Veterinary antibacterial drug-loaded hydrogel dressing as well as preparation method and application thereof
By mixing the polyvinylpyrrolidone solution with citric acid and polyvinyl alcohol solution and irradiating it, a veterinary antibacterial potable hydrogel dressing with a stable three-dimensional network structure was prepared, which solved the problems of poor mechanical properties and poor biodegradability of the existing hydrogel dressing, achieved efficient drug loading and controlled release, and enhanced the antibacterial properties and biocompatibility of the dressing.
Patent Information
- Application Number
- CN202510380331.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-28
- Publication Date
- 2025-06-27
AI Technical Summary
The physical crosslinking network of existing hydrogel dressings is not stable enough, resulting in poor mechanical properties, uneven drug release, high production costs and poor biodegradability, which affects its application.
By mixing the polyvinylpyrrolidone solution with the crosslinking agent citric acid, polyvinyl alcohol solution and viscosal reducer anhydrous ethanol, and irradiation treatment, a veterinary antibacterial potable hydrogel dressing with a stable three-dimensional network structure was prepared.
It improves the load and controlled release ability of the drug, enhances the skin patchability and antibacterial properties of the dressing, improves biocompatibility and biodegradability, and reduces the potential risks of long-term implantation.
Smart Images
Figure CN120204455A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of hydrogel dressings, and particularly relates to a veterinary antibacterial drug-loaded hydrogel dressing, a preparation method thereof, and an application thereof. Background Art
[0002] Hydrogels can be applied to multiple aspects such as veterinary drug preparations, wound dressings, drug delivery systems, vaccine adjuvants, antibacterial treatments, and wound management. Common preparation methods of hydrogels include: 1. Double-crosslinking technology: A double-crosslinked antibacterial hydrogel dressing with controllable release of gallium ions is prepared by combining raw materials such as N-isopropylacrylamide, chitosan, and polyethylene glycol diacrylate, and through steps such as stirring, polymerization, freeze-drying, and loading. This dressing can achieve rapid or slow controlled release of gallium ions at different temperatures, and at the same time has good mechanical flexibility and water absorption and swelling properties, which helps to fit the wound and absorb exudate; 2. Physical and chemical crosslinking methods: The preparation methods of temperature-sensitive antibacterial hydrogels mainly include physical crosslinking methods and chemical crosslinking methods. Physical crosslinking relies on intermolecular forces such as hydrogen bonds to form a reversible three-dimensional network structure, while chemical crosslinking forms a permanent network through chemical bonds to ensure the responsiveness of the hydrogel under external environmental stimuli; 3. pH responsiveness: A pH-responsive antibacterial hydrogel wound dressing realizes pH sensitivity by connecting pH-sensitive monomers, introducing positively charged quaternary ammonium salts as side chains, and loading cationic antibacterial drugs; 4. Nanoparticle technology: By introducing different forms of nanoparticles such as nanoparticles, nanospheres, or nanocapsules into the hydrogel, the swelling rate and drug release efficiency of the hydrogel can be improved. The interaction between nanoparticles and the increase in external temperature can promote the release of drugs; 5. Regulation of drug loading mode: By adjusting the concentration of antibacterial agents, pore size, and copolymer monomer ratio in the hydrogel, the release rate of antibacterial agents can be controlled, and effective regulation of drug release can be achieved.
[0003] However, the above methods all have certain problems. For example, the physical crosslinking network of the hydrogel may not be stable enough in some cases, resulting in poor mechanical properties or easy disintegration of crosslinking points, which may affect the sustained release of drugs and the durability of the dressing; in addition, the production cost of the hydrogel dressing is high, which will affect its popularization and application in the market; furthermore, some hydrogels have poor biodegradability and may have potential cytotoxicity. Therefore, there is an urgent need to provide a new hydrogel dressing to overcome the above problems. Summary of the Invention
[0004] In view of this, the purpose of the present invention is to provide a veterinary antibacterial drug-loaded hydrogel dressing, a preparation method thereof, and an application thereof. A veterinary antibacterial drug-loaded hydrogel dressing is prepared by mixing a polyvinylpyrrolidone solution and a polyvinyl alcohol solution, and adding a crosslinking agent and a viscosity reducer.
[0005] To achieve the above-mentioned invention object, the present invention provides the following technical solutions:
[0006] The present invention provides a preparation method of a veterinary antibacterial drug-loaded hydrogel dressing, comprising the following steps:
[0007] 1) Mix a polyvinylpyrrolidone solution and a cross-linking agent to obtain a mixed solution A;
[0008] 2) Mix the mixed solution A and a polyvinyl alcohol solution to obtain a mixed solution B;
[0009] 3) Mix the mixed solution B and a viscosity reducer to obtain a mixed solution C, and irradiate the mixed solution C to obtain a veterinary antibacterial drug-loaded hydrogel dressing.
