A method of preparing an acrylic-based copolymer functional dressing

Abstract

The application discloses a preparation method of an acrylic acid-based copolymer functional dressing. The method uses hydrogen peroxide and ascorbic acid as an oxidation-reduction initiator, uses acrylic acid and N-vinyl pyrrolidone as a base material, adds eugenol, and prepares a functional dressing with in-vitro antibacterial activity, free radical scavenging performance and good adhesion through a free radical polymerization reaction.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a preparation method of an acrylic copolymer functional dressing. BACKGROUND

[0002] Chronic wounds have a high prevalence and are expensive and long to treat, and remain a major challenge for global health care systems. Chronic wounds are difficult to heal under the influence of chronic inflammation, bacterial infection and cell aging, leading to amputation, sepsis and other consequences. Therefore, effective treatment of wounds is essential to accelerate wound healing, and the current way to treat wounds is to use dressings to help wound healing. Traditional dressings are widely used due to their low price and convenience. However, traditional dressings need to be frequently disinfected and replaced according to clinical experience, and they also have no ability to promote wound healing, increasing the risk of wound infection and damage to new skin tissue. With the development of medicine, traditional dressings that can only provide limited protection for wounds cannot meet people's demand for wound treatment.

[0003] In a healthy human body, invading pathogens are usually eliminated, which activates the immune system to avoid bacterial infection. However, once the immune system fails to clear the pathogens, infection occurs, leading to deterioration of internal tissues at the wound site, thereby slowing down wound healing. Gram-positive bacteria and gram-negative bacteria are the main pathogens that cause skin contamination and wound infection. It is crucial to develop medical dressings that can prevent bacterial invasion and prevent microbial growth.

[0004] Therefore, it is extremely important to develop a multifunctional medical dressing that can regulate the inflammatory microenvironment of the wound, prevent bacterial infection and accelerate wound healing. SUMMARY

[0005] The present application aims to provide a preparation method of an acrylic copolymer functional dressing, which uses hydrogen peroxide and ascorbic acid as an oxidation-reduction initiator, acrylic acid and N-vinyl pyrrolidone as a base material, and adds eugenol, to prepare a functional dressing with in vitro antibacterial activity, free radical scavenging performance and good adhesion through a free radical polymerization reaction.

[0006] To achieve the above-mentioned purpose, the solution of the present application is:

[0007] A preparation method of an acrylic copolymer functional dressing, comprising the following steps:

[0008] Step 1: Under a nitrogen atmosphere, first add L-ascorbic acid to a dimethyl sulfoxide solution to obtain a dimethyl sulfoxide mixed solution containing L-ascorbic acid;

[0009] Step 2, then sequentially add N-vinyl pyrrolidone, acrylic acid and eugenol to the dimethyl sulfoxide mixed solution obtained in step 1, and stir to obtain a fully mixed mixed solution, and the molar amount ratio of the N-vinyl pyrrolidone, acrylic acid and eugenol is 1:1:0.05-1:1:0.30;

[0010] Step 3, then add hydrogen peroxide to the mixed solution obtained in step 2, and polymerize at 15-45℃ for 0.5-5h to obtain a viscous liquid;

[0011] Step 4, then pour the viscous liquid obtained in step 3 into 2-5 times the volume of an organic solvent to precipitate and obtain a precipitate;

[0012] Step 5, then wash the precipitate obtained in step 4 with water, freeze it at-20--10℃, and freeze-dry to obtain a solid;

[0013] Step 6, finally disperse the solid in an ethanol-water solution, and after the solvent is volatilized, a film is formed to obtain the acrylic copolymer functional dressing;

[0014] In the preparation method, the molar amount of L-ascorbic acid added in step 1 is 1%-4% of the total molar amount of N-vinyl pyrrolidone and acrylic acid added in step 2, and the molar amount ratio of hydrogen peroxide added in step 3 to L-ascorbic acid added in step 1 is 1:1-1:3.

[0015] The total concentration of N-vinyl pyrrolidone and acrylic acid in the mixed solution in step 2 is 10wt%-50wt%.

[0016] In step 4, the organic solvent is one or more of ethyl acetate, n-hexane and petroleum ether.

[0017] In step 6, the volume fraction of the ethanol-water solution is 50%.

[0018] The preparation flowchart of the present application is shown in Figure 1 Based on the technical solution of the present application, the polyvinyl pyrrolidone using N-vinyl pyrrolidone as a monomer has excellent biocompatibility, but its mechanical properties and thermal stability are poor, and it does not have adhesion effect, so it is not suitable to be used alone as a medical dressing substrate; the polyacrylic acid using acrylic acid as a monomer has excellent adhesion, better film-forming property and hydrophilicity; eugenol has good antioxidant and antibacterial properties, and can also improve the adhesion of polyacrylic acid. Therefore, using acrylic acid and N-vinyl pyrrolidone as the substrate of the dressing, and introducing eugenol, the components can synergistically act to prepare a medical functional dressing with excellent performance.

