A dressing for diabetic foot wound and preparation method thereof

Abstract

The present invention relates to a dressing for diabetic foot wound and a preparation method thereof, and belongs to the field of biomedical dressings. The dressing for diabetic foot wound of the present invention comprises a primary inner dressing layer, a secondary outer dressing layer and an external protective layer arranged in sequence; the primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, the shell layer is carboxymethyl cellulose sucrose octasulfate silver complex, and the core layer is polylactic acid sodium percarbonate complex; the secondary outer dressing layer is formed by pH-responsive oxygen-loaded hydrogel coated on one side of the primary inner dressing layer; the external protective layer is a bandage coated with a polyethylene glycol sodium bicarbonate complex. The dressing, through a multi-stage structure, plays a role in coordination, on the basis of ensuring that the dressing absorbs the exudate of the diabetic foot wound well, introduces a material and structure that can continuously provide oxygen, provides a moist and oxygen-rich environment for the diabetic foot wound, and is conducive to accelerating wound healing.

Description

Technical Field

[0001] The invention relates to the field of biomedical dressings, and in particular to a dressing for diabetic foot wounds and a preparation method thereof. Background Art

[0002] Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. It remains a major and serious public health problem. Diabetic foot ulcers are associated with impaired physical function, decreased quality of life, and increased utilization of healthcare resources. Approximately 18.6 million people worldwide are affected by diabetic foot ulcers each year. Difficulty in healing of skin wounds in patients with diabetic foot is a common skin complication. Neuropathy, secondary infection from trauma, and arterial occlusive disease are its main pathophysiological mechanisms. Due to its complex pathogenesis and high infection rates caused by pathogenic bacteria such as Staphylococcus aureus and hemolytic Streptococcus, it greatly increases the difficulty and cost of treatment, and seriously affects the health and comfort of patients.

[0003] Oxygen plays a core role in the wound healing process. In the early stages of wound healing, the low oxygen environment of the wound tissue is an important stimulus for the secretion of multiple cytokines and angiogenesis, but in the subsequent stages, high oxygen often plays a more important role. For diabetic wounds, the oxygen partial pressure in the injured area is low, which prevents the key steps of healing such as collagen and angiogenesis from proceeding normally, and the wound does not heal for a long time.

[0004] Therefore, how to innovate the design of dressings, introduce materials and structures that can continuously provide oxygen while ensuring good absorption of exudate by the dressings, so that the diabetic foot dressing can improve local tissue hypoxia while ensuring the moisture of the wound surface, has become a direction that needs to be focused on. Summary of the invention

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a dressing for diabetic foot wounds and a preparation method thereof, aiming to solve the problem that the oxygen partial pressure in the local area of ​​diabetic wound damage is low, the fluid absorption effect is poor and there is a lack of oxygen supply, which makes it impossible for key healing steps such as collagen and angiogenesis to proceed normally, and the wound does not heal for a long time.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a dressing for diabetic foot wounds, comprising a primary inner dressing layer, a secondary outer dressing layer and an outer protective layer arranged in sequence; the primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, in which the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex, and the core layer is a polylactic acid-sodium percarbonate complex; the secondary outer dressing layer is formed by coating a pH-responsive oxygen-loaded hydrogel (also referred to as a "secondary outer dressing mixture") on one side of the primary inner dressing layer, and the pH-responsive oxygen-loaded hydrogel is coated on the secondary outer dressing mixture. The aerogel (secondary outer dressing mixture) includes a hydrogel matrix and an oxygen-carrying mesoporous material loaded in the hydrogel matrix; the hydrogel matrix includes olefin dibasic acid, acrylamide substances, olefin quaternary ammonium salt substances and N,N-methylenebisacrylamide; the oxygen-carrying mesoporous material is obtained by mixing a mesoporous material with tetradecafluorohexane, ultrasonically treating the mixture and filling it with oxygen; the outer protective layer is a bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the outer protective layer is compounded with the secondary outer dressing layer (the side away from the primary inner dressing layer) through the polyethylene glycol-sodium bicarbonate complex.

[0008] The dressing for diabetic foot wounds of the present invention comprises nano core-shell structured fibers prepared by coaxial electrospinning as a primary inner dressing layer, a coated pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) as a secondary outer dressing layer, and a bandage coated with a polyethylene glycol-sodium bicarbonate complex as an external protective layer. The multi-level structure works synergistically, and on the basis of ensuring that the dressing absorbs the exudate of the diabetic foot wound well, materials and structures that can continuously provide oxygen are introduced to provide a moist and oxygen-rich environment for the diabetic foot wound, which is conducive to accelerating wound healing.

[0009] The primary inner dressing layer has nano core-shell structure fibers, and the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex. The carboxymethyl cellulose in the carboxymethyl cellulose-sucrose octasulfate silver complex can form a gel on the surface of the diabetic foot wound, effectively absorb exudate, and prevent the exudate from flowing back. While maintaining a moist environment, it also plays a role in isolating bacteria and resisting infection. The sucrose octasulfate silver in the carboxymethyl cellulose-sucrose octasulfate silver complex will be released during the process of the primary inner dressing layer absorbing the exudate, and will contact the diabetic foot wound, thereby reducing the activity of matrix metalloproteinases, stabilizing growth factors, and preventing them from being degraded by matrix metalloproteinases, thereby reducing the wound healing time. The core layer is a polylactic acid-sodium percarbonate complex. The polylactic acid in the polylactic acid-sodium percarbonate complex will gradually degrade during the use of the dressing on diabetic foot wounds, exposing the sodium percarbonate. After the sodium percarbonate comes into contact with the exudate absorbed by the shell layer, it can slowly decompose and release oxygen near the wound. The oxygen release improves the re-epithelialization and structure of the epidermis and dermis in the healing skin tissue, thereby promoting wound healing.

