Medical dressing cross-linked by visible light, medical dressing assembly and preparation method of medical dressing assembly

Abstract

The invention discloses a medical dressing cross-linked by visible light, a medical dressing assembly and a preparation method of the medical dressing cross-linked by visible light, the medical dressing is in a solution form, the medical dressing comprises methacrylated deferrited lactoferrin, casein, an oxidizing agent and a photosensitizer, the mass concentration of the methacrylated deferrited lactoferrin is 0.03-0.07 g / mL, the mass concentration of the casein is 0.03-0.07 g / mL, and the mass concentration of the oxidizing agent is 0.03-0.07 g / mL. The mass concentration of the casein is 0.03 to 0.07 g / mL; the amount-of-substance concentration of the oxidizing agent is 0.05 mol / L to 0.1 mol / L; the amount-of-substance concentration of the photosensitizer is 0.005 mol / L to 0.01 mol / L. According to the medical dressing, visible light is utilized for in-situ light curing, protein hydrogel is directly formed on a target part, rapid closing of a wound is achieved, potential bacterial contamination is isolated, and use is convenient.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of medical materials, in particular to a medical dressing, a medical dressing assembly and a preparation method thereof. BACKGROUND

[0002] In the prior art, there are many hydrogels with at least one of the functions of sterilization, inflammation reduction and repair promotion, but different types of hydrogels have their own disadvantages. According to the search, a Chinese patent application with the publication number CN116421775A discloses a lactoferrin gel dressing, which is prepared by wrapping lactoferrin-chitosan nanofibers and dopamine-wrapped graphene oxide fibers into an antibacterial gel. The antibacterial property is achieved by adding a slow-release drug, rather than the antibacterial property of the gel itself.

[0003] A Chinese patent application with the publication number CN116251224A prepares a double-layer dressing comprising an inner layer and an outer layer. The outer layer is a polyurethane film, and the inner layer is a composite gel of betaine-modified hyaluronic acid and lactoferrin. The dressing adds quaternary ammonium salt with antibacterial effect, and the forming of the hydrogel is carried out by vacuum drying, which takes a long time.

[0004] A Chinese patent with the publication number CN106075598B discloses a photocrosslinking sericin protein hydrogel. The methyl methacryl-grafted sericin protein can be made into a hydrogel. The hydrogel is cured by ultraviolet light, which has a high requirement for light sources.

[0005] Therefore, it is necessary to provide a hydrogel with excellent antibacterial performance and more convenient use. SUMMARY

[0006] Therefore, the application provides a medical dressing which can be crosslinked by visible light, has ideal mechanical properties and excellent antibacterial performance.

[0007] A medical dressing crosslinked by visible light, which is in the form of a solution, and comprises the following components: methacrylated deferrinated lactoferrin, casein, an oxidizing agent and a photosensitizer. The mass concentration of the methacrylated deferrinated lactoferrin is 0.03-0.07 g / mL; the mass concentration of the casein is 0.03-0.07 g / mL; the molar concentration of the oxidizing agent is 0.05-0.1 mol / L; and the molar concentration of the photosensitizer is 0.005-0.01 mol / L.

[0008] The following optional modes are provided, but are not additional limitations on the above general scheme, and are only further supplements or preferences. Without technical or logical contradictions, each optional mode can be combined with the above general scheme, and can also be combined between multiple optional modes.

[0009] The methacrylated apo-lactoferrin has strong ability to bind heme, and has 7-13 binding sites for heme and 14-20 binding sites for iron ions. The KD value of the lactoferrin for binding heme is 0.015 nM-2.02 nM. The iron saturation of the methacrylated apo-lactoferrin is 10 mg / g or more. The methacrylated apo-lactoferrin is prepared by methacrylation treatment of low-iron lactoferrin, and the methacrylation treatment is performed using methacrylic anhydride, wherein the grafting rate of the methacrylic anhydride is 30%-100%. The low-iron lactoferrin refers to lactoferrin with an iron content of less than 0.15 mg / g, and the lactoferrin is derived from colostrum, milk and whey of mammals such as bovine, human and camel, and can also be recombinant lactoferrin obtained by fermentation of genetically engineered bacteria and plants.

