Antibacterial composite hydrogel dressing as well as preparation method and application thereof

Abstract

The invention discloses an antibacterial composite hydrogel dressing as well as a preparation method and application thereof. The antibacterial composite hydrogel dressing is prepared from the following raw materials: carboxymethyl chitosan, polyvinyl alcohol, hydroxyethyl cellulose and a modifier; the preparation method comprises the following steps: adding a mixed aqueous solution of carboxymethyl chitosan and polyvinyl alcohol into an oxidized hydroxyethyl cellulose aqueous solution, and standing to obtain the antibacterial composite hydrogel dressing. The problems that a single hydrogel carrier is general in mechanical performance, drug release capacity and antibacterial performance are solved, a sterile healing environment is provided for skin wounds, and the hydrogel has good market application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and specifically relates to an antibacterial composite hydrogel dressing and a preparation method and application thereof. Background Art

[0002] Traditional dressings mainly use dry gauze and oil gauze to treat skin wounds, providing a basic protective barrier for the wound surface. However, in terms of key aspects such as breathability, antibacterial properties and biocompatibility, it is difficult to meet the demand for high-quality dressings in the modern medical market. In contrast, hydrogel dressings, as a new type of modern dressing that has emerged in recent years, lead the medical hydrogel market with its excellent performance. It can not only create a moist healing environment for wounds, but also has excellent cell compatibility, promoting cell growth and repair.

[0003] Carboxymethyl chitosan (CMCS) and polyvinyl alcohol (PVA) have always been commonly used substrate materials in wound dressings. They are widely available and non-toxic. CMCS is soluble in neutral water and has high adhesion, biocompatibility and gel-forming properties, all of which make it a good wound dressing material. PVA is one of the few synthetic polymer materials with good biocompatibility and degradability. Due to its high crystallinity and high cross-linking density, it has also become a common choice for gel materials.

[0004] At present, when preparing hydrogels by chemical crosslinking methods, the crosslinking agents are usually toxic substances such as aldehydes and adipic dihydrazide. The use of these crosslinking agents will indirectly bring certain safety hazards during the use of hydrogels. It is urgent to develop a hydrogel dressing without any crosslinking agent with toxic risks to meet market demand. Summary of the invention

[0005] The purpose of the present invention is to provide an antibacterial composite hydrogel dressing and its preparation method and application, which solves the problem that a single hydrogel carrier has poor mechanical properties, drug release capacity and antibacterial properties. The use of oxidized hydroxyethyl cellulose (OHEC) with its low toxicity and rich aldehyde active groups as a green crosslinking agent for preparing hydrogel will solve this problem well.

[0006] In order to solve the problems of the prior art, the technical solution adopted by the present invention is:

[0007] An antibacterial composite hydrogel dressing is prepared by adding an aqueous solution of oxidized hydroxyethyl cellulose obtained by modifying hydroxyethyl cellulose into a mixed aqueous solution of polyvinyl alcohol and carboxymethyl chitosan, that is, the oxidized hydroxyethyl cellulose network is chemically cross-linked on the basis of the physical network of polyvinyl alcohol and carboxymethyl chitosan to complete the physical and chemical double cross-linking.

[0008] The preparation method of the above antibacterial composite hydrogel dressing comprises the following steps:

[0009] Step 1, adding a modifier to a 1-2% by mass aqueous solution of hydroxyethyl cellulose, reacting at 25° C. in the dark for 24 hours, and after the modification treatment, dialyzing and centrifuging to collect the supernatant, and drying to obtain oxidized hydroxyethyl cellulose;

[0010] Step 2, dripping a 3-5% by mass carboxymethyl chitosan aqueous solution into a 0.5-2% by mass polyvinyl alcohol aqueous solution, stirring at 20-30° C. for 15-30 minutes to obtain a prepolymer solution;

[0011] Step 3, mixing the prepolymer solution and the oxidized hydroxyethyl cellulose aqueous solution evenly, and letting it stand at 20-30° C. for 1-2 hours to obtain an antibacterial composite hydrogel dressing.

