Hypoallergenic and antibacterial wound dressing as well as preparation method and application thereof

Abstract

The invention provides a low-sensitization antibacterial wound dressing as well as a preparation method and application thereof, and relates to the technical field of medical dressings. The tea tree oil is used as an antibacterial component of the wound dressing for the first time, and the problem that allergy is prone to occurring due to the fact that silver ions are used as antibacterial agents in antibacterial dressings is solved. The novel antibacterial wound dressing is provided by improving the components and the preparation method of the wound dressing, and the wound dressing has excellent mechanical properties and biocompatibility, has a rapid hemostasis effect and can be widely applied to medical scenes. In addition, the wound dressing disclosed by the invention can also realize rapid degradation of soil microorganisms, and is green and environment-friendly.

Description

Technical Field

[0001] The present application relates to the technical field of medical dressings, and in particular to a low-allergenic, antibacterial wound dressing and a preparation method and application thereof. Background Art

[0002] The number of people who die from trauma each year in the world is about 4.5 million, of which about 40% of the deaths are caused by uncontrollable bleeding and bleeding-related complications. At present, in clinical hemostasis work, in addition to suturing, tissue adhesives (various patches, rubber plugs, glue, pastes and sprays, etc.) also arise as new hemostasis means. However, existing hemostatic gauze, hemostatic fibers and hemostatic bandages and other hemostatic materials have certain limitations in use, such as poor hemostatic effect, easy adhesion to wounds and not easy to change dressings, and inability to treat infected and suppurated wounds. Therefore, in order to reduce unnecessary deaths caused by blood loss, it is imperative to develop materials with better hemostatic effect.

[0003] Polyvinyl alcohol (PVA) is a polyhydroxy water-soluble biodegradable material made by hydrolyzing polyvinyl acetate (PVAc) under strong alkaline conditions. It is a white flake, flocculent or powdery solid, odorless, and can be completely degraded into H2O and CO2. It has the characteristics of good hydrophilicity, high chemical stability, good biological affinity, and biodegradability, and has a wide range of applications in biology and medicine.

[0004] However, PVA contains a large number of hydroxyl groups on its molecular chain. The exposed hydroxyl groups are easy to combine with water in the environment to produce hydrogen bonds. After absorbing water, the water resistance, mechanical properties, and barrier properties will change, which limits its use. In addition, although PVA has good biocompatibility and can provide a good healing environment for wounds, it does not have antibacterial properties. Ag is currently commonly used + ions as antimicrobial agents, but Ag + Ions can easily cause allergies, resulting in inflammatory or allergic reactions in patients, causing secondary injuries to patients.

[0005] In summary, there is an urgent need for a hemostatic material that has good hemostatic properties, mechanical properties, excellent biocompatibility, and is non-irritating and hypoallergenic. Summary of the invention

[0006] In order to solve the above problems, the present invention provides a low-allergenic antibacterial wound dressing, which has good hemostatic and mechanical properties, can meet the use requirements of wound dressings, has high biocompatibility and good safety, and can be degraded by soil microorganisms after being discarded.

[0007] On the one hand, the present application provides a hypoallergenic, antibacterial wound dressing, which includes: polyvinyl alcohol, gelatin, calcium acetate, tea tree oil, and an adjuvant.

[0008] The present application provides an antibacterial, hypoallergenic, tear-resistant, fast-hemostatic, and degradable wound dressing.

[0009] The tensile strength of the wound dressing can reach up to 9.59 MPa at most, and the elongation at break can reach up to 187.48% at most.

[0010] The wound dressing can achieve rapid hemostasis within 36 seconds, and can achieve rapid hemostasis within 28 seconds after adding effective ingredients such as thrombin.

[0011] Furthermore, the auxiliary agent is selected from one or more of poloxamer 188, poloxamer 407, and poloxamer 105.

[0012] Furthermore, the auxiliary agent is poloxamer 407.

