Hydrogel wound dressing and preparation method thereof

Abstract

The invention discloses a hydrogel wound dressing and a preparation method thereof, and relates to the technical field of wound dressing. The invention adjusts the formula of the hydrogel wound dressing so that it can be prepared at room temperature without using an extra container, and at the same time, by adding hydrophilic seaweed fiber, the toughness of the gel is improved, and the breakage, fracture and gel deficiency caused by insufficient gel strength are reduced.

Description

Technical Field

[0001] The invention relates to the technical field of wound dressing, and in particular to a hydrogel wound dressing and a preparation method thereof. Background Art

[0002] As a hydrophilic polymer with a three-dimensional network structure, hydrogel has shown broad application prospects in biomedicine, agriculture, environmental protection and other fields. Radiation synthesis is an important means of preparing hydrogels, mainly including direct irradiation solution and frozen irradiation solution. However, both methods face certain challenges in practical applications, which limit the preparation efficiency and performance of hydrogels. Among them, the direct irradiation solution method directly irradiates the hydrogel precursor solution to induce the cross-linking reaction of the polymer chain to form a hydrogel. It has the following problems: 1) Container dependence: plastic trays or molds are required to be used to hold the hydrogel precursor solution, and the sealing and stability of the container are required to prevent the hydrogel precursor solution from overflowing; 2) Transportation and packaging: high requirements for sealed packaging or smooth transportation increase logistics costs and operational complexity; 3) The hydrogel used in wound dressings without freezing cycles has the problem of poor gel toughness and easy damage and lack of gel, which affects the use effect. The frozen irradiation solution method is to freeze the hydrogel precursor solution and then irradiate it, and use the freezing environment to control the shape and structure of the hydrogel. The following problems exist: 1) Complex process: additional freezing, storage and transportation steps are required, which prolongs the manufacturing time; 2) Increased energy consumption: the freezing process and storage conditions consume more energy, which increases the preparation cost. In addition, the existing irradiated hydrogels, while pursuing a simple process, are difficult to ensure the ideal properties of high gel strength and high cross-linking degree.

[0003] In view of the shortcomings of the current irradiation process, it is urgent to produce hydrogels with higher strength while simplifying the process steps and optimizing the production conditions. Summary of the invention

[0004] The technical problem to be solved by the present invention is: to overcome the shortcomings of the prior art, to provide a hydrogel wound dressing and a preparation method thereof, and to enable the preparation of the hydrogel wound dressing to be completed at room temperature by adjusting the formula of the hydrogel wound dressing without the need for an extra container. At the same time, by adding hydrophilic seaweed fiber, the toughness of the gel is improved, and the breakage, fracture and gel deficiency caused by insufficient gel strength are reduced.

[0005] The technical solution of the present invention is:

[0006] In one aspect, the present invention provides a method for preparing a hydrogel wound dressing, wherein the hydrogel wound dressing has a three-layer structure, a gel layer in the middle and release layers on both sides, and the preparation method comprises the following steps:

[0007] S1: adding the cross-linked main body into water, heating and stirring to obtain a mixed aqueous solution;

[0008] S2: adding natural colloid into the mixed aqueous solution, heating and stirring to dissolve, and obtaining a uniform solution, wherein the natural colloid comprises gelatin and glycyrrhizic acid;

[0009] S3: adding seaweed fibers with a length of 65-85 mm into the uniform solution, maintaining the temperature, and stirring to make them dispersed evenly to obtain a dispersion;

[0010] S4: pouring the dispersion into the coating machine hopper, maintaining the temperature, and performing ultrasound to arrange the seaweed fibers in one direction and degas the dispersion;

[0011] S5: After cooling the dispersion, evenly coat the dispersion on the release layer to obtain a gel layer, and attach another release layer on the gel layer by a coating machine so that the release layer is sandwiched between the two release layers;

[0012] S6: Cutting, cleaning and drying after cooling;

[0013] S7: Continue 60 Co is irradiated by gamma rays to form a hydrogel wound dressing;

[0014] Calculated by weight, the added amount of the cross-linked main body is 5.5-7.5 parts, the added amount of water is 70.3-79.5 parts, the added amount of gelatin is 7-10 parts, the added amount of glycyrrhizic acid is 3-4.2 parts, and the added amount of seaweed fiber is 5-8 parts; the cross-linked main body includes 1.5-2.5 parts of polyvinyl alcohol 1799, 3.5-4.5 parts of polyvinyl pyrrolidone K90 and 0.5-1 part of polyacrylic acid.

