CN113384738A - Preparation method of tretinoin dressing for promoting wound healing - Google Patents
Preparation method of tretinoin dressing for promoting wound healing Download PDFInfo
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
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- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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Abstract
The invention relates to the field of wound treatment, in particular to a preparation method of a tretinoin dressing for promoting wound healing, which combines natural antibacterial anti-inflammatory agent propolis and tretinoin for use, can effectively promote the formation of ordered collagen cross-linked fibers in a wound and improve the wound healing rate; the dressing is a wound dressing in a foam form, can retain a large amount of liquid, controllably releases a bioactive agent, has long-term drug release, and provides long-acting antibacterial protection.
Description
Technical Field
The invention relates to the field of wound treatment, in particular to a preparation method of a tretinoin dressing for promoting wound healing.
Background
Wound healing is generally divided into four phases: (1) hemostasis is carried out; (2) the inflammation stage, which mainly acts on removing bacteria and debris, prepares for tissue growth; (3) in the proliferation stage, granulation tissues fill a wound bed to form new blood vessels, contract the wound and generate epithelial cells to cover the wound; (4) in the maturation stage, collagen fibers reorganize and restore strength and flexibility.
The wound dressing provides a moist protective barrier against infection and contamination, and is easy to use and replace. However, the existing method has the problems of poor biocompatibility, incapability of effectively preventing wound infection, slow speed of promoting wound healing and the like, and has great limitation in application. Therefore, there is a need to develop a multifunctional biomedical dressing with antibacterial, anti-inflammatory and wound healing promoting functions.
Many natural substances have antibacterial and anti-inflammatory effects, and can be used for accelerating wound healing and preventing infection. Propolis is one of the propolis components, and is composed of resin, wax, pollen, polyphenol and essential oil, and can accelerate wound healing of mice by regulating inflammatory transcription factor NF-kB and related inflammatory factors, and has antibacterial, antioxidant and anti-inflammatory effects. However, these antibacterial and anti-inflammatory agents do not significantly promote tissue and fibroplasia, resulting in slower wound healing.
Tretinoin (tretinoin), which is a metabolic intermediate of vitamin A in vivo, can correct or prevent abnormality caused by harmful factors to biochemical components and morphological structures of dermal connective tissue when skin is physiologically aged or damaged by drugs, ultraviolet radiation and trauma, stimulate synthesis of skin extracellular matrix protein, accelerate formation of new connective tissue bands on the upper part of dermis, and improve the tension strength of wound. Tretinoin has no influence on normal skin collagen synthesis. In addition, retinoic acid has inhibitory activity on leukocyte chemotaxis, thereby playing an anti-inflammatory role. Furthermore, all-trans retinoic acid has no direct influence on sebaceous glands and secretion thereof.
Therefore, the natural antibacterial anti-inflammatory agent and the tretinoin are used together, so that the ordered collagen crosslinking fibers can be effectively promoted to be formed in the wound, and the wound healing rate is improved.
Disclosure of Invention
In order to solve the problems, the invention provides a preparation method of a tretinoin dressing for promoting wound healing, which combines propolis which is a natural antibacterial anti-inflammatory agent with tretinoin for use, can effectively promote the formation of ordered collagen cross-linked fibers in a wound and improve the wound healing rate; the dressing is a wound dressing in the form of foam, can retain a large amount of liquid and can controllably release bioactive agents.
The invention specifically adopts the technical scheme that:
a preparation method of a tretinoin dressing for promoting wound healing comprises the following steps:
s1: dissolving reaction amount polyvinyl alcohol in 95 ℃ distilled water, stirring until the reaction amount polyvinyl alcohol is dissolved, and then cooling to room temperature to obtain polyvinyl alcohol solution;
in the polyethylene solution obtained in the step, the concentration of the polyvinyl alcohol is 4% (v/v).
S2: dissolving reaction amount of sodium alginate in distilled water at 40 ℃, stirring until the sodium alginate is dissolved, and then cooling to room temperature to obtain a sodium alginate solution;
in the sodium alginate solution obtained in the step, the concentration of the sodium alginate is 4% (v/v).
S3: mixing the obtained polyvinyl alcohol solution and sodium alginate solution according to the volume ratio of 1-3:1, and stirring the mixture until the mixture is uniform to obtain a base material solution;
s4: mixing and dissolving reaction amount tretinoin, propolis and an activating agent;
in the step, the dosage of the tretinoin, the propolis and the activator is 16-20:1-2:20-22 by mass ratio.
