Artificial dressing, use of artificial dressing for promoting wound healing and method of manufacturing artificial dressing

Abstract

To provide an artificial dressing suitable for promoting wound healing and a method for manufacturing the artificial dressing.SOLUTION: The artificial dressing comprises a gelatin, a polysorbate-20 and a glutaraldehyde. The manufacturing method of the artificial dressing comprises subjecting the composition of the gelatin, the glutaraldehyde and the polysorbate-20 to a mixing and foaming step, a molding step, and a freeze-drying step in sequence. The artificial dressing has obvious pores and is capable of absorbing liquid about 25 to 35 times its own weight.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a dressing and its use, in particular to an artificial dressing and its use for promoting wound healing. [Background technology]

[0002] Diabetic foot ulcers (DFUs) are one of the serious complications of diabetes, and patients with DFUs account for 25% of the total diabetic population. Of these, 50% of patients require amputation, and the mortality rate within 5 years after amputation is as high as 50%. For diabetic foot ulcers, moist wound healing is performed to adjust the balance of the extracellular matrix and promote wound healing.

[0003] Moist wound healing provides a moist environment for the wound, performs autolytic debridement of the wound, reduces pain, activates collagen synthesis and promotes keratinocytes, allowing cells to migrate within the wound bed and promote wound healing. Moist wound healing heals 3-5 times faster than traditional dressings (gauze, bandages, etc.). Dressings commonly used in moist wound healing include foam, hydrocolloid, and hydrogel. Foam dressings commercially available for moist wound healing are mainly collagen dressings, but their cost is high. Summary of the Invention [Problem to be solved by the invention]

[0004] The main ingredient used in the artificial bandage of the present invention is gelatin, which has the advantages of biocompatibility, low cost, and ability to absorb water and form a gel. Furthermore, the artificial bandage of the present invention is a sheet-like gelatin bandage (SIPSIP). TM ), has obvious pores, can absorb about 25 to 35 times its own weight in liquid, and no collapse was observed in thermal collapse experiments and application tests. Furthermore, animal experiments have shown that, compared with commercially available bandages, the artificial bandage of the present invention can promote wound healing when applied dry, and can grow functional tissue in the wound when applied wet. [Means for solving the problem]

[0005] The present invention provides an artificial dressing for promoting wound healing, the dressing comprising gelatin, polysorbate 20 (tween 20), and glutaraldehyde.

[0006] In a specific embodiment, the gelatin has a concentration of 5% (g / mL, w / v) to 10% (g / mL, w / v), the polysorbate 20 (tween 20) has a concentration of 0.005% (mL / mL, v / v) to 0.1% (mL / mL, v / v), and the glutaraldehyde has a concentration of 0.01% (mL / mL, v / v) / v to 0.3% (mL / mL, v / v).

[0007] The present invention also provides an artificial bandage having a thickness of 1 mm to 10 mm.

[0008] In a particular embodiment, the artificial dressing has a pore size of between 60 μm and 70 μm.

[0009] In another particular embodiment, the artificial dressing has a porosity of between 60% and 67%.

[0010] Wounds in the context of the present invention include, but are not limited to, contusions, knife wounds, general acute wounds, first / second degree burns, surgical wounds, pressure sores and ulcers.

[0011] The artificial bandage of the present invention is in sheet form.

[0012] The artificial bandage of the present invention becomes gel-like when moistened or absorbs tissue fluid.

[0013] The artificial bandage of the present invention is resistant to high-energy gamma radiation exposure doses of 15 kGy to 25 kGy, and its texture and function are not affected.

[0014] The present invention also relates to a method for producing a foaming composition comprising the steps of: (1) mixing gelatin, glutaraldehyde, and polysorbate-20 to form a mixture, and stirring the mixture to foam; After the mixing and foaming step is completed, a molding step is performed in which the mixture is poured into a mold and spread evenly. and (3) performing a freeze-drying step by placing the mold in a freeze-dryer to freeze and dry the mold to form the artificial bandage.