[0015] Preferably, in steps S1 and S2, the stirring temperature is 75-85°C.

[0016] Preferably, in step S4, the ultrasonic frequency is 20-30 kHz, the ultrasonic time is 5-10 min, and the ultrasonic direction is along the discharge direction of the hopper.

[0017] Preferably, in step S5, the thickness of the gel layer is 1.9-2.1 mm, and the thickness of the release layer is 5-6 μm.

[0018] Preferably, in step S6, the cleaning is performed by soaking in purified water, the soaking time is 14-16 seconds, the drying temperature is 75-80° C., and the drying time is 6-7 minutes.

[0019] Preferably, in step S7, 60 The gamma ray irradiation dose of Co is 15-30 kGy.

[0020] In the preparation process, the cross-linking body should be dissolved before the natural colloid, because the natural colloid is easy to coagulate when dissolved, and as a condensed body, the viscosity of the natural colloid after dissolution is large, which is not suitable for further dissolution of other raw materials. When the two are not completely dissolved, they appear turbid, which can be used as a basis for whether they are completely dissolved. After complete dissolution, they will be a transparent liquid.

[0021] The cross-linking subject and the natural gum are the subjects of radiation cross-linking. After irradiation, the cross-linking subject will produce free radicals and cross-link with each other to form a hydrogel. Gelatin in natural gum is a natural gum that cools and solidifies. After being miscible with glycyrrhizic acid and cooled, it will produce molecular chain entanglement and cross-linking as well as hydrogen bond interactions, which makes gelatin and glycyrrhizic acid sufficient to form a high-strength and high-toughness gel. After the cross-linking subject is mixed with the natural gum and cooled and solidified, the cross-linking subject is only slightly entangled and cross-linked with the natural gum, and it is fixed in the gel by the natural gum; and during subsequent irradiation molding, the cross-linking subject will undergo free radical polymerization under high-energy ray irradiation, resulting in a chemical cross-linking reaction between the cross-linking subjects, and its own molecular weight will also be increased due to polymerization, so that the natural gum and the cross-linking subject form a stable and tough hydrogel.

[0022] In addition, through ultrasound, the seaweed fibers in the coating machine hopper are oriented and arranged in the dispersion along the direction of ultrasound. The seaweed fibers after ultrasound will be arranged in a directional manner. Since there is adhesion between the gel and the seaweed fibers, when external force is applied to the gel as a whole, the force will be transmitted to the seaweed fibers. The seaweed fibers have good toughness, so the gel and seaweed fibers form an overall composite material, which greatly improves the strength of the composite material in the direction of the seaweed fibers and enhances the toughness of the composite material.

[0023] In another aspect, the present invention provides a hydrogel wound dressing, which is prepared by the above-mentioned method for preparing the hydrogel wound dressing.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] 1. The present invention adjusts the formula of the hydrogel wound dressing so that it can be cooled, solidified and transported at room temperature without the need for additional containers. At the same time, the present invention adds hydrophilic seaweed fiber to improve the toughness of the gel and reduce the breakage, fracture and gel deficiency caused by insufficient gel strength.

[0026] 2. The present invention utilizes the property of natural colloid that it can be cooled and solidified at room temperature to allow the prepared hydrogel wound dressing to undergo preliminary solidification, thereby ensuring that the hydrogel wound dressing can remain in a solid state and is convenient for shaping and transportation; by adjusting the ratio of each raw material, the problem of compatibility between natural colloid and other raw materials is solved.

[0027] 3. In the process of preparing the hydrogel wound dressing, the present invention keeps the hydrogel in a solid gel state, which can save the steps of freezing the gel or placing it on a tray, thus solving the problems of high energy consumption of freezing, which will limit the process conditions and prolong the process time, and high cost of placing the tray and the need to cooperate with freezing to form a solid block. Therefore, the present invention introduces natural colloid that can be condensed into a gel at room temperature, which not only ensures its safety in the use of wound dressing, but also greatly improves the process conditions.