[0010] The hydrogel matrix of the secondary outer dressing layer can be cross-linked to form a hydrogel network structure, effectively adsorb exudate, and improve the average liquid absorption rate of the material as a whole. A large amount of oxygen is dissolved in tetradecafluorohexane in the oxygen-carrying mesoporous material. As an oxygen carrier, it has good biocompatibility and high oxygen affinity. The tetradecafluorohexane that carries oxygen is combined with the mesoporous material to construct an oxygen release switch, which can accurately control the release of oxygen. The secondary outer dressing layer can achieve continuous supply of oxygen through pH response. When the secondary outer dressing layer is in weak alkaline conditions, the carboxyl groups in the hydrogel network structure are ionized under alkaline conditions, resulting in an increase in repulsion in the hydrogel network structure in the secondary outer dressing layer, and the hydrogel network is changed from a tight hydrogel network to a loose and porous network structure, which is conducive to the release of oxygen by tetradecafluorohexane in the oxygen-carrying mesoporous material, and the continuous supply of oxygen by the secondary outer dressing layer is achieved through pH response.

[0011] In order to facilitate the continuous supply of oxygen to the secondary outer dressing layer through pH response, the present invention is cleverly designed to composite a bandage coated with a polyethylene glycol-sodium bicarbonate complex as an external protective layer on the secondary outer dressing layer. On the one hand, the bandage can provide mechanical protection for the diabetic foot wound and maintain the dressing fixed. On the other hand, the polyethylene glycol in the polyethylene glycol-sodium bicarbonate complex has good adhesion, which can well adhere the bandage to the secondary outer dressing layer to play a protective role; at the same time, the sodium bicarbonate in the polyethylene glycol-sodium bicarbonate complex absorbs water to create a weakly alkaline environment, promote the secondary outer dressing layer to form a loose and porous network structure, and promote the release of oxygen.

[0012] In summary, the dressing for diabetic foot wounds described in the present invention works together through the primary inner dressing layer, the secondary outer dressing layer and the external protective layer, and utilizes continuous oxygen delivery to regulate cell proliferation, migration and new blood vessel formation, and can form a gel on the surface of the diabetic foot wound, effectively absorb exudate, prevent the exudate from flowing back, and maintain a moist environment.

[0013] Furthermore, the pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) also includes a cationic antibacterial drug, and the cationic antibacterial drug is polyhexamethyleneguanidine hydrochloride. Polyhexamethyleneguanidine hydrochloride can provide antibacterial properties.

[0014] Furthermore, the hydrogel matrix also includes an initiator and an accelerator. Preferably, the initiator is ammonium persulfate; the accelerator is tetramethylethylenediamine. Adding the initiator and the accelerator is helpful to accelerate the formation of the hydrogel network structure.

[0015] Preferably, in the hydrogel matrix, the olefin dibasic acid is itaconic acid, the acrylamide substance is acrylamide, and the olefin quaternary ammonium salt substance is allyltrimethylammonium chloride. Itaconic acid, acrylamide, allyltrimethylammonium chloride, and N,N'-methylenebisacrylamide can be cross-linked under the action of an initiator and a promoter to form a hydrogel network structure.

[0016] Preferably, the oxygen-carrying mesoporous material is oxygen-carrying mesoporous silica, and the mesoporous material is mesoporous silica. The present invention preferably uses mesoporous silica to make oxygen-carrying mesoporous silica as the oxygen-carrying mesoporous material. Of course, those skilled in the art can also select other oxygen-carrying mesoporous materials or other mesoporous materials according to actual needs.

[0017] A second aspect of the present invention provides a method for preparing any of the above-mentioned dressings for diabetic foot wounds, comprising the following steps:

[0018] S1: using carboxymethyl cellulose-sucrose octasulfate silver composite solution as the shell layer spinning solution and polylactic acid-sodium percarbonate composite solution as the core layer spinning solution, obtaining nano core-shell structure fibers by coaxial electrospinning, and drying to obtain a primary inner dressing layer;

[0019] S2: coating the pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer obtained in S1, and after drying, forming a secondary outer dressing layer on one side of the primary inner dressing layer, thereby obtaining a two-stage composite dressing;

[0020] S3: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the bandage, and then compounding one side of the secondary outer dressing layer in the two-stage composite dressing obtained in S2 with the side of the bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and obtaining the dressing for diabetic foot wounds after drying.

[0021] Furthermore, the preparation method of the carboxymethyl cellulose-sucrose octasulfate silver composite solution is as follows: 8-12 parts by weight of sodium sucrose octasulfate is dissolved in 120-180 parts by weight of deionized water, and eluted by ion exchange resin to obtain a sucrose octasulfate acidic solution; 16-24 parts by weight of sodium carboxymethyl cellulose is dissolved in 160-240 parts by weight of deionized water to obtain a sodium carboxymethyl cellulose solution; 0.8-1.2 parts by weight of silver nitrate is dissolved in 160-240 parts by weight of deionized water to obtain a silver nitrate solution; 25-35 parts by weight of sucrose octasulfate acidic solution, 45-55 parts by weight of sodium carboxymethyl cellulose solution, and 5-15 parts by weight of silver nitrate solution are mixed, and the pH is adjusted to 12 and then reacted to obtain the carboxymethyl cellulose-sucrose octasulfate silver composite solution.