[0015] In a particular embodiment, the gelatin has a concentration of 5% (w / v) to 10% (w / v).

[0016] In another particular embodiment, the concentration of polysorbate-20 is 0.005% (v / v) to 0.1% (v / v).

[0017] In another particular embodiment, the concentration of the glutaraldehyde is 0.01% (v / v) to 0.3% (v / v).

[0018] The present invention also provides a method of using the composition to promote wound healing which comprises applying the above-described artificial dressing to a wound in a patient.

[0019] In a particular embodiment, the composition is used for moist wound healing.

[0020] The present invention also provides the use of a composition for the manufacture of an artificial dressing for promoting wound healing, said composition comprising gelatin, polysorbate-20, and glutaraldehyde.

[0021] In certain embodiments, the composition promotes wound healing by (1) absorbing tissue fluids in the wound, (2) inhibiting the growth of granuloma in the wound, (4) reducing inflammation in the wound, (4) promoting angiogenesis in the wound tissue, and (5) reducing adhesions to the wound.

[0022] In another specific embodiment, the wound includes, but is not limited to, contusions, knife wounds, general acute wounds, first / second degree burns, surgical wounds, pressure sores and ulcers. Effect of the Invention

[0023] Based on the above, the prosthetic wound dressing, its use for promoting wound healing and the method of manufacture of the present invention have the following advantages:

[0024] (1) The artificial bandage of the present invention has clear pores and can absorb about 25 to 35 times its own weight in liquid. In thermal collapse experiments and application tests, no collapse was observed.

[0025] (2) The artificial dressing of the present invention can promote wound healing when applied dry, and can promote the growth of functional tissue within the wound when applied wet.

[0026] (3) The artificial bandage of the present invention is significantly cheaper than conventional moist wound healing methods and conventional bandages, and the artificial bandage of the present invention has a wider range of uses.

[0027] (4) The artificial dressing of the present invention can absorb tissue fluids in wounds, inhibit the proliferation of granulation tissue in wounds, promote angiogenesis in wound tissues, and promote wound healing.

[0028] In order to make the technical features and achievable technical effects of the present invention more comprehensible, preferred embodiments and detailed descriptions are provided below. [Brief description of the drawings]

[0029] [Figure 1] 1 is a flow chart for manufacturing an artificial bandage of the present invention. [Diagram 2]2A-2E are cross-sectional views of gelatin bandages cross-linked with different glutaraldehyde concentrations of the present invention, where FIG. 2A shows a glutaraldehyde concentration of 0.30%, FIG. 2B shows a glutaraldehyde concentration of 0.20%, FIG. 2C shows a glutaraldehyde concentration of 0.10%, FIG. 2D shows a glutaraldehyde concentration of 0.05%, and FIG. 2E shows a glutaraldehyde concentration of 0.01%. [Diagram 3] Fig. 3 is a test chart for an artificial bandage, in which Fig. 3(A) shows the results of a thermal decay test of the artificial bandage, and Fig. 3(B) shows the results of an application test of the artificial bandage. [Figure 4] FIG. 1 is a schematic diagram of an animal experiment using an artificial bandage. [Diagram 5] FIG. 1 is a schematic diagram of analyzing the wound area of ​​mice using ImageJ software. [Figure 6] FIG. 13. Statistical plot of wound area of ​​mice in different bandage treatment groups from days 0 to 31. [Figure 7] H&E staining analysis of skin sections from animal experiments (Group A: NC group). The orange arrow indicates the wound bed, the green arrow indicates neutrophil, the red circle indicates granuloma, and the light pink spindle-shaped area in the right image is a fibroblast. The scale bar in the left image is 1 mm, and the scale bar in the right image is 100 μm. [Figure 8] H&E staining analysis of skin sections from animal experiments (Group B: Commercial collagen dressing PC group). The orange arrow indicates the wound bed, the green arrow indicates polymorphonuclear leukocytes, the red circle indicates granulation tissue, and the light pink spindle-shaped area in the right image is a fibroblast. The scale bar in the left image is 1 mm, and the scale bar in the right image is 100 μm. [Figure 9] H&E staining analysis of skin sections from animal experiments (Group C: artificial bandage dry application group). Orange arrows indicate wound bed, blue arrows indicate neofunctional tissue, red arrows indicate neovessels, light pink areas in the right image indicate collagen, and spindle-shaped areas indicate fibroblasts. Scale bar in the left image is 1 mm, scale bar in the right image is 100 μm. [Figure 10]H&E staining analysis of skin sections from animal experiments (Group D: group with moist artificial dressing). The orange arrow indicates the wound bed, the blue arrow indicates a monocyte, and the red arrow indicates new functional tissue. The scale bar of the left image is 1 mm, and the scale bar of the right image is 100 μm. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] In order to facilitate understanding of the technical features, contents, advantages, and effects that the present invention can achieve, the present invention will be described in detail below in the form of an embodiment using drawings. The drawings used therein are only used for explanation and auxiliary explanation, and may not represent the true ratio or exact configuration of the present invention after implementation. Therefore, the ratio and configuration relationship of the attached drawings should not be interpreted as limiting the actual scope of the rights of the present invention. In addition, in order to facilitate understanding, the same elements are described with the same reference numerals in the following embodiments.