[0019] The preparation method of the acrylic copolymer functional dressing of the present application has the following beneficial effects:

[0020] 1. The reaction process is green, safe, and has no use of toxic and harmful drugs and solvents, and has good biocompatibility;

[0021] 2. The functional dressing prepared has in-vitro antibacterial activity, free radical scavenging performance and good adhesion, and thus can play a role in regulating the wound inflammatory microenvironment, preventing bacterial infection and accelerating wound healing, and has important application significance in the biological medicine field. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is a preparation flowchart of the present application;

[0023] Figure 2 is an infrared spectrum of the functional dressing prepared in Example 1 and the comparative example, wherein Poly(AA-co-NVP) corresponds to the functional dressing prepared in the comparative example, and Poly(AA-co-NVP-co-EUG) corresponds to the functional dressing prepared in Example 1;

[0024] Figure 3 is a nuclear magnetic resonance spectrum of the functional dressing prepared in Example 1. DETAILED DESCRIPTION

[0025] In order to further explain the technical scheme of the present application, the present application will be described in detail below through specific examples.

[0026] I. Preparation of materials

[0027] Example 1

[0028] A preparation method of an acrylic copolymer functional dressing, comprising the following steps:

[0029] Step 1. Under a nitrogen atmosphere, 0.67g of L-ascorbic acid was first added to a 50g dimethyl sulfoxide solution, and after the L-ascorbic acid was completely dissolved, a dimethyl sulfoxide mixed solution containing L-ascorbic acid was obtained;

[0030] Step 2. Then 6.00g of N-vinylpyrrolidone, 3.89g of acrylic acid and 0.44g of eugenol (molar ratio of 1:1:0.05) were sequentially added to the dimethyl sulfoxide mixed solution obtained in step 1, and a fully mixed mixed solution was obtained by stirring;

[0031] Step 3. Then 35uL of hydrogen peroxide was added to the mixed solution obtained in step 2, and polymerization was carried out at 30℃ for 3h to obtain a viscous liquid;

[0032] Step 4. Then the viscous liquid obtained in step 3 was poured into 150mL of ethyl acetate to precipitate, and white precipitate was obtained;

[0033] Step 5, then the white precipitate obtained in step 4 is washed with water for 3 times, and is frozen at -20℃, and is freeze-dried to obtain a white solid;

[0034] Step 6, finally, 1.0g of the white solid is dispersed in 50mL of an ethanol-water solution with a volume fraction of 50%, and a film is formed after the solvent is volatilized to obtain an acrylic copolymer functional dressing.

[0035] Example 2

[0036] A preparation method of an acrylic copolymer functional dressing, comprising the following steps:

[0037] Step 1, under a nitrogen atmosphere, 0.67g of L-ascorbic acid is first added to a 50g dimethyl sulfoxide solution, and after the L-ascorbic acid is completely dissolved, a dimethyl sulfoxide mixed solution containing L-ascorbic acid is obtained;

[0038] Step 2, then 6.00g of N-vinylpyrrolidone, 3.89g of acrylic acid and 0.89g of eugenol (molar ratio of 1:1:0.10) are sequentially added to the dimethyl sulfoxide mixed solution obtained in step 1, and a fully mixed mixed solution is obtained by stirring;

[0039] Step 3, then 35uL of hydrogen peroxide is added to the mixed solution obtained in step 2, and polymerization is carried out at 30℃ for 3h to obtain a viscous liquid;

[0040] Step 4, then the viscous liquid obtained in step 3 is poured into 150mL of ethyl acetate to precipitate to obtain a white precipitate;

[0041] Step 5, then the white precipitate obtained in step 4 is washed with water for 3 times, and is frozen at -20℃, and finally freeze-dried to obtain a white solid;

[0042] Step 6, finally, 1.0g of the white solid is dispersed in 50mL of an ethanol-water solution with a volume fraction of 50%, and a film is formed after the solvent is volatilized to obtain an acrylic copolymer functional dressing.