[0010] The oxidizing agent is at least one of sodium persulfate, ammonium persulfate and potassium persulfate. The photosensitizer is a trispyridine ruthenium complex. The oxidizing agent and the photosensitizer are used to catalyze the reaction of the methacrylated apo-lactoferrin and casein, and the reaction mechanism is shown in Figure 1a 、 Figure 1b The methacrylated apo-lactoferrin and casein undergo cross-linking reaction under the action of visible light to form a protein hydrogel.

[0011] The medical dressing provided in the application forms a protein hydrogel by in-situ photocuring, the protein hydrogel can quickly seal and isolate potential bacterial contamination, and the cross-linking of the hydrogel can be completed in the range of visible light (400-760 nm wavelength), which greatly reduces the requirement for light source and is more convenient to use.

[0012] The methacrylated apo-lactoferrin used in the medical dressing has strong adsorption capacity for heme, and can cut off the source of iron available to bacteria by adsorbing heme, thereby achieving good antibacterial effect.

[0013] The medical dressing is in the form of a solution, and the solvent can be 0.01M phosphate buffer (PBS, pH=7.4) or water. The dissolution of casein needs to be carried out under alkaline conditions, so the pH is adjusted to alkaline when the casein solution is prepared, and the stirring at 200-300 rpm is used to promote the dissolution of casein.

[0014] In the medical dressing, the mass ratio of the methacrylated apo-lactoferrin to casein is 1:0.1-10. The molar ratio of the oxidizing agent to the photosensitizer is 200:0.25-5. The ratio of the methacrylated apo-lactoferrin to the oxidizing agent is 3-14 g:1 mol.

[0015] The methacrylated apo-lactoferritin is a component directly acting against bacteria in the medical dressing, and its content directly affects the antibacterial effect. A low content may result in poor antibacterial effect. The casein and the methacrylated apo-lactoferritin are cross-linked to form a hydrogel, and the content of the casein affects the mechanical properties of the protein hydrogel. The amount of the oxidizing agent and the photosensitizer is determined according to the amount of the methacrylated apo-lactoferritin and the casein.

[0016] The total concentration of the methacrylated apo-lactoferritin and the casein in the medical dressing is 5% to 30%, i.e. 0.05 g / mL to 0.3 g / mL. The content of the methacrylated apo-lactoferritin and the casein also determines the viscosity of the medical dressing. The viscosity of the medical dressing can be adjusted by adjusting the content within the aforementioned range.

[0017] After the components in the medical dressing are configured into a solution, the solution needs to be filtered through a filter membrane (filtration pore size is 0.1 μm to 0.22 μm) to remove microorganisms or dust introduced in the preparation process, and also to remove the particles of the aggregated or denatured protein, so as to obtain a medical dressing which maintains good biological activity and is clean and free of microbial pathogens.

[0018] The application also provides a medical dressing assembly, which comprises a pushing device, and the pushing device comprises: a first chamber, which is filled with a first solution containing methacrylated apo-lactoferritin and casein, wherein the mass concentration of the methacrylated apo-lactoferritin in the first solution is 3 to 7 g / 100 mL, and the mass concentration of the casein is 3 to 7 g / 100 mL; a second chamber, which is filled with a second solution containing an oxidizing agent and a photosensitizer for catalyzing the reaction of the methacrylated apo-lactoferritin and the casein, wherein the volume ratio of the first solution to the second solution is 20:3 to 20:1; a switching device for isolating or connecting the first chamber and the second chamber; a driving member for outputting the mixed solution in the first chamber and the second chamber.

[0019] The switching device is a control valve assembly, which is used to control the isolation and connection state of the first chamber and the second chamber. The control valve assembly can be a three-way valve. The first interface of the three-way valve is connected with the first chamber, the second interface is connected with the second chamber, and the third interface is used as an outlet of the medical dressing. In use, the first chamber and the second chamber are connected by controlling the control valve assembly, and the solutions in the first chamber and the second chamber are mixed by the reciprocating pushing action of the driving member, and then are output through the third interface of the control valve.