[0031] Additionally, the terms used throughout this specification and patent application generally have the ordinary meaning of each term used in the art, in the context disclosed herein, and in the particular context, unless otherwise specified. Certain terms used to describe the present invention are explained below or elsewhere in this specification to provide those skilled in the art with additional guidance in describing the present invention.

[0032] The use of "first", "second", "third", etc. herein does not imply any particular order or priority, and is not used to limit the invention, but is intended to distinguish only between components or operations that are described with the same technical terminology.

[0033] Secondly, when words such as "including," "including," "having," "containing," and the like are used in this specification, they are all open terms, meaning including but not limited to.

[0034] The following examples are non-limiting and merely representative of various aspects and features of the present invention.

[0035] The present invention provides an artificial bandage for promoting wound healing, comprising a composition of gelatin, polysorbate 20 (tween 20) and glutaraldehyde. The composition is used to manufacture an artificial bandage for promoting wound healing. The composition can be used as a moist therapy or a dry patch therapy. The thickness of the artificial bandage is 1 mm to 10 mm, the pore size of the artificial bandage is 60 μm to 70 μm, and the porosity of the artificial bandage is 60% to 67%. The artificial bandage is in a sheet form. The artificial bandage becomes gel-like by moistening or absorbing tissue fluid. The artificial bandage of the present invention is resistant to gamma ray high energy radiation exposure dose (15 kGy to 25 kGy) and is not affected in texture or function. Such wounds include, but are not limited to, contusions, knife wounds, common acute wounds, first / second degree burns, surgical wounds, pressure sores and ulcers (eg, diabetic foot ulcers).

[0036] Example 1: The procedure for manufacturing an artificial bandage is shown in FIG.

[0037] A method for producing an artificial bandage includes the following steps.

[0038] (1) Mixing and foaming step S10: 5% (g / mL, w / v) to 10% (g / mL, w / v) gelatin, 0.005% (mL / mL, v / v) to 0.1% (mL / mL, v / v) polysorbate 20, and 0.01% (mL / mL, v / v) to 0.3% (mL / mL, v / v) glutaraldehyde are mixed to form a mixture, which is then stirred to foam. Among these, the concentrations of the gelatin, polysorbate 20, and glutaraldehyde can be any value and range within the corresponding numerical ranges described above, and the remainder is water. Gelatin in the manufacture of artificial bandages in the present invention refers to an aqueous gelatin solution with a gelatin concentration of 5% (g / mL, w / v) to 10% (g / mL, w / v). This concentration may be any value and range within this range. In the present invention, for example, a commercially available stirrer (HMB-312SS, microemulsion homogenizer manufactured by Zenka Confidential Co., Ltd.) is used to perform the stirring and foaming step, but is not limited thereto. The stirring time in the stirring and foaming step is, for example, 10 minutes to 15 minutes, but is not limited thereto, and the stirring speed is, for example, 1500 rpm to 3000 rpm, but is not limited thereto. The stirring time and stirring speed of the present invention may be any value and any range within the corresponding numerical ranges above, or other values ​​or ranges outside the corresponding numerical ranges above, and as long as the above composition (gelatin, glutaraldehyde, and polysorbate-20) can be mixed uniformly and foamed, all of them are included in the scope of protection claimed by the present invention. The above-mentioned compositions may be supplied from, for example, commercially available products, including but not limited to, gelatin purchased from Sigma-Aldrich (trade name G2500), glutaraldehyde purchased from Tokyo Chemical Industry (TCI) (trade name G0068), and polysorbate-20 purchased from Sigma-Aldrich (trade name P1379).