[0022] As a preferred scheme of the above scheme, the preparation method of the carboxymethyl cellulose-sucrose octasulfate silver composite solution is as follows: weigh 10 parts by weight of sodium sucrose octasulfate and dissolve it in 150 parts by weight of deionized water, elute it through IR-120H ion exchange resin, and collect the eluate to obtain a sucrose octasulfate acidic solution; weigh 20 parts by weight of sodium carboxymethyl cellulose and add it to 200 parts by weight of deionized water, stir it magnetically at a temperature of 50°C for 8 hours, and cool it to room temperature to obtain a sodium carboxymethyl cellulose solution; weigh 1 part by weight of silver nitrate solid and dissolve it in 200 parts by weight of deionized water, and fully dissolve it to obtain a silver nitrate solution; mix 30 parts by weight of sucrose octasulfate acidic solution, 50 parts by weight of sodium carboxymethyl cellulose solution, and 10 parts by weight of silver nitrate solution, then add 1 mol / L sodium hydroxide solution to adjust the pH to 12, and then react at a temperature of 60°C for 1 hour to obtain a carboxymethyl cellulose-sucrose octasulfate silver composite solution.

[0023] Furthermore, the preparation method of the polylactic acid-sodium percarbonate composite solution is: adding 16-24 parts by weight of polylactic acid and 8-12 parts by weight of sodium percarbonate into 80-120 parts by weight of dichloromethane, and stirring to obtain the polylactic acid-sodium percarbonate composite solution.

[0024] As a preferred scheme of the above scheme, the preparation method of the polylactic acid-sodium percarbonate composite solution is: add 20 parts by weight of polylactic acid and 10 parts by weight of sodium percarbonate into 100 parts by weight of dichloromethane, and stir magnetically at room temperature for 12 hours to obtain the polylactic acid-sodium percarbonate composite solution.

[0025] Furthermore, in S1, the conditions for coaxial electrospinning are: the syringe propulsion speed of the shell layer spinning solution is 0.5-1.0 ml / h, the syringe propulsion speed of the core layer spinning solution is 0.1-0.3 ml / h, the needle voltage is 18-25 kv, the receiving distance is 15-18 cm, the temperature is 30-40 ° C, the humidity is 35-45%, and the spinning time is 1-2 h.

[0026] Furthermore, the preparation method of the pH responsive oxygen-loaded hydrogel (secondary outer dressing mixed solution) is as follows: 8-12 parts by weight of olefin dibasic acid are added to 240-360 parts by weight of a strong alkaline solution with a mass concentration fraction of 1.5-2.0% for treatment; then 40-60 parts by weight of oxygen-carrying mesoporous material, 40-60 parts by weight of acrylamide substances, 16-24 parts by weight of olefin quaternary ammonium salt substances, 0.32-0.48 parts by weight of N,N'-methylenebisacrylamide (0.48-0.72 parts by weight of initiator, 0.24-0.36 parts by weight of promoter, and 0.16-0.24 parts by weight of cationic antibacterial drugs may also be added), and the pH responsive oxygen-loaded hydrogel (secondary outer dressing mixed solution) is obtained by ultrasonic oscillation reaction.

[0027] As a preferred scheme of the above scheme, the preparation method of the pH responsive oxygen-loaded hydrogel (secondary outer dressing mixture) is as follows: 10 parts by weight of itaconic acid are added to 300 parts by weight of a sodium hydroxide solution with a mass concentration of 1.7%, and the mixture is treated in an ice water bath for 1 hour, and then 50 parts by weight of oxygen-loaded mesoporous silica, 50 parts by weight of acrylamide, 20 parts by weight of allyltrimethylammonium chloride, 0.4 parts by weight of N,N'-methylenebisacrylamide, 0.6 parts by weight of ammonium persulfate, 0.3 parts by weight of tetramethylethylenediamine, and 0.2 parts by weight of polyhexamethyleneguanidine hydrochloride are added, and the mixture is reacted by ultrasonic oscillation for 0.5 hours to uniformly disperse the mixture to obtain the pH responsive oxygen-loaded hydrogel (secondary outer dressing mixture).

[0028] Furthermore, the preparation method of the oxygen-carrying mesoporous material is: 80-120 parts by weight of the mesoporous material is transferred into a container, 100-150 parts by weight of tetradecafluorohexane is added for ultrasound after vacuuming; 100-120 parts by weight of PBS buffer is added for ultrasound, and then 150-200 parts by weight of oxygen is filled and vacuum freeze-dried to obtain the oxygen-carrying mesoporous material.

[0029] As a preferred solution of the above scheme, the oxygen-carrying mesoporous material is oxygen-carrying mesoporous silica, and the preparation method of the oxygen-carrying mesoporous silica is as follows: 100 parts by weight of mesoporous silica is transferred into a rubber stopper bottle, 150 parts by weight of tetradecafluorohexane is added after vacuuming, and ultrasonicated for 0.5 hours, and then 120 parts by weight of PBS buffer is added and ultrasonicated for 0.5 hours, and then 200 parts by weight of oxygen is filled into the solution, and vacuum freeze-dried to obtain oxygen-carrying mesoporous silica. Tetradecafluorohexane can dissolve a large amount of oxygen, and as an oxygen carrier, it has good biocompatibility and high oxygen affinity. The tetradecafluorohexane carrying oxygen is combined with mesoporous silica to construct an oxygen release switch, which can accurately control the release of oxygen.

[0030] As a preferred scheme of the above scheme, the preparation method of the mesoporous silica is as follows: 20 parts by weight of hexadecyltrimethylammonium chloride and 1 part by weight of triethanolamine are dissolved in 200 parts by weight of deionized water, heated and stirred to 95°C, then 20 parts by weight of tetraethyl orthosilicate and 10 parts by weight of bis-[3-(triethoxysilyl)propyl]-tetrasulfide are added, stirring is continued for 4 hours, centrifuged, washed with water, and washed with alcohol to obtain mesoporous silica. Tetraethyl orthosilicate is hydrolyzed in an alkaline aqueous solution, and an inner mesoporous structure is assembled using micelles as templates, and bis-[3-(triethoxysilyl)propyl]-tetrasulfide is added as a pore expander, and the pore expander continues to self-assemble to form micelles, and the hydrolysis product of tetraethyl orthosilicate will assemble using the micelles as templates to form an outer mesoporous structure.