[0020] The switching device is a mixing chamber in controllable communication with the first chamber and the second chamber, the mixing chamber is provided with an outflow pipe, in use, the driving member drives the solutions in the first chamber and the second chamber to flow into the mixing chamber for mixing, and then output through the outflow pipe.

[0021] The components in the medical dressing can be cross-linked under visible light, so it is necessary to store the components separately during storage. The medical dressing assembly provides a storage method for a medical dressing, in which the components are placed in a first chamber and a second chamber isolated from each other, the first chamber stores a first solution containing methacrylated deferrated lactoferrin and casein, and the second chamber stores a second solution containing an oxidizing agent and a photosensitizer. When needed, the first solution and the second solution are mixed in the mixing chamber and then flow out through the outflow pipe. The mixing chamber can be provided with a partition and other structures to assist uniform mixing.

[0022] Optionally, the medical dressing assembly further comprises a portable light source for initiating the reaction of methacrylated deferrated lactoferrin and casein.

[0023] The medical dressing provided by the present application can perform cross-linking reaction under visible light. In order to accelerate the cross-linking reaction speed, a light source with larger power can be configured at the same time to make the cross-linking reaction more rapid.

[0024] The power of the visible light source: 3.50~53.5mW / cm 2 The distance of light source irradiation: 1~5cm, irradiation time: 30-90s.

[0025] Optionally, the speed ratio of the first solution and the second solution flowing into the mixing chamber is 20:3~1. The speed ratio of the first solution and the second solution flowing into the mixing chamber is consistent with the volume ratio of the first solution and the second solution.

[0026] Optionally, the dosage ratio of methacrylated deferrated lactoferrin in the first solution to the photosensitizer in the second solution is 3~14g:1mol.

[0027] Optionally, in the first solution, the mass ratio of methacrylated deferrated lactoferrin to casein is 1:0.5~2.

[0028] Optionally, the oxidizing agent is at least one of sodium persulfate, ammonium persulfate and potassium persulfate; the photosensitizer is a trispyridine ruthenium complex, and in the second solution, the molar concentration of the oxidizing agent is 0.5~1mol / L, and the molar concentration of the photosensitizer is 0.05~0.1mol / L.

[0029] Optionally, in the second solution, the molar ratio of the oxidizing agent to the photosensitizer is 10:0.5~1.5.

[0030] Optionally, the first solution and the second solution are respectively filtered through a filter membrane with a pore size of 0.1-0.22 μm.

[0031] Optionally, the first solution is obtained by mixing a methacrylated deferrinated lactoferritin solution and a casein solution, the mass concentration of the methacrylated deferrinated lactoferritin solution is 6-14 g / 100 mL, the mass concentration of the casein solution is 6-14 g / 100 mL, and the volume ratio of the methacrylated deferrinated lactoferritin solution to the casein solution is 1:0.5-1.5.

[0032] Optionally, the second solution is obtained by mixing an oxidizing agent solution and a photosensitizer solution, the molar concentration of the oxidizing agent solution is 1-2 mol / L, the molar concentration of the photosensitizer solution is 0.1-0.2 mol / L, and the volume ratio of the oxidizing agent solution to the photosensitizer solution is 20:1-3.

[0033] The application further provides a protein hydrogel for sterilization, which is formed by visible light curing of methacrylated deferrinated lactoferritin and casein under the action of an oxidizing agent and a photosensitizer.

[0034] The wavelength range of the visible light for the light curing is 400-760 nm. The mass ratio of the methacrylated deferrinated lactoferritin to the casein is 1:0.1-10. The molar ratio of the oxidizing agent to the photosensitizer is 200:0.25-5. The ratio of the methacrylated deferrinated lactoferritin to the oxidizing agent is 3-14 g:1 mol.

[0035] The application further provides a preparation method of a medical dressing, which comprises the following steps: Methacrylated deferrinated lactoferritin solution, casein solution, oxidizing agent solution and photosensitizer solution are respectively prepared, and the solutions are mixed according to a predetermined volume ratio to obtain a mixed solution, which is the medical dressing.

[0036] Optionally, the mass concentration of the methacrylated deferrinated lactoferritin solution is 6-14 g / mL.

[0037] Optionally, the mass concentration of the casein solution is 6-14 g / mL.

