A dressing for external wounds, a patch and a preparation method and application thereof

Abstract

The application provides a wound dressing for external injury, a plaster and a preparation method and application thereof, and belongs to the technical field of external plasters. The wound dressing for external injury provided by the application comprises the following raw materials in parts by weight: calcined white vitriol 0.5-1.5 parts, flammulina velutipes polysaccharide 5-10 parts, and water 100 parts. The flammulina velutipes polysaccharide and the calcined white vitriol are combined in the application, the flammulina velutipes polysaccharide is economical and easy to obtain, and has high biological activity; the plant polysaccharide and metal ions can form a chelate with a network structure; a wound dressing for external injury is prepared; the dressing has excellent biocompatibility and degradability, good water absorption and water retention, can absorb wound exudates, and can provide a moist environment for the wound, which is beneficial to wound healing; and the dressing also has the effects of anti-inflammation and bacteriostasis, thereby promoting wound healing. The preparation method of the dressing and the plaster is simple, the curative effect is remarkable, and the application has strong application and promotion value.

Description

Technical Field

[0001] This invention belongs to the field of external dressing technology, and particularly relates to a dressing for external wounds, a dressing, its preparation method and application. Background Technology

[0002] Chronic bacterial skin wounds, especially full-thickness wounds, often lead to abscesses and pain, and even amputation and death, undoubtedly posing a significant challenge to the medical field. Currently, the primary strategy for treating infected wounds in clinical practice remains the use of antibiotics. However, the overuse of antibiotics often leads to the emergence of drug-resistant strains, making the treatment of infected wounds increasingly unsatisfactory. Therefore, developing an antibiotic-free or non-resistant wound dressing holds great promise for medical applications.

[0003] In recent years, polymer materials have been widely used in the preparation of wound dressings. However, natural polymer dressings still have significant shortcomings in terms of mechanical properties and multifunctionality. Although synthetic polymers have better mechanical properties, they are inferior to natural polymers in terms of cytotoxicity and biocompatibility. Therefore, it is necessary to explore biocompatible, biodegradable, and multifunctional natural / synthetic polymers and their composites for external application.

[0004] Applying herbal plasters is one of the most commonly used external treatment methods in Traditional Chinese Medicine (TCM) clinical practice. TCM plasters are characterized by their simplicity, convenience, low cost, and good efficacy, and are widely used to treat surgical conditions such as injuries, sores, and skin diseases. Traditional TCM plasters often involve pulverizing or crushing medicinal materials to extract their juice, or adding excipients, and then applying them to the affected area. The plasters rely on the penetrating action of the medicinal material and the adhesive properties of the excipients to achieve the effects of removing blood stasis, promoting tissue regeneration, relieving pain, and reducing swelling. However, traditional TCM plasters have complex formulations, large dosages, and difficulty in identifying the effective components, thus failing to meet the needs of modern trauma medication. Therefore, it is necessary to use modern scientific and technological methods to prepare TCM plasters with clearly defined ingredients and definite efficacy. Summary of the Invention

[0005] In view of this, the present invention addresses the problems of antibiotic resistance, poor biocompatibility, poor biodegradability, and poor multifunctionality of wound dressings for external injuries, which are easily caused by the use of antibiotics. It provides a wound dressing that can be used for external injuries, is antibiotic-free, has good water absorption and water retention, can absorb wound exudate, provide a moist environment for the wound, promote wound healing, and also has anti-inflammatory and antibacterial effects.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a dressing for external wounds, comprising the following raw materials in parts by weight: 0.5-1.5 parts calcined alum, 5-10 parts enoki mushroom polysaccharide, and 100 parts water.

[0008] The present invention also provides a method for preparing the above-mentioned dressing, comprising the following steps: mixing calcined alum, enoki mushroom polysaccharide and water to obtain the dressing.

[0009] Preferably, the stirring time is 1-2 hours.

[0010] The present invention also provides the application of the above-described dressing or preparation method in the preparation of products for treating external wounds.

