CN111184906B

CN111184906B - PVA-based liquid dressing and preparation method thereof

Info

Publication number: CN111184906B
Application number: CN202010102098.7A
Authority: CN
Inventors: 刘颖; 郑玉霞; 任学宏
Original assignee: Jiangnan University
Current assignee: Guangzhou Dayu Chuangfu Technology Co ltd
Priority date: 2020-02-19
Filing date: 2020-02-19
Publication date: 2020-12-29
Anticipated expiration: 2040-02-19
Also published as: CN111184906A

Abstract

The invention discloses a PVA (polyvinyl alcohol) -based liquid dressing and a preparation method thereof, belonging to the technical field of medical treatment. The preparation method of the liquid dressing comprises the following steps: (1) adding 1, 2-epoxy-4-vinyl cyclohexane EVC into a polyvinyl alcohol PVA solution, and uniformly stirring, wherein the molar ratio of PVA to EVC is (1-3): (1-3) obtaining a PVA/EVC mixed solution; (2) adding xanthan gum and glycerol into the PVA/EVC mixed solution obtained in the step (1), and continuously and uniformly stirring to obtain a mixed solution; (3) and (3) adding an antibacterial agent/ethanol solution into the mixed solution obtained in the step (2), fully stirring, and removing bubbles to obtain the liquid dressing. The liquid dressing prepared by the invention has flexible hand feeling, transparent appearance, water vapor permeability and good antibacterial property, and can be completely torn off after being dried to form a film without residue.

Description

PVA-based liquid dressing and preparation method thereof

Technical Field

The invention relates to a PVA-based liquid dressing and a preparation method thereof, belonging to the technical field of medical treatment.

Background

Bacteria, fungi and microorganisms are widely existed in the daily life environment, and if the human skin is abraded or damaged, the wound healing can be delayed if the human skin cannot be effectively treated in time, the wound is easy to suffer from infection, and even serious complications are caused. Therefore, research on wound dressings is of particular importance.

At present, more traditional dressings such as absorbent cotton and gauze are clinically applied, the liquid absorption capacity of the dressings is too strong, cell survival and tissue regeneration are not facilitated, granulation tissues formed in the wound healing process are easy to adhere to the dressings, and secondary damage is caused when the dressings are replaced and removed. In addition, they need to be fixed by medical adhesive tapes in the using process, and the using range is limited. More and more researchers are focusing on the development of new dressings. It is expected that a novel wound dressing which has excellent properties and is more suitable for clinical application can be prepared.

As a wound dressing, it is required to have an antibacterial effect, which can block the invasion of bacteria and microorganisms to a wound, and can effectively sterilize and diminish inflammation at an infected wound to promote healing. At present, researches on antibacterial agents at home and abroad mainly comprise organic antibacterial agents, inorganic antibacterial agents, natural antibacterial agents, macromolecular antibacterial agents and the like, but the antibacterial agents have certain defects, such as weak antibacterial capacity, slow sterilization speed, high price and the like.

Therefore, how to prepare and use the dressing which is convenient and fast and is suitable for daily superficial skin wounds is a problem which needs to be solved urgently at present.

Disclosure of Invention

In order to solve at least one of the above problems, the present invention provides a liquid dressing and a method for preparing the same. The liquid dressing has the advantages of transparent appearance, water vapor permeability and good antibacterial performance, and can be completely torn off after being dried into a film without residue.

The first purpose of the invention is to provide a preparation method of a liquid dressing, which comprises the following steps:

(1) adding 1, 2-epoxy-4-vinyl cyclohexane EVC into a polyvinyl alcohol PVA solution, and uniformly stirring, wherein the molar ratio of PVA to EVC is (1-3): (1-3) obtaining a PVA/EVC mixed solution;

(2) adding xanthan gum and glycerol into the PVA/EVC mixed solution obtained in the step (1), and continuously and uniformly stirring to obtain a mixed solution;

(3) and (3) adding an antibacterial agent/ethanol solution into the mixed solution obtained in the step (2), fully stirring, and removing bubbles to obtain the liquid dressing.

In one embodiment, the molar ratio of PVA to EVC in step (1) is 2: 1.

in one embodiment, the mass fraction of the PVA solution in the step (1) is 2-12%, that is, 2-12g of PVA is added into 88-98g of water, and the PVA accounts for 2-12% of the total solution; preferably, the mass fraction of the polyvinyl alcohol PVA solution is 8%.