[0028] 4. The present invention uses gelatin and glycyrrhizic acid to compound. The polymer chains generated by the two during the dissolution process are entangled with each other under the shear force of stirring to form a physically cross-linked structure, which can further increase the strength of the gel and still maintain good water retention after irradiation. At the same time, in the process of preparing the hydrogel wound dressing, the present invention performs ultrasonic treatment on the dispersion liquid added with seaweed fiber, so that the seaweed fiber can achieve the effect of directional arrangement, thereby combining with the gel to form a composite material, which plays a toughening role and makes the gel not easy to break and lack of glue. In addition, glycyrrhizic acid itself has an antibacterial effect, so the present invention does not need to add additional preservatives when preparing the hydrogel wound dressing. DETAILED DESCRIPTION

[0029] In order to enable persons skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention.

[0030] The hydrogel wound dressings in the following examples have a three-layer structure, with a gel layer in the middle and release layers on both sides.

[0031] Example 1

[0032] The preparation method of the hydrogel wound dressing of this embodiment comprises the following steps:

[0033] S1: adding the cross-linked main body into purified water, heating to 85°C, and stirring at a speed of 800 r / min for 15 min to obtain a mixed aqueous solution;

[0034] S2: adding natural colloid into the mixed aqueous solution, continuing heating to maintain 85°C, and stirring at a speed of 1000 r / min for 20 min to dissolve it to obtain a uniform solution, wherein the natural colloid includes gelatin and glycyrrhizic acid;

[0035] S3: Add seaweed fibers with a length of 65 mm into the uniform solution, continue heating to maintain 85°C, and stir at a speed of 1000 r / min for 2 min, then stop stirring to make it evenly dispersed to obtain a dispersion;

[0036] S4: pour the dispersion into the coating machine hopper, continue heating to maintain 85°C, and use ultrasound at a frequency of 25kHz for 10 minutes. The ultrasound direction is consistent with the discharge direction to make the seaweed fibers unidirectionally arranged and defoam the dispersion;

[0037] S5: After cooling the dispersion, evenly coat it on a release layer with a thickness of 5 μm, with a coating thickness of 2 mm and a coating speed of 15 m / min to obtain a gel layer, and attach another release layer with a thickness of 5 μm on the gel layer by a coating machine, so that the release layer is sandwiched between the two release layers;

[0038] S6: After cooling, the pieces are cut, then rinsed by immersing in purified water for 15 seconds, and then dried in an oven at 80°C for 7 minutes;

[0039] S7: Seal the package and bag it, then 60 Co was irradiated by gamma rays with an irradiation dose of 25 kGy and an irradiation rate of 2 MeV to obtain a hydrogel wound dressing.

[0040] In the hydrogel wound dressing of this embodiment, the addition amount of each raw material is shown in Table 1:

[0041] Table 1 Addition amount of each raw material in the hydrogel wound dressing of Example 1

[0042]

[0043] Example 2

[0044] The preparation method of the hydrogel wound dressing of this embodiment comprises the following steps:

[0045] S1: adding the cross-linked main body into purified water, heating to 75°C, and stirring at a speed of 800 r / min for 15 min to obtain a mixed aqueous solution;

[0046] S2: adding natural colloid into the mixed aqueous solution, continuing heating to maintain 75°C, and stirring at a speed of 1000 r / min for 20 min to dissolve it to obtain a uniform solution, wherein the natural colloid includes gelatin and glycyrrhizic acid;

[0047] S3: Add seaweed fibers with a length of 70 mm into the uniform solution, continue heating to maintain 75°C, and stir at a speed of 1000 r / min for 2 min, then stop stirring to make it evenly dispersed to obtain a dispersion;

[0048] S4: pour the dispersion into the coating machine hopper, continue heating to maintain 75°C, and use ultrasound at a frequency of 30kHz for 5 minutes. The ultrasound direction is consistent with the discharge direction to make the seaweed fibers unidirectionally arranged and defoam the dispersion;

[0049] S5: After cooling the dispersion, evenly coat it on a release layer with a thickness of 6 μm, with a coating thickness of 2.1 mm and a coating speed of 15 m / min to obtain a gel layer, and attach another release layer with a thickness of 6 μm on the gel layer by a coating machine, so that the release layer is sandwiched between the two release layers;

[0050] S6: After cooling, the pieces are cut, then rinsed by immersing in purified water for 16 seconds, and then dried in an oven at 75°C for 6.5 minutes;

[0051] S7: Seal the package and bag it, then 60 Co was irradiated by gamma rays with an irradiation dose of 30 kGy and an irradiation rate of 2 MeV to obtain a hydrogel wound dressing.