[0011] Preferably, the product includes a dressing.

[0012] The present invention also provides a dressing for external wounds, the dressing comprising a release layer, a dressing layer and a base fabric layer, wherein the dressing layer comprises the aforementioned dressing.

[0013] Preferably, the thickness of the dressing layer is 1-2 mm.

[0014] Preferably, the release layer is glassine silicone paper or ordinary release paper.

[0015] Preferably, the base fabric layer is glassine silicone paper, ordinary release paper, or medical adhesive tape.

[0016] The present invention also provides a method for preparing the above-mentioned dressing, comprising the following steps: applying the above-mentioned dressing to a base fabric layer with a thickness of 1-2 mm, and then applying a release layer.

[0017] The beneficial effects of this invention are:

[0018] This invention combines readily available and highly bioactive *Flammulina velutipes* polysaccharide with calcined alum, utilizing the chelate structure formed by the plant polysaccharide and metal ions to prepare a wound dressing suitable for infected external injuries. This dressing exhibits excellent biocompatibility and biodegradability, as well as good water absorption and retention, absorbing wound exudate and providing a moist environment conducive to wound healing. It also possesses anti-inflammatory and antibacterial properties, further promoting wound healing. The dressing and patch preparation method provided by this invention are simple, have significant therapeutic effects, and possess strong application and promotion value. Attached Figure Description

[0019] Figure 1 The results of external wound conditions in rats in each group are shown. A is the model group, B is the positive group, C is the alum application group, and D is the ordinary application group.

[0020] Figure 2The results of routine blood tests in rats in each group are shown below. Compared with the blank group, the p < 0.05 in the model group is indicated by #, and the p < 0.01 is indicated by ##. Compared with the model group, the p < 0.05 in the positive group, alum application group, and ordinary application group is indicated by *, and the p < 0.01 is indicated by **. Compared with the ordinary application group, the p < 0.01 in the positive group and alum application group is indicated by ▲▲.

[0021] Figure 3 The levels of inflammatory factors in rats in each group are shown. Compared with the blank group, the p-value of the model group is <0.01, indicated by ##; compared with the model group, the p-value of the positive group, alum application group, and ordinary application group is <0.01, indicated by **; compared with the ordinary application group, the p-value of the positive group and alum application group is <0.05, indicated by ▲. Detailed Implementation

[0022] This invention provides a dressing for external wounds, comprising the following raw materials in parts by weight: 0.5-1.5 parts calcined alum, 5-10 parts enoki mushroom polysaccharide, and 100 parts water.

[0023] In this invention, the calcined alum is preferably prepared by the following method: Alum is placed in a calcination container and heated over a high flame until melted. Calcination continues until the alum expands and becomes a white, honeycomb-like solid, and then completely dried to obtain the calcined alum. In this invention, the calcined alum can also be obtained through conventional commercial purchases. In this invention, the *Flammulina velutipes* polysaccharide is preferably prepared by the following steps: *Flammulina velutipes* is dehydrated and dried, then extracted with water. The extract is concentrated under reduced pressure, and anhydrous ethanol is added to adjust the alcohol concentration to 75%. The mixture is allowed to stand overnight, the lower precipitate is separated, and the precipitate is freeze-dried to obtain the final product. The preferred amount of water used for extraction is 10 times the weight of the *Flammulina velutipes*, the preferred extraction temperature is 100°C, the preferred extraction time is 3 hours, and the preferred number of extractions is 3 times. In this invention, the *Flammulina velutipes* polysaccharide can also be obtained through conventional commercial purchases. In the dressing of this invention, the water is preferably purified water, and this invention does not have a specific limitation on the specific source of the purified water.

[0024] This invention uses enoki mushroom polysaccharide as a matrix, combined with Al from alum. 3+ The metal chelate, which forms a cross-linked network structure with ions, possesses excellent water absorption and retention properties. It can absorb wound exudate and provide a moist environment for the wound, thereby promoting wound healing. In addition, the wound dressing for external injuries provided by this invention also has antibacterial and anti-inflammatory effects, as well as biocompatibility and biodegradability.