[0038] Optionally, the molar concentration of the oxidizing agent solution is 1-2 mol / L.

[0039] Optionally, the molar concentration of the photosensitizer solution is 0.1-0.2 mol / L.

[0040] Optionally, the volume ratio of the methacrylated apo-lactoferrin solution, the casein solution, the oxidant solution, and the photosensitizer solution is 150-250:150-250:15-25:1.

[0041] Optionally, the medical dressing is obtained by filtering the mixed solution with a filter membrane.

[0042] The application also provides a method for sterilizing in vitro by using the medical dressing, wherein the medical dressing is applied to the target position in an expected amount, and visible light with a wavelength of 400-760 nm is applied to form the protein hydrogel with sterilization effect.

[0043] The application also provides a method for sterilizing in vitro by using the medical dressing assembly, comprising the following steps: The pushing member is driven to push the first solution in the first chamber and the second solution in the second chamber into the mixing chamber, and the first solution and the second solution are uniformly mixed in the mixing chamber, and then the medical dressing is output to the target position through the outflow pipe; The medical dressing is applied to the target position in an expected amount, and visible light with a wavelength of 400-760 nm is applied to form the protein hydrogel with sterilization effect.

[0044] The application provides a wound treatment method, comprising the following steps: The medical dressing is applied to the wound site, and visible light with a wavelength of 400-760 nm is applied to form the protein hydrogel.

[0045] The medical dressing completely covers the wound, and visible light is applied for 30-90 seconds.

[0046] The medical dressing provided by the application is in-situ photocured by visible light, directly forms a protein hydrogel at the target position, realizes rapid sealing of the wound, and isolates potential bacterial contamination, and is convenient to use, wherein the methacrylated apo-lactoferrin has good hemoglobin adsorption capacity, cuts off the source of iron available to bacteria, and thus has good antibacterial effect. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1a Different states of ruthenium atoms in the catalyst participating in the solidification of the hydrogel; Figure 1b The light solidification mechanism of the protein hydrogel; Figure 2 The structure diagram of the pushing device; Figure 3 The schematic diagram of the pushing device extruding the medical dressing; Figure 4Changes in compression modulus of the protein hydrogel prepared in Example 1 with respect to irradiation time; Figure 5 Changes in the amount of hematin adsorbed by the protein hydrogel prepared in Example 1 with respect to time; Figure 6 Antibacterial effect of the protein hydrogel prepared in Example 1; Figure 7 Iron content in different bacteria after the protein hydrogel prepared in Example 1 was incubated with hematin; Figure 8 Antibacterial activity of the protein hydrogel prepared in Example 1 against different bacteria; Figure 9 Graph of the relationship between the indentation depth of different protein hydrogels and different pressures; Figure 10 Graph of the compression modulus of different protein hydrogels; Figure 11 Graph of the relationship between the shear stress and shear strain of different protein hydrogels; Figure 12 Shear strength values of different protein hydrogels; Figure 13 Graph of the amount of hematin adsorbed by different protein hydrogels; Figure 14 Photos of different protein hydrogels adsorbing hematin; Figure 15 Graph of the antibacterial effect of different protein hydrogels against Staphylococcus aureus; Figure 16 Graph of the antibacterial effect of different protein hydrogels against Escherichia coli; Figure 17 Photos of different protein hydrogels co-cultured with Staphylococcus aureus and Escherichia coli. DETAILED DESCRIPTION

[0048] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of protection of the present application.

[0049] In order to better describe and illustrate the embodiments of the present application, one or more drawings can be referred to, but additional details or examples used to describe the drawings should not be considered as limiting the scope of any one of the inventions, the presently described embodiments, or the preferred modes of the present application.