In one embodiment, the polyvinyl alcohol PVA in step (1) is a polyvinyl alcohol 1788 type, the alcoholysis degree is 87.0-89.0 (mol/mol), and the relative molecular mass: 44.05.

in one embodiment, step (1) is specifically: preparing a PVA solution with the mass fraction of 2-12%, and heating at 90 ℃ until the PVA solution is completely dissolved; then cooling to 70 ℃, adding 1, 2-epoxy-4-vinyl cyclohexane EVC, wherein the molar ratio of PVA to EVC is 2:1, stirring uniformly to obtain a PVA/EVC mixed solution.

In one embodiment, the heating in step (1) is oil bath heating.

In one embodiment, the stirring in step (1) is specifically: the stirring speed is 800-1200rpm, and the stirring time is 3-15 h.

In one embodiment, the EVC of step (1) has a formula as shown in formula 1:

in one embodiment, the mass ratio of the xanthan gum in the step (2) to the PVA/EVC mixed solution in the step (1) is 0.5: 100.

in one embodiment, the mass ratio of the glycerin in the step (2) to the PVA/EVC mixed solution in the step (1) is (1-10): 100.

in one embodiment, the stirring in step (2) is specifically: the stirring speed is 800-1200rpm, and the stirring time is 10-20 h.

In one embodiment, the antimicrobial agent of step (3) is 1-chloro-2, 2,5, 5-tetramethyl-4-imidazolidinone MC having the formula shown in formula 2:

in one embodiment, the ethanol of step (3) is anhydrous ethanol.

In one embodiment, the mass ratio of the antibacterial agent/ethanol solution in the step (3) to the mixed solution in the step (2) is (5-30): 100.

in one embodiment, the mass ratio of the antibacterial agent to ethanol in the antibacterial agent/ethanol solution in step (3) is (0.1-1): 100.

in one embodiment, the stirring in the step (3) is manual stirring, specifically, the stirring is performed uniformly by using a glass rod, and the stirring time is 5-10 min.

In one embodiment, the bubble removal in the step (3) is specifically ultrasonic bubble removal, the ultrasonic power is set to be 300-500W, and the ultrasonic time is 20-60 min.

In one embodiment, the method for preparing the liquid dressing comprises the following steps:

(1) preparing a PVA solution with the mass fraction of 8%, and heating at 90 ℃ until the PVA solution is completely dissolved; then cooling to 70 ℃, adding 1, 2-epoxy-4-vinyl cyclohexane EVC, wherein the molar ratio of PVA to EVC is 2:1, uniformly stirring to obtain a PVA/EVC mixed solution;

(2) adding xanthan gum and glycerol into the PVA/EVC mixed solution in the step (1), wherein the mass ratio of the xanthan gum to the PVA/EVC mixed solution in the step (1) is 0.5: 100, respectively; the mass ratio of the glycerol to the PVA/EVC mixed solution in the step (1) is 5: 100, continuously stirring uniformly at 70 ℃ to obtain a mixed solution, and then cooling the mixed solution to room temperature;

(3) adding an antibacterial agent/ethanol solution into the mixed solution in the step (2), wherein the mass ratio of the antibacterial agent/ethanol solution to the mixed solution in the step (2) is 25: 100, the mass ratio of the antibacterial agent to the ethanol in the antibacterial agent/ethanol solution is 0.2: 100, respectively; fully stirring and removing bubbles to obtain the liquid dressing.

In one embodiment, the 1, 2-epoxy-4-vinylcyclohexane EVC is available from Merrill Chemicals, Inc.; polyvinyl alcohol PVA, glycerol, xanthan gum and ethanol are purchased from national medicine group chemical reagents, while the antibacterial agent 1-chloro-2, 2,5, 5-tetramethyl-imidazoline MC is purchased from Hangzhou gold warehouse chemical industry, and all the reagents are not further purified.

The second object of the present invention is a liquid dressing obtained by the manufacturing method of the present invention.

A third object of the invention is a wound dressing comprising said liquid dressing of the invention.

A fourth object of the invention is the use of a liquid dressing according to the invention for the treatment of daily superficial skin wounds.

In one embodiment, the liquid dressing of the present invention is applied to the superficial skin wound surface, dried to form a film, and removed after a period of use.

The invention has the beneficial effects that:

(1) the invention combines the advantages of two polymer materials of polyvinyl alcohol PVA and xanthan gum, adds glycerin as a plasticizing and moisturizing component, adopts a blending method, adds the high-efficiency N-halamine antibacterial agent MC into the whole system by taking ethanol as a solvent, and develops the novel liquid dressing PVA/EVC/MC.

(2) The liquid dressing has good film forming effect (the film forming time is about 20min), soft hand feeling and no residue after being torn off.

(3) After the liquid dressing is formed into a film, 6.12 logs of staphylococcus aureus and 6.04 logs of escherichia coli can be killed within 5min, and excellent antibacterial performance is shown.

