A dressing for skin wounds, its preparation method and application

Abstract

The present invention discloses a dressing for skin wounds, its preparation method and application, belonging to the technical field of hydrogels; the dressing for skin wounds provided by the present invention comprises the following raw materials: carboxymethyl cellulose, polyvinyl alcohol, metal chelate, cannabidiol and tobramycin; the metal chelate is a TA / Fe chelate formed by the chelation reaction of trivalent iron ions and tannic acid. The dressing for skin wounds provided by the present invention has excellent mechanical properties, adhesion properties, hemostatic, antibacterial and anti-inflammatory properties, and the effect of promoting wound healing, and can be widely applied to the preparation of drugs for treating trauma. Moreover, the preparation method of the dressing for skin wounds provided by the present invention is simple in operation and is beneficial to practical application.

Description

Technical Field

[0001] The present invention belongs to the technical field of hydrogels, and particularly relates to a dressing for skin wounds, a preparation method thereof, and an application thereof. Background Art

[0002] The skin is the largest organ of the human body and has various functions such as secretion, absorption, and protection. As the first line of defense for the body to resist external stimuli, the skin plays a role in protecting the body from various physical, chemical, and microbial factors. When the skin is damaged, timely and effective treatment is the key to rapid wound healing. Wound repair is a continuous and complex process, which can be roughly divided into the coagulation and hemostasis stage, the inflammation stage, the proliferation stage, and the remodeling stage. Traditional wound dressings have defects such as being unable to provide a suitable microenvironment for wound healing and being unable to inhibit the generation of wound inflammation. Therefore, it is necessary to explore a dressing that can both quickly stop bleeding and achieve effective anti-inflammatory effects. Summary of the Invention

[0003] The purpose of the present invention is to overcome the deficiencies of the above-mentioned prior art and provide a dressing for skin wounds, a preparation method thereof, and an application thereof, which have excellent mechanical properties, adhesion properties, antibacterial properties, and excellent wound treatment effects.

[0004] To achieve the above purpose, in the first aspect of the present invention, the present invention provides a dressing for skin wounds, and the dressing for skin wounds comprises the following raw materials: carboxymethyl cellulose, polyvinyl alcohol, metal chelate, cannabidiol, and tobramycin;

[0005] The metal chelate is a TA / Fe chelate formed by the chelation reaction of trivalent iron ions and tannic acid.

[0006] The dressing for skin wounds provided by the present invention is prepared by selecting the compounding of carboxymethyl cellulose and polyvinyl alcohol, and selecting a TA / Fe chelate formed by the chelation reaction of trivalent iron ions and tannic acid for cross-linking reaction, so that the obtained dressing for skin wounds has excellent adhesion properties and high cross-linking strength, and thus has excellent mechanical properties. Specifically, it has good elongation at break and tensile strength. At the same time, the present invention introduces cannabidiol and tobramycin into the dressing for skin wounds. On the one hand, there is a good compounding effect between cannabidiol and tobramycin, and the two compoundings have excellent antibacterial, hemostatic, and anti-inflammatory effects, thereby being able to effectively promote wound healing. On the other hand, the hydrogel formed by carboxymethyl cellulose and polyvinyl alcohol can not only stably load cannabidiol and tobramycin, but also have a synergistic effect on the efficacy of cannabidiol and tobramycin, further enhancing the antibacterial, hemostatic, analgesic, anti-inflammatory, and wound healing promoting effects of the dressing for skin wounds.

[0007] In one embodiment, the mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol is 1:(0.3 - 1.2).

[0008] Exemplarily, the mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol can be any point value or any two - point range value between 1:(0.3 - 1.2), such as 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, etc.

[0009] The research of the present invention finds that the mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol not only affects the cross - linking strength of the dressing, thus affecting the mechanical properties and adhesion properties of the dressing, but also affects the stability of the subsequent loading of cannabidiol and tobramycin, thereby affecting the antibacterial, anti - inflammatory and hemostatic effects of the dressing.

[0010] Preferably, the mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol is 1:(0.5 - 0.8).

[0011] The research of the present invention finds that when the mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol is further selected to be 1:(0.5 - 0.8), the comprehensive performance of the obtained dressing is more excellent.

[0012] In one embodiment, the viscosity - average molecular weight of the polyvinyl alcohol is 100000 - 150000.

[0013] It should be noted that the polyvinyl alcohol provided by the present invention can be self - made or purchased through conventional commercial channels.