[0043] Example 3

[0044] A preparation method of an acrylic copolymer functional dressing, comprising the following steps:

[0045] Step 1, under a nitrogen atmosphere, 0.67g of L-ascorbic acid is first added to a 50g dimethyl sulfoxide solution, and after the L-ascorbic acid is completely dissolved, a dimethyl sulfoxide mixed solution containing L-ascorbic acid is obtained;

[0046] Step 2, then 6.00 g of N-vinyl pyrrolidone, 3.89 g of acrylic acid and 1.77 g of eugenol (molar ratio of 1:1:0.20) were sequentially added to the dimethyl sulfoxide mixed solution obtained in step 1, and the mixed solution was stirred to obtain a fully mixed solution;

[0047] Step 3, then 35 uL of hydrogen peroxide was added to the mixed solution obtained in step 2, and polymerization was carried out at 30°C for 3 h to obtain a viscous liquid;

[0048] Step 4, then the viscous liquid obtained in step 3 was poured into 150 mL of ethyl acetate to precipitate, and white precipitate was obtained;

[0049] Step 5, then the white precipitate obtained in step 4 was washed with water for 3 times, and was frozen at -20°C, and then freeze-dried to obtain a white solid;

[0050] Step 6, finally, 1.0 g of the white solid was dispersed in 50 mL of an ethanol-water solution with a volume fraction of 50%, and a film was formed after the solvent was volatilized to obtain an acrylic copolymer functional dressing.

[0051] Comparative Example

[0052] A preparation method of an acrylic copolymer functional dressing, comprising the following steps:

[0053] Step 1, under a nitrogen atmosphere, 0.67 g of L-ascorbic acid was first added to a 50 g dimethyl sulfoxide solution, and after the L-ascorbic acid was completely dissolved, a dimethyl sulfoxide mixed solution containing L-ascorbic acid was obtained;

[0054] Step 2, then 6.00 g of N-vinyl pyrrolidone and 3.89 g of acrylic acid (molar ratio of 1:1) were sequentially added to the dimethyl sulfoxide mixed solution obtained in step 1, and the mixed solution was stirred to obtain a fully mixed solution;

[0055] Step 3, then 35 uL of hydrogen peroxide was added to the mixed solution obtained in step 2, and polymerization was carried out at 30°C for 3 h to obtain a viscous liquid;

[0056] Step 4, then the viscous liquid obtained in step 3 was poured into 150 mL of ethyl acetate to precipitate, and white precipitate was obtained;

[0057] Step 5, then the white precipitate obtained in step 4 was washed with water for 3 times, and was frozen at -20°C, and then freeze-dried to obtain a white solid;

[0058] Step 6, finally, 1.0 g of the white solid was dispersed in 50 mL of an ethanol-water solution with a volume fraction of 50%, and a film was formed after the solvent was volatilized to obtain an ordinary functional dressing.

[0059] II. Structure Characterization

[0060] The infrared spectrum of the functional dressing prepared in Example 1 and Comparative Example is shown in Figure 1, and the functional dressing prepared in Example 1 was dissolved in deuterated dimethyl sulfoxide solution, and the measured Figure 2 HNMR is shown in Figure 2. 1 HNMR is shown in Figure 2. Figure 3

[0061] Figure 2 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm

[0062] Figure 3 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm -1 The main chain structure C-H stretching vibration absorption peak is at 2945 cm

[0063] III. Performance test

[0064] 1. Swelling performance

[0065] The functional dressings prepared in each example and comparative example were soaked in physiological saline, and the swelling rate and water content were tested after 24 h, and the test results are shown in Table 1. The results show that the swelling rate and water content of the functional dressing prepared in the examples are high, which further shows that the addition of eugenol can improve the swelling rate and water content of the functional dressing, and with the increase of the content of eugenol, the swelling rate and water content of the functional dressing are increased to different degrees.

[0066] Table 1 Swelling performance of functional dressing

[0067] Swelling rate (%) Moisture content (%) Example 1 147.23 51.52 Example 2 158.35 51.69 Example 3 165.81 51.77 Comparative Example 101.43 48.73

[0068] 2. Adhesion strength

[0069] The functional dressings prepared in each example and the comparative example were respectively made into a film with a size of 10 mm x 10 mm, the film was adhered to the surface of pigskin, and another piece of pigskin was covered on the film to perform an adhesion strength test, and the test results are shown in Table 2, which shows that the functional dressings prepared in the examples have good adhesion strength, and the addition of eugenol can improve the adhesion strength of the functional dressings, and the adhesion strength of the functional dressings gradually increases with the increase of the amount of eugenol.