(4) The liquid dressing prepared by the invention has no cytotoxicity in the using process and is expected to be applied to superficial epidermal wound healing.

(5) The invention can make the film formed by the liquid dressing become relatively flexible and elastic through the co-heating reaction of PVA and EVC.

(6) The raw materials adopted by the invention are cheap and are suitable for industrial use.

(7) The ethanol adopted by the invention plays two roles in the dressing, one is a solvent of the antibacterial agent, and the ethanol can dissolve the antibacterial agent, so that the uniformity of the antibacterial agent in the whole liquid dressing during later-stage mixing can be ensured; on the other hand, the ethanol has strong volatility, can effectively reduce the time required by film forming of the dressing, has higher applicability, improves the use feeling, and is more convenient to use.

Drawings

FIG. 1 is a comparison of the effects of examples 1 and 5 on the system state of the solution, wherein the mass ratio of the antibacterial agent MC/ethanol solution in a-g to the mixed solution in the step (2) is 0: 100. 5: 100. 10: 100. 15: 100. 20: 100. 25: 100. 30: 100.

fig. 2 is a use of a mold to simulate a liquid dressing.

FIG. 3 is a graph showing the influence of the mass ratio of the MC/ethanol solution of different antibacterial agents and the mixed solution of the step (2) on the film forming time in examples 1 and 5.

FIG. 4 is a graph showing the influence of the mass ratio of the different antibacterial agents MC to ethanol in the antibacterial agent MC/ethanol solutions of examples 1 and 6 on the chlorine content of the prepared PVA/EVC/MC film.

FIG. 5 shows PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 10)¹⁷atoms/cm²) And obtaining the X-ray diffraction pattern of the antibacterial dressing film.

FIG. 6 shows the original PVA and the PVA/EVC/MC (3.24X 1017 atoms/cm) of example 1²) And obtaining a mechanical property test chart of the antibacterial dressing film.

FIG. 7 shows PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 10)¹⁷atoms/cm²) Obtaining an AFM image of the antibacterial dressing film; wherein a is PVA; b is PVA/EVC; c is PVA/EVC/MC 3.24X 10 of example 1¹⁷atoms/cm²。

FIG. 8 shows the results of measuring the water vapor transmission rate of PVA, PVA/EVC, and the film material produced from PVA/EVC/MC of example 1.

FIG. 9 shows the survival rates of MC3T3-E1 cells cultured at 6 concentrations in the presence of PVA, PVA/EVC, and the membrane extract (n-3) prepared from PVA/EVC/MC of example 1.

FIG. 10 shows the cell morphology and cell viability of MC3T3-E1 cells incubated with PVA, PVA/EVC, and the membrane extract (100ppm) prepared in example 1, and observed by light microscope; wherein A is PVA; b is PVA/EVC; c is PVA/EVC/MC 3.24X 10 of example 1¹⁷atoms/cm²。

FIG. 11 is a schematic diagram of a film prepared from PVA/EVC/MC of example 1.

FIG. 12 is a diagram showing a sample of PVA, a PVA solution after EVC blending reaction, and a PVA/EVC mixed solution; PVA, PVA solution after EVC blending reaction and PVA/EVC mixed solution are sequentially arranged from left to right.

Detailed Description

The following description of the preferred embodiments of the present invention is provided for the purpose of better illustrating the invention and is not intended to limit the invention thereto.

The various detection methods are as follows:

determination of chlorine content: the chlorine content of the antibacterial PVA/EVC/MC film was determined by an iodine amount/thiosulfate titration method. Taking different membrane samples (size: 2cm multiplied by 2cm) and putting the membrane samples into 20mL of deionized water, adding 0.3g of potassium iodide and 2mL of starch solution with the mass fraction of 1%, stirring the mixture at room temperature for 30min until the solution turns dark blue, and titrating the solution by using sodium thiosulfate until the blue color disappears. The chlorine content of the produced film (chlorine content on the film surface) was calculated by the following formula (1):

wherein N is the normality of the sodium thiosulfate solution used for titration, and V is the volume (mL) of the sodium thiosulfate solution consumed; s is the area (cm) of the film sample²) And the average value of each group of samples is obtained by measuring three times.

Measurement of mechanical properties: the mechanical properties of the films were measured using a computer controlled electronic universal tester (3385H) (INSTRON, Norwood, MA, USA) according to ASTM D3039. The tensile strength and elongation at break of the film were determined by tensile testing. Briefly, the samples were cut into a rectangle (30 mm. times.100 mm) and tested at a tensile speed of 5 mm/min. Each sample was tested three times, and the average value was taken, and the tensile strength (2) and tensile elongation (3) were calculated as follows:

where N break and A sample are the force (N) required to snap the membrane and the cross-sectional area (mm) of the specimen, respectively²). L is the increase in length of the film breaking point (mm); l is the original length.