[0012] As an improvement, the mass fraction of hydroxyethyl cellulose in step 1 is 1%, and the dialysis time is 3-5 days.

[0013] As an improvement, the modifier in step 1 is sodium periodate, and the mass ratio of hydroxyethyl cellulose to the modifier is 1:1-3. Too high or too low a mass ratio of hydroxyethyl cellulose to the modifier will affect the degree of oxidation of hydroxyethyl cellulose.

[0014] A further improvement is that in step 1, the mass ratio of hydroxyethyl cellulose to the modifier is 1:2.

[0015] A further improvement is that in step 2, the mass fraction of the carboxymethyl chitosan aqueous solution is 4%, the mass fraction of the polyvinyl alcohol aqueous solution is 2%; and the mixing volume ratio of the carboxymethyl chitosan aqueous solution to the polyvinyl alcohol aqueous solution is 4:1.

[0016] As an improvement, in step 2, the stirring temperature is 25° C. and the stirring time is 15 min.

[0017] As an improvement, the mass fraction of the hydroxyethyl cellulose aqueous solution in step 3 is 2-6%, and the volume ratio of the oxidized hydroxyethyl cellulose aqueous solution to the carboxymethyl chitosan aqueous solution in the prepolymerization solution is 1:4.

[0018] A further improvement is that in step 3, the mass fraction of the oxidized hydroxyethyl cellulose aqueous solution is 2-6%, the standing temperature is 25° C., and the standing time is 1 hour.

[0019] Application of the antibacterial composite hydrogel dressing prepared by the above preparation method in medical tissue adhesive.

[0020] Beneficial effects:

[0021] Compared with the prior art, the antibacterial composite hydrogel dressing of the present invention and its preparation method and application have the following advantages:

[0022] (1) The antibacterial composite hydrogel dressing of the present invention is prepared by combining physical crosslinking and chemical crosslinking between CMCS, PVA and OHEC, with a short crosslinking time, a simple production method, no need for any crosslinking agent with toxic potential, and high environmental friendliness;

[0023] (2) The antibacterial composite hydrogel dressing of the present invention has excellent antibacterial effect, can have excellent inhibitory effect on Escherichia coli, Staphylococcus aureus, etc., effectively prevents bacterial infection of wounds, and expands the application field of the dressing;

[0024] (3) The antibacterial composite hydrogel dressing of the present invention has good adhesion properties, can properly prevent abrasions, accelerate wound healing, and shorten the treatment cycle. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a comparison chart of the peel strength of the hydrogel dressings prepared in Examples 1-3 and Comparative Example 1;

[0026] Figure 2 This is a comparison chart of the swelling properties of the hydrogel dressings prepared in Examples 1-3 and Comparative Example 1;

[0027] Figure 3 This is a comparison chart of the antibacterial effects of the hydrogel dressings prepared in Examples 1-3 and Comparative Example 1. DETAILED DESCRIPTION

[0028] The following examples will enable those skilled in the art to more fully understand the present invention, but are not intended to limit the present invention in any way.

[0029] Example 1

[0030] (1) Weigh 3 g of hydroxyethyl cellulose (HEC) and dissolve it in 300 ml of distilled water. Add 6 g of sodium periodate (NaIO 4 ) was dissolved in HEC aqueous solution, stirred at a constant speed, and reacted at 25°C in the dark for 24 hours. After the reaction, 2 ml of ethylene glycol (CH 2 OH) 2 Continue stirring for 30 min to remove unreacted NaIO 4 Then, the reaction solution was dialyzed in deionized water for 3 days through a dialysis bag (MWCO: 8000-14,000Da), with the water changed 3 times a day. Finally, the supernatant was collected by centrifugation and freeze-dried to obtain oxidized hydroxyethyl cellulose (OHEC).

[0031] (2) Weigh 0.8 g of carboxymethyl chitosan (CMCS) and dissolve it in 20 ml of distilled water to prepare a 4% CMCS aqueous solution. Then, weigh 0.1 g of polyvinyl alcohol (PVA) and dissolve it in 5 ml of distilled water to prepare a 2% PVA aqueous solution. Finally, according to the volume ratio of CMCS aqueous solution and PVA aqueous solution of 4:1, 20 ml of 4% CMCS and 5 ml of 2% PVA were mixed evenly and stirred for 15 minutes to obtain a prepolymer solution.