[0050] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0051] Preparation of methacrylamide-derived lactoferrin The preparation method of methacrylamide-derived lactoferrin includes the following steps: (1) Add acetic acid, sodium acetate (molar ratio of 1:1) and EDTA to a PBS solution with pH 2.0 to prepare a mixture, and then dissolve lactoferrin powder (Bega, Australia) in the mixture at room temperature to prepare a lactoferrin solution with a concentration of 0.5 g / 100 mL. The mixture contained 0.01 M PBS, 0.1 M acetic acid and sodium acetate, and 500 mM EDTA. (2) The lactoferrin solution obtained in step (1) was placed into a dialysis bag and the dialysis bag was placed in PBS solution for dialysis for 72 hours. The retentate after dialysis was pre-frozen at -50°C and then freeze-dried under a vacuum of 1 Pa to obtain a deferroferrin with an iron content of 0.0139 mg / g. The PBS solution was changed continuously during the dialysis process. The concentration of the PBS solution was gradually reduced. The concentration of the PBS solution was gradually reduced from 0.1 M to 0.05 M from 0 to 24 hours, from 0.05 M to 0.01 M from 24 to 48 hours, and from 0.01 M to 0 M from 48 to 72 hours. The molecular weight cutoff of the dialysis bag is 3500 Da; (3) The deferroferrin obtained in step (2) is subjected to methacrylamide treatment to obtain lactoferrin with strong iron absorption capacity. (3.1) Dissolve the aborted lactoferrin in a PBS solution with a pH of 2 at room temperature to prepare a stock solution of aborted lactoferrin with a concentration of 10 g / 100 ml; (3.2) Under high-speed stirring at 600 rpm, methacrylic anhydride was added to the defermented lactoferrin stock solution, and then the pH value was adjusted to 7. The reaction was continuously stirred at 25℃ for 2 h. After the reaction, the solution was dialyzed for 48 h, then concentrated by ultrafiltration and filtered twice with a filter membrane with a pore size of 0.22 μm. The filtrate was pre-frozen at -50℃ and then freeze-dried under a vacuum of 1 Pa to obtain lactoferrin with a ferric iron saturation content of 14.43 mg / g and strong iron adsorption capacity. The ratio of methacrylic anhydride to lactoferrin is 0.03 mL / 1 g, and the grafting degree of methacryloyl groups on lactoferrin, which has a strong iron-absorbing capacity, is 30%.

[0052] Example 1 A method for preparing a medical dressing, comprising the following steps: (1) Solution preparation Methacrylated apo-lactoferritin (Apo-LfMA) solution: Dissolve the methacrylated apo-lactoferritin powder (obtained by the preparation method described above) in phosphate buffer solution (PBS) at room temperature to prepare a methacrylated apo-lactoferritin solution with a mass concentration of 10 g / 100 mL. The methacrylated apo-lactoferritin is a white powder, easily soluble in water, and after dissolution, it is a transparent colorless to white liquid.

[0053] Casein solution: Dissolve the casein powder in phosphate buffer solution (PBS) containing 0.1 mol / L sodium hydroxide at room temperature, and prepare a casein solution with a mass concentration of 10 g / 100 mL under stirring at 200-300 rpm. The casein is a white powder, soluble in water, and after dissolution, it is a white liquid.

[0054] Sodium persulfate (SPS) solution: Dissolve the sodium persulfate powder in PBS at room temperature to prepare a sodium persulfate solution with a molar concentration of 1 mol / L. The sodium persulfate is a white powder, easily soluble in water, and after dissolution, it is a transparent colorless liquid.

[0055] Trispyridine ruthenium chloride (Ru) solution: Dissolve the trispyridine ruthenium chloride hexahydrate powder in PBS at room temperature to prepare a trispyridine ruthenium chloride solution with a molar concentration of 0.1 mol / L. The trispyridine ruthenium chloride hexahydrate is an orange-yellow powder, easily soluble in water, and after dissolution, it is an orange-yellow liquid.

[0056] (2) Preparation of antibacterial protein pre-gel solution After thoroughly mixing the methacrylated apo-lactoferritin solution, casein solution, sodium persulfate solution, and trispyridine ruthenium chloride solution according to the volume ratio of 100:100:20:1, filter the mixed solution twice using a filter membrane (filter membrane pore size 0.1 μm) to obtain a sterile antibacterial protein pre-gel solution; (3) Irradiate the antibacterial protein pre-gel solution with white visible light (7.5 W / cm 2 ) for 90 s to initiate polymerization of the antibacterial protein pre-gel solution to form a hydrogel, which is then solidified and shaped to obtain an antibacterial protein hydrogel capable of rapidly absorbing hematin.