[0031] Furthermore, the preparation method of the polyethylene glycol-sodium bicarbonate composite liquid comprises: dissolving 16-24 parts by weight of polyethylene glycol in 80-120 parts by weight of chloroform, adding 8-12 parts by weight of sodium bicarbonate, stirring and dispersing the mixture uniformly to obtain the polyethylene glycol-sodium bicarbonate composite liquid.

[0032] As a preferred scheme of the above scheme, the preparation method of the polyethylene glycol-sodium bicarbonate composite liquid is: dissolving 20 parts by weight of polyethylene glycol in 100 parts by weight of chloroform, and after sufficient dissolution, adding 10 parts by weight of sodium bicarbonate, stirring and dispersing evenly to obtain the polyethylene glycol-sodium bicarbonate composite liquid.

[0033] Furthermore, the drying temperature in S1 is 40-60°C, and the drying time is 4-8h; the drying temperature in S2 is 50-70°C, and the time is 2-4h; the drying temperature in S3 is 40-50°C, and the time is 24-48h.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] (1) In the dressing for diabetic foot wounds of the present invention, the sodium percarbonate in the primary inner dressing layer can slowly decompose and release oxygen near the wound after coming into contact with the exudate, and the external protective layer can create a weak alkaline environment by absorbing water through sodium bicarbonate, thereby promoting the secondary outer dressing to form a loose and porous network structure in the weak alkaline environment, and continuously provide oxygen through pH response. The primary inner dressing, the secondary outer dressing and the external protective layer work together to regulate cell proliferation, migration and new blood vessel formation at the diabetic foot wound by continuously delivering oxygen.

[0036] (2) In the dressing for diabetic foot wounds of the present invention, the carboxymethyl cellulose in the primary inner dressing layer can form a gel on the surface of the diabetic foot wound, effectively absorb exudate, prevent the exudate from flowing back, and maintain a moist environment. At the same time, the hydrogel network structure of the secondary outer dressing layer can also effectively absorb exudate, thereby increasing the average liquid absorption rate of the entire material. DETAILED DESCRIPTION

[0037] For the convenience of understanding the present invention, the present invention lists the following embodiments. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0038] The sources of some components in the following examples and comparative examples are as follows:

[0039] Preparation of carboxymethyl cellulose-sucrose octasulfate silver composite solution: weigh 10 parts by weight of sodium sucrose octasulfate (CAS No. 74135-10-7) and dissolve it in 150 parts by weight of deionized water, elute it through IR-120H ion exchange resin (purchased from Rohm and Haas Company), collect the eluate to obtain sucrose octasulfate acidic solution; weigh 20 parts by weight of sodium carboxymethyl cellulose (CAS No. 9004-32-4) and add it to 200 parts by weight of deionized water, stir it magnetically at 50°C for 8 hours, and cool it down. The mixture was cooled to room temperature to obtain a sodium carboxymethyl cellulose solution; 1 part by weight of solid silver nitrate (CAS No. 7761-88-8) was weighed and dissolved in 200 parts by weight of deionized water to fully dissolve to obtain a silver nitrate solution; 30 parts by weight of sucrose octasulfate acid solution, 50 parts by weight of sodium carboxymethyl cellulose solution and 10 parts by weight of silver nitrate solution were mixed, and 1 mol / L sodium hydroxide solution was added to adjust the pH to 12, and then reacted at 60° C. for 1 hour to obtain a carboxymethyl cellulose-sucrose octasulfate silver composite solution.

[0040] Preparation of carboxymethyl cellulose solution: Weigh 20 parts by weight of carboxymethyl cellulose (CAS No. 9000-11-7) and add it to 200 parts by weight of deionized water, stir it with magnetic force at 50° C. for 8 hours, and cool it to room temperature to obtain a sodium carboxymethyl cellulose solution.

[0041] Preparation of polylactic acid-sodium percarbonate composite solution: 20 parts by weight of polylactic acid (purchased from Shenzhen Boli Biomaterials Co., Ltd., model PLLA-25) and 10 parts by weight of sodium percarbonate (CAS No. 15630-89-4) were added to 100 parts by weight of dichloromethane (CAS No. 75-09-2), and magnetic stirring was carried out at room temperature for 12 hours to obtain a polylactic acid-sodium percarbonate composite solution.

[0042] Preparation of polylactic acid solution: 20 parts by weight of polylactic acid (purchased from Shenzhen Boli Biomaterial Co., Ltd., model PLLA-25) were added to 100 parts by weight of dichloromethane (CAS No. 75-09-2), and magnetically stirred at room temperature for 12 hours to obtain a polylactic acid solution.

[0043] Preparation of mesoporous silica: 20 parts by weight of hexadecyltrimethylammonium chloride (CAS No. 112-02-7) and 1 part by weight of triethanolamine (CAS No. 102-71-6) were dissolved in 200 parts by weight of deionized water, heated and stirred to 95°C, and then 20 parts by weight of ethyl orthosilicate (CAS No. 78-10-4) and 10 parts by weight of bis-[3-(triethoxysilyl)propyl]-tetrasulfide (CAS No. 40372-72-3) were added, and stirring was continued for 4 hours, centrifuged, washed with water, and washed with alcohol to obtain mesoporous silica.

