 1-24 hours.

4. A biomaterial, characterized in that, It is prepared by the preparation method according to any one of claims 1-3.

5. The use of the biomaterial of claim 4 in the preparation of wound dressings, medical filler materials or skin care products.

6. A facial mask, characterized in that, Includes liquid A and liquid B; The liquid A comprises the biomaterials and whitening skincare ingredients as described in claim 4; Solution B is an aqueous solution of calcium salt.

7. The facial mask according to claim 6, characterized in that, The method for preparing the facial mask includes: applying liquid A to the skin surface, then spraying liquid B, and forming a film to obtain the facial mask.

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