[0010] Preferably, the mass percentage concentration of the polyvinylpyrrolidone solution in step 1) is 1% - 50%.
[0011] Preferably, the cross-linking agent in step 1) includes citric acid, hyaluronic acid or glycerol, and the addition amount of the cross-linking agent is 0.1% - 30% of the volume of the polyvinylpyrrolidone solution.
[0012] Preferably, the mass percentage concentration of the polyvinyl alcohol solution in step 2) is 5% - 20%.
[0013] Preferably, the volume ratio of the polyvinyl alcohol solution to the polyvinylpyrrolidone solution is 1 - 99:1 - 99.
[0014] Preferably, the pH of the mixed solution B in step 2) is 4 - 8.
[0015] Preferably, the viscosity reducer in step 3) includes absolute ethanol, and the addition amount of the viscosity reducer is 0.1% - 30% of the volume of the mixed solution B.
[0016] Preferably, the intensity of the irradiation in step 3) is 1 - 25 kGy, and the irradiation time is 1 - 100 s.
[0017] The present invention also provides a veterinary antibacterial drug-loaded hydrogel dressing prepared by the above-mentioned preparation method.
[0018] The present invention also provides the application of the veterinary antibacterial drug-loaded hydrogel dressing prepared by the above-mentioned preparation method or the veterinary antibacterial drug-loaded hydrogel dressing in the preparation of a wound dressing.
[0019] Compared with the prior art, the present invention has the following beneficial effects:
[0020] The three-dimensional network structure of the antibacterial drug-loaded hydrogel dressing for veterinary use provided by the present invention provides more loading sites for drug molecules, which can improve the drug loading and controlled release capabilities; it also has excellent skin adhesiveness and antibacterial properties, and can significantly inhibit the proliferation of Staphylococcus aureus and Pseudomonas aeruginosa; it can also improve biocompatibility and biodegradability, ensure its safety in the body and reduce the potential risks of long-term implantation, and has no toxic or side effects.
[0021] The antibacterial drug-loaded hydrogel dressing for veterinary use provided by the present invention can also be given additional functions by further chemical modification or adding other active ingredients (such as antibacterial agents, growth factors, etc.) to meet specific treatment needs, so that it has broad application potential in the fields of drug delivery, tissue engineering and regenerative medicine. Brief Description of the Drawings
[0022] Figure 1 is the SEM detection result diagram of the antibacterial drug-loaded hydrogel dressing for veterinary use;
[0023] Figure 2 is the FT-IR detection result diagram of the antibacterial drug-loaded hydrogel dressing for veterinary use;
[0024] Figure 3 is the antibacterial experiment result diagram of the antibacterial drug-loaded hydrogel dressing for veterinary use;
[0025] Figure 4 is the drug loading experiment result diagram of the antibacterial drug-loaded hydrogel dressing for veterinary use loaded with berberine hydrochloride;
[0026] Figure 5 is the release experiment result diagram of the antibacterial drug-loaded hydrogel dressing for veterinary use loaded with berberine hydrochloride (wherein, the area within the red frame is the area where the antibacterial drug-loaded hydrogel dressing for veterinary use without berberine hydrochloride is applied, and the area within the green frame is the area where the antibacterial drug-loaded hydrogel dressing for veterinary use loaded with berberine hydrochloride is attached). Detailed Embodiments
[0027] The present invention provides a preparation method of an antibacterial drug-loaded hydrogel dressing for veterinary use, comprising the following steps:
[0028] 1) Mix the polyvinylpyrrolidone solution and the crosslinking agent to obtain a mixed solution A;
[0029] 2) Mix the mixed solution A and the polyvinyl alcohol solution to obtain a mixed solution B;
[0030] 3) Mix the mixed solution B and the viscosity reducer to obtain a mixed solution C, and irradiate the mixed solution C to obtain the antibacterial drug-loaded hydrogel dressing for veterinary use.