[0013] Furthermore, the wound dressing comprises, by weight: 5-8 parts of polyvinyl alcohol, 1-5 parts of gelatin, 1-5 parts of calcium acetate, 1-5 parts of tea tree oil, and 1-5 parts of an auxiliary agent.

[0014] Furthermore, the wound dressing comprises, by weight: 6 parts of polyvinyl alcohol, 3 parts of gelatin, 2 parts of calcium acetate, 1 part of tea tree oil, and 1 part of an auxiliary agent.

[0015] The present invention uses tea tree oil as an antibacterial component of wound dressings for the first time, solving the problem of easy allergies caused by silver ions as antibacterial agents in antibacterial dressings. In addition, in order to solve the problem of decreased tear resistance after adding tea tree oil, the present application effectively improves the mechanical properties of wound dressings by adding poloxamer 407 as an auxiliary agent in the system, so that it can be widely used in medical products.

[0016] Those skilled in the art may also add known active ingredients of wound dressings, such as fibrinogen, thrombin and other functional ingredients or drug ingredients according to actual needs.

[0017] Excipients may also be added to the wound dressing, and the excipients may be appropriate cosolvents, adhesives, disintegrants, fillers, stabilizers, and the like.

[0018] On the other hand, the present application also provides a method for preparing the wound dressing, the method comprising the following steps:

[0019] Step 1, dissolving polyvinyl alcohol and gelatin in water, stirring at 40-80° C. for 10-20 min to obtain a mixed component;

[0020] Step 2: Add calcium acetate, tea tree oil and poloxamer 407 to the mixed components, homogenize 1-5 times under a pressure of 6000-8000 psi, and freeze-dry to obtain a wound dressing.

[0021] Furthermore, the reaction condition in step 1 is stirring at 60° C. for 15 min.

[0022] Furthermore, in step 2, the homogenization condition is homogenization twice at a pressure of 6000 psi.

[0023] In this application, wound dressings were prepared by high-pressure homogenization for the first time, proving that under specific high-pressure homogenization conditions, the structural tightness of the wound dressings can be effectively enhanced, the dispersibility can be improved, and the mechanical properties of the wound dressings can be further improved.

[0024] Preferably, the preparation method further comprises the step of standing to defoam, more preferably, standing to defoam for 15 minutes.

[0025] Those skilled in the art may select the size of the wound dressing according to actual needs, and therefore the specific size is not limited too much herein.

[0026] In a preferred embodiment, the preparation method of the wound dressing comprises: dissolving 5-8g polyvinyl alcohol and 1-5g gelatin in water at 40-80°C and stirring for 10-20min to mix evenly, adding 1-5g calcium acetate, 1-5mL tea tree oil, and 1-5g poloxamer 407, homogenizing 1-5 times at a pressure of 6000-8000psi, mixing evenly, taking out the mixed film liquid and standing it for 10-30min to defoam, and putting it into a mold for freeze drying to form a freeze-dried film.

[0027] In a preferred embodiment, the preparation method of the wound dressing comprises: dissolving 6 g of polyvinyl alcohol and 3 g of gelatin in water at 60° C. and stirring for 15 min to mix well, then adding 2 g of calcium acetate, 1 mL of tea tree oil, and 1 g of poloxamer 407, homogenizing twice under a pressure of 6000 psi, mixing well, taking out the mixed film liquid and standing it for 15 min to defoam, and putting it into a mold for freeze drying to form a freeze-dried film.

[0028] On the other hand, the present application also provides the use of the wound dressing or the wound dressing prepared by the method in preparing medical supplies for non-diagnostic and therapeutic purposes.

[0029] On the other hand, the present application also provides the use of tea tree oil or the wound dressing or the wound dressing prepared by the method in antibacterial and hemostatic treatment for non-therapeutic diagnostic purposes.

[0030] The present invention has the following beneficial effects:

[0031] The present invention uses tea tree oil as an antibacterial component of wound dressing for the first time, thereby solving the problem of easy allergy caused by using silver ions as antibacterial agents in antibacterial dressings.