Preferably, the amount of tretinoin, propolis and the activator is 16:1:20 by mass.
S5: adding the base material solution obtained in the step S3 into the mixed substance in the step S4, and stirring the mixture until the mixture is uniform;
s6: adding hydrochloric acid to adjust the pH value to be 2, adding glutaraldehyde, and slowly stirring to obtain a dressing solution;
the amount of glutaraldehyde used in the dressing solution obtained in this step was 0.075% (v/v).
S7: the dressing solution was introduced into a mould, frozen at-80 ℃ for 0.5-5h and lyophilized at-50 ℃ for 24h to give a dressing in the form of a foam.
Has the advantages that:
1) the invention combines the natural antibacterial anti-inflammatory agent and the tretinoin for use, thereby not only eliminating bacteria at wounds and avoiding infection, but also effectively promoting the formation of ordered collagen crosslinking fibers in the wounds and improving the wound healing rate.
2) The wound dressing in the form of foam can retain a large amount of liquid and controllably release bioactive agents; has long-term drug release and long-acting antibacterial protection.
Drawings
FIG. 1 is a bar graph of porosity for each example and comparative example.
FIG. 2 is a plot of the swelling rate for each example.
FIG. 3 is a line graph showing propolis release rates of the examples.
Fig. 4 is a line graph of tretinoin release rate for each example.
Detailed Description
The invention is further illustrated below with reference to the figures and examples.
Example 1
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 1:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, add 8g tween 80, 0.5g tretinoin and 10g propolis, avoid light, stir to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 0.5h and lyophilized at-50 ℃ for 24h to give a dressing in the form of a foam.
Example 2
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 2:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, add 8g tween 80, 0.5g tretinoin and 10g propolis, avoid light, stir to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 1h and lyophilized at-50 ℃ for 24h to give a dressing in the form of a foam.
Example 3
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 3:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, add 8g tween 80, 0.5g tretinoin and 10g propolis, avoid light, stir to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 2h and lyophilized at-50 ℃ for 24h to give a dressing in the form of a foam.
Comparative example 1
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 1:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, 8g of tween 80 was added, avoiding light, and stirred to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 0.5h and lyophilized at-50 ℃ for 24h to give a single dressing in the form of a foam.
Comparative example 2
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 1:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, add 8g tween 80, 0.5g tretinoin, avoid light, stir to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 1h and lyophilized at-50 ℃ for 24h to give a single dressing in the form of a foam.
Comparative example 3
(1) Dissolving polyvinyl alcohol in distilled water at 95 ℃ until the concentration reaches 4% (v/v), stirring until the polyvinyl alcohol is dissolved, and then cooling to room temperature;
(2) sodium alginate was dissolved in distilled water at 40 ℃ to a concentration of 4% (V/V), dissolved by stirring, and then cooled to room temperature.
(3) Mixing the polyvinyl alcohol solution and the sodium alginate solution in a beaker according to the ratio of 1:1, and stirring the mixture until the mixture is uniform.
(4) In a new beaker, 8g of Tween 80 and 10g of propolis were added, without light, and stirred to dissolve.
(5) And (4) respectively adding 100ml of mixed polyvinyl alcohol and sodium alginate solution into the beaker in the step 4, and stirring until the mixture is uniform.
(6) Hydrochloric acid was added to lower the pH to 2, then 0.75% glutaraldehyde was added and stirred slowly for 30 min.
(7) The solution was introduced into a silicon mould, frozen at-80 ℃ for 2h and lyophilized at-50 ℃ for 24h to give a blank dressing in the form of a foam.
The porosity of each example and the control example was tested as follows:
the porosity was measured by ethanol displacement and the porosity P was calculated by the following formula:
wherein WiIs the initial mass of the material, WfIs the mass of the sample after saturation treatment with ethanol, ViIs the initial volume of the sample, and ρ is the density of pure ethanol, about 0.789 g/ml. The experiment was independently repeated three times.
The test results are shown in fig. 1.
Examples 1 to 3 and comparative examples 1 to 3 each had a high porosity, so that the addition of propolis or tretinoin did not affect the pores formed in the base material (polyvinyl alcohol and sodium alginate). The porosity of examples 1-3 is above 80%, which ensures good absorption and breathability, and the absorption of wound exudate by the dressing avoids tissue maceration, which may degrade growing tissue due to matrix metalloproteinases and other biochemical components contained in the exudate. Meanwhile, the moist environment of the wound can be kept, and the wound healing is promoted.