[0032] (3) Weigh 0.1 g of oxidized hydroxyethyl cellulose and dissolve it in 5 ml of distilled water, prepare a 2% OHEC aqueous solution, then mix the OHEC aqueous solution and the carboxymethyl chitosan aqueous solution in the prepolymer solution in a volume ratio of 1:4, stir for 15 minutes, and stand at 25°C for 1 hour to obtain an antibacterial composite hydrogel dressing.

[0033] Example 2

[0034] Except that the oxidized hydroxyethyl cellulose in step (3) is changed to 0.2 g and the mass fraction of the OHEC aqueous solution is 4%, the rest is the same as in Example 1.

[0035] Example 3

[0036] Except that the amount of oxidized hydroxyethyl cellulose in step (3) is changed to 0.3 g and the mass fraction of the OHEC aqueous solution is 6%, the rest is the same as in Example 1.

[0037] Comparative Example 1

[0038] Weigh 0.8g of carboxymethyl chitosan (CMCS) and dissolve it in 20ml of distilled water to prepare a 4% CMCS aqueous solution. Then, weigh 0.1g of polyvinyl alcohol (PVA) and dissolve it in 5ml of distilled water to prepare a 2% PVA aqueous solution. Finally, according to the volume ratio of CMCS aqueous solution and PVA aqueous solution of 4:1, 20ml of 4% CMCS and 5ml of 2% PVA were mixed evenly, stirred for 15min, and allowed to stand at 25°C for 1h to obtain PVA / CMCS hydrogel dressing.

[0039] Performance Testing

[0040] The PVA / CMCS hydrogel dressings prepared in the above Examples 1-3 and Comparative Example 1 were characterized by adhesion strength test, antibacterial property, and swelling property, as follows:

[0041] Adhesion strength test: Take two pieces of fresh pig skin (50mm long, 20mm wide, 2-3mm thick), prepare the sample one night in advance, apply the hydrogel dressing on the surface of one piece of pig skin, and then take another piece to cover the applied part, apply a pressure of 8N to the cross-linked part, and after 3 hours, use a universal electronic tensile testing machine to test the adhesion strength at a speed of 10mm / min.

[0042] Antibacterial performance test: Staphylococcus aureus and Escherichia coli were first cultured in liquid culture medium, then the bacterial suspension was centrifuged and dispersed in physiological saline to a concentration of 10 6 CFU / mL, and use this as the test bacterial suspension. Put the adhesive into 1mL of the bacterial suspension and place it under near infrared spectroscopy (808nm, 2W / cm 2 ) for 12 minutes. Then, 100 μL of the treated bacterial suspension was transferred to a solid culture medium at 37°C. After overnight culture, the colonies were photographed and counted to obtain the inhibition rate.

[0043] Swelling performance test: Weigh the dried hydrogel sample and record the mass, place it in an appropriate amount of PBS buffer, and soak it at a constant temperature of 25°C. Take it out at a set time interval, absorb the excess solvent and weigh it, and calculate the swelling ratio. Continue testing until swelling equilibrium, draw a swelling ratio-time curve, and analyze the swelling rate, equilibrium time and other properties based on it, and compare the samples of Examples 1-3 and Comparative Example 1.

[0044] Figure 1 The results of the bonding strength test show that as the content of oxidized hydroxyethyl cellulose increases, the bonding strength of the hydrogel dressing also increases. Among them, the bonding strength of Example 3 reaches 29 Kpa.

[0045] Figure 2 The swelling performance test results show that with the increase of oxidized hydroxyethyl cellulose content, the swelling rate of the hydrogel dressing shows a downward trend and basically reaches swelling equilibrium after 48 hours. The swelling rate is below 200%, which is within the reasonable swelling range of medical adhesives.

[0046] Figure 3 The results of the antibacterial performance test show that as the content of oxidized hydroxyethyl cellulose increases, the antibacterial effect on Escherichia coli and Staphylococcus aureus is enhanced.