[0052] In the hydrogel wound dressing of this embodiment, the addition amount of each raw material is shown in Table 2:

[0053] Table 2 Addition amount of each raw material in the hydrogel wound dressing of Example 2

[0054]

[0055] Example 3

[0056] The preparation method of the hydrogel wound dressing of this embodiment comprises the following steps:

[0057] S1: adding the cross-linked main body into purified water, heating to 80°C, and stirring at a speed of 800r / min for 15min to obtain a mixed aqueous solution;

[0058] S2: adding natural colloid into the mixed aqueous solution, continuing heating to maintain 80°C, and stirring at a speed of 1000 r / min for 20 min to dissolve it to obtain a uniform solution, wherein the natural colloid includes gelatin and glycyrrhizic acid;

[0059] S3: adding seaweed fibers with a length of 85 mm into the uniform solution, continuing to heat to maintain 80°C, stirring at a speed of 1000 r / min for 2 min, and then stopping stirring to make it evenly dispersed to obtain a dispersion;

[0060] S4: pour the dispersion into the coating machine hopper, continue heating to maintain 80°C, and use ultrasound at a frequency of 20kHz for 9 minutes. The ultrasound direction is consistent with the discharge direction to make the seaweed fibers unidirectionally arranged and defoam the dispersion;

[0061] S5: After cooling the dispersion, evenly coat it on a release layer with a thickness of 5.5 μm, with a coating thickness of 1.9 mm and a coating speed of 15 m / min to obtain a gel layer, and attach another release layer with a thickness of 5.5 μm on the gel layer by a coating machine, so that the release layer is sandwiched between the two release layers;

[0062] S6: After cooling, the pieces are cut, then rinsed by immersing in purified water for 14 seconds, and then dried in an oven at 78°C for 6 minutes;

[0063] S7: Seal the package and bag it, then 60 Co was irradiated by gamma rays with an irradiation dose of 15 kGy and an irradiation rate of 2 MeV to obtain a hydrogel wound dressing.

[0064] In the hydrogel wound dressing of this embodiment, the addition amount of each raw material is shown in Table 3:

[0065] Table 3 Addition amount of each raw material in the hydrogel wound dressing of Example 3

[0066]

[0067] Comparative Example 1

[0068] The difference from Example 1 is that the addition amount of each raw material is as shown in Table 4.

[0069] Table 4 Addition amount of each raw material in the hydrogel wound dressing of comparative example 1

[0070]

[0071] Comparative Example 2

[0072] The difference from Example 1 is that the addition amount of each raw material is as shown in Table 5.

[0073] Table 5 Addition amount of each raw material in the hydrogel wound dressing of comparative example 2

[0074]

[0075] Comparative Example 3

[0076] The difference from Example 1 is that no polyacrylic acid is added to the cross-linked matrix.

[0077] Comparative Example 4

[0078] The difference from Example 1 is that polyvinyl pyrrolidone K90 is not added to the cross-linked matrix.

[0079] Comparative Example 5

[0080] The difference from Example 1 is that polyvinyl alcohol 1799 is not added to the cross-linked matrix.

[0081] Comparative Example 6

[0082] The difference from Example 1 is that no gelatin is added to the natural colloid.

[0083] Comparative Example 7

[0084] The difference from Example 1 is that no glycyrrhizic acid is added to the natural gum.

[0085] Comparative Example 8

[0086] The difference from Example 1 is that the amount of gelatin added is 12 parts.

[0087] Comparative Example 9

[0088] The difference from Example 1 is that the added amount of glycyrrhizic acid is 5 parts.

[0089] Comparative Example 10

[0090] The difference from Example 1 is that step S3 is not performed, and the uniform solution of step S2 is used instead of the dispersion in steps S4 and S5.

[0091] Comparative Example 11

[0092] The difference from Example 1 is that the added amount of seaweed fiber is 10 parts.