Measurement of Water vapor passage Rate: testing of Water Vapor Transmission Rate (WVTR) was performed for several film materials according to ASTM method (2010 standard). Specifically, a small beaker with the diameter of 30mm is taken, 20mL of distilled water is filled in the beaker, a circular membrane sample with the diameter slightly larger than 30mm is used for covering the opening of the beaker, and the beaker is fixed and sealed by a rubber ring; the beaker was then placed in an incubator at 30 ℃ and a Relative Humidity (RH) of 50. + -. 5% and weighed every 24h, and the weight loss of water was recorded as a function of time. The water vapor delivery rate was calculated by dividing the slope of the linear regression equation in this function by the mouth area of the small beaker. Specifically, the calculation formula of the water vapor passage rate is shown in the following formula (4):

wherein S is the slope of the linear regression equation (g.h)^-1) A is the area (m) of the mouth of the small beaker²)。

And (3) testing antibacterial performance: the membranes were tested for their antimicrobial efficacy using the modified AATCC 100-2004 method. The bacteria used were gram-negative Staphylococcus aureus (ATCC 6538) and gram-positive Escherichia coli (ATCC 43895). The specific operation is as follows: 25 μ L of the bacterial suspension was pipetted into the center of the membrane sample (2.54 cm. times.2.54 cm) and another piece of the sample was covered and the sterilized weight placed on top to allow adequate contact between the sample and the bacteria. When the contact time reaches 5, 10 and 30min, the sample is transferred to a container containing 5mL of NaS sterilized at high temperature₂O₃Centrifuging the solution to quench the active chlorine in the sample; after vortexing for 2min, taking a proper amount of solution in a centrifuge tube, sequentially diluting the solution by 10, 100 and 1000 times by using a phosphoric acid buffer solution, and respectively taking 100 mu L of the solution to inoculate onto an agar plate (nutrient agar is purchased from national drug group chemical reagents, Inc.); and then transferring the mixture to an incubator at 37 ℃, and after incubation for 24h, recording the colony number and calculating the sterilization result.

In vitro cytotoxicity test: the cytocompatibility of the films formed by the liquid dressing was studied using a mouse preosteoblastic cell line (MC3T 3-E1). The specific operation is as follows: cutting the prepared film sample into 6cm²Soaking in 90% alcohol for 20min before cell inoculation for sterilization; then further purified by soaking in Phosphate Buffered Saline (PBS) for 5 minutes; subsequently, the process of the present invention,placing the soaked sample in a 48-well plate, and soaking the sample for 24 hours by using a DMEM (Gibco) culture medium to obtain an extracting solution with the concentration of 100 ppm; continuously diluting the obtained extractive solution for 5 times to obtain extractive solutions (50, 25, 12.5, 6.25, 3.125ppm) with different concentration gradients; then inoculating MC3T3-E1 cells on a 96-well plate, wherein the cell density is 4000 cells/well; then at 37 ℃ with 5% CO₂After the culture in the incubator for 1 day, the culture medium of the experimental group is changed into the extracting solution, and the fresh DMEM culture medium of the control group is changed. Three replicates per sample were run, followed by one additional day of incubation, and cytotoxicity of the supplied samples against MC3T3-E1 cells was determined using cell counting Kit-8(CCK-8, Nanjing, China, Tokyo); the absorbance (OD) of the sample at 450nm was measured with a microplate reader (Bio Tek Instruments, Inc.100Tigan Street), and the cell viability was determined by the following formula (5) with the OD value of the PBS solution at this wavelength as a blank:

example 1

A preparation method of a liquid dressing comprises the following steps:

(1) preparing a PVA solution with the mass fraction of 8% (the mass ratio of the PVA to the water is 8: 92), and heating the PVA solution in an oil bath kettle at the temperature of 90 ℃ until the PVA solution is completely dissolved; cooling to 70 ℃, adding EVC (the molar ratio of PVA to EVC is 2: 1), stirring (the stirring speed is 1000rpm) and reacting for 5 hours to obtain a PVA/EVC mixed solution;

(2) adding xanthan gum (accounting for 0.5 percent of the mass of the PVA/EVC mixed solution) and glycerol (accounting for 5 percent of the mass of the PVA/EVC mixed solution) into the PVA/EVC mixed solution obtained in the step (1), and continuously stirring for 12 hours to obtain a mixed solution marked as PVA/EVC;

(3) adding an antibacterial agent MC/ethanol solution into the mixed solution in the step (2), wherein the mass ratio of the antibacterial agent MC/ethanol solution to the mixed solution in the step (2) is 25: 100, the mass ratio of the antibacterial agent MC to the ethanol in the antibacterial agent MC/ethanol solution is 0.2: 100, respectively; fully and uniformly stirring, and removing bubbles by ultrasonic (ultrasonic power 300W, ultrasonic time 30min) to obtain the PVA/EVC/MC antibacterial liquid dressing.