[0025] The present invention also provides a method for preparing the above-mentioned dressing, comprising the following steps: mixing calcined alum, enoki mushroom polysaccharide and water to obtain the dressing.

[0026] In the preparation method described in this invention, preferably, enoki mushroom polysaccharides are first mixed with water to form an enoki mushroom polysaccharide matrix, and then calcined alum is added to the enoki mushroom polysaccharide matrix and mixed evenly. The calcined alum is preferably pulverized and sieved before being added; the sieve mesh size is preferably 100-300 mesh, more preferably 200 mesh. In this invention, the stirring time is preferably 1-2 hours.

[0027] This invention also provides the application of the above-described dressing or preparation method in the preparation of products for treating external wounds. In this invention, the product preferably comprises a dressing.

[0028] The present invention also provides a dressing for external wounds, the dressing comprising a release layer, a dressing layer and a base fabric layer, wherein the dressing layer comprises the aforementioned dressing.

[0029] In this invention, the thickness of the dressing layer is preferably 1-2 mm, and the dressing layer preferably uses the aforementioned dressing as the sole effective active ingredient. The release layer is preferably glassine silicone paper or ordinary release paper, and the base fabric layer is preferably glassine silicone paper, ordinary release paper, or medical adhesive tape. This invention does not specifically limit the specific source of the glassine silicone paper, ordinary release paper, or medical adhesive tape.

[0030] The present invention also provides a method for preparing the above-mentioned dressing, comprising the following steps: applying the above-mentioned dressing to a base fabric layer with a thickness of 1-2 mm, and then applying a release layer.

[0031] In this invention, the coating area is preferably 1-2 cm smaller than the edge of the base fabric. This invention does not specifically limit the shape of the base fabric layer; depending on the application area, the base fabric layer can be processed into a rectangle, an arc shape, or a butterfly shape. The area of ​​the release layer depends on the area of ​​the base fabric layer, and preferably, the area of ​​the release layer is equal to the area of ​​the base fabric layer.

[0032] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0033] Unless otherwise specified, the following embodiments are all conventional methods.

[0034] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0035] Example 1

[0036] Commercially available enoki mushrooms were dehydrated and dried, then extracted with 10 times the amount of water (extraction temperature was 100℃, extraction time was 3 hours, and extraction was repeated 3 times). The extract was concentrated under reduced pressure, and anhydrous ethanol was added to adjust the alcohol concentration to 75%. The mixture was allowed to stand overnight, the lower precipitate was separated, and the precipitate was freeze-dried to obtain enoki mushroom polysaccharide.

[0037] Take alum (purchased from Anguo Juyitang Pharmaceutical Co., Ltd.) fragments, place them in a calcining container, heat them over high heat until they melt, continue calcining until they expand and become a white honeycomb-like solid, dry them completely, take them out, let them cool, and you will get calcined alum.

[0038] First, dissolve 5g of enoki mushroom polysaccharide in 100g of purified water to make enoki mushroom polysaccharide matrix; then, pulverize calcined alum, pass it through a 100-mesh sieve, take 1g and add it to the enoki mushroom polysaccharide matrix, mix well, and stir at a uniform speed for 2 hours to make a dressing.

[0039] Apply the dressing evenly to the medical adhesive tape (purchased from Henan Yu'an Medical Technology Development Co., Ltd.) with a thickness of 1 mm. The dressing application area is less than 1 cm from the edge of the base fabric. Apply a release layer of glassine silicone paper (purchased from Jiangsu Pingyu New Materials Co., Ltd.) to the base fabric area to obtain the dressing.