[0044] Preparation of oxygen-loaded mesoporous silica: 100 parts by weight of mesoporous silica was transferred into a rubber stopper bottle, and after evacuation, 150 parts by weight of tetradecafluorohexane (CAS No. 355-42-0) was added and ultrasonicated for 0.5 h, and then 120 parts by weight of PBS buffer (purchased from Beijing Solebow Technology Co., Ltd.) was added and ultrasonicated for 0.5 h. After the ultrasonication was completed, 200 parts by weight of oxygen (purchased from Shenzhen Yuejia Gas Co., Ltd., 98% purity) was slowly filled into the solution, and vacuum freeze-dried to obtain oxygen-loaded mesoporous silica.

[0045] Preparation of pH responsive oxygen-loaded hydrogel (secondary outer dressing mixture): 10 parts by weight of itaconic acid (CAS No. 97-65-4) were added to 300 parts by weight of a sodium hydroxide solution with a mass concentration of 1.7%, and the mixture was treated in an ice water bath for 1 hour. Then, 50 parts by weight of oxygen-loaded mesoporous silica, 50 parts by weight of acrylamide (CAS No. 79-06-1), 20 parts by weight of allyltrimethylammonium chloride (CAS No. 1516-27-4), 0.4 parts by weight of N,N'-methylenebisacrylamide (CAS No. 110-26-9), 0.6 parts by weight of ammonium persulfate (CAS No. 7727-54-0), 0.3 parts by weight of tetramethylethylenediamine (CAS No. 110-18-9), and 0.2 parts by weight of polyhexamethyleneguanidine hydrochloride (CAS No. 57028-96-3) were added, and the mixture was reacted by ultrasonic oscillation for 0.5 hours to uniformly disperse the pH responsive oxygen-loaded hydrogel (secondary outer dressing mixture).

[0046] Preparation of polyethylene glycol-sodium bicarbonate composite liquid: 20 parts by weight of polyethylene glycol (CAS No. 25322-68-3) is dissolved in 100 parts by weight of chloroform (CAS No. 67-66-3). After fully dissolved, 10 parts by weight of sodium bicarbonate (CAS No. 144-55-8) is added, and the polyethylene glycol-sodium bicarbonate composite liquid is obtained after stirring and dispersing evenly.

[0047] Medical bandage: purchased from Hai's Heinuo.

[0048] Example 1

[0049] The present embodiment provides a dressing for diabetic foot wounds, comprising a primary inner dressing layer, a secondary outer dressing layer and an external protective layer arranged in sequence. The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, in which the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex and the core layer is a polylactic acid-sodium percarbonate complex; the secondary outer dressing layer is formed by coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer; the external protective layer is a medical bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the external protective layer is compounded with the side of the secondary outer dressing layer away from the primary inner dressing layer through the polyethylene glycol-sodium bicarbonate complex.

[0050] This embodiment also provides a method for preparing a dressing for diabetic foot wounds, comprising the following steps:

[0051] Step S1: using carboxymethyl cellulose-sucrose octasulfate silver composite solution as shell layer spinning solution, using polylactic acid-sodium percarbonate composite solution as core layer spinning solution, controlling the syringe propulsion speed of the shell layer spinning solution to be 1.0 ml / h, the syringe propulsion speed of the core layer spinning solution to be 0.3 ml / h, the needle voltage to be 18 kv, the receiving distance to be 18 cm, the temperature to be 40° C., the humidity to be 35%, the spinning time to be 1 h, obtaining nano core-shell structure fibers by coaxial electrospinning, drying at 50° C. for 6 h, and obtaining a primary inner dressing layer;

[0052] Step S2: coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer in step S1, drying at 60° C. for 3 h, and forming a secondary outer dressing layer on one side of the primary inner dressing layer, thereby obtaining a two-stage composite dressing;

[0053] Step S3: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the medical bandage, and then compounding one side of the secondary outer dressing layer in the two-stage composite dressing obtained in step S2 with the side of the medical bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and drying at a temperature of 50° C. for 24 hours to obtain a dressing for diabetic foot wounds.

[0054] Example 2

[0055] The present embodiment provides a dressing for diabetic foot wounds, comprising a primary inner dressing layer, a secondary outer dressing layer and an external protective layer arranged in sequence. The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, in which the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex and the core layer is a polylactic acid-sodium percarbonate complex; the secondary outer dressing layer is formed by coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer; the external protective layer is a medical bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the external protective layer is compounded with the side of the secondary outer dressing layer away from the primary inner dressing layer through the polyethylene glycol-sodium bicarbonate complex.

[0056] This embodiment also provides a method for preparing a dressing for diabetic foot wounds, comprising the following steps:

[0057] Step S1: using carboxymethyl cellulose-sucrose octasulfate silver composite solution as shell layer spinning solution, using polylactic acid-sodium percarbonate composite solution as core layer spinning solution, controlling the syringe propulsion speed of the shell layer spinning solution to be 0.5 ml / h, the syringe propulsion speed of the core layer spinning solution to be 0.1 ml / h, the needle voltage to be 25 kv, the receiving distance to be 15 cm, the temperature to be 30° C., the humidity to be 45%, the spinning time to be 2 h, obtaining nano core-shell structure fibers by coaxial electrospinning, drying at 50° C. for 6 h, and obtaining a primary inner dressing layer;

[0058] Step S2: coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer in step S1, drying at 60° C. for 3 h, and forming a secondary outer dressing layer on one side of the primary inner dressing layer, thereby obtaining a two-stage composite dressing;

[0059] Step S3: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the medical bandage, and then compounding one side of the secondary outer dressing layer in the two-stage composite dressing obtained in step S2 with the side of the medical bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and drying at a temperature of 40° C. for 48 hours to obtain a dressing for diabetic foot wounds.