[0014] It should be noted that the viscosity - average molecular weight of the polyvinyl alcohol is obtained by the viscosity method using an Ubbelohde viscometer.

[0015] Exemplarily, the viscosity - average molecular weight of the polyvinyl alcohol can be any point value or any two - point range value between 100000 - 150000, such as 100000, 110000, 120000, 130000, 140000, 150000, etc.

[0016] The research of the present invention finds that the viscosity - average molecular weight of the polyvinyl alcohol not only affects the loading effect of cannabidiol and tobramycin, but also affects its interaction with the carboxymethyl cellulose. Thus, after adding the metal chelate, it will affect the cross - linking effect; when the viscosity - average molecular weight of the polyvinyl alcohol is further selected within the range given by the present invention, the comprehensive effect of the obtained product is more excellent.

[0017] In one embodiment, the degree of substitution of the carboxymethyl cellulose is 2.0 - 2.5.

[0018] It should be noted that carboxymethyl cellulose with different degrees of substitution can be obtained by self - preparation or purchased commercially.

[0019] It should be noted that the degree of substitution of carboxymethyl cellulose is obtained by testing with infrared spectroscopy.

[0020] The research of the present invention finds that the degree of substitution of carboxymethyl cellulose will also affect the performance of the product. Specifically, it will affect the interaction with polyvinyl alcohol, thus affecting the cross - linking effect under the cross - linking action of metal chelates, and at the same time, it will also affect the loading effect of cannabidiol and tobramycin; when the degree of substitution of carboxymethyl cellulose is further selected to be 2.0 - 2.5, the comprehensive effect of the obtained product is more excellent.

[0021] Exemplarily, the degree of substitution of the carboxymethyl cellulose can be any point value or any two - point range value between 2.0 - 2.5, such as 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, etc.

[0022] In one embodiment, in the metal chelate, the molar ratio of ferric ions to tannic acid is 1:(0.3 - 0.8).

[0023] It should be noted that the TA / Fe chelate formed by the chelation reaction of ferric ions and tannic acid can adopt the conventional chelation methods in the art.

[0024] Exemplarily, in the metal chelate, the molar ratio of ferric ions to tannic acid can be any point value or any two - point range value between 1:(0.3 - 0.8), such as 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, etc.

[0025] The research of the present invention finds that in the metal chelate, the molar ratio of ferric ions to tannic acid will affect the interaction between carboxymethyl cellulose, polyvinyl alcohol, tannic acid and ferric ions, thus affecting the cross - linking effect, and further affecting the mechanical properties and adhesion properties of the formed dressing. Synchronously, while affecting the cross - linking effect, it will also affect the antibacterial, anti - inflammatory, hemostatic and wound - healing promotion effects of the dressing.

[0026] Preferably, in the metal chelate, the molar ratio of ferric ions to tannic acid is 1:(0.5 - 0.6).

[0027] The research of the present invention finds that when the molar ratio of ferric ions to tannic acid in the metal chelate is further selected to be 1:(0.5 - 0.6), the comprehensive effect of the obtained dressing is more excellent.

[0028] In one embodiment, the molar ratio of cannabidiol to tobramycin is 1:(1 - 6).

[0029] Exemplarily, the molar ratio of cannabidiol to tobramycin can be any point value or any two-point range value between 1:(1 - 6), such as 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, etc.

[0030] Preferably, the molar ratio of cannabidiol to tobramycin is 1:(2 - 4).

[0031] Cannabidiol has functions such as bactericidal, analgesic, anti-inflammatory, antioxidant, and anti-anxiety, and has rich downstream application scenarios. Its main value lies in the medical field. Tobramycin is an aminoglycoside antibiotic that has good antibacterial effects against the vast majority of bacteria and can be used for infections caused by a variety of sensitive bacteria, and has good anti-inflammatory effects. The research of the present invention finds that the mass ratio between cannabidiol and tobramycin will affect the comprehensive performance of the dressing, especially the effects of antibacterial, anti-inflammatory, hemostasis, and promoting wound healing. When the molar ratio of cannabidiol to tobramycin is further selected to be 1:(1 - 6), especially 1:(2 - 4), the comprehensive performance of the obtained product is better.

[0032] In the second aspect of the present invention, the present invention provides a preparation method of the dressing for skin wounds, and the preparation method includes the following steps: mixing and dissolving carboxymethyl cellulose and polyvinyl alcohol to obtain a dressing matrix solution, then sequentially mixing the dressing matrix solution, cannabidiol solution, and tobramycin solution and stirring, and then adding a metal chelate solution, stirring, and standing to form a gel to obtain a dressing for skin wounds.