[0032] The present invention provides a new antibacterial wound dressing by improving the composition and preparation method of the wound dressing, and the wound dressing has excellent mechanical properties and biocompatibility, has a rapid hemostatic effect, and can be widely used in medical scenarios. In addition, the wound dressing of the present invention can also achieve rapid degradation of soil microorganisms, which is green and environmentally friendly. DETAILED DESCRIPTION

[0033] In order to more clearly illustrate the overall concept of the application, the following is described in detail by way of embodiment. In the following description, a large amount of specific details are provided to provide a more thorough understanding of the present invention. However, it is obvious to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some technical features well known in the art are not described.

[0034] If no specific conditions are specified in the examples, the experiments were carried out according to conventional conditions or conditions recommended by the manufacturer.

[0035] Among them, tea tree oil was purchased from Shanghai Ruichu Biotechnology Co., Ltd., and polyvinyl alcohol (CAS No.: 9002-89-5), gelatin (CAS No.: 9000-70-8), calcium acetate (CAS No.: 62-54-4), poloxamer 407 (CAS No.: 9003-11-6), poloxamer 188, poloxamer 105, glycerol, and chitosan were purchased from Merck.

[0036] Unless otherwise specified, in the following embodiments, the reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0037] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional techniques in microbiology, biochemistry, analytical chemistry, cell culture, and related fields conventional in the technical field.

[0038] In addition, the "water" mentioned in the present invention includes any feasible water that can be used in the art, such as deionized water, distilled water, ion exchange water, double distilled water, high-purity water, and purified water.

[0039] In the following examples, unless otherwise specified, % means wt %, i.e. weight percentage.

[0040] Example 1

[0041] In order to find new antimicrobial ingredients suitable for wound dressings and solve the problem of Ag +Ions can easily cause allergies, causing inflammation or allergic reactions in patients, which can lead to secondary injuries to patients. In this embodiment, the antibacterial and anti-allergic properties of the antibacterial agent components used in hemostatic materials were screened. The specific screening process is as follows:

[0042] 6 g of polyvinyl alcohol and 3 g of gelatin were dissolved in 50 mL of water at 60 °C and stirred for 15 min. Then, 2 g of calcium acetate and different types of antibacterial agents were added and stirred evenly. The mixed film liquid was taken out and allowed to stand for 15 min to defoam, and then placed in a 5x5 (cm) mold and freeze-dried to prepare a freeze-dried film. The specific composition formula is shown in Table 1.

[0043] In this example, the most common bacteria Escherichia coli and Staphylococcus aureus were selected as examples for the related test of antibacterial performance, and the effects of the above samples on the survival of Escherichia coli and Staphylococcus aureus were tested. Specifically, the samples were sterilized under ultraviolet light for 120 minutes and then placed in a concentration of 10 6 CFU / mL of bacterial suspension was incubated at 37℃ for 4h, and the same volume of sterile PBS was used as a blank control group. After the incubation time, 50μL of bacterial suspension was taken, spread on the plate, and then incubated in a 37℃ incubator for 24h. The colonies on the plate were counted, and all experiments were designed in triplicate, and the calculation results involved were the arithmetic mean. The antibacterial rate was calculated using the following formula:

[0044] Antibacterial rate (%) = (number of colonies in the sample group - number of colonies in the blank control group) / number of colonies in the blank control group * 100%. The antibacterial rate results are shown in Table 1.

[0045] Table 1

[0046]

[0047]

[0048] As shown in Table 1, the antibacterial rate experimental results against Escherichia coli prove that chitosan and tea tree oil as antibacterial agents for wound dressings can achieve an anti-Escherichia coli effect similar to that of silver ions. However, the anti-Staphylococcus aureus effect of chitosan is not ideal.