[0039] (2) Molding step S20: After the above mixing and foaming step is completed, the mixture is poured into a mold and spread flat. The mold is a container having a storage space, but the mold of the present invention is not limited to a specific form or style and may be any form or style.

[0040] (3) Freeze-drying step S30: The mold is placed in a pre-cooled (pre-cooling temperature -20°C to -60°C) freeze-dryer, frozen, and freeze-dried to form an artificial bandage. The freeze-dryer is, for example, a 15-liter shelf-type freeze-dryer, model TYFD80015, purchased from Taiheiyo Co., Ltd. The composition of the artificial bandage after freeze-drying includes 92.6% (g / mL, w / v) to 99.8% (g / mL, w / v) gelatin, 0.05% (mL / mL, v / v) to 1.85% (mL / mL, v / v) polysorbate 20 (tween 20), and 0.15% (mL / mL, v / v) to 5.55% (mL / mL, v / v) glutaraldehyde. Similarly, the concentrations of gelatin, polysorbate-20, and glutaraldehyde in the artificial dressing after lyophilization can be any value and any range within the corresponding numerical ranges given above.

[0041] The above freezing procedure is completed by freeze-drying according to the operation steps and freeze-drying parameters of the tray freeze-dryer. The freezing parameters of the freeze-dryer are as shown in Table 1.

[0042] Table 1. Freeze drying parameters for the tray freeze dryer.

[0043] [Table 1]

[0044] The freeze-drying time of the freeze-drying step S30 is listed in Table 1, but the present invention is not limited thereto, and any freeze-drying time is within the scope of the present invention as long as a freeze-dried artificial dressing is obtained. For example, the freeze-drying time is more than 1 hour.

[0045] Example 2: Scanning electron microscopy (SEM) images of artificial bandages

[0046] The artificial bandage produced above was used as a test sample. The test sample was cut in a cross-sectional view, fixed to a dedicated stage with copper tape, moved to a gold plating device, evacuated to 40 Pa, and plated with platinum for 60 seconds to increase the conductivity of the test sample. The stage containing the test sample was placed in the sample chamber of a scanning electron microscope, the working distance of the stage was adjusted, and then the sample chamber was evacuated and the image of the test sample was observed through the screen, and the three-dimensional coordinate XYZ axis knobs were adjusted to align the stage position with the field of view, and the test sample was scanned with an electron beam intensity of Spotsize 50 and a voltage of 15 kV. The surface morphology and structure of the artificial bandage observed were shown in Figure 2, and the recorded images were captured.

[0047] Example 3: Porosity of artificial dressings

[0048] The SEM images of Example 2 were imported into conventional ImageJ software to estimate the pore diameter and porosity of the artificial dressing at various glutaraldehyde concentrations. By using the image scale to correct and convert the pixel ratio of each image file, adjusting the threshold interval of the light-dark contrast of the image, filtering out the noise shadows that are too small, and selecting the hole area to be calculated, the average pore diameter and porosity area of ​​the artificial dressing can be estimated and counted. The porosity of the artificial dressing calculated using the software ImageJ from the photographs obtained by SEM is shown in Table 2.