[0033] The preparation method of the dressing for skin wounds provided by the present invention is simple in operation and is conducive to practical production applications; specifically, the metal chelate provided by the present invention contains tannic acid and iron ions; among them, tannic acid is an effective gel adhesion unit, which can grab polymer chains through hydrogen bonds and ionic bonds and can crosslink polymer chains through coordination bonds in the presence of iron ions, thereby forming a dressing with excellent crosslinking effects; during the crosslinking process of the above substances, due to the presence of hydroxyl groups in cannabidiol and hydroxyl groups and amino groups in tobramycin, the above groups can also form hydrogen bonds or ionic bonds with amino groups in macromolecules, thereby obtaining a dressing with stable loading; making the prepared dressing have excellent comprehensive performance.

[0034] In one embodiment, the mass percentage of the solute in the dressing matrix solution is 1 - 5%.

[0035] In one embodiment, the concentration of cannabidiol in the cannabidiol solution is 0.02 - 0.3 mol / L.

[0036] In one embodiment, the concentration of tobramycin in the tobramycin solution is 0.08 - 0.5 mol / L.

[0037] In one embodiment, in the metal chelate solution, the concentration of metal ions is 0.2 - 0.8 mol / L.

[0038] The present invention has found through research that when further selecting the mass percentage of the solute or the molar concentration of the solute in the above solution within the above ranges respectively, a dressing can be formed preferably.

[0039] In one embodiment, the volume ratio of the dressing matrix solution, cannabidiol solution, and metal chelate solution is dressing matrix solution:cannabidiol solution:metal chelate solution = 1:(0.1 - 4):(0.5 - 1.5).

[0040] The present invention has found through research that when further selecting the volume ratio between each solution within the above range, a good gelation reaction can be achieved in better cooperation with the preferred range of solute mass percentage or solute molar concentration.

[0041] In one embodiment, the solvent of the dressing matrix solution includes deionized water.

[0042] In one embodiment, the solvent of the cannabidiol solution includes absolute ethanol.

[0043] In one embodiment, the solvent of the tobramycin solution includes ionic water.

[0044] In one embodiment, the solvent of the metal chelate solution includes deionized water.

[0045] In one embodiment, the temperature for stirring is 30 - 50 °C, and the temperature for standing is 20 - 40 °C.

[0046] In one embodiment, after sequential mixing, stirring is carried out at a rotation speed of 300 - 500 rpm for 5 - 10 min after adding each solution to ensure thorough mixing.

[0047] In one embodiment, the stirring time after adding the metal chelate solution is 40 - 120 seconds.

[0048] In one embodiment, the time for standing and gelation is 50 - 150 seconds.

[0049] In the third aspect of the present invention, the present invention provides the application of the dressing for skin wounds in the preparation of a drug for promoting wound healing.

[0050] The dressing for skin wounds provided by the present invention can not only effectively inhibit bacteria, but also has the effects of hemostasis, pain relief, and anti - inflammation. Therefore, it can be widely applied to the treatment of promoting wound healing.

[0051] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0052] The dressing for skin wounds provided by the present invention is prepared by selecting the compound of carboxymethyl cellulose and polyvinyl alcohol, and selecting the TA / Fe chelate formed by the chelation reaction of ferric ions and tannic acid for crosslinking reaction, so that the obtained dressing has excellent adhesion performance and high crosslinking strength, and thus has excellent mechanical properties. Specifically, it has good elongation at break and tensile strength. At the same time, the present invention introduces cannabidiol and tobramycin into the dressing. On the one hand, there is a good compounding effect between cannabidiol and tobramycin, and the compounding of the two has excellent antibacterial, hemostatic and anti-inflammatory effects, so as to effectively promote wound healing. On the other hand, the dressing substrate formed by carboxymethyl cellulose and polyvinyl alcohol can not only stably load cannabidiol and tobramycin, but also produce a synergistic effect on the efficacy of cannabidiol and tobramycin, further enhancing the antibacterial, hemostatic, analgesic, anti-inflammatory and wound healing promoting effects of the dressing. In addition, the preparation method of the dressing provided by the present invention is simple to operate and is beneficial to actual production. Description of the Drawings

[0053] Figure 1 Photograph of the gel formed by the dressing prepared in Example 1;

[0054] Figure 2 Photograph of the inverted state of the dressing prepared in Example 1. Detailed Embodiments

[0055] To better illustrate the purpose, technical solution and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0056] The reagents, methods and equipment used in the present invention, unless otherwise specified, are all conventional reagents, methods and equipment in the art.