The PVA/EVC/MC antibacterial liquid dressing is subjected to performance test, and the test results are shown in the following table 1:

TABLE 1 PVA, PVA/EVC and PVA/EVC/MC antibacterial liquid dressing of example 1 films against Staphylococcus aureus^aAnd Escherichia coli^bAntibacterial results of

^aThe number of inoculated bacteria was 1.32X 10⁶(6.12log) CFU/sample.

^bThe number of inoculated bacteria was 1.12X 10⁶(6.04log) CFU/s sample.

^cThe chlorine content of the film sample was 3.24X 10¹⁷atoms/cm²。

Pure PVA film and PVA/EVC film are used as control samples, and the chlorine content is 3.24 multiplied by 10¹⁷atoms/cm²The PVA/EVC/MC membranes used as test samples were inoculated with 1.32X 10 cells respectively⁶(6.12log) CFU/specimen and 1.12X 10⁶(6.04log) CFU/specimen of Staphylococcus aureus and Escherichia coli, and the antibacterial effect test was performed, and the test results are shown in Table 1. It can be seen from Table 1 that the PVA only film and the PVA/EVC film showed a certain "inhibitory" effect on both bacteria, and both bacteria were reduced to some extent, because some of the bacteria adhered to the surface of the film. Moreover, the PVA/EVC film reduces bacteria more than the PVA film, and the result is probably that the PVA/EVC film has better hydrophilicity and can adhere to more bacteria. But the PVA/EVC/MC film obtained after the MC is doped has more excellent antibacterial performance and can kill all inoculated staphylococcus aureus and escherichia coli within 5 min. The bactericidal efficiency of the PVA/EVC/MC film is due to the strong antibacterial activity of the N-halamine-based compound MC, which inactivates microorganisms by directly transferring covalently bonded chlorine or dissociated chlorine to the surface of bacteria.

Example 2

A preparation method of a liquid dressing comprises the following steps:

(1) preparing a PVA solution with the mass fraction of 10% (the mass ratio of the PVA to the water is 10: 90), and heating the PVA solution in an oil bath kettle at the temperature of 90 ℃ until the PVA solution is completely dissolved; cooling to 70 ℃, adding EVC (the molar ratio of PVA to EVC is 1: 1), stirring (the stirring speed is 1000rpm), and reacting for 12 hours to obtain a PVA/EVC mixed solution;

(2) adding xanthan gum (accounting for 0.5 percent of the mass of the PVA/EVC mixed solution) and glycerol (accounting for 2 percent of the mass of the PVA/EVC mixed solution) into the PVA/EVC mixed solution obtained in the step (1), and continuously stirring for 12 hours to obtain a mixed solution marked as PVA/EVC;

(3) adding an antibacterial agent MC/ethanol solution into the mixed solution in the step (2), wherein the mass ratio of the antibacterial agent MC/ethanol solution to the mixed solution in the step (2) is 25: 100, the mass ratio of the antibacterial agent MC to the ethanol in the antibacterial agent MC/ethanol solution is 0.7: 100, respectively; fully and uniformly stirring, and removing bubbles by ultrasonic (ultrasonic power 300W, ultrasonic time 30min) to obtain the PVA/EVC/MC antibacterial liquid dressing.

The PVA/EVC/MC antibacterial liquid dressing is subjected to performance test, and the test results are shown in the following table 2:

TABLE 2 PVA, PVA/EVC and PVA/EVC/MC antiseptic liquid dressings of example 1 films obtained against Staphylococcus aureus^aAnd Escherichia coli^bAntibacterial results of

^aThe number of inoculated bacteria was 1.32X 10⁶(6.12log) CFU/sample.

^bThe number of inoculated bacteria was 1.12X 10⁶(6.04log) CFU/s sample.

^dThe chlorine content of the film sample was 8.30X 10¹⁷atoms/cm²。

As can be seen from table 2: the chlorine content of the visible film sample was 3.24X 10¹⁷atoms/cm²It is sufficient to kill all the two inoculated bacteria and a rapid inactivation (5min) can be achieved. So as to followThe prepared sample preferably has an MC/ethanol concentration of 0.2% to meet the application requirement.