[0049] In this embodiment, the safety of the sample was tested. Specifically, the cytotoxicity experiment was performed by CCK-8 detection to detect the cytotoxicity of different samples, and human venous endothelial cells were selected for in vitro cell compatibility evaluation. The material extract co-culture method was adopted, wherein the sample extracts were 25, 50, 75 and 100 μg / mL respectively. The extracts of different concentrations were co-cultured with endothelial cells. After 24 hours, the culture medium containing the extract was removed, and CCK-8 culture medium was added to each well, and co-cultured in the incubator for 4 hours. The OD value was measured at a wavelength of 450nm using an enzyme labeled analyzer. The effect of the sample on the cell proliferation ability was calculated by the following formula, which is the cell survival rate.

[0050] Cell survival rate (%) = [H (drug added) - H (blank) / [H (0 drug added) - H (blank)] × 100%

[0051] Among them, H (drug addition): OD value of wells containing cells, CCK-8, and extract; H (0 drug addition): OD value of wells containing cells and CCK-8; H (blank): OD value of wells without cells.

[0052] In order to ensure the repeatability of the experimental samples, three groups of parallel tests were performed for each sample, and the arithmetic mean was calculated. The results are shown in Table 2.

[0053] Table 2

[0054] Antimicrobial agents Amount of antimicrobial agent added (g or mL) Cell survival rate (%) Silver Ion 1 88.81 Chitosan 1 82.13 Chlorhexidine 1 86.72 Tea Tree Oil 1 92.18

[0055] As can be seen from the results in Table 2, this embodiment proves that tea tree oil as an antibacterial agent has better biocompatibility and safety than silver ions.

[0056] In addition, in this embodiment, a skin irritation test was conducted on the above samples. The specific experiments include:

[0057] Rats were selected as experimental materials. Before administration, the back skin of the rats was roughly symmetrically depilated without damaging the skin. The self-control method was adopted. The blank control (water) was applied to the left side of the depilated skin, and the right side of the depilated skin was covered with the above sample. The presence of erythema and edema at the administration site after 48 hours was observed and recorded. The judgment criteria are shown in Table 3, and the irritation scores are shown in Table 4. The number of rats in each group remained the same, and the scores were averaged.

[0058] Table 3

[0059]

[0060] Table 4

[0061] Antimicrobial agents Amount of antimicrobial agent added (g or mL) score Silver Ion 1 0.2 Tea Tree Oil 1 0 Tea Tree Oil 0.5 0.4 Tea Tree Oil 1.5 0.2

[0062] From the results in Table 4, it can be seen that the use of tea tree oil as the antibacterial agent component of wound dressing can take into account the excellent characteristics of high safety, low sensitization and high antibacterial rate, especially when the addition amount of tea tree oil is 1 mL, the experimental rats have no adverse reactions.

[0063] Example 2

[0064] However, in the actual experiment, the inventor found that after adding tea tree oil, the tear resistance of the sample decreased. Therefore, in order to further improve the mechanical properties of the wound dressing, different additives were tried in this example. The specific experimental process is as follows:

[0065] 6 g of polyvinyl alcohol and 3 g of gelatin were dissolved in 50 mL of water at 60 °C and stirred for 15 min. Then, 2 g of calcium acetate and 1 mL of tea tree oil and adjuvant were added and stirred evenly. The mixed film liquid was taken out and allowed to stand for 15 min to defoam, and then placed in a 5x5 (cm) mold and freeze-dried to prepare a freeze-dried film. The specific composition formula is shown in Table 5.

[0066] The mechanical properties test method includes: cutting the sample into strips of the same size, selecting 5 points of the sample, measuring with a film thickness gauge and calculating the average value as the thickness of the film (mm). Fixing the sample on an intelligent electronic tensile tester to measure the tensile strength (Mpa) and elongation at break E (%), the initial length of the tensile clamp distance is 50mm, the tensile rate is 100mm / min, and each sample is tested 3 times. The formulas for tensile strength TS and elongation at break E (%) are as follows.

[0067]

[0068]

[0069] The test results of tensile strength and elongation at break are shown in Table 5.