[0057] Carboxymethyl cellulose 1: The degree of substitution is 2.3, self-made. The preparation method includes the following steps: Take 2 g of cellulose and add it to 25 mL of a mixed solution (the mixed solution includes a 40% sodium hydroxide aqueous solution and a n-butanol solution with a mass ratio of 1:4), stir and react at room temperature for 50 min, then dropwise add 9 mL of a n-butanol solution of chloroacetic acid (in the n-butanol solution of chloroacetic acid, the mass percentage of chloroacetic acid is 80%), continue to stir for 15 min after the dropping is completed, and then add 1.5 g of sodium hydroxide (slowly add, control the reaction system temperature ≤ 40 °C); after the addition is completed, raise the temperature to 70 °C and react for 100 min; then add 4 mL of 45% sodium hydroxide aqueous solution and raise the temperature to 75 °C and react for 60 min. After the reaction is completed, use glacial acetic acid to neutralize the pH value of the system to 7, then centrifuge, collect the solid and wash and dry to obtain carboxymethyl cellulose with a degree of substitution of 2.1.

[0058] Carboxymethyl cellulose 2: The degree of substitution is 1.6, self-made. The difference in the preparation method from carboxymethyl cellulose 1 lies in adjusting the reaction temperature, time and the addition amount of sodium hydroxide.

[0059] Carboxymethyl cellulose 3: The degree of substitution is 2.8, self-made. The difference in the preparation method from carboxymethyl cellulose 1 lies in adjusting the reaction temperature, time and the addition amount of sodium hydroxide.

[0060] Polyvinyl alcohol 1: The viscosity-average molecular weight is 100,000, commercially available.

[0061] Polyvinyl alcohol 2: The viscosity-average molecular weight is 150,000, commercially available.

[0062] Polyvinyl alcohol 3: The viscosity-average molecular weight is 80,000, commercially available.

[0063] Polyvinyl alcohol 4: The viscosity-average molecular weight is 200,000, commercially available.

[0064] Metal chelate 1: In the metal chelate, the molar ratio of ferric ion to tannic acid is 1:0.5; self-made. The preparation method includes the following steps: Weigh 0.1 mol of anhydrous ferric chloride in a beaker, dissolve it in deionized water, add 0.05 mol of tannic acid to it and mix well, then add sodium bicarbonate to adjust the pH value of the system to about 7, let it stand until black precipitates appear, filter, wash and dry to obtain metal chelate 1.

[0065] Metal chelate 2: In the metal chelate, the molar ratio of ferric ion to tannic acid is 1:0.3; self-made. The difference in the preparation method from metal chelate 1 lies in adjusting the addition amount of tannic acid.

[0066] Metal chelate 3: In the metal chelate, the molar ratio of ferric ion to tannic acid is 1:0.8; self-made. The difference in the preparation method from metal chelate 1 lies in adjusting the addition amount of tannic acid.

[0067] Example 1

[0068] The embodiment of the present invention provides a dressing for skin wounds. The preparation method of the dressing includes the following steps:

[0069] (1) Preparation of the dressing matrix solution: Weigh carboxymethyl cellulose 1 and polyvinyl alcohol 1 in a mass ratio of 1:0.5 and dissolve them in deionized water to prepare a dressing matrix solution with a mass percentage of solute of 2%.

[0070] (2) Preparation of the metal chelate solution: Dissolve metal chelate 1 in an aqueous deionized solution to prepare a metal chelate solution with a ferric ion concentration of 0.4 mol / L.

[0071] (3) Preparation of cannabidiol solution: Dissolve cannabidiol in absolute ethanol to prepare a cannabidiol solution with a temperature of 40 - 45 °C and a concentration of 0.1 mol / L;

[0072] (4) Preparation of tobramycin solution: Dissolve tobramycin in deionized water to prepare a tobramycin solution with a temperature of 40 - 45 °C and a concentration of 0.1 mol / L;

[0073] (5) Preparation of the dressing: Place 1 mL of the dressing matrix solution in a container, control the temperature of the container at 40 - 45 °C, add 1 mL of the cannabidiol solution, stir at a speed of 400 rpm for 5 min, then add 2 mL of the tobramycin solution and stir at a speed of 400 rpm for 5 min, then add 1 mL of the metal chelate solution and stir at a speed of 400 rpm for 1 min, and then let it stand at room temperature and observe for 1 min to form a hydrogel, obtaining the dressing (in this step, the molar ratio of cannabidiol to tobramycin is 1:2).