Example 3

The PVA solution in example 1 was adjusted to 6%, 10%, and 12% by mass, and the other parameters were kept constant, and performance tests were performed.

The test result shows that: when the PVA mass fraction is low, the solution prepared by the method of the embodiment 1 is thin, the film forming property is poor, and the required film forming time is long; when the mass fraction of PVA is higher, the liquid dressing obtained after the xanthan gum is doped is too thick, and the use is very inconvenient.

Example 4

The molar ratio of PVA to EVC in step (1) of example 1 was adjusted to 3:1, 1:1, 3:2, 2:3, 1:2, 1:3, and other parameters were kept constant, and performance tests were performed.

The liquid dressings obtained in examples 1 and 4 (by adding different amounts of the double-active monomer EVC to the PVA solution) were formed into films by a solution casting method, so that a series of films with properties and performances different from those of the original PVA film were obtained, and the obtained films were subjected to mechanical property tests, the test results of which are shown in table 3:

table 3 mechanical property test results of the films prepared in examples 1 and 4

As can be seen from table 3: when the molar ratio of PVA to EVC was gradually decreased, that is, the amount of EVC added was smaller, the tensile strength of the resulting film material was lower, but the elongation at break was increased, and it was seen that the original PVA became relatively flexible after the heat blending reaction by EVC. In addition, the transparency is reduced and the tensile properties are improved compared with PVA.

FIG. 6 shows the original PVA and the PVA/EVC/MC of example 1 (3.24X 10)¹⁷atoms/cm²) And obtaining a mechanical property test chart of the antibacterial dressing film. As can be seen from fig. 6: two films prepared under the same condition are viewed immediately after film forming, and the original PVA film is dry and transparent, has plastic hand feeling and cannot be stretched; when the molar ratio of PVA to EVC isAt 2:1, the resulting film is flexible and stretchable. In addition, during the experiment, when the addition amount of EVC monomer is large (the molar ratio of PVA to EVC is less than 1), the obtained film has similar oily substances on the surface after about 12 hours, and the subsequent use can be influenced. Thus, the optimal molar ratio of PVA to EVC is 2: 1.

Table 4 shows PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 1017 atoms/cm)²) And testing the mechanical property of the obtained film. As can be seen from table 4: compared with the PVA film, the tensile strength and the elongation of the PVA/EVC film are respectively improved from 18.32 +/-1.20 MPa and 206 +/-8 percent to 20.14 +/-0.91 MPa and 249 +/-10 percent. The tensile strength of the film material is significantly reduced (about 38%) when the antimicrobial MC is incorporated, but the elongation at break is greatly increased (44%). The mechanical properties of the PVA/EVC/MC film prepared in example 1 show that the PVA/EVC/MC film has good applicability when being used as a wound dressing for wound surfaces and can be applied to the abrasion of joints and the like.

TABLE 4 PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 1017 atoms/cm)²) Mechanical property test results of the obtained film

Example 5

The mass ratio of the antibacterial agent MC/ethanol solution in example 1 to the mixed solution of step (2) was adjusted to 5: 100. 10: 100. 15: 100. 20: 100. 30: 100, and other parameters are kept unchanged, and performance tests are carried out.

Example 6

The mass ratio of the antibacterial agent MC to ethanol in the antibacterial agent MC/ethanol solution in example 1 was 0.1: 100. 0.3: 100. 0.5: 100. 0.7: 100. 1: 100, and other parameters are kept unchanged, and performance tests are carried out.

FIG. 1 is a comparison of the effects of examples 1 and 5 on the system state of the solution, wherein the mass ratio of the antibacterial agent MC/ethanol solution in a-g to the mixed solution in the step (2) is 0: 100. 5: 100. 10: 100. 15: 100. 20: 100. 25: 100. 30: 100. as can be seen from the figure: with the increase of the dosage of the added antibacterial agent MC/ethanol solution, the PVA/EVC mixed solution gradually changes from a thick milky yogurt state to a transparent gum state, but when the mass fraction of ethanol reaches 30%, white flocculent precipitates appear in the mixed solution after 30 days of standing storage, and the suspected ethanol-insoluble xanthan gum is precipitated after a large amount of ethanol is added. Therefore example 1 selected 25: 100 is the optimal solution.

Fig. 2 is a use of a mold to simulate a liquid dressing. The use of the PVA/EVC/MC liquid dressing of example 1 on the surface of human skin was simulated using a specially prepared glass mold. As can be seen from the figure: the liquid dressing can form a very soft and skin-friendly film after being dried, and can be completely torn off without residues. Compared with the traditional dressing, the dressing is easier to peel off from the wound surface, and less harmful peeling off is caused to the wound surface in the epithelialization process. And the transparent can also conveniently check the wound healing condition without removing the dressing.