[0060] Example 3

[0061] The present embodiment provides a dressing for diabetic foot wounds, comprising a primary inner dressing layer, a secondary outer dressing layer and an external protective layer arranged in sequence. The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, in which the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex and the core layer is a polylactic acid-sodium percarbonate complex; the secondary outer dressing layer is formed by coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer; the external protective layer is a medical bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the external protective layer is compounded with the side of the secondary outer dressing layer away from the primary inner dressing layer through the polyethylene glycol-sodium bicarbonate complex.

[0062] This embodiment also provides a method for preparing a dressing for diabetic foot wounds, comprising the following steps:

[0063] Step S1: using carboxymethyl cellulose-sucrose octasulfate silver composite solution as shell layer spinning solution, using polylactic acid-sodium percarbonate composite solution as core layer spinning solution, controlling the syringe propulsion speed of the shell layer spinning solution to be 0.8 ml / h, the syringe propulsion speed of the core layer spinning solution to be 0.2 ml / h, the needle voltage to be 20 kv, the receiving distance to be 16 cm, the temperature to be 35° C., the humidity to be 40%, the spinning time to be 1.2 h, obtaining nano core-shell structure fibers by coaxial electrospinning, drying at 50° C. for 6 h, and obtaining a primary inner layer dressing;

[0064] Step S2: coating a pH-responsive oxygen-loaded hydrogel (secondary outer dressing mixture) on one side of the primary inner dressing layer in step S1, drying at 60° C. for 3 h, and forming a secondary outer dressing layer on one side of the primary inner dressing layer, thereby obtaining a two-stage composite dressing;

[0065] Step S3: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the medical bandage, and then compounding one side of the secondary outer dressing layer in the two-stage composite dressing obtained in step S2 with the side of the medical bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and drying at a temperature of 48° C. for 40 hours to obtain a dressing for diabetic foot wounds.

[0066] Comparative Example 1

[0067] This comparative example provides a composite dressing, comprising a primary inner dressing layer, a secondary outer dressing layer and an outer protective layer arranged in sequence, which is basically the same as Example 1, except that the shell layer is replaced with carboxymethyl cellulose and the core layer is replaced with polylactic acid.

[0068] The preparation method of the composite dressing of this comparative example is basically the same as that of Example 1, except that in this comparative example, the shell layer spinning solution is replaced by a carboxymethyl cellulose solution, and the core layer spinning solution is replaced by a polylactic acid solution.

[0069] Comparative Example 2

[0070] This comparative example provides a composite dressing, comprising a primary inner dressing layer, a secondary outer dressing layer and an outer protective layer arranged in sequence, which is basically the same as Example 1, except that the outer protective layer is a medical bandage and is not coated with a polyethylene glycol-sodium bicarbonate complex.

[0071] The preparation method of the composite dressing of this comparative example is basically the same as that of Example 1, except that in step S3 of this comparative example, the medical bandage is directly composited with one side of the secondary outer dressing layer in the two-stage composite dressing of step S2 without coating the polyethylene glycol-sodium bicarbonate composite liquid.

[0072] Comparative Example 3

[0073] The present comparative example provides a composite dressing, comprising a primary inner dressing layer and an outer protective layer arranged in sequence. The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, wherein the shell layer is carboxymethyl cellulose and the core layer is polylactic acid; the outer protective layer is a medical bandage, and the outer protective layer is bonded to the primary inner dressing layer.

[0074] A method for preparing a composite dressing in this comparative example comprises the following steps:

[0075] Step S1: using carboxymethyl cellulose solution as the shell layer spinning solution and polylactic acid solution as the core layer spinning solution, controlling the syringe pushing speed of the shell layer spinning solution to be 0.8 ml / h, the syringe pushing speed of the core layer spinning solution to be 0.2 ml / h, the needle voltage to be 20 kv, the receiving distance to be 16 cm, the temperature to be 35° C., the humidity to be 40%, the spinning time to be 1.2 h, obtaining nano core-shell structure fibers by coaxial electrospinning, drying at 50° C. for 6 h, and obtaining a primary inner dressing layer;

[0076] Step S2: Laminating the primary inner dressing layer obtained in step S1 with the medical bandage to obtain a composite dressing.

[0077] Comparative Example 4

[0078] The present comparative example provides a composite dressing, comprising a primary inner dressing layer and an outer protective layer arranged in sequence. The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, wherein the shell layer is carboxymethyl cellulose and the core layer is polylactic acid; the outer protective layer is a medical bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the outer protective layer is composited with the primary inner dressing layer through the polyethylene glycol-sodium bicarbonate complex.

[0079] A method for preparing a composite dressing in this comparative example comprises the following steps:

[0080] Step S1: using carboxymethyl cellulose solution as the shell layer spinning solution and polylactic acid solution as the core layer spinning solution, controlling the syringe pushing speed of the shell layer spinning solution to be 0.8 ml / h, the syringe pushing speed of the core layer spinning solution to be 0.2 ml / h, the needle voltage to be 20 kv, the receiving distance to be 16 cm, the temperature to be 35° C., the humidity to be 40%, the spinning time to be 1.2 h, obtaining nano core-shell structure fibers by coaxial electrospinning, drying at 50° C. for 6 h, and obtaining a primary inner dressing layer;

[0081] Step S2: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the medical bandage, and then laminating one side of the primary inner dressing layer obtained in step S1 with the side of the medical bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and drying at a temperature of 48° C. for 40 hours to obtain a composite dressing.