[0074] Among them, the schematic diagram of the hydrogel formation of the prepared dressing is as Figure 1 shown, and the inverted state after hydrogel formation is as Figure 2 shown.

[0075] Example 2

[0076] The embodiment of the present invention provides a dressing for skin wounds, and the preparation method of the dressing includes the following steps:

[0077] (1) Preparation of the dressing matrix solution: Weigh carboxymethyl cellulose 1 and polyvinyl alcohol 1 in a mass ratio of 1:0.5 and dissolve them in deionized water to prepare a dressing matrix solution with a mass percentage of the solute of 4%;

[0078] (2) Preparation of the metal chelate solution: Dissolve metal chelate 1 in an aqueous deionized solution to prepare a metal chelate solution with a concentration of iron ions of 0.6 mol / L;

[0079] (3) Preparation of cannabidiol solution: Dissolve cannabidiol in absolute ethanol to prepare a cannabidiol solution with a temperature of 35 - 40 °C and a concentration of 0.3 mol / L;

[0080] (4) Preparation of tobramycin solution: Dissolve tobramycin in deionized water to prepare a tobramycin solution with a temperature of 35 - 40 °C and a concentration of 0.5 mol / L;

[0081] (5)Preparation of the dressing: Place 1 mL of the dressing matrix solution in a container, control the temperature of the container at 35 - 40 °C, add 4 mL of the cannabidiol solution, stir at a speed of 400 rpm for 5 min, then add 4.8 mL of the tobramycin solution and stir at a speed of 400 rpm for 5 min. Next, add 1.5 mL of the metal chelate solution and stir at a speed of 400 rpm for 1 min. Then, let it stand at room temperature and observe for 1 min to form a hydrogel, obtaining the dressing (in this step, the molar ratio of cannabidiol to tobramycin is 1:2).

[0082] Example 3

[0083] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that the mass ratio of carboxymethylcellulose 1 to polyvinyl alcohol 1 in step (1) is 1:0.8.

[0084] Example 4

[0085] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that the mass ratio of carboxymethylcellulose 1 to polyvinyl alcohol 1 in step (1) is 1:0.3.

[0086] Example 5

[0087] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that the mass ratio of carboxymethylcellulose 1 to polyvinyl alcohol 1 in step (1) is 1:1.2.

[0088] Example 6

[0089] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that polyvinyl alcohol 2 is used to replace polyvinyl alcohol 1 in step (1).

[0090] Example 7

[0091] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that polyvinyl alcohol 3 is used to replace polyvinyl alcohol 1 in step (1).

[0092] Example 8

[0093] An embodiment of the present invention provides a dressing for skin wounds. The only difference in the preparation method of the dressing from that of Example 1 is that polyvinyl alcohol 4 is used to replace polyvinyl alcohol 1 in step (1).

[0094] Example 9

[0095] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that carboxymethyl cellulose 2 is used to replace carboxymethyl cellulose 1 in step (1).

[0096] Example 10

[0097] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that carboxymethyl cellulose 3 is used to replace carboxymethyl cellulose 1 in step (1).

[0098] Example 11

[0099] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that metal chelate 2 is used to replace metal chelate 1 in step (2).

[0100] Example 12

[0101] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that metal chelate 3 is used to replace metal chelate 1 in step (2).

[0102] Example 13

[0103] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that in step (5), the added volumes of cannabidiol solution and tobramycin solution are changed, keeping the total moles of the two unchanged, but the molar ratio of cannabidiol to tobramycin becomes cannabidiol:tobramycin = 1:4.

[0104] Example 14

[0105] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that in step (5), the added volumes of cannabidiol solution and tobramycin solution are changed, keeping the total moles of the two unchanged, but the molar ratio of cannabidiol to tobramycin becomes cannabidiol:tobramycin = 1:1.

[0106] Example 15

[0107] An embodiment of the present invention provides a dressing for skin wounds. The only difference between the preparation method of this dressing and that of Example 1 is that in step (5), the added volumes of cannabidiol solution and tobramycin solution are changed, keeping the total moles of the two unchanged, but the molar ratio of cannabidiol to tobramycin becomes cannabidiol:tobramycin = 1:6.

[0108] Comparative Example 1

[0109] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (1), the mass percentage of the solute in the hydrogel matrix solution remains unchanged, but only carboxymethyl cellulose 1 is added.