FIG. 3 is a graph showing the influence of the mass ratio of the MC/ethanol solution of the antibacterial agent and the mixed solution of the step (2) on the film formation time in examples 1 and 5. As can be seen from the figure: the ratio of the MC/ethanol solution of the antibacterial agent is inversely related to the time required for drying and film forming, and the larger the mass ratio of the MC/ethanol solution of the antibacterial agent is, the shorter the time required for film forming is. And the mixing of the ethanol reduces the film forming time from 47.8 to 21.4min, and the required time is shortened by about 55 percent.

The liquid dressings obtained in example 1 and example 6 were poured into glass petri dishes of the same specification, and dried at 37 ℃ to form a film, thereby obtaining an antibacterial PVA/EVC/MC film.

FIG. 4 is a graph showing the influence of the mass ratio of the different antibacterial agents MC to ethanol in the antibacterial agent MC/ethanol solutions of examples 1 and 6 on the chlorine content of the prepared PVA/EVC/MC film. As can be seen from the figure: the chlorine content of the obtained antibacterial PVA/EVC/MC film is higher as the mass ratio of the antibacterial agent MC to ethanol is increased. According to the literature, when the chlorine content of the N-halamine antibacterial material film reaches 1.82X 10¹⁶atoms/cm²When the composition is used, staphylococcus aureus and escherichia coli with logarithmic values of 6.04 and 6.27 respectively can be killed within 10 min. Therefore, the chlorine content of 3.24X 1 is adopted in the subsequent tests0¹⁷atoms/cm²The antibacterial PVA/EVC/MC film.

FIG. 5 shows PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 1017 atoms/cm)²) And obtaining the X-ray diffraction pattern of the antibacterial dressing film. As can be seen from fig. 5: a characteristic diffraction peak of PVA appears at 2 θ of 20.04 °. With the addition of xanthan gum, the diffraction peak of the PVA/EVC film shifts to a position where 2 θ is 19.41 °, and the peak width, the peak intensity and the peak area are increased compared with PVA, which indicates that the crystalline state changes, and the crystalline state may be attributed to the amorphous property of xanthan gum, so that the crystallinity of the PVA/EVC film is reduced, and the molecular chain arrangement tends to be loose. In addition, the diffraction peak intensity of the PVA/EVC/MC film is slightly reduced along with the doping of the MC.

FIG. 7 shows PVA, PVA/EVC and PVA/EVC/MC of example 1 (3.24X 10)¹⁷atoms/cm²) Obtaining an AFM image of the antibacterial dressing film; wherein a is PVA; b is PVA/EVC; c is PVA/EVC/MC 3.24X 10 of example 1¹⁷atoms/cm². As can be seen in fig. 7 a: the surface of the pure PVA film presents a relatively flat microstructure. The surface of the resulting PVA/EVC film (fig. 7b) after incorporation of EVC, xanthan gum and glycerol exhibited a very regular network structure, and this apparent morphological difference was probably due to incorporation of xanthan gum. Xanthan gum is used as a polysaccharide macromolecular compound, has higher relative molecular weight, and the pyruvic acid group and acetyl group of the xanthan gum side chain can reversely wind the main chain through hydrogen bonds or electrostatic action to form a rod-shaped spiral structure secondary structure and can form a more complex reticular spiral complex structure through non-covalent bond action. In aqueous solution, the macromolecular helical structure is completely unfolded to form a more regular network structure. In addition, the membrane PVA/EVC/MC (3.24X 10) added with the N-halamine antibacterial agent MC¹⁷atoms/cm²) Compared with the film (fig. 7c), the film has no obvious change in the micro-morphology and still has a network structure, but the pore size of the network is slightly increased, and probably the content of the xanthan gum in the system is relatively slightly reduced due to the incorporation of the MC/ethanol solution, and the macromolecular chains of the xanthan gum have a relatively loose structure.

The water vapor permeability is an important parameter for evaluating the suitability of a certain wound dressing, the healing of a wound surface can be accelerated in a moderately humid environment, the healing process can be delayed to a certain extent when the wound surface is too dry, and the wound surface infection can be caused in a high-humidity environment.