[0049] Table 2. Pore size analysis results of artificial bandages in SEM images

[0050] [Table 2]

[0051] From the SEM images of each group, the artificial bandages of each group have complete and dense porosity, and the results of calculations by software show that the pore size is distributed between 60 and 70 μm on average, and the porosity is about 60% to 67%. This shows that glutaraldehyde in this concentration range does not affect the pore size and porosity of the artificial bandage. The porosity of the artificial bandage may be any value and range within the above numerical range (60% to 67%).

[0052] Example 4: Water absorbency of artificial bandages

[0053] The water absorbency of the artificial dressings was tested according to standard method EN-13726-1.

[0054] From Table 3, 4 cm 2 The synthetic dressing was found to be able to absorb 25 to 35 times its own weight in liquid.

[0055] Table 3. Results of water absorption tests on artificial dressings (I) and (II)

[0056] [Table 3]

[0057] TIFF2025039549000005.tif128155

[0058] Example 5: Thermal Disintegration Test of Artificial Bandage

[0059] The purpose of this thermal decay test is to determine whether the artificial dressing will disintegrate. In the thermal decay test, the artificial dressing is subjected to extreme conditions, immersed in excess liquid and left in an environment with a temperature of 37°C for 24 hours.

[0060] The artificial bandage was placed in 4 mL of deionized water and left in an incubator at 37°C for 24 hours. After 24 hours, the artificial bandage was taken out and photographed, as shown in Figure 3(A). Figure 3(A) shows the results of a test to see whether the artificial bandage would thermally disintegrate when irradiated with gamma rays (γ-rays) of different intensities.

[0061] From FIG. 3(A), it can be seen that the artificial dressing of the present invention can retain its hydrocolloid texture and does not disintegrate after being exposed to various radiation intensities and harsh test conditions.

[0062] Example 6: Testing the adhesiveness of artificial dressings

[0063] The results in FIG. 3(A) show that the artificial bandage does not collapse, so the present invention uses these results to test the actual situation when the artificial bandage is attached to the hand.

[0064] A 2 cm x 2 cm artificial bandage was applied to the arm, 0.75 mL of saline was dropped onto it, and it was covered with a waterproof and breathable bandage sheet (e.g., Tegaderm manufactured by 3M) and left for 7 hours. After 7 hours, a photograph was taken again to observe whether the artificial bandage was easily peeled off from the hand and whether it stuck to the waterproof and breathable bandage sheet (e.g., Tegaderm), as shown in Figure 3(B). Figure 3(B) shows the results of testing the adhesiveness of the artificial bandage by irradiating it with gamma rays of various intensities. From Figure 3(B), it was found that the artificial bandage could be peeled off from the skin and the waterproof and breathable bandage sheet (e.g., Tegaderm), the appearance maintained a certain integrity, and it was not sticky.

[0065] Example 7: Animal studies on artificial bandages

[0066] As shown in Figure 4, wound healing by artificial bandage was observed through a mouse wound animal model. The day before performing trauma surgery, the hair on the back of the mouse needs to be shaved. The above mice were purchased from the National Laboratory Animal Center of Taiwan (BALB / cByJNar1 strain). On the day of surgery, the mouse was intraperitoneally injected (anesthetic amount: 80 mg / kg to 160 mg / kg), and the hind limbs were pressed to observe the pain response. After confirming deep anesthesia, a 1 × 1 cm area was marked on the back using a marker pen. 2The trauma surgery is completed when a square is drawn on the back of the mouse, the epidermis is lifted with forceps, and the epidermis on the back is cut according to the drawn rectangle. One week after the surgery, the experimental mice were subcutaneously injected daily (analgesic dose: 5 mg / kg), and the health condition of the mice after surgery was observed and recorded. After the surgery, the experimental mice were wrapped in artificial bandages (1.25 × 1.25 cm 2 The wounds were dressed and changed every 2 days, and the wound healing status was recorded. The dressings were changed for 4 weeks until the wounds were completely closed.