[0070] Table 5

[0071] Additives Addition amount (g) Tensile strength TS(Mpa) Elongation at break E(%) Poloxamer 188 1 6.47 141.92 Poloxamer 407 1 8.10 163.34 Poloxamer 105 1 6.61 147.21 glycerin 1 7.16 144.06 Poloxamer 407 0.5 7.46 143.60 Poloxamer 407 1.5 7.18 160.66

[0072] It can be seen from the results in Table 5 that the addition of poloxamer 407 as an adjuvant can effectively improve the mechanical properties of the wound dressing of the present application and solve the problem of decreased tear resistance of the sample after adding tea tree oil.

[0073] Example 3

[0074] This example further screens and improves the experimental conditions based on the preferred conditions of Example 1 and Example 2. The details are as follows:

[0075] After 6 g of polyvinyl alcohol and 3 g of gelatin were dissolved in 50 mL of water for reaction, 2 g of calcium acetate, 1 mL of tea tree oil, and 1 g of poloxamer 407 were added, and the mixture was homogenized twice under high pressure to mix evenly. The mixed film solution was taken out and allowed to stand for 15 min to defoam, and then placed in a mold for freeze drying to prepare a freeze-dried film. The specific reaction conditions are shown in Table 6. The mechanical properties of the test samples were tested using the same test method as in Example 2.

[0076] Table 6

[0077]

[0078] From the results in Table 6, it can be seen that the introduction of high-pressure homogenization can make the wound dressing structure more compact, improve the dispersion of the material, and further improve the mechanical properties of the wound dressing.

[0079] Example 4

[0080] This embodiment provides a method for preparing a wound dressing, comprising:

[0081] Dissolve 6 g of polyvinyl alcohol and 3 g of gelatin in 50 mL of water at 60 ° C and stir for 15 min to mix well. Then add 2 g of calcium acetate, 1 mL of tea tree oil and 1 g of poloxamer 407. Homogenize twice under a pressure of 6000 psi to mix well. Take out the mixed film liquid and let it stand for 15 min to defoam. Put it into a mold and freeze-dry it to make a freeze-dried film.

[0082] Example 5

[0083] This embodiment provides a method for preparing a wound dressing, comprising:

[0084] Dissolve 4 g of polyvinyl alcohol and 3 g of gelatin in 50 mL of water at 60 ° C and stir for 15 min to mix well. Then add 2 g of calcium acetate, 1 mL of tea tree oil and 1 g of poloxamer 407. Homogenize twice under a pressure of 6000 psi to mix well. Take out the mixed film liquid and let it stand for 15 min to defoam. Put it into a mold and freeze-dry it to make a freeze-dried film.

[0085] Example 6

[0086] This embodiment provides a method for preparing a wound dressing, comprising:

[0087] Dissolve 6 g of polyvinyl alcohol and 2 g of gelatin in 50 mL of water at 60 ° C and stir for 15 min to mix well. Then add 2 g of calcium acetate, 1 mL of tea tree oil and 1 g of poloxamer 407. Homogenize twice under a pressure of 6000 psi to mix well. Take out the mixed film liquid and let it stand for 15 min to defoam. Put it into a mold and freeze-dry it to make a freeze-dried film.

[0088] Example 7

[0089] This embodiment provides a method for preparing a wound dressing, comprising:

[0090] Dissolve 6 g of polyvinyl alcohol and 3 g of gelatin in 50 mL of water at 60 ° C and stir for 15 min to mix well. Then add 2 g of glycerol, 1 mL of tea tree oil and 1 g of poloxamer 407. Homogenize twice under a pressure of 6000 psi to mix well. Take out the mixed film liquid and let it stand for 15 min to defoam. Put it into a mold and freeze-dry it to make a freeze-dried film.

[0091] Example 8

[0092] This embodiment provides a method for preparing a wound dressing, comprising:

[0093] Dissolve 6 g of polyvinyl alcohol and 3 g of gelatin in 50 mL of water at 60 ° C and stir for 15 min to mix well. Then add 2 g of calcium acetate, 1 mL of tea tree oil, 1 g of poloxamer 407, 1 g of thrombin lyophilized powder, and 1 g of fibrinogen. Homogenize twice under a pressure of 6000 psi to mix well. Take out the mixed film liquid and let it stand for 15 min to defoam. Put it into a mold and freeze-dry it to make a lyophilized film.