[0057] The protein hydrogel prepared in Example 1 is characterized as follows: Figure 4Figure a shows the state of the protein hydrogel (the yellow part within the dashed boundary) without light exposure (in Example 1, the white visible light was the white light emitted by a mobile phone flashlight). It has good fluidity and flows downward under the influence of gravity. The preparation process of the protein hydrogel shown in Figure a is the same as that in Example 1, except that it was not exposed to white visible light. Figure 4 Figure b shows the state of the protein hydrogel (yellow part within the dashed boundary) after 30 seconds of light exposure. Its fluidity has decreased, and it does not flow significantly under the influence of gravity. Figure 4 Figure c shows the compressive modulus of the protein hydrogel under different light exposure durations. The compressive modulus gradually increases with the increase of light exposure time.

[0058] See Figure 5 As shown, the curve of heme adsorption by the protein hydrogel over time is included. Figure 5 As shown in Figure a, the protein hydrogel can rapidly adsorb heme, achieving saturation adsorption within 1 hour. See Figure a for a photograph of the protein hydrogel before adsorption. Figure 5 Figure b shows a photograph of the protein hydrogel after 24 hours of heme adsorption. Figure 5 As shown in Figure c.

[0059] See Figure 6 As shown, the protein hydrogel exhibits good antibacterial effects against bacteria such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA).

[0060] See Figure 7 As shown, after bacteria were co-incubated with heme and protein hydrogel in phosphate buffer, the iron content within the bacteria decreased. This indicates that the protein hydrogel, by adsorbing heme, limited the bacteria's uptake of iron from heme. Due to heme starvation, the bacteria were unable to grow and reproduce normally, thus achieving an antibacterial effect. Figure 7 The control group consisted of bacteria incubated in phosphate buffer without heme and protein hydrogel.

[0061] See Figure 8 As shown, the protein hydrogel exhibits good antibacterial effects against several clinically resistant bacteria, including Staphylococcus aureus 25923, Escherichia coli 25922, Pseudomonas aeruginosa 27853, and Acinetobacter baumannii 17978.

[0062] Examples 2-4 The raw material composition of the protein hydrogels in Examples 2-4 is shown in Table 1.

[0063] Table 1

[0064] Medical dressings are cured under visible light to form protein hydrogels. Each component of the medical dressing is prepared into a solution, and the solutions are mixed according to a predetermined volume ratio. The final mixed solution is the medical dressing. The concentrations in Table 1 are the concentrations of each component in the medical dressing. Specifically, component A is the concentration of methacrylamide lactoferrin in the medical dressing; component B is the concentration of casein in the medical dressing; component C is the concentration of methacrylamide lactoferrin in the medical dressing; and component D is the concentration of methacrylamide lactoferrin in the medical dressing.

[0065] In Table 1, LC3:7 indicates that the mass ratio of methacrylamide lactoferrin to casein in medical dressings is 3:7; LC5:5 indicates that the mass ratio of methacrylamide lactoferrin to casein in medical dressings is 5:5; and LC7:3 indicates that the mass ratio of methacrylamide lactoferrin to casein in medical dressings is 7:3.

[0066] The compressive modulus of the protein hydrogel was determined using nanoindentation. The load detected by the nanoprobe when indentations of different depths were created is shown in [reference needed]. Figure 9 As shown, the results of the compression modulus measurement are available in [reference needed]. Figure 10 As shown, the compressive moduli of the protein hydrogels corresponding to LC 3:7, LC 5:5, and LC 7:3 are 15.06±0.5774 kPa, 17.80±0.4990 kPa, and 16.14±0.4890 kPa, respectively. There is no significant difference in the compressive modulus between the protein hydrogels corresponding to LC 3:7 and LC 7:3. The protein hydrogel corresponding to LC 5:5 has a higher compressive modulus, which may be based on its more compact hydrogel structure.