[0082] Comparative Example 5

[0083] This comparative example provides a composite dressing, comprising a primary inner dressing layer and an outer protective layer arranged in sequence, which is basically the same as comparative example 3, except that the shell layer is a carboxymethyl cellulose-sucrose octasulfate silver complex, and the core layer is a polylactic acid-sodium percarbonate complex.

[0084] This comparative example provides a method for preparing a composite dressing, which is basically the same as comparative example 3, except that in this comparative example, the shell layer spinning solution is replaced by a carboxymethyl cellulose-sucrose octasulfate silver composite solution, and the core layer spinning solution is replaced by a polylactic acid-sodium percarbonate composite solution.

[0085] Performance Testing

[0086] The dressings of Examples 1-3 and Comparative Examples 1-5 were respectively subjected to performance tests, and the test methods were as follows:

[0087] Liquid absorption property test: Take the dressing and weigh it to get its dry weight g1; then soak the dressing in a PBS solution at a constant temperature of 23±2℃ for 24 hours, take out the dressing, weigh it, and get its wet weight after liquid absorption g2; 24-hour average liquid absorption rate = .

[0088] Oxygen release concentration test: Soak the dressing in a PBS solution at a constant temperature of 23±2°C for 24 hours, and measure the dissolved oxygen content of the soaking solution with a dissolved oxygen meter (instrument name 550A, manufactured by YSI Company, USA), which is the oxygen release concentration of the dressing.

[0089] The above performance test data is shown in Table 1.

[0090] Table 1 Performance test results

[0091]

[0092] From the above content, it can be seen that the dressings for diabetic foot wounds of Examples 1-3 of the present invention use nano core-shell structured fibers prepared by coaxial electrospinning as the primary inner dressing layer, a coated pH-responsive oxygen-loaded hydrogel as the secondary outer dressing layer, and a medical bandage coated with a polyethylene glycol-sodium bicarbonate complex as the external protective layer to obtain a dressing for diabetic foot wounds, and the dressing has a 24-hour average liquid absorption rate of 0.311-0.317 g / g·hr, and a 24-hour oxygen release concentration of 15.6-15.8 mg / L.

[0093] Compared with the dressing for diabetic foot wounds of Example 1, the composite dressing of Comparative Example 1 does not use carboxymethyl cellulose-sucrose octasulfate silver composite solution as the shell layer spinning liquid, nor does it use polylactic acid-sodium percarbonate composite solution as the core layer spinning liquid. The liquid absorption rate of the composite dressing of Comparative Example 1 decreases, and the oxygen release concentration decreases.

[0094] Compared with the dressing for diabetic foot wounds of Example 1, the composite dressing of Comparative Example 2 does not use polyethylene glycol-sodium bicarbonate composite liquid in the external protective layer. Instead, the medical bandage is directly composited with the secondary outer dressing layer, and the oxygen release concentration of the composite dressing of Comparative Example 2 is reduced.

[0095] Compared with the dressing for diabetic foot wounds of Example 1, the composite dressing of Comparative Example 3 does not use carboxymethyl cellulose-sucrose octasulfate silver composite solution as the shell layer spinning solution in the primary inner dressing layer, and does not use polylactic acid-sodium percarbonate composite solution as the core layer spinning solution; in addition, the composite dressing of Comparative Example 3 does not include a secondary outer dressing layer, and the medical bandage is directly composited with the primary inner dressing layer; none of the layers in the composite dressing of Comparative Example 3 adopts the technical innovation of the present invention, and the composite dressing of Comparative Example 3 has an average liquid absorption rate of 0.054 g / g·hr in 24 hours, and an oxygen release concentration of 10.2 mg / L in 24 hours. Compared with the dressing for diabetic foot wounds of Example 1, the liquid absorption rate is significantly reduced, and the oxygen release concentration is significantly reduced.

[0096] Compared with the dressing for diabetic foot wounds of Example 1, the composite dressing of Comparative Example 4 uses a bandage coated with a polyethylene glycol-sodium bicarbonate complex as an external protective layer. Although it provides a weakly alkaline environment, the composite dressing of Comparative Example 4 lacks a secondary outer dressing layer. Compared with the dressing for diabetic foot wounds of Example 1, the oxygen release concentration is lower. Compared with the composite dressing of Comparative Example 3, the oxygen release concentration does not change significantly.

[0097] Compared with the dressing for diabetic foot wounds of Example 1, the composite dressing of Comparative Example 5 uses a carboxymethyl cellulose-sucrose octasulfate silver composite solution as the shell layer spinning solution, and a polylactic acid-sodium percarbonate composite solution as the core layer spinning solution. Although the composite dressing of Comparative Example 5 has an increased liquid absorption rate and an improved oxygen release concentration compared with the composite dressing of Comparative Example 3, the liquid absorption rate and oxygen release concentration are lower than those of the dressing for diabetic foot wounds of Example 1.

[0098] The dressing for diabetic foot wounds of the present invention works synergistically through a multi-level structure. On the basis of ensuring that the dressing has a good effect of absorbing exudate, materials and structures that can continuously provide oxygen are introduced to provide a moist and oxygen-rich environment for the diabetic foot wound, which is conducive to accelerating wound healing.

[0099] The above-mentioned embodiments only express several implementation methods of the present invention, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the invention patent. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, and the present invention is also intended to include these modifications and modifications.