[0093] Comparative Example 12

[0094] The difference from Example 1 is that the length of the seaweed fiber is 100 mm.

[0095] Comparative Example 13

[0096] The difference from Example 1 is that the length of the seaweed fiber is 50 mm.

[0097] Comparative Example 14

[0098] The difference from Example 1 is that in step S4, ultrasonic treatment is not performed.

[0099] With reference to GB / T 528-2009 Determination of tensile stress-strain properties of vulcanized rubber or thermoplastic rubber and GB / T1704-2008 Determination of impact strength and crushing strength of hard rubber, the hydrogel wound dressings prepared in Examples 1-3 and Comparative Examples 1-14 were tested for tensile and compressive properties. The tensile properties were tested using a 1A dumbbell-shaped spline, the tensile speed was 100 mm / min, and the tensile direction was in accordance with the direction of the seaweed fiber. The test results are shown in Table 6:

[0100] Table 6 Tensile performance test results of hydrogel wound dressings prepared in Examples 1-3 and Comparative Examples 1-14

[0101]

[0102] It can be seen from Example 1 and Comparative Example 1 that when the total amount of each raw material added except purified water is too low, the gel has poor formability after solidification and is easily damaged during the actual condensation process; and the final gel still has problems such as partial damage and lack of gel after irradiation. It can be seen from Example 1 and Comparative Example 2 that when the total amount of each raw material added except purified water is too high, it will lead to incomplete dissolution during the heating and dissolving process, resulting in the appearance of insoluble clots in the solution, and the hardness of the hydrogel wound dressing after molding is too large, lacks elasticity, and is easily damaged when bent.

[0103] It can be seen from Example 1 and Comparative Examples 3-5 that when polyacrylic acid, polyvinyl pyrrolidone K90 or polyvinyl alcohol 1799 is not added, the degree of radiation crosslinking of the gel is reduced, resulting in a decrease in the strength of the final formed gel and lower elasticity, which is manifested as a low elongation at break, and a decrease in both tensile strength and compressive strength.

[0104] It can be seen from Example 1 and Comparative Example 6 that when gelatin is not added, the whole cannot be cooled and solidified, and the initial cross-linking strength of the gel is greatly reduced. Finally, a plastic tray must be used to prepare the gel, and the elasticity and strength of the gel are relatively low, which is manifested in a low elongation at break, and a decrease in tensile strength and compressive strength.

[0105] It can be seen from Example 1 and Comparative Example 7 that when glycyrrhizic acid is not added, there will be a lack of physical entanglement and cross-linking between gelatin and glycyrrhizic acid, which ultimately leads to the gel obtained by solidification being brittle and having low toughness. After radiation cross-linking, it exhibits a low elongation at break, and both the tensile strength and compressive strength are reduced.

[0106] It can be seen from Example 1 and Comparative Example 8 that when the gelatin content is too high, the viscosity will be too high during the dissolution process, the hardness of the gel will be too high after cooling, the elongation at break will be too small, and it will lack elasticity and will not meet the use requirements.

[0107] It can be seen from Example 1 and Comparative Example 9 that when the glycyrrhizic acid content is too high, the cross-linking ratio balance of glycyrrhizic acid and gelatin will be broken, and the gel will appear too soft and brittle, and ultimately exhibit low elongation at break, and low tensile strength and compressive strength.

[0108] It can be seen from Example 1 and Comparative Example 10 that when seaweed fiber is not added, the gel lacks the toughening effect of the seaweed fiber, so that the strength of the final formed gel is lower. Due to the lack of the binding effect of the seaweed fiber, the elasticity is also reduced, which is manifested in the reduction of tensile strength, compressive strength and elongation at break.

[0109] It can be seen from Example 1 and Comparative Example 11 that after irradiation, polyacrylic acid, polyvinyl alcohol 1799 and polyvinyl pyrrolidone K90 are cross-linked by irradiation free radicals to form a gel, which is compounded with seaweed fiber, wherein the gel serves as a matrix and the seaweed fiber serves as a reinforcement, thereby increasing the overall strength of the gel; at the same time, due to the binding effect of the seaweed fiber, the overall gel deficiency phenomenon of the gel is reduced. When the amount of seaweed fiber added is too little, the reinforcing effect is limited, but when the amount added is too much, the seaweed fibers in the gel are easily adsorbed to each other, resulting in excessive local content, which ultimately leads to a low content of the gel matrix in this area, and a low combination and bonding effect, which ultimately leads to the performance of the hydrogel wound dressing being not uniform enough, and its stable performance cannot be measured.