[0067] The characterization results of the shear strength of the protein hydrogel can be found in [reference needed]. Figure 11 , Figure 12 As shown, Figure 11 This represents the relationship between shear stress and shear strain. Figure 12 The shear strength values ​​of the protein hydrogels for different groups are shown. The shear strengths of the protein hydrogels corresponding to LC 3:7 and LC 5:5 are 105.0±3.738 kPa and 94.95±0.8680 kPa, respectively, which are significantly higher than the shear strength of the protein hydrogel corresponding to LC 7:3 (65.69±1.748 kPa). The trend of shear strength variation may be due to the reduction of tyrosine residues in the pre-hydrogel system.

[0068] For the adsorption effect of protein hydrogels on heme, please refer to [reference needed]. Figure 13 , Figure 14 As shown, see Figure 13As shown, all protein hydrogels reached the maximum amount of hematin absorption within 4 hours in 500 uM hematin solution, while LC 5:5 and LC 7:3 each corresponded to a protein hydrogel that showed significantly faster hematin absorption (50% of the maximum absorption amount reached within 15 min) compared to LC 3:7, because the lower content of methacrylated apo-lactoferritin in the LC 3:7 corresponded protein hydrogel resulted in fewer hematin binding pockets in the protein hydrogel network, and the effect of absorbing hematin was relatively poor. See the photos of the protein hydrogels before absorption, 1 hour after hematin absorption, and 24 hours after hematin absorption in different groups Figure 14 As shown, the LC 3:7 corresponded protein hydrogel had a lighter color after absorbing hematin for 24 hours, indicating that it absorbed less hematin.

[0069] See the antibacterial effect of the protein hydrogel Figure 15 、 Figure 16 、 Figure 17 As shown, the antibacterial results of S. aureus are Figure 15 , Figure 16 the antibacterial results of E. coli are Figure 17 , and the photos of S. aureus and E. coli after being cultured together for 12 hours by different groups of protein hydrogels are Figures 15 to 17 As can be seen, in the preliminary antibacterial experiment in vitro, the LC 5:5 and LC 7:3 each corresponded protein hydrogel had similar antibacterial ability, killing more than 99% of bacteria within 8 hours, while the LC 3:7 corresponded protein hydrogel showed poor antibacterial performance, and the difference in antibacterial performance of the protein hydrogel was related to the content of the effective antibacterial component methacrylated apo-lactoferritin.

[0070] Medical dressing assembly The medical dressing assembly includes not only a medical dressing, but also a pushing device. See the structural diagram of the pushing device in Figure 2 and Figure 3 As shown, the pushing device includes: a first chamber 1 and a second chamber 2 that are isolated from each other; a mixing chamber 3 (i.e., a switching device) that is controllably communicated with the first chamber 1 and the second chamber 2; and a driving element 5 that pushes the solution in the first chamber 1 and the second chamber 2 into the mixing chamber 3 after mixing, and then flows out through an outflow pipe 4.

[0071] The mixing chamber 3 is provided with the outflow pipe 4. When the medical dressing is stored or transported, the first chamber 1, the second chamber 2, and the mixing chamber 3 are not communicated. When the medical dressing is used, the mixing chamber 3 is communicated with the first chamber 1 and the second chamber 2. The on-off of the first chamber 1, the second chamber, and the mixing chamber 3 can be realized by using a valve.

[0072] The volume of the first chamber 1 and the second chamber 2 is different, and the volume ratio of the first chamber 1 to the second chamber is 20:3~1.

[0073] The first chamber 1 is used to infuse the first solution, and the first solution contains methacrylated deferrinated lactoferritin and casein; the second chamber 2 is used to infuse the second solution, and the second solution contains an oxidizing agent and a photosensitizer for catalyzing the reaction of methacrylated deferrinated lactoferritin and casein. The volume ratio of the first solution to the second solution is 20:3~1.

[0074] In the first solution, the mass concentration of methacrylated deferrinated lactoferritin is 3~7g / 100mL, and the mass concentration of casein is 3~7g / 100mL. In the second solution, the molar concentration of the oxidizing agent is 0.5~1mol / L, and the molar concentration of the photosensitizer is 0.05~0.1mol / L.