[0110] Comparative Example 2

[0111] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (1), the mass percentage of the solute in the hydrogel matrix solution remains unchanged, but only polyvinyl alcohol 1 is added.

[0112] Comparative Example 3

[0113] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (1), carboxymethyl chitosan is used to replace carboxymethyl cellulose 1.

[0114] Comparative Example 4

[0115] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (2), a PA / Fe chelate is used to replace metal chelate 1.

[0116] Comparative Example 5

[0117] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (5), the cannabidiol solution is not added, and the volume of the tobramycin solution is changed so that the total molar amount of tobramycin is the same as the total molar amount of cannabidiol and tobramycin in Example 1.

[0118] Comparative Example 6

[0119] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that in step (5), the tobramycin solution is not added, and the volume of the cannabidiol solution is changed so that the total molar amount of cannabidiol is the same as the total molar amount of cannabidiol and tobramycin in Example 1.

[0120] Comparative Example 7

[0121] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that gentamicin is used to replace tobramycin.

[0122] Comparative Example 8

[0123] The comparative example of the present invention provides a dressing for skin wounds. The only difference between the preparation method of the dressing and that of Example 1 is that cannabidiol and tobramycin are not added.

[0124] Effect Example

[0125] The performance of the dressings for skin wounds prepared in Effect Examples 1 - 15 and Comparative Examples 1 - 8 of the present invention was verified, including the following aspects:

[0126] 1. Mechanical Property Test

[0127] The dressings in the examples and comparative examples were prepared into dumbbell shapes, with a total length of 30 mm, a width of 10 mm, dumbbell parts on both sides, and a sample part in the middle. The sample length was 20 mm, the sample width (i.e., the shortest distance in the middle of the dumbbell) was 10 mm, and the sample thickness was 1 mm. With a set tensile rate of 25 mm / min, a WDW - 50 microcomputer - controlled electronic universal testing machine was used to measure the tension (N) and elongation (mm) at the time of sample fracture. Each sample was repeated 5 times and the average value was taken to calculate the tensile strength and elongation at break of the dressing;

[0128] Among them, the tensile strength (σ) of the dressing is the ratio of the maximum tensile stress of the gel to the cross - sectional area of the sample, that is, where: σ is the tensile strength in MPa, F max is the maximum tensile stress in N, and A is the cross - sectional area of the sample (sample width × sample thickness) in mm 2 ; the elongation at break (ε) is the ratio of the deformed length of the sample at the time of tensile fracture to the initial length, that is, where ε (%) is the elongation at break, L 0 and L max are the initial and fracture lengths of the sample in mm respectively;

[0129] The results obtained are shown in Table 1.

[0130] 2. Adhesion Property

[0131] A hydrogel strength tester was used to conduct a peeling experiment to test the adhesion energy of the gel; the test method was to refer to the standard of "GB / T2791 - 1995_T - peel strength test method for adhesives - Flexible material to flexible material", and according to the peeling angle, it was divided into 180° peeling test, that is, T - peel test; the adhesion strength was determined by testing the force required for the sample to be peeled from the adhesion interface, and the results obtained are shown in Table 1.

[0132] 3. Bacteriostatic Property Test

[0133] Two types of strains were selected for testing, namely Gram-positive bacteria (Staphylococcus) and Gram-negative bacteria (Escherichia coli). The agar diffusion method was used to test the antibacterial effect of the dressing on the strains. The dressing was applied to the surface of the agar plate respectively, and then bacterial solutions with different concentrations were dropped in the center of the dressing surface. They were incubated at 37 °C for 24 hours respectively, and the inhibitory effects of different types of dressings on Gram-positive bacteria (Staphylococcus) and Gram-negative bacteria (Escherichia coli) were observed and recorded; the antibacterial rates of Gram-positive bacteria (Staphylococcus) and Gram-negative bacteria (Escherichia coli) corresponding to all test groups were calculated respectively, and the average values of the antibacterial rates of Gram-positive bacteria (Staphylococcus) and Gram-negative bacteria (Escherichia coli) were taken respectively; the group without applying the dressing was used as the control group;

[0134] The calculation formula of the antibacterial rate: (control group bacterial concentration - experimental group bacterial concentration) / control group bacterial concentration * 100%, and the calculated results are shown in Table 1.

[0135] 4. Biocompatibility test

[0136] The test was carried out with reference to GB / T 16886.5-2003. Among them, the biotoxicity score: no cytotoxicity (0), slight cytotoxicity (1), moderate cytotoxicity (2), severe cytotoxicity (3); the test results are shown in Table 1.