[0040] Example 2

[0041] First, dissolve 10g of enoki mushroom polysaccharide (purchased from Xi'an An'ao Biotechnology Co., Ltd.) in 100g of purified water to prepare enoki mushroom polysaccharide matrix; then, pulverize calcined alum (purchased from Anguo Juyitang Pharmaceutical Co., Ltd.), pass it through a 300-mesh sieve, and add 0.5g of the calcined alum to the above enoki mushroom polysaccharide matrix, mix well, and stir at a uniform speed for 1 hour to prepare a dressing.

[0042] Apply the dressing evenly to the medical adhesive tape at a thickness of 2mm, with the dressing application area being less than 2cm from the edge of the base fabric. Apply a release liner (purchased from Jiangsu Pingyu New Materials Co., Ltd.) on the base fabric area to obtain the dressing.

[0043] Example 3

[0044] First, dissolve 5g of enoki mushroom polysaccharide in 100g of purified water to prepare enoki mushroom polysaccharide matrix; then, pulverize calcined alum, pass it through a 200-mesh sieve, and add 1.5g of the calcined alum to the above enoki mushroom polysaccharide matrix, mix well, and stir at a uniform speed for 1.5h to prepare a dressing.

[0045] Apply the dressing evenly to the medical adhesive tape with a thickness of 1.5 mm. The dressing application area should be less than 1 cm from the edge of the base fabric. Apply a glassine silicone release layer to the base fabric area to obtain the dressing.

[0046] Example 4

[0047] Comparison of the antibacterial effects of alum and calcined alum

[0048] Alum (purchased from Anguo Juyitang Pharmaceutical Co., Ltd.) and calcined alum (obtained by calcining alum using the method described in Example 1) were dissolved in MHB liquid medium to prepare a stock solution with a concentration of 200 mg / mL. The minimum inhibitory concentration (MIC) of alum and calcined alum against Staphylococcus aureus was screened using an isostatic dilution method. Specifically, one sample was placed in every three wells of a 96-well plate, with 200 μL of stock solution added to the first well of each row, followed by isostatic dilutions. Finally, 100 μL of diluted Staphylococcus aureus solution (concentration 2 × 10⁻⁶) was added to each well. 5 After incubating the sample at 37℃ for 20 hours, visual observation revealed that the minimum inhibitory concentrations (MICs) of alum and calcined alum were 12.5 mg / mL and 6.25 mg / mL, respectively. This indicates that the MIC of alum decreased and the antibacterial effect increased after calcination.

[0049] Example 5

[0050] Comparison of the antibacterial effects of calcined alum, enoki mushroom polysaccharide, and mixtures thereof

[0051] The minimum inhibitory concentrations (MICs) of calcined alum, *Flammulina velutipes* polysaccharide (prepared in Example 1), and a mixture of the two (1:5) against *Staphylococcus aureus* were compared using an equal dilution method, similar to that in Example 4. The results showed that the MICs of calcined alum, *Flammulina velutipes* polysaccharide, and their mixture (1:5) were 6.25 mg / mL, 12.5 mg / mL, and 1.5625 mg / mL, respectively, indicating that the combination of calcined alum and *Flammulina velutipes* polysaccharide reduced the MIC and enhanced the antibacterial effect.

[0052] Example 6

[0053] Comparison of the antibacterial effects of mixtures of calcined alum and enoki mushroom polysaccharides in different proportions

[0054] The minimum inhibitory concentration (MIC) of calcined alum and *Flammulina velutipes* polysaccharide at ratios of 1:1, 1:2.5, 1:5, 1:10, 1:20, and 1:30 (mass ratio) was compared using the same dilution method as in Example 4. The results are shown in Table 1. The mixtures of calcined alum and *Flammulina velutipes* polysaccharide exhibited strong antibacterial activity in the 1:2.5–1:20 ratio range.

[0055] Table 1. Antibacterial effects of mixtures of calcined alum and enoki mushroom polysaccharides at different ratios.