[0047] The above test results are shown in Table 1.

[0048] Table 1 Comparison of various properties of antibacterial composite hydrogels under different parameters

[0049]

[0050] As can be seen from Table 1, the PVA / CMCS hydrogel cross-linked by carboxymethyl cellulose (CMCS) and polyvinyl alcohol (PVA) in Comparative Example 1 has low cytotoxicity, but is inferior to the antibacterial composite hydrogel prepared by carboxymethyl cellulose, polyvinyl alcohol and oxidized hydroxyethyl cellulose in terms of swelling rate and antibacterial performance. In addition, as the content of oxidized hydroxyethyl cellulose increases, the adhesion strength also increases.

[0051] In summary, the antibacterial composite hydrogel prepared by the present invention has good bonding strength, antibacterial performance, good swelling rate and no cytotoxicity, which can meet the requirements of practical applications.

[0052] It should be noted that the above content only illustrates the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. For ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications all fall within the protection scope of the claims of the present invention.

Claims

1. An antibacterial composite hydrogel dressing, characterized in that: The antibacterial composite hydrogel dressing is prepared by adding an oxidized hydroxyethyl cellulose aqueous solution obtained by modifying hydroxyethyl cellulose to a mixed aqueous solution of polyvinyl alcohol and carboxymethyl chitosan, that is, the oxidized hydroxyethyl cellulose network is chemically cross-linked on the basis of the physical network of polyvinyl alcohol and carboxymethyl chitosan to complete the physical and chemical double cross-linking.

2. The method for preparing the antibacterial composite hydrogel dressing according to claim 1, characterized in that: The following steps are involved: Step 1, adding a modifier to a 1-2% by mass aqueous solution of hydroxyethyl cellulose, reacting at 25° C. in the dark for 24 hours, and after the modification treatment, dialyzing and centrifuging to collect the supernatant, and drying to obtain oxidized hydroxyethyl cellulose; Step 2, dripping a 3-5% by mass carboxymethyl chitosan aqueous solution into a 0.5-2% by mass polyvinyl alcohol aqueous solution, stirring at 20-30° C. for 15-30 minutes to obtain a prepolymer solution; Step 3, mixing the prepolymer solution and the oxidized hydroxyethyl cellulose aqueous solution evenly, and letting it stand at 20-30° C. for 1-2 hours to obtain an antibacterial composite hydrogel dressing.

3. The preparation method according to claim 2, characterized in that: In step 1, the mass fraction of hydroxyethyl cellulose is 1%, and the dialysis time is 3-5 days.

4. The preparation method according to claim 2, characterized in that: The modifier in step 1 is sodium periodate, and the mass ratio of hydroxyethyl cellulose to the modifier is 1:1-3.

5. The preparation method according to claim 4, characterized in that: In step 1, the mass ratio of hydroxyethyl cellulose to the modifier is 1:

2.

6. The preparation method according to claim 2, characterized in that: In step 2, the mass fraction of the carboxymethyl chitosan aqueous solution is 4%, and the mass fraction of the polyvinyl alcohol aqueous solution is 2%; the mixing volume ratio of the carboxymethyl chitosan aqueous solution to the polyvinyl alcohol aqueous solution is 4:

1.

7. The preparation method according to claim 2, characterized in that: In step 2, the stirring temperature is 25° C. and the stirring time is 15 min.

8. The preparation method according to claim 2, characterized in that: The mass fraction of the hydroxyethyl cellulose aqueous solution in step 3 is 2-6%, and the volume ratio of the oxidized hydroxyethyl cellulose aqueous solution to the carboxymethyl chitosan aqueous solution in the prepolymerization solution is 1:

4.

9. The preparation method according to claim 2, characterized in that: In step 3, the mass fraction of the oxidized hydroxyethyl cellulose aqueous solution is 2-6%, the standing temperature is 25° C., and the standing time is 1 hour.

10. Use of the antibacterial composite hydrogel dressing prepared by any one of the preparation methods of claims 2 to 9 in medical tissue adhesives.

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