[0137] 5. Hemostasis effect test

[0138] The whole blood coagulation index (BCI) test was used for evaluation. Specifically, a 0.5×0.5 cm square dressing was placed in a centrifuge tube and incubated in a 37 °C constant temperature water bath for 5 min. Subsequently, 200 μL of blood (containing 3.8 wt% anticoagulant sodium citrate, where the volume ratio of sodium citrate solution to blood during preparation is 1:9) and 20 μL of CaCl 2 (0.2 mol / L) solution were added to the dressing. After incubating at 37 °C for 5 min, 25 mL of distilled water was slowly added along the tube wall to remove the uncoagulated blood cells. It was shaken evenly at 50 rpm / min in a 37 °C constant temperature shaker for 5 min, and then left to stand at room temperature for 5 min. The absorbance value OD of the supernatant of each sample was measured with a 545 nm ultraviolet spectrophotometer. The calculation formula of the coagulation index (BCI) is: BCI(%) = [OD sample / OD control ×100%, where OD control is the absorbance value of the blank sample, and OD sample is the absorbance value of the sample supernatant; the calculated results are shown in Table 1.

[0139] 6. Anti-inflammatory effect test

[0140] The mice were divided into an experimental group, a control group, and a λ-carrageenan group, with 5 mice in each group on average. In the experimental group, equal amounts of the dressings prepared in the examples and comparative examples were applied to the right hind paws of the mice. The control group and the λ-carrageenan group were not treated. Then, an equal amount of λ-carrageenan was injected into the plantar surface to induce paw edema in the mice (the control group was not treated). After 24 h, the thicknesses of the right hind paws of the mice in each group were measured respectively, and the average value was calculated. The smaller the thickness, the more obvious the inhibitory effect on edema, that is, the better the anti-inflammatory effect. The thicknesses of the right hind paws obtained from the test are shown in Table 1.

[0141] 7. Wound healing effect test

[0142] 1) Take 115 SPF-grade rats (BALB / c, female, 6 weeks old, body weight 25 ± 4 g). After one week of adaptive feeding, hair removal was performed one day before making the trauma model. The mice were anesthetized with an animal anesthesia machine and fixed on the operating table. First, most of the hair on the back of the mice was removed with a hair clipper. Subsequently, a cotton swab was moistened and dipped in depilatory cream to wipe the clipped area, and left for a few minutes. Then, the excess depilatory cream was wiped off with a cotton ball, and a clean cotton ball dipped in 0.9% physiological saline was used to wipe the skin at the depilated area to wash away the residual depilatory cream on the skin and prevent skin burns. After wiping, the skin at the depilated area was dried with a clean cotton ball;

[0143] 2) Establish a full-thickness skin trauma model on the back of the mice: The depilated mice were anesthetized with an animal anesthesia machine and fixed on the operating table. After disinfecting the skin with alcohol, a circular full-thickness skin excision wound with an area of 1×1 cm was created on the back using sterile surgical instruments. The mice were randomly divided into 23 groups, with 5 mice in each group on average, corresponding to the numbers of Examples 1-15 and Comparative Examples 1-8 respectively;

[0144] 3) The dressing was adhered to the wound surface, and the wound edge was fixed with a medical sterile transparent fixing tape. Finally, the mice were caged and raised according to the requirements of small animal welfare.

[0145] 4) The observation period was 1 hour, 8 hours, 12 hours, 24 hours, 48 hours, and 7 days. The rats with better wound healing within 7 days were recorded, and the wound healing rate was the proportion of rats with better wound healing; among them, the wound healing was divided into 3 grades. The first grade was better healing, the second grade was scabbing / local slight redness, and the third grade was partial scabbing / redness. The results obtained are shown in Table 1.

[0146] Table 1

[0147]

[0148] As can be seen from Table 1, when the technical solution provided by the present invention is adopted, the obtained dressing has good mechanical properties, adhesion properties, antibacterial properties, hemostatic properties, anti-inflammatory properties, and the ability to promote wound healing; specifically, the tensile strength of the obtained dressing is above 24.9 MPa, the elongation at break is above 119%, the peel force is above 33.9 kg·m / S 2 above, the antibacterial rate is above 95.4%, the biological toxicity is all at level 0, the BCI is below 31.4%, the foot thickness in the anti-inflammatory test is below 3.2 mm, and the wound healing rate is above 80%;