[0056]

[0057] Example 7

[0058] Comparison of the anti-inflammatory effects of alum and calcined alum

[0059] Alum and calcined alum (obtained by calcining alum using the method described in Example 1) were dissolved in DMEM culture medium to prepare a drug solution with a concentration of 100 μg / mL. The phagocytic effect of alum and calcined alum on RAW264.7 cells was investigated using relative phagocytosis rate. Specifically, logarithmic growth phase RAW264.7 cells were taken and phagocytosed at a concentration of 1 × 10⁻⁶ cells / mL. 5 Cells were seeded at a density of 1 / 2 well in 96-well plates and cultured at 37°C with 5% CO2. After cell adhesion, the cells were starved for 20 h. Then, 100 μL of alum and calcined alum solution were added to each group, while 100 μL of blank culture medium was added to the blank group and control group. Each group had 6 replicates, and the cells were cultured for 20 h. Except for the blank control group, each well was treated with LPS at a final concentration of 5 μg / mL for 4 h. The supernatant was discarded, and 200 μL of 0.1% neutral red solution was added. The cells were incubated for 1 h, the neutral red solution was discarded, and the cells were washed three times with pre-warmed PBS. 200 μL of acetic acid-anhydrous ethanol (1:1) cell lysis buffer was added to each well, and the cells were incubated overnight at 4°C. The OD value at 570 nm was measured using a microplate reader. The results showed that the relative phagocytic rates of alum and calcined alum on inflammatory cells were 107.7% and 174.8%, respectively, indicating that the relative phagocytic rate of cells increased and the anti-inflammatory effect was enhanced after calcination of alum.

[0060] Relative phagocytic rate (RSR) (%) = (OD experimental group - OD blank group) / (OD control group - OD blank group) × 100%.

[0061] Example 8

[0062] Comparison of the anti-inflammatory effects of calcined alum, enoki mushroom polysaccharide, and mixtures thereof

[0063] The phagocytic activity of calcined alum, enoki mushroom polysaccharide, and a mixture thereof (1:5) on RAW264.7 cells was compared using an inflammatory cell phagocytosis assay, following the same method as in Example 7. The results showed that the relative phagocytic rates of calcined alum, enoki mushroom polysaccharide, and their mixture (1:5) on inflammatory cells were 174.1%, 142.3%, and 186.6%, respectively, indicating that the combination of calcined alum and enoki mushroom polysaccharide increased the relative phagocytic rate of inflammatory cells and enhanced the anti-inflammatory effect.

[0064] Example 9

[0065] Comparison of the anti-inflammatory effects of mixtures of calcined alum and enoki mushroom polysaccharides in different proportions

[0066] The phagocytic activity of calcined alum and *Flammulina velutipes* polysaccharide mixtures at mass ratios of 1:1, 1:2.5, 1:5, 1:10, 1:20, and 1:30 on RAW264.7 cells was compared using an inflammatory cell phagocytosis assay, following the same method as in Example 7. The results are shown in Table 2. The mixtures of calcined alum and *Flammulina velutipes* polysaccharide exhibited strong anti-inflammatory effects in the 1:2.5–1:20 range.

[0067] Table 2. Anti-inflammatory effects of mixtures of calcined alum and enoki mushroom polysaccharides in different proportions.

[0068]

[0069] Example 10

[0070] The therapeutic effects of the dressing obtained in Example 1 and ordinary adhesive bandage on skin injuries in rats

[0071] Fifty healthy male SD rats weighing 180-220g were selected and, after one week of acclimatization, randomly divided into five groups: a control group, a model group, a positive control group, the Example 1 dressing group (alum dressing group), and a regular dressing group, with 10 rats in each group. Except for the control group, the fur on the backs of all rats in the other groups was shaved, and a 1.5cm square piece of skin was cut off with a scalpel, creating a 1.5cm long wound extending to the muscle layer. In the positive control group, mupirocin ointment was applied to a regular adhesive bandage and then placed on the wound; in the Example 1 dressing group, the dressing described in Example 1 was applied to the wound; in the regular dressing group, a regular adhesive bandage was applied to the wound; and the model group received no treatment. The dressings were changed daily for three consecutive days. After the drug administration was completed, the wounds of the rats in each group were observed, mortality rates were recorded, and peripheral blood counts were measured. Simultaneously, the serum levels of inflammatory factors IL-6 and TNF-α were detected using ELISA.