[0067] Example 8: Animal Studies - Wound Area Statistics

[0068] The wound images were imported into ImageJ software to estimate the area, and the scale bar in the image was used to correct and convert the pixel ratio of each image file, and the original skin morphology around the wound was considered as the boundary standard to circle the area of ​​the unhealed wound in the image, and the wound area was calculated, as shown in Figure 5.

[0069] Example 9: Animal Studies - Tissue Sections

[0070] It takes about 30 days from the completion of the incision surgery to healing and closure of the experimental mice. After the mice were sacrificed, skin tissue was taken from the new area of ​​the wound, embedded and stained, and stained with hematoxylin-eosin (H&E), and H&E pathological sections were prepared to observe the difference between the new epidermal tissue and the original epidermal tissue. In the H&E sections, new epidermis and proliferated fibroblasts were observed, and the following three points are used as criteria to judge the degree of wound bed healing: (1) Fibroblasts can synthesize and secrete collagen, so the degree of wound bed recovery can also be judged by the difference in collagen compactness. The higher the compactness, the more complete the wound healing. (2) The representative cell of acute inflammation is polymorphonuclear leukocytes (neutrophils). During acute inflammation, cells die quickly, and at this time, polymorphonuclear leukocytes enter the inflamed tissue and phagocytose necrotic cells and bacteria, so if polymorphonuclear leukocytes are seen in the sectioned tissue, it indicates that the wound is in the acute inflammatory stage. And (3) representative cells of chronic inflammation are monocytes and lymphocytes. Chronic inflammation has a barrier effect against lesions, but long-term chronic inflammation can cause connective tissue hyperplasia. If monocytes and lymphocytes are seen in the section, it indicates that the wound is in the chronic inflammatory stage. If fibrous connective tissue granuloma appears, it is the result of long-term chronic inflammation.

[0071] The experiment was divided into several groups, and a commercially available collagen foam dressing was used as the experimental control group. The groups are shown in Table 4. In addition to comparing with the control group, to understand the difference between dry and wet dressing and the optimal method of using the artificial dressing, the dressing in group D was moistened in advance to observe the results of wound healing.

[0072] Table 4. Experimental group division

[0073] [Table 4]

[0074] Table 5. Wound healing rate, standard deviation, and coefficient of variation (%) from 0 to 23 days.

[0075] [Table 5]

[0076] Figure 6 shows that the wound areas of groups A to D are all approaching healing by the 23rd day. The wound healing rate, standard deviation, and coefficient of variation calculated based on Figure 6 are shown in Table 5. The wound healing rate is the percentage of the wound area that closes within each period, and the standard deviation and coefficient of variation indicate the degree of change in the wound healing rate. The smaller the standard deviation and coefficient of variation, the smaller the change in the wound healing rate, indicating that the wound healing rate of this group is relatively stable, and a stable wound healing rate promotes wound healing. The coefficients of variation of the no-bandage group and the moist artificial bandage group (groups A and D) are similar, indicating that the stability of the wound healing rate of the moist artificial bandage group is similar to that of the no-bandage group. Although the commercially available collagen bandage group (group B) had a fast initial wound healing rate, the overall coefficient of variation was the highest among the four groups, indicating that the wound healing process was unstable. The group that received the dry artificial dressing (group C) had the smallest coefficient of variation among the four groups, suggesting that the wound was the most stable in the healing stage and had the best prognosis.

[0077] Example 10: Animal experiments - Analysis of tissue section results

[0078] The results of histological sections from the undressed group (Group A) are shown in Figure 7. There was fibrosis in the wound bed, proliferated granulation tissue on the surface, and polymorphonuclear leukocytes deep in the tissue, indicating that the wound was still in the acute inflammatory stage.

[0079] The results of histological sections of the commercial dressing group (group B) are shown in Figure 8. Although there was fibrosis in the wound bed, the structure was relatively loose, there was still granulation tissue on the surface, and there were polymorphonuclear leukocytes deep in the tissue, indicating that the wound was still in the acute inflammatory stage.