[0031] In the present invention, a polyvinylpyrrolidone solution and a crosslinking agent are mixed to obtain a mixed solution A. The preparation method of the polyvinylpyrrolidone solution is preferably as follows: polyvinylpyrrolidone powder is added to deionized water to obtain a polyvinylpyrrolidone solution; the mass percentage concentration of the polyvinylpyrrolidone solution is preferably 1% to 50%, more preferably 5% to 45%; the crosslinking agent includes citric acid, hyaluronic acid or glycerol. Citric acid as a crosslinking agent can form an esterification reaction with the hydroxyl groups in the PVA molecule, or form physical hydrogen bonds between PVA and PVP, enhancing the mechanical properties of the veterinary antibacterial drug-loaded hydrogel dressing; the biodegradability and non-toxicity of citric acid make it a green crosslinking agent, and as an organic acid, it has certain antibacterial properties; the introduction of citric acid also provides pH sensitivity for the veterinary antibacterial drug-loaded hydrogel dressing, which can be ionized at different pH values, thus affecting the swelling and drug release behavior of the hydrogel; it can also reduce the degradation of the veterinary antibacterial drug-loaded hydrogel dressing during storage and application, improving its long-term stability; as a natural substance, citric acid reduces the possible side effects caused by chemical crosslinking agents, improving the safety of the veterinary antibacterial drug-loaded hydrogel dressing. The addition amount of the crosslinking agent is preferably 0.1% to 30% of the volume of the polyvinylpyrrolidone solution, more preferably 5% to 25% of the volume of the polyvinylpyrrolidone solution.
[0032] In the present invention, the mixed solution A and a polyvinyl alcohol solution are mixed to obtain a mixed solution B. The preparation method of the polyvinyl alcohol solution is preferably as follows: polyvinyl alcohol powder is added to deionized water and heated in a water bath to obtain a polyvinyl alcohol solution. The temperature of the water bath heating is preferably 60 to 100 °C, more preferably 70 to 90 °C; the mass percentage concentration of the polyvinyl alcohol solution is preferably 5% to 20%, more preferably 7.5% to 17.5%; the volume ratio of the polyvinyl alcohol solution to the polyvinylpyrrolidone solution is preferably 1 to 99:1 to 99, more preferably 5 to 20:5 to 20.
[0033] In the present invention, PVA (polyvinyl alcohol) contains a large number of hydroxyl groups (-OH), and PVP (polyvinylpyrrolidone) also contains hydroxyl groups. Citric acid contains three carboxyl groups (-COOH) and can be used as a crosslinking agent to react with the hydroxyl groups of PVA and PVP to form an esterification reaction. The following are the simplified reaction equations:
[0034] PVA-OH + citric acid → PVA-OOCCH2CH2COOH + H2O
[0035] PVP-OH + citric acid → PVP-OOCCH2CH2COOH + H2O
[0036] In these reactions, the hydroxyl groups on the molecular chains of PVA and PVP react with the carboxyl groups of citric acid to form ester bonds and release water molecules. The formed ester bonds can promote the crosslinking between PVA and PVP molecules, thereby enhancing the mechanical properties and stability of the antibacterial drug-loaded hydrogel dressing for veterinary use; PVA and PVP can exhibit different responsiveness at different temperatures, enabling them to form a film rapidly under body temperature conditions. In addition, the carboxyl groups of citric acid can further react with other hydroxyl groups on the molecular chains of PVA and PVP to form a more complex crosslinked network, further enhancing the stability and durability of the network.
[0037] In the present invention, mixture B and a viscosity reducer are mixed to obtain mixture C, and mixture C is subjected to irradiation treatment to obtain the antibacterial drug-loaded hydrogel dressing for veterinary use. The pH of mixture B is preferably 4 to 8, more preferably 5 to 7; the viscosity reducer includes absolute ethanol, and the addition amount of the viscosity reducer is preferably 0.1% to 30% of the volume of mixture B, more preferably 5% to 25% of the volume of mixture B; mixture C is preferably placed in an aluminum foil bag before irradiation, and the filling amount of mixture C is preferably 0.1 to 50 g / bag, more preferably 5 to 45 g / bag; the irradiation method is preferably γ-ray irradiation, the irradiation intensity is preferably 1 to 25 kGy, more preferably 5 to 20 kGy; the irradiation time is preferably 1 to 100 s, more preferably 5 to 95 s.
[0038] The technical solutions provided by the present invention are described in detail below in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.
[0039] Example 1
[0040] A certain amount of polyvinylpyrrolidone (PVP) powder is taken and dissolved in deionized water to prepare a solution with a mass fraction of 40%. The polyvinylpyrrolidone solution and citric acid accounting for 3% of the volume of the polyvinylpyrrolidone solution are mixed to obtain mixture A.
[0041] A certain amount of polyvinyl alcohol (PVA, 10 - 100 mPa·s, degree of alcoholysis: 87.0 - 89.0 mol%) powder is taken and dissolved in deionized water in a constant temperature water bath with a water bath temperature of 80°C to prepare a polyvinyl alcohol solution with a mass fraction of 10%. Mixture A and the polyvinyl alcohol solution are mixed to obtain mixture B, and the pH of mixture B is adjusted to 6. The volume ratio of the polyvinyl alcohol solution to the polyvinylpyrrolidone solution is 1:1.