[0149] As can be seen from Example 1 and Comparative Examples 1-2, when only carboxymethyl cellulose or only polyvinyl alcohol is used, the mechanical properties and adhesion properties of the obtained dressing are significantly reduced, and the antibacterial rate also shows a certain downward trend; as can be seen from Example 1 and Comparative Example 3, when carboxymethyl chitosan is used to replace carboxymethyl cellulose, the mechanical properties and adhesion properties cannot achieve the effects of the present invention; as can be seen from Example 1 and Examples 3-5, the mass ratio of carboxymethyl cellulose and polyvinyl alcohol also affects the comprehensive performance of the product; as can be seen from Example 1 and Examples 6-10, the viscosity-average molecular weight of polyvinyl alcohol and the degree of substitution of carboxymethyl cellulose also affect the comprehensive performance of the product.

[0150] As can be seen from Example 1 and Comparative Example 4, when the selected metal chelate is not the substance in the present invention, the comprehensive performance of the obtained product shows a certain decline; as can be seen from Example 1 and Examples 11-12, the molar ratio of ferric ions and tannic acid in the metal chelate also affects the comprehensive performance of the product.

[0151] As can be seen from Example 1 and Comparative Examples 5-6, when either tobramycin or cannabidiol is not added, the hemostatic, antibacterial, anti-inflammatory, and wound healing promotion effects of the obtained product are significantly reduced; as can be seen from Example 1 and Comparative Example 7, when tobramycin is replaced with other substances, the effects of the present invention cannot be achieved; as can be seen from Example 1 and Examples 13-15, the molar ratio of cannabidiol and tobramycin also affects the comprehensive performance of the product.

[0152] Finally, it should be noted that the above embodiments are used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A dressing for skin wounds, characterized in that: The dressing for skin wounds comprises the following raw materials: carboxymethyl cellulose, polyvinyl alcohol, metal chelate, cannabidiol and tobramycin; The metal chelate is a TA / Fe chelate formed by the chelation reaction of trivalent iron ions and tannic acid; The mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol is 1:(0.3-1.2); The viscosity average molecular weight of the polyvinyl alcohol is 100000-150000; The degree of substitution of the carboxymethyl cellulose is 2.0-2.5; In the metal chelate, the molar ratio of trivalent iron ion to tannic acid is 1:(0.3-0.8); The molar ratio of cannabidiol to tobramycin is 1:(1-6).

2. The dressing for skin wounds according to claim 1, characterized in that: The mass ratio of the carboxymethyl cellulose to the polyvinyl alcohol is 1:(0.5-0.8).

3. The dressing for skin wounds according to claim 1, characterized in that: In the metal chelate, the molar ratio of trivalent iron ion to tannic acid is 1:(0.5-0.6).

4. The dressing for skin wounds according to claim 1, characterized in that: The molar ratio of cannabidiol to tobramycin is 1:(2-4).

5. The method for preparing a dressing for skin wounds according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: Carboxymethyl cellulose and polyvinyl alcohol are mixed and dissolved to obtain a dressing base solution, and then the dressing base solution, cannabidiol solution and tobramycin solution are sequentially mixed and stirred, and then the metal chelate solution is added, stirred and allowed to stand to form a gel, thereby obtaining a dressing for skin wounds.

6. The preparation method according to claim 5, characterized in that: Satisfy at least one of the following: a. The mass percentage of the solute in the dressing matrix solution is 1-5%; b. The concentration of cannabidiol in the cannabidiol solution is 0.02-0.3 mol / L; c. The concentration of tobramycin in the tobramycin solution is 0.08-0.5 mol / L; d. In the metal chelate solution, the concentration of metal ions is 0.2-0.8 mol / L.

7. The preparation method according to claim 5, characterized in that: The volume ratio of the dressing matrix solution, cannabidiol solution and metal chelate solution is hydrogel matrix solution: cannabidiol solution: metal chelate solution = 1: (0.1-4): (0.5-1.5).

8. The preparation method according to claim 5, characterized in that: Satisfy at least one of the following: e. The solvent of the dressing matrix solution comprises deionized water; f. The solvent of the cannabidiol solution includes anhydrous ethanol; g. The solvent of the tobramycin solution comprises deionized water; h. The solvent of the metal chelate solution includes deionized water.

9. The preparation method according to claim 5, characterized in that: The stirring temperature is 30-50°C, and the standing temperature is 20-40°C.

10. Use of the dressing for skin wounds according to any one of claims 1 to 4 in the preparation of a medicament for promoting wound healing.

Images