[0080] The results of tissue sections from the artificial bandage dry application group (group C) are shown in Figure 9. The wound bed had prominent pale pink fibroblast and collagen tissue, the wound was fibrotic and had a dense structure, but no inflammatory reaction such as leukocytes was observed, the skin surface was intact, and some newly formed functional tissue and blood vessels were also observed, suggesting that the wound had reached the late proliferation and remodeling stages.

[0081] The results of tissue sections from the group with the wet artificial dressing (group D) are shown in Figure 10. Mild fibrosis and granulation tissue were observed in the wound bed, and functional tissue proliferation of the skin was also observed. Distribution of mononuclear cells was observed under the wound bed, and the wound was presumed to be in the late stage of inflammation.

[0082] Combining the results of wound healing and tissue sections, the internal tissues of the no-bandage group (group A) and commercial bandage group (group B) were still in the acute inflammatory stage, the fibrotic tissue structure was relatively loose, and there was granulation tissue on the surface, which was relatively prone to scarring. In the artificial bandage dry-applied group (group C), there was no inflammatory reaction in the internal tissues, and some newly formed functional tissues and blood vessels could also be observed. The fibrotic tissue structure of the wound was dense, the skin surface was intact, and no scars were formed.

[0083] When comparing the wound healing status of the wet and dry artificial bandage groups (groups C and D), the dry artificial bandage group (group C) showed a faster wound healing rate because the bandage itself absorbed the tissue, while the wet artificial bandage group (group D) showed more new structural tissue and blood vessels. The reason for this was presumed to be that chronic inflammatory responses promote the formation of new functional tissue and new blood vessels in the skin.

[0084] The results of the tissue sections are consistent with those in Table 5. In Table 5, the artificial bandage dry patch group (group C) has the smallest coefficient of variation and the most stable wound healing rate. Compared with the section results in Figure 9, the artificial bandage dry patch group (group C) has the best condition after healing. In the commercially available bandage group (group B), the initial wound healing rate is fast, but the overall coefficient of variation is the highest. Comparing the cross-sectional results in Figure 8, the wound surface has granulation tissue formed, but the deep tissue is still in the acute inflammation stage, indicating that the wound has not fully healed. In order to promote wound healing, in addition to a stable healing rate, fibrous tissue with a dense structure is also required, so the artificial bandage of the present invention meets the above perspective and can promote wound healing.

[0085] Example 11: Method of using the artificial bandage

[0086] According to the experimental results, the best way to use the artificial bandage of the present invention is as follows: In the early stage of wound healing, the artificial bandage was directly applied dry to promote the growth of fibroblasts and collagen. In the later stage of wound healing, the tissue fluid was relatively reduced, so the artificial bandage was moistened by adding a small amount of water to promote the functional tissue and angiogenesis of the epidermis, and the wound was most completely cared for. The artificial bandage of the present invention is a composition used for moist wound healing, which contains gelatin, polysorbate-20, and glutaraldehyde, and the composition (1) absorbs tissue fluid of the wound, (2) inhibits the growth of granulation tissue of the wound, (4) reduces inflammation of the wound, (4) promotes angiogenesis in the wound tissue, and (5) reduces adhesion to the wound, thereby promoting wound healing. Among them, the above wounds include, but are not limited to, bruises, knife wounds, general acute wounds, first-degree / second-degree burns, surgical wounds, bedsores, and ulcers.

[0087] In summary, the artificial dressing, its use for promoting wound healing and the method of manufacture of the present invention have the following advantages:

[0088] (1) The artificial bandage of the present invention has clear pores and can absorb about 25 to 35 times its own weight in liquid. In thermal collapse experiments and application tests, no collapse was observed.

[0089] (2) The artificial dressing of the present invention can promote wound healing when applied dry, and can promote the growth of functional tissue within the wound when applied wet.

[0090] (3) The artificial bandage of the present invention is significantly cheaper than conventional moist wound healing methods and conventional bandages, and the artificial bandage of the present invention has a wider range of uses.