[0042] Mixture B and absolute ethanol accounting for 15% of the volume of mixture B are mixed to obtain mixture C. 10 g of mixture C is placed in an aluminum foil bag and irradiated with γ-rays at an irradiation intensity of 10 kGy for 50 s to prepare the antibacterial drug-loaded hydrogel dressing for veterinary use.
[0043] Example 2
[0044] Take a certain amount of polyvinylpyrrolidone (PVP) powder and dissolve it in deionized water to prepare a solution with a mass fraction of 50%. Mix the polyvinylpyrrolidone solution with hyaluronic acid accounting for 5% of the volume of the polyvinylpyrrolidone solution to obtain mixture A.
[0045] Take a certain amount of polyvinyl alcohol (PVA, 10 - 100 mPa·s, degree of alcoholysis: 87.0 - 89.0 mol%) powder. In a constant temperature water bath with a water bath temperature of 60 °C, dissolve it in deionized water to prepare a polyvinyl alcohol solution with a mass fraction of 5%. Mix mixture A and the polyvinyl alcohol solution to obtain mixture B, and adjust the pH of mixture B to 4. The volume ratio of the polyvinyl alcohol solution to the polyvinylpyrrolidone solution is 1:99.
[0046] Mix mixture B with absolute ethanol accounting for 0.1% of the volume of mixture B to obtain mixture C. Place 5 g of mixture C in an aluminum foil bag and irradiate it under γ-ray irradiation with an irradiation intensity of 1 kGy for 1 s to prepare a veterinary antibacterial drug-loaded hydrogel dressing.
[0047] Example 3
[0048] Take a certain amount of polyvinylpyrrolidone (PVP) powder and dissolve it in deionized water to prepare a solution with a mass fraction of 1%. Mix the polyvinylpyrrolidone solution with glycerol accounting for 10% of the volume of the polyvinylpyrrolidone solution to obtain mixture A.
[0049] Take a certain amount of polyvinyl alcohol (PVA, 10 - 100 mPa·s, degree of alcoholysis: 87.0 - 89.0 mol%) powder. In a constant temperature water bath with a water bath temperature of 100 °C, dissolve it in deionized water to prepare a polyvinyl alcohol solution with a mass fraction of 20%. Mix mixture A and the polyvinyl alcohol solution to obtain mixture B, and adjust the pH of mixture B to 8. The volume ratio of the polyvinyl alcohol solution to the polyvinylpyrrolidone solution is 99:1.
[0050] Mix mixture B with absolute ethanol accounting for 30% of the volume of mixture B to obtain mixture C. Place 40 g of mixture C in an aluminum foil bag and irradiate it under γ-ray irradiation with an irradiation intensity of 25 kGy for 100 s to prepare a veterinary antibacterial drug-loaded hydrogel dressing.
[0051] Experimental Example 1
[0052] 1. SEM test
[0053] The veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 was freeze-dried at -80 °C to obtain a dry hydrogel sample. It was sputter-coated with gold at room temperature, and its three-dimensional structure was photographed using SEM. The microstructure of the gel was confirmed at magnifications of ×600, ×1500, and ×3000 to prove the possibility of drug encapsulation.
[0054] Experimental results: As Figure 1 shown. From Figure 1 it can be seen that by observing under the electron microscope at magnifications of ×600, ×1500, and ×3000, it was found that the veterinary antibacterial drug-loaded hydrogel dressing had a rich three-dimensional network structure, proving its good crosslinking property and drug loading capacity.
[0055] 2. FTIR test
[0056] The Fourier transform infrared spectrum of the veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 was measured at room temperature, and its chemical structure was observed in the range of 4000 cm -1 ~450 cm -1 to prove its crosslinking method.
[0057] Experimental results: As Figure 2 shown. From Figure 2 it can be seen that through FT-IR measurement, an absorbable peak of relatively broad -OH stretching vibration was observed in the vicinity of 3400 cm -1 -3300 cm -1 . This blunt peak proved that a large number of intermolecular hydrogen bonds were contained in this gel structure.
[0058] 3. Antibacterial efficacy test
[0059] The veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 was tested according to 1121 in Part IV of the Chinese Pharmacopoeia. Staphylococcus aureus (G+) and Pseudomonas aeruginosa (G-) were selected as the bacterial strains, and the test was carried out according to the method in the pharmacopoeia to prove the antibacterial property of the veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1.