[0072] The results are as follows Figures 1-3 As shown, by Figure 1 As can be seen, in the model group rats, the wounds became purulent and the infection deepened, resulting in secondary infection and a mortality rate of 30%. In the positive group rats, the wounds began to heal, there was no secondary infection, and no deaths occurred. In the group treated with this invention, the wounds began to heal, there was no secondary infection, and no deaths occurred. In the ordinary treatment group, wound healing was slower, secondary infection occurred, and the mortality rate was 10%.

[0073] Depend on Figure 2Blood routine results showed that, compared with the blank group, the model group had significantly lower white blood cell (WBC) and platelet (PLT) counts (P < 0.01), significantly lower hemoglobin (HGB) levels, and significantly higher red blood cell (RBC) counts (P < 0.05). Compared with the model group, the positive group had significantly higher WBC and PLT counts (P < 0.01), significantly lower RBC counts (P < 0.01), and significantly higher HGB levels (P < 0.05); the patch group of this invention showed increased WBC and PLT counts, but no significant difference (P > 0.05), significantly increased HGB levels (P < 0.01), significantly decreased RBC counts (P < 0.01), and significantly increased HGB levels (P < 0.05); and no significant differences were found in any indicators in the ordinary bandage group. Compared with the ordinary dressing group, the positive group and the dressing group of the present invention showed significantly increased WBC and PLT (P<0.01), significantly increased HGB content (P<0.01), and significantly decreased RBC content (P<0.01).

[0074] Depend on Figure 3 The ELISA results showed that, compared with the control group, the levels of IL-6 and TNF-α in the model group were significantly increased (P < 0.01). Compared with the model group, the levels of IL-6 in the positive group, alum application group, and ordinary application group were significantly decreased (P < 0.01), the levels of TNF-α in the positive group and alum application group were significantly decreased (P < 0.01), and the level of TNF-α in the ordinary application group decreased but was not significantly different (P > 0.05). Compared with the ordinary application group, the level of TNF-α in the alum application group was significantly decreased (P < 0.05).

[0075] The above results indicate that, compared with traditional dressings in the field, the dressing of the present invention has a good effect in preventing external infection.

[0076] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A dressing for external wounds, characterized in that, The ingredients include the following parts by weight: 0.5-1.5 parts calcined alum, 5-10 parts enoki mushroom polysaccharide, and 100 parts water.

2. The method for preparing the dressing according to claim 1, characterized in that, The process includes the following steps: mixing calcined alum, enoki mushroom polysaccharide, and water to obtain the dressing.

3. The preparation method according to claim 2, characterized in that, The stirring time is 1-2 hours.

4. The use of the dressing according to claim 1 or the dressing prepared by the preparation method according to any one of claims 2-3 in the preparation of products for treating external wounds.

5. The application according to claim 4, characterized in that, The product includes patches.

6. A dressing for external wounds, characterized in that, The dressing includes a release layer, a dressing layer, and a base fabric layer, wherein the dressing layer includes the dressing as described in claim 1.

7. The dressing according to claim 6, characterized in that, The thickness of the dressing layer is 1-2 mm.

8. The dressing according to claim 6, characterized in that, The release layer is glassine silicone paper.

9. The dressing according to claim 6, characterized in that, The release layer is ordinary release paper.

10. The dressing according to claim 6, characterized in that, The base fabric layer is glassine silicone paper or medical adhesive bandage.

11. The dressing according to claim 6, characterized in that, The base fabric layer is ordinary release paper.

12. The method for preparing the dressing according to any one of claims 6-11, characterized in that, The procedure includes the following steps: applying the dressing of claim 1 to the base fabric layer with a thickness of 1-2 mm, and then applying the release layer.

Images