[0070] Table 2 Adhesion strength of the functional dressings

[0071] Adhesion strength (kPa) Example 1 24.83 Example 2 28.03 Example 3 31.35 Comparative Example 22.38

[0072] 3. Radical scavenging ability

[0073] The hydroxyl radical scavenging ability of the functional dressings prepared in each example and the comparative example was tested: EDTA-Fe solution and 1.6 mg / mL sample solution were prepared with pure water, 0.36 mg / mL crocus solution and 3.00% hydrogen peroxide solution were prepared with PBS buffer solution with pH = 7.4, 1.0 mL sample solution, 0.5 mL EDTA-Fe solution, 1.0 mL PBS solution, 1.0 mL crocus solution and 1.0 mL hydrogen peroxide solution were sequentially added in a test tube, and the test tube was oscillated at 50°C for 1 h, and the absorbance at 520 nm was measured, and the absorbance value was recorded as A. S A control group A used PBS instead of sample solution, and a blank group A0 was a mixture of 1.0 mL crocus solution and 3.5 mL PBS solution, and the hydroxyl radical scavenging ability was calculated according to the following formula, and the test results are shown in Table 3. The results show that the functional dressings prepared in the examples have good hydroxyl radical scavenging ability, and the addition of eugenol can improve the hydroxyl radical scavenging ability of the functional dressings, and the hydroxyl radical scavenging ability of the prepared dressings is improved with the increase of the content of eugenol.

[0074]

[0075] Table 3 Radical scavenging ability of the functional dressings

[0076] Radical scavenging ability (%) Example 1 15.76 Example 2 31.20 Example 3 48.12 Comparative Example 2.57

[0077] 4. In vitro antibacterial performance test

[0078] The in vitro antibacterial performance of the functional dressings prepared in each example and the comparative example was tested by the inhibition zone method, and E. coli and S. aureus were used as quality control bacteria, and the test results are shown in Table 4, which shows that the functional dressings prepared in the examples have inhibitory effect on E. coli and S. aureus, and the antibacterial effect is enhanced with the increase of the content of eugenol.

[0079] Table 4 antibacterial performance (inhibition zone width) of medical functional dressing

[0080] E. coli (mm) S. aureus (mm) Example 1 1.94 2.04 Example 2 2.15 2.36 Example 3 2.57 2.83 Comparative Example 0.57 0.62

[0081] From the above data, it can be found that the preparation method of the acrylic acid-based copolymer functional dressing has the following beneficial effects:

[0082] 1. The reaction process is green and safe, no toxic and harmful drugs and solvents are used, and the biocompatibility is good;

[0083] 2. The functional dressing prepared has in vitro antibacterial activity, free radical scavenging performance and good adhesion, so it can play a role in regulating the inflammatory microenvironment of the wound, preventing bacterial infection and accelerating wound healing, and has important application significance in the field of biological medicine.

[0084] The above examples and drawings do not limit the product form and style of the present application, and any appropriate changes or modifications made by those skilled in the art shall be considered as not departing from the patent scope of the present application.

Claims

1. A method of preparing an acrylic based copolymer functional dressing, characterized by: The method comprises the following steps: Step 1, under a nitrogen atmosphere, first adding L-ascorbic acid into a dimethyl sulfoxide solution to obtain a mixed dimethyl sulfoxide solution containing L-ascorbic acid; Step 2, then sequentially adding to the dimethyl sulfoxide mixed solution obtained in Step 1 N - vinyl pyrrolidone, acrylic acid and eugenol, stirring to obtain a well-mixed mixed solution, the N - the molar amount ratio of vinyl pyrrolidone, acrylic acid and eugenol is 1:1:0.05~1:1:0.30; Step 3, then adding hydrogen peroxide into the mixed solution obtained in step 2, and polymerizing at 15-45°C for 0.5-5 h to obtain a viscous liquid; Step 4, then precipitating the viscous liquid obtained in step 3 in 2-5 times volume of an organic solvent to obtain a precipitate; Step 5, then washing the precipitate obtained in step 4 with water, freezing it at -20 to -10°C, and freeze-drying to obtain a solid; Step 6, finally dispersing the solid in an ethanol-water solution, forming a film after the solvent is volatilized, and obtaining the acrylic copolymer functional dressing; In the preparation method, the molar amount of L-ascorbic acid added in step 1 is 1% to 4% of the total molar amount of the vinyl pyrrolidone and the acrylic acid added in step 2 N - the molar amount ratio of the hydrogen peroxide added in step 3 to the L-ascorbic acid added in step 1 is 1:1 to 1:

3. In step 2, the N - the total concentration of vinylpyrrolidone and acrylic acid in the mixed solution is 10 wt %~50 wt %.

2. A process for the preparation of an acrylic based copolymer functional dressing as claimed in claim 1, wherein: In step 4, the organic solvent is one or more of ethyl acetate, n-hexane and petroleum ether.

3. A process for the preparation of an acrylic based copolymer functional dressing as claimed in claim 1, wherein: In step 6, the volume fraction of the ethanol-water solution is 50%.

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