The swelling rate and drug release rate of each example were tested as follows:
swelling Rate
The swelling ratio was calculated by measuring the maximum amount of PBS absorbed by the sample per unit time. Briefly, the samples were placed in a petri dish containing PBS. After a defined period of time (e.g., 0.1 minute, 0.25 minute, etc.), the sponge is collected with forceps and excess water is gently removed from the surface with filter paper. The samples were weighed and returned to the PBS solution. The experiment was independently repeated three times.
The test results are shown in fig. 2.
The swelling ratio reflects the water absorption performance of the material, and the examples 1-3 can absorb more than 2 times of the liquid by weight of the material, which shows that the material has good adsorbability. The swelling rate is related to the hydrophilicity and hydrophobicity of the material, and the swelling capacity of the material is reduced along with the reduction of the proportion of the sodium alginate.
Rate of drug release
Drug release was measured using Franz diffusion cells. A donor cell was loaded with 5mL PBS at 37 deg.C to simulate human tissue temperature, and a recipient cell contained 30 mLPBS. The samples were immersed in the donor wells and 3ml of PBS was aspirated from the receiving wells at regular intervals for measurement and 3ml of fresh PBS was added back to the receiving wells. The propolis concentration was calculated by the absorbance of the test solution at 299 nm.
Since tretinoin is poorly water soluble, 2% tween 80 was added to PBS to facilitate tretinoin dissolution. The retinoic acid concentration is calculated by the absorbance of the test solution at 350 nm.
The test results are shown in fig. 3 and 4.
Fig. 3 and 4 show the release rates of propolis and tretinoin, respectively, and examples 1-3 all have long-term drug release and provide long-lasting antimicrobial protection.
Claims (6)
1. A preparation method of a tretinoin dressing for promoting wound healing is characterized by comprising the following steps:
s1: dissolving reaction amount polyvinyl alcohol in 95 ℃ distilled water, stirring until the reaction amount polyvinyl alcohol is dissolved, and then cooling to room temperature to obtain polyvinyl alcohol solution;
s2: dissolving reaction amount of sodium alginate in distilled water at 40 ℃, stirring until the sodium alginate is dissolved, and then cooling to room temperature to obtain a sodium alginate solution;
s3: mixing the obtained polyvinyl alcohol solution and sodium alginate solution according to the volume ratio of 1-3:1, and stirring the mixture until the mixture is uniform to obtain a base material solution;
s4: mixing and dissolving reaction amount tretinoin, propolis and an activating agent;
s5: adding the base material solution obtained in the step S3 into the mixed substance in the step S4, and stirring the mixture until the mixture is uniform;
s6: adding hydrochloric acid to adjust the pH value to be 2, adding glutaraldehyde, and slowly stirring to obtain a dressing solution;
s7: introducing the dressing solution into a mold, freezing at-80 deg.C for 0.5-5h, and lyophilizing at-50 deg.C for 24h to obtain the dressing.
2. The method for preparing a tretinoin dressing for promoting wound healing according to claim 1, wherein the concentration of polyvinyl alcohol in the solution of S1 polyvinyl alcohol is 4% (v/v).
3. The method for preparing a tretinoin dressing for promoting wound healing according to claim 1, wherein the concentration of sodium alginate in the sodium alginate solution of S2 is 4% (v/v).
4. The method for preparing a tretinoin dressing for promoting wound healing according to claim 1, wherein the tretinoin, the propolis and the activator are used in an amount of 16-20:1-2:20-22 by mass in S4.
5. The method for preparing a tretinoin dressing for promoting wound healing according to claim 1 or 4, wherein the activator is Tween-80.
6. The method for preparing a tretinoin dressing for promoting wound healing according to claim 1, wherein the amount of glutaraldehyde used in the S6 dressing solution is 0.075% (v/v).
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| CN108421082A (en) * | 2018-04-23 | 2018-08-21 | 闫金银 | The preparation method of graphene oxide wound dressing with antibacterial anti-scar double action |
| CN109260508A (en) * | 2018-08-08 | 2019-01-25 | 华南理工大学 | A kind of polyvinyl alcohol/Sodium Alginate Hydrogel Films preparation method with promotion skin fibroblasts proliferative functionality |
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