Claims

1. A dressing for diabetic foot wounds, characterized in that: It includes a primary inner dressing layer, a secondary outer dressing layer and an outer protective layer which are arranged in sequence; The primary inner dressing layer is composed of nano core-shell structure fibers prepared by coaxial electrospinning, wherein the shell layer of the nano core-shell structure fibers is a carboxymethyl cellulose-sucrose octasulfate silver complex, and the core layer is a polylactic acid-sodium percarbonate complex; The secondary outer dressing layer is formed by coating a pH-responsive oxygen-loaded hydrogel on one side of the primary inner dressing layer, wherein the pH-responsive oxygen-loaded hydrogel comprises a hydrogel matrix and an oxygen-loaded mesoporous material loaded in the hydrogel matrix; the hydrogel matrix comprises an olefin dibasic acid, an acrylamide substance, an olefin quaternary ammonium salt substance and N,N-methylenebisacrylamide; the oxygen-loaded mesoporous material is obtained by mixing a mesoporous material with tetradecafluorohexane, ultrasonically treating the mixture and filling the mixture with oxygen; wherein the olefin dibasic acid is itaconic acid, the acrylamide substance is acrylamide, the olefin quaternary ammonium salt substance is allyltrimethylammonium chloride, the oxygen-loaded mesoporous material is oxygen-loaded mesoporous silica, and the mesoporous material is mesoporous silica; The outer protective layer is a bandage coated with a polyethylene glycol-sodium bicarbonate complex, and the outer protective layer is compounded with the secondary outer dressing layer through the polyethylene glycol-sodium bicarbonate complex.

2. The dressing for diabetic foot wound according to claim 1, characterized in that: The pH-responsive oxygen-loaded hydrogel further comprises a cationic antibiotic, and the cationic antibiotic is polyhexamethyleneguanidine hydrochloride.

3. The dressing for diabetic foot wound according to claim 1 or 2, characterized in that: The hydrogel matrix also includes an initiator and an accelerator; the initiator is ammonium persulfate, and the accelerator is tetramethylethylenediamine.

4. A method for preparing a dressing for diabetic foot wounds according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1: Using carboxymethyl cellulose-sucrose octasulfate silver composite solution as the shell layer spinning solution and polylactic acid-sodium percarbonate composite solution as the core layer spinning solution, nano core-shell structure fibers are obtained by coaxial electrospinning, and a primary inner dressing layer is obtained after drying; S2: coating the pH-responsive oxygen-loaded hydrogel on one side of the primary inner dressing layer obtained in S1, and forming a secondary outer dressing layer on one side of the primary inner dressing layer after drying, so as to obtain a two-stage composite dressing; S3: coating the polyethylene glycol-sodium bicarbonate composite liquid on one side of the bandage, and then compounding one side of the secondary outer dressing layer in the two-stage composite dressing obtained in S2 with the side of the bandage coated with the polyethylene glycol-sodium bicarbonate composite liquid, and obtaining the dressing for diabetic foot wounds after drying.

5. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: The preparation method of the carboxymethyl cellulose-sucrose octasulfate silver composite solution is as follows: 8-12 parts by weight of sodium sucrose octasulfate is dissolved in 120-180 parts by weight of deionized water, and eluted by ion exchange resin to obtain a sucrose octasulfate acidic solution; 16-24 parts by weight of sodium carboxymethyl cellulose is dissolved in 160-240 parts by weight of deionized water to obtain a sodium carboxymethyl cellulose solution; 0.8-1.2 parts by weight of silver nitrate is dissolved in 160-240 parts by weight of deionized water to obtain a silver nitrate solution; 25-35 parts by weight of sucrose octasulfate acidic solution, 45-55 parts by weight of sodium carboxymethyl cellulose solution, and 5-15 parts by weight of silver nitrate solution are mixed, and the pH value is adjusted to 12 and then reacted to obtain the carboxymethyl cellulose-sucrose octasulfate silver composite solution.

6. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: The preparation method of the polylactic acid-sodium percarbonate composite solution is as follows: 16-24 parts by weight of polylactic acid and 8-12 parts by weight of sodium percarbonate are added into 80-120 parts by weight of dichloromethane, and stirred to obtain the polylactic acid-sodium percarbonate composite solution.

7. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: In S1, the conditions for coaxial electrospinning are: the syringe propulsion speed of the shell layer spinning solution is 0.5-1.0 ml / h, the syringe propulsion speed of the core layer spinning solution is 0.1-0.3 ml / h, the needle voltage is 18-25 kv, the receiving distance is 15-18 cm, the temperature is 30-40 ° C, the humidity is 35-45%, and the spinning time is 1-2 h.

8. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: The preparation method of the pH responsive oxygen-loaded hydrogel is as follows: 8-12 parts by weight of olefin dibasic acid are added to 240-360 parts by weight of a strong alkaline solution with a mass concentration of 1.5-2.0% for treatment; then 40-60 parts by weight of oxygen-carrying mesoporous material, 40-60 parts by weight of acrylamide substances, 16-24 parts by weight of olefin quaternary ammonium salt substances, and 0.32-0.48 parts by weight of N,N'-methylenebisacrylamide are added, and the pH responsive oxygen-loaded hydrogel is obtained by ultrasonic oscillation reaction.

9. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: The preparation method of the oxygen-carrying mesoporous material is as follows: 80-120 parts by weight of the mesoporous material is transferred into a container, 100-150 parts by weight of tetradecafluorohexane is added for ultrasonication after vacuuming; 100-120 parts by weight of PBS buffer is added for ultrasonication, and then 150-200 parts by weight of oxygen is filled in and vacuum freeze-dried to obtain the oxygen-carrying mesoporous material.

10. The method for preparing a dressing for diabetic foot wounds according to claim 4, characterized in that: The preparation method of the polyethylene glycol-sodium bicarbonate composite liquid comprises: dissolving 16-24 parts by weight of polyethylene glycol in 80-120 parts by weight of chloroform, adding 8-12 parts by weight of sodium bicarbonate, stirring and dispersing the mixture to obtain the polyethylene glycol-sodium bicarbonate composite liquid.

Images