[0091] (4) The artificial dressing of the present invention can absorb tissue fluids in wounds, inhibit the proliferation of granulation tissue in wounds, promote angiogenesis in wound tissues, and promote wound healing.

[0092] The above is merely illustrative and not limiting. Any equivalent modifications or variations that do not depart from the spirit and scope of the present invention are intended to be included in the appended patent scope. [Explanation of symbols]

[0093] S10, S20, S30: Step

Claims

1. 1. An artificial dressing suitable for promoting wound healing, comprising: An artificial dressing comprising gelatin, polysorbate 20 (tween 20), and glutaraldehyde.

2. The artificial bandage according to claim 1, wherein the gelatin has a concentration of 5% (g / mL, w / v) to 10% (g / mL, w / v), the polysorbate 20 (tween 20) has a concentration of 0.005% (mL / mL, v / v) to 0.1% (mL / mL, v / v), and the glutaraldehyde has a concentration of 0.01% (mL / mL, v / v) to 0.3% (mL / mL, v / v).

3. The artificial bandage of claim 1, wherein the thickness of the artificial bandage is between 1 mm and 10 mm.

4. The artificial bandage according to claim 1, wherein the pore size of the artificial bandage is between 60 μm and 70 μm.

5. The artificial bandage of claim 1, wherein the porosity of the artificial bandage is between 60% and 67%.

6. The artificial bandage of claim 1 , wherein the wound includes, but is not limited to, bruises, knife wounds, general acute wounds, first / second degree burns, surgical wounds, bedsores and ulcers.

7. The artificial bandage of claim 1 , wherein the artificial bandage is in sheet form.

8. The artificial bandage according to claim 1 , which becomes gel-like by humidification or by absorbing tissue fluid.

9. The artificial bandage of claim 1, which is resistant to high-energy gamma radiation exposure doses (15 kGy to 25 kGy) without affecting texture or function.

10. 2. A method for producing an artificial bandage according to claim 1, comprising the steps of: Step (1) of mixing gelatin, glutaraldehyde, and polysorbate-20 to form a mixture, and stirring to foam the mixture; After the mixing and foaming step is completed, a molding step is performed in which the mixture is poured into a mold and spread evenly. and (3) performing a freeze-drying step by placing the mold in a freeze-dryer to freeze and dry the mold to form an artificial dressing.

11. The method of claim 10, wherein the concentration of the gelatin is from 5% (w / v) to 10% (w / v).

12. 11. The method of claim 10, wherein the concentration of polysorbate-20 is from 0.005% (v / v) to 0.1% (v / v).

13. 11. The method of claim 10, wherein the concentration of glutaraldehyde is from 0.01% (v / v) to 0.3% (v / v).

14. 13. A method of using a composition to promote wound healing comprising applying the artificial dressing of claim 1 to a wound of a patient, said artificial dressing functioning as the composition.

15. The method of claim 14, wherein the composition is used for moist wound healing.

16. 1. Use of a composition for the manufacture of an artificial dressing for promoting wound healing, comprising: A use comprising the steps of providing a composition comprising gelatin, polysorbate-20, and glutaraldehyde, and subjecting said composition to a mixing, foaming, molding, and freeze-drying step.

17. 17. The use according to claim 16, wherein the composition has a gelatin concentration of 5% (g / mL, w / v) to 10% (g / mL, w / v), a polysorbate 20 (tween 20) concentration of 0.005% (mL / mL, v / v) to 0.1% (mL / mL, v / v), and a glutaraldehyde concentration of 0.01% (mL / mL, v / v) to 0.3% (mL / mL, v / v).

18. 17. The use of claim 16, wherein the composition promotes wound healing by: (1) absorbing tissue fluids in the wound; (2) inhibiting the growth of granulation tissue in the wound; (4) reducing inflammation in the wound; (4) promoting angiogenesis in the wound tissue; and (5) reducing adhesions to the wound.

19. 17. The use according to claim 16, wherein the wounds include bruises, knife wounds, general acute wounds, first / second degree burns, surgical wounds, bedsores and ulcers.

Images