[0075] In use of the medical dressing, the mixing chamber 3 is in communication with the first chamber 1 and the second chamber 2, and the driving member 5 simultaneously pushes the first solution in the first chamber 1 and the second solution in the second chamber 2 into the mixing chamber 3 for mixing, and the mixed solution is the medical dressing. The medical dressing is extruded to the target position through the outflow pipe 4, and covers an appropriate thickness and area, and is cured by visible light irradiation. The irradiation time of the visible light is 1~3 minutes, and the irradiation time is related to the power of the light source. In the case of emergency curing, the power of the light source can be increased, for example, a matched independent light source is used. In the case of no emergency, the flashlight function of a mobile phone can be used to provide light to complete the photocuring.

[0076] The technical features of the above-described embodiments can be combined in any manner. To make the description concise, all possible combinations of the technical features in the above-described embodiments are not described, but as long as the combinations of the technical features do not contradict, they should be considered within the scope of the present disclosure.

[0077] The above-described embodiments only express several implementation manners of the present application, and the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that for ordinary skilled persons in the art, some modifications and improvements can be made without departing from the concept of the present application, and these are within the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A medical dressing that utilizes visible light cross-linking, characterized in that, The medical dressing is in solution form and comprises: methacrylamide lactoferrin, casein, an oxidant, and a photosensitizer, wherein the mass concentration of methacrylamide lactoferrin is 0.03~0.07 g / mL; the mass concentration of casein is 0.03~0.07 g / mL; the molar concentration of the oxidant is 0.05~0.1 mol / L; and the molar concentration of the photosensitizer is 0.005-0.01 mol / L.

2. A medical dressing assembly, characterized in that, The medical dressing assembly includes a pushing device, the pushing device comprising: A first chamber is filled with a first solution containing methacrylamide lactoferrin and casein. The mass concentration of methacrylamide lactoferrin in the first solution is 3-7 g / 100 mL, and the mass concentration of casein is 3-7 g / 100 mL. The second chamber is filled with a second solution containing an oxidant and a photosensitizer for catalyzing the reaction of methacrylamide deferroferrin and casein, wherein the volume ratio of the first solution to the second solution is 20:3 to 20:

1. A switching device for isolating or connecting the first chamber and the second chamber; The driving component mixes the solutions in the first and second chambers before outputting them.

3. The medical dressing assembly as described in claim 2, characterized in that, The ratio of methacrylamide-derived lactoferrin in the first solution to photosensitizer in the second solution is 3-14 g: 1 mol.

4. The medical dressing assembly as described in claim 2, characterized in that, In the first solution, the mass ratio of methacrylamide deferroferrin to casein is 1:0.5~2.

5. The medical dressing assembly as described in claim 2, characterized in that, The oxidant is at least one of sodium persulfate, ammonium persulfate, and potassium persulfate; the photosensitizer is a terpyridine ruthenium complex. In the second solution, the molar concentration of the oxidant is 0.5~1 mol / L, and the molar concentration of the photosensitizer is 0.05~0.1 mol / L.

6. The medical dressing assembly as described in claim 2, characterized in that, In the second solution, the molar ratio of the oxidant to the photosensitizer is 10:0.5~1.

5.

7. The medical dressing assembly as described in claim 2, characterized in that, The first and second solutions were respectively filtered through a filter membrane with a pore size of 0.1 μm to 0.22 μm.

8. The medical dressing assembly as described in claim 2, characterized in that, The first solution is obtained by mixing a methacrylamide deferroferrin solution and a casein solution, wherein the mass concentration of the methacrylamide deferroferrin solution is 6~14 g / 100 mL, the mass concentration of the casein solution is 6~14 g / 100 mL, and the volume ratio of the methacrylamide deferroferrin solution to the casein solution is 1:0.5~1.

5.

9. The medical dressing assembly as described in claim 2, characterized in that, The second solution is obtained by mixing an oxidant solution and a photosensitizer solution, wherein the molar concentration of the oxidant solution is 1~2 mol / L, the molar concentration of the photosensitizer solution is 0.1~0.2 mol / L, and the volume ratio of the oxidant solution to the photosensitizer solution is 20:1~3.

10. A method for preparing a medical dressing as described in claim 1, characterized in that, Includes the following steps: A solution of methacrylamide deferroferrin, a solution of casein, an oxidant solution, and a photosensitizer solution are prepared separately. The solutions are then mixed in a predetermined volume ratio to obtain a mixed solution, which is the medical dressing.

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