[0110] It can be seen from Example 1 and Comparative Example 12 that if the length of the seaweed fibers is too long, the seaweed fibers will not be arranged unidirectionally in the gel, but will curl and entangle, resulting in the gel being unable to improve the tensile properties in the direction of the fiber arrangement; and due to the existence of curling and entanglement, the strength of the gel in the entanglement point area is different from that in other areas, resulting in the area around the entanglement point being easily damaged first when the gel is subjected to force, resulting in the performance of the hydrogel wound dressing being not uniform enough, and its stable performance cannot be measured.

[0111] It can be seen from Example 1 and Comparative Example 13 that when the length of the seaweed fibers is too short, the seaweed fibers have less contact with each other and cannot transfer stress, so the reinforcement effect is extremely limited, which ultimately manifests as a decrease in the tensile strength and compressive strength of the hydrogel wound dressing.

[0112] It can be seen from Example 1 and Comparative Example 14 that when the gel is not subjected to ultrasonic treatment, the seaweed fibers in the gel cannot be arranged unidirectionally, resulting in a decrease in both the tensile strength and the compressive strength of the gel.

Claims

1. A method for preparing a hydrogel wound dressing, characterized in that: The hydrogel wound dressing has a three-layer structure, with a gel layer in the middle and release layers on both sides. The preparation method includes the following steps: S1: adding the cross-linked main body into water, heating and stirring to obtain a mixed aqueous solution; S2: adding natural colloid into the mixed aqueous solution, heating and stirring to dissolve, and obtaining a uniform solution, wherein the natural colloid comprises gelatin and glycyrrhizic acid; S3: adding seaweed fibers with a length of 65-85 mm into the uniform solution, maintaining the temperature, and stirring to make them dispersed evenly to obtain a dispersion; S4: pouring the dispersion into the coating machine hopper, maintaining the temperature, and performing ultrasound to arrange the seaweed fibers in one direction and degas the dispersion; S5: After cooling the dispersion, evenly coat the dispersion on the release layer to obtain a gel layer, and attach another release layer on the gel layer by a coating machine so that the release layer is sandwiched between the two release layers; S6: Cutting, cleaning and drying after cooling; S7: Continue 60 Co is irradiated by gamma rays to form a hydrogel wound dressing; Calculated by weight, the added amount of the cross-linked main body is 5.5-7.5 parts, the added amount of water is 70.3-79.5 parts, the added amount of gelatin is 7-10 parts, the added amount of glycyrrhizic acid is 3-4.2 parts, and the added amount of seaweed fiber is 5-8 parts; the cross-linked main body includes 1.5-2.5 parts of polyvinyl alcohol 1799, 3.5-4.5 parts of polyvinyl pyrrolidone K90 and 0.5-1 part of polyacrylic acid.

2. The method for preparing the hydrogel wound dressing according to claim 1, characterized in that: In steps S1 and S2, the stirring temperature is 75-85°C.

3. The method for preparing the hydrogel wound dressing according to claim 1, characterized in that: In step S4, the ultrasonic frequency is 20-30 kHz, the ultrasonic time is 5-10 min, and the ultrasonic direction is along the discharge direction of the hopper.

4. The method for preparing the hydrogel wound dressing according to claim 1, characterized in that: In step S5, the thickness of the gel layer is 1.9-2.1 mm, and the thickness of the release layer is 5-6 μm.

5. The method for preparing the hydrogel wound dressing according to claim 1, characterized in that: In step S6, the cleaning is performed by immersing in purified water, the immersion time is 14-16 seconds, the drying temperature is 75-80° C., and the drying time is 6-7 minutes.

6. The method for preparing the hydrogel wound dressing according to claim 1, characterized in that: In step S7, 60 The gamma ray irradiation dose of Co is 15-30 kGy.

7. A hydrogel wound dressing, characterized in that: The hydrogel wound dressing is prepared by the preparation method of any one of claims 1 to 6.

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