[0094] Test Example 1

[0095] In this test example, the hemostatic properties of the wound dressing were tested using Examples 4-8 as samples.

[0096] Rats were selected as experimental subjects. After the rats were anesthetized with chloral hydrate solution, a 2 cm wound was cut on the rat thigh to expose the femoral artery, and then cut with a scalpel, affixed with a sample wound dressing, and the timing was started to observe whether there was bleeding around. When there was no bleeding, the timing was stopped, that is, the hemostasis time. The blank control group was not treated in any way. The results are shown in Table 7.

[0097] Table 7

[0098] Example Hemostasis time (s) Example 4 36 Example 5 47 Example 6 45 Example 7 52 Example 8 28 Commercially available products (chitosan dressings) 50 Blank control group 154

[0099] It can be seen from the results in Table 7 that the wound dressings prepared by the methods of Examples 4 and 8 of the present application can stop bleeding quickly.

[0100] Test Example 2

[0101] In this test example, the soil burial method was used to test the degradation performance of the wound dressings of Example 4 and Example 8 under outdoor natural conditions.

[0102] The wound dressings of Example 4 and Example 8 were buried in grassland soil at a depth of 10 cm. The experiment lasted for 12 days. The degradation performance was measured by weight loss rate. The weight loss rate calculation formula is as follows. The results are shown in Table 8.

[0103]

[0104] Table 8

[0105] Example Weight loss rate (%) Example 4 12.58 Example 8 12.56 Commercially available products (chitosan dressings) 8.41

[0106] As can be seen from the results in Table 8, this embodiment proves that the wound dressings of Examples 4 and 8 have good degradation properties and are easily biodegradable.

[0107] The above is only an embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. A hypoallergenic, antibacterial wound dressing, characterized in that: The wound dressing comprises: polyvinyl alcohol, gelatin, calcium acetate, tea tree oil and an adjuvant.

2. The wound dressing according to claim 1, characterized in that The auxiliary agent is selected from one or more of poloxamer 188, poloxamer 407 and poloxamer 105.

3. The wound dressing according to claim 2, characterized in that The auxiliary agent is poloxamer 407.

4. The wound dressing according to claim 1, characterized in that Calculated by weight, the wound dressing comprises: 5-8 parts of polyvinyl alcohol, 1-5 parts of gelatin, 1-5 parts of calcium acetate, 1-5 parts of tea tree oil, and 1-5 parts of auxiliary agent.

5. The wound dressing according to claim 2, characterized in that Calculated by weight, the wound dressing comprises: 6 parts of polyvinyl alcohol, 3 parts of gelatin, 2 parts of calcium acetate, 1 part of tea tree oil, and 1 part of an auxiliary agent.

6. A method for preparing a wound dressing according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: Step 1, dissolving polyvinyl alcohol and gelatin in water, stirring at 40-80° C. for 10-20 min to obtain a mixed component; Step 2: Add calcium acetate, tea tree oil and poloxamer 407 to the mixed components, homogenize 1-5 times under a pressure of 6000-8000 psi, and freeze-dry to obtain a wound dressing.

7. The preparation method according to claim 4, characterized in that: The reaction condition in step 1 is stirring at 60° C. for 15 min.

8. The preparation method according to claim 4, characterized in that: The homogenization condition in step 2 is homogenization at a pressure of 6000 psi for 2 times.

9. Use of the wound dressing according to any one of claims 1 to 5 or the wound dressing prepared by the method according to any one of claims 6 to 8 in preparing medical supplies for non-diagnostic and therapeutic purposes.

10. Use of tea tree oil or a wound dressing as claimed in any one of claims 1 to 5 or a wound dressing prepared by any one of claims 6 to 8 in antibacterial and hemostatic treatment for non-therapeutic diagnostic purposes.

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