FIG. 8 shows the results of measuring the water vapor transmission rates of PVA, PVA/EVC and the film material prepared in example 1. As can be seen from the figure: with a pure PVA film (82 g/m)²h) In contrast, PVA/EVC and PVA/EVC/MC (3.24X 10)¹⁷atoms/cm²) The water vapor transmission rate of the membrane is obviously improved, and the water vapor transmission rate is respectively 160g/m²h and 172g/m²h. This result is largely attributed to glycerol and xanthan gum, which are hydrophilic substances, so that the membrane material prepared has good binding capacity to water. At the same time, the unique microstructure of the PVA/EVC and PVA/EVC/MC films shown in fig. 7 provides some channels for water vapor transmission, increasing the likelihood of their passage. It has been reported that the WVTR of the existing commercial wound dressings is 33-208g/m²h, the water vapor transmission rate of the PVA/EVC/MC film prepared in the example 1 meets the requirement of an ideal wound dressing, and is expected to be applied to wound healing.

Good biocompatibility is a basic requirement of wound dressings. FIG. 9 shows the survival rates of MC3T3-E1 cells cultured at 6 concentrations in the presence of PVA, PVA/EVC, and the membrane extract (n-3) prepared from PVA/EVC/MC of example 1. As can be seen from the figure: after the cells are incubated for 24 hours by the extracting solutions of the three membranes with different concentrations, the survival rate of the cells exceeds 80 percent.

FIG. 10 shows the cell morphology and cell viability of MC3T3-E1 cells incubated with PVA, PVA/EVC, and the membrane extract (100ppm) prepared in example 1, and observed by light microscope; wherein A is PVA; b is PVA/EVC; c is PVA/EVC/MC 3.24X 10 of example 1¹⁷atoms/cm². As can be seen from the figure: after the cells are incubated for 24 hours by the extracting solutions of the three membranes with different concentrations, no obvious cell morphology change is seen.

As can be seen in conjunction with fig. 9 and 10: the PVA, PVA/EVC and PVA/EVC/MC liquid dressing has no cytotoxicity to MC3T3-E1 cells, is relatively safe as a wound dressing, and has good potential of biomedical application.

FIG. 11 is a schematic diagram of a film prepared from PVA/EVC/MC of example 1. As can be seen from the figure: the film prepared from PVA/EVC/MC in example 1 is transparent in appearance, and is beneficial to checking the wound healing condition after being applied to a wound surface, and the dressing does not need to be removed. Can be torn off after the wound surface is healed.

FIG. 12 is a diagram showing a sample of PVA, a PVA solution after EVC blending reaction, and a PVA/EVC mixed solution; PVA, PVA solution after EVC blending reaction and PVA/EVC mixed solution are sequentially arranged from left to right. As can be seen from the figure: the pure PVA solution is clear and transparent; the solution after EVC blending reaction is turbid compared with the previous solution, and PVA and EVC are uniformly mixed; after the xanthan gum and the glycerol are added and fully and uniformly mixed, the obtained PVA/EVC is white in appearance, is thicker than the original PVA solution, and has greatly reduced fluidity, which is attributed to the fact that the xanthan gum has excellent dissolubility in the aqueous solution and better thickening and stabilizing effects.

Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. The preparation method of the liquid dressing is characterized by comprising the following steps:

(1) preparing a polyvinyl alcohol (PVA) solution, heating at 90 ℃ until the PVA solution is completely dissolved, then cooling to 70 ℃, adding 1, 2-epoxy-4-vinyl cyclohexane EVC, uniformly stirring, and reacting for 5-12 h, wherein the molar ratio of PVA to EVC is 1-3: 1-3, obtaining a PVA/EVC mixed solution;

(3) adding an antibacterial agent/ethanol solution into the mixed solution obtained in the step (2), fully stirring, and removing bubbles to obtain the liquid dressing;

wherein the mass ratio of the xanthan gum in the step (2) to the PVA/EVC mixed solution in the step (1) is 0.5: 100, respectively; the mass ratio of the glycerol in the step (2) to the PVA/EVC mixed solution in the step (1) is 1-10: 100, respectively; the mass ratio of the antibacterial agent to the ethanol in the antibacterial agent/ethanol solution in the step (3) is 0.1-1: 100, respectively; the antibacterial agent in the step (3) is 1-chloro-2, 2,5, 5-tetramethyl-4-imidazolidinone MC.

2. The method according to claim 1, wherein the molar ratio of PVA to EVC in step (1) is 2: 1.

3. the preparation method according to claim 1, comprising the following steps:

(1) preparing a PVA solution with the mass fraction of 8%, and heating at 90 ℃ until the PVA solution is completely dissolved; and then cooling to 70 ℃, adding 1, 2-epoxy-4-vinyl cyclohexane EVC, and reacting for 5-12 h, wherein the molar ratio of PVA to EVC is 2:1, uniformly stirring to obtain a PVA/EVC mixed solution;

4. A liquid dressing obtained by the production method according to any one of claims 1 to 3.

5. A wound patch comprising the liquid dressing of claim 4.