[0060] Experimental results: As Figure 3 shown. From Figure 3 it can be seen that the veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 reduced both Staphylococcus aureus and Pseudomonas aeruginosa by ≥1.0 log within 7 days, ≥3.0 log at 14 days, and there was no resuscitation at 28 days, indicating that the veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 had antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa.
[0061] 4. Drug loading test
[0062] Berberine hydrochloride was loaded into the veterinary antibacterial drug-loaded hydrogel dressing prepared in Example 1 to obtain a yellow gel.
[0063] ① Drug loading test
[0064] At room temperature, the veterinary antibacterial drug-loaded hydrogel dressing loaded with berberine hydrochloride was attached to the skin surface. After it was applied, its fitting state with the skin was observed to prove that the veterinary antibacterial drug-loaded hydrogel dressing could be normally applied after loading the drug.
[0065] Experimental results: As Figure 4 shown. It can be seen from Figure 4 that the veterinary antibacterial drug-loaded hydrogel dressing loaded with berberine hydrochloride can be completely applied to the epidermis, with no warping at the edges and good film-forming property.
[0066] ② Release test
[0067] Using the modified Franz diffusion cell method, the veterinary antibacterial drug-loaded hydrogel dressing loaded with berberine hydrochloride was applied to the surface of porcine skin. The side without the gel was immersed in the extraction solution (0.9% NaCl solution), and the side with the gel was in the air. The whole reaction cell should be sealed. The extraction solution was continuously stirred at 32 °C, and the transdermal release study of the drug was observed at 24 h.
[0068] Experimental results: As Figure 5 shown. It can be seen from Figure 5 that the yellow drug penetrated into the dermis layer, proving that the drug could be normally released and absorbed.
[0069] According to the drug loading test and the release test, it can be known that adding the drug to the veterinary antibacterial drug-loaded hydrogel dressing has no influence on drug loading and drug release, proving that this veterinary antibacterial drug-loaded hydrogel dressing can load the drug.
[0070] From the above examples and experimental examples, it can be seen that the three-dimensional network structure of the veterinary antibacterial drug-loaded hydrogel dressing of the present invention provides more loading sites for drug molecules, can improve the drug loading and controlled release capabilities; also has excellent skin adhesiveness and antibacterial properties, and can significantly inhibit the proliferation of Staphylococcus aureus and Pseudomonas aeruginosa; can also improve biocompatibility and biodegradability, ensure its safety in the body and reduce the potential risk of long-term implantation, and has no toxic and side effects.
[0071] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.
Claims
1. A method for preparing an antibacterial drug-loaded hydrogel dressing for animals, characterized in that: The following steps are involved: 1) mixing a polyvinyl pyrrolidone solution and a cross-linking agent to obtain a mixed solution A; 2) mixing the mixed solution A and the polyvinyl alcohol solution to obtain a mixed solution B; 3) Mixing the mixed solution B and the viscosity reducer to obtain a mixed solution C, and irradiating the mixed solution C to obtain an antibacterial drug-loaded hydrogel dressing for veterinary use.
2. The preparation method according to claim 1, characterized in that: The mass percentage concentration of the polyvinyl pyrrolidone solution in step 1) is 1% to 50%.
3. The preparation method according to claim 1, characterized in that: Step 1) The cross-linking agent includes citric acid, hyaluronic acid or glycerol, and the added amount of the cross-linking agent is 0.1% to 30% of the volume of the polyvinyl pyrrolidone solution.
4. The preparation method according to claim 1, characterized in that: Step 2) The mass percentage concentration of the polyvinyl alcohol solution is 5% to 20%.
5. The preparation method according to claim 1, characterized in that: The volume ratio of the polyvinyl alcohol solution to the polyvinyl pyrrolidone solution is 1-99:1-99.
6. The preparation method according to claim 1, characterized in that: Step 2) The pH of the mixed solution B is 4-8.
7. The preparation method according to claim 1, characterized in that: Step 3) The viscosity reducer includes anhydrous ethanol, and the added amount of the viscosity reducer is 0.1% to 30% of the volume of the mixed solution B.
8. The preparation method according to claim 1, characterized in that: Step 3) The intensity of the irradiation is 1 to 25 kGy, and the time of the irradiation is 1 to 100 s.
9. The veterinary antibacterial drug-loaded hydrogel dressing prepared by the preparation method according to any one of claims 1 to 8.
10. Use of the veterinary antibacterial drug-loaded hydrogel dressing prepared by the preparation method according to any one of claims 1 to 8 or the veterinary antibacterial drug-loaded hydrogel dressing according to claim 9 in the preparation of wound dressings.