A nano medical gel dressing and its preparation method

Abstract

The present invention relates to a nano medical gel dressing and a preparation method thereof. Gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate are used as raw materials. After mixing, a medical dressing gel is obtained through crosslinking. The raw materials used in the present invention are non-toxic and harmless, have good biocompatibility, can form a film to cover the wound surface, play a physical protection role, reduce external stimulation to the wound surface, and thus promote tissue repair. The formed three-dimensional network structure has good stability, excellent water absorption and storage effects, strong drug loading capacity. Nano titanium dioxide and polyhexamethylene guanidine improve the antibacterial efficiency and persistence through synergistic antibacterial effects, achieving the purpose of rapid sterilization. At the same time, the overall density of the gel increases, the polymer entanglement is tighter, the compressive strength is improved, and at the same time, the tensile strength and elongation at break are increased, and the mechanical properties are excellent.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical gel dressings, and particularly relates to a nano medical gel dressing and a preparation method thereof. Background Art

[0002] As the tissue of the human body's epidermis, the skin plays a role in protecting the internal environment of the body and maintaining its stability. The ultimate goal of the treatment after skin injury is to reconstruct the skin barrier function. Medical dressings with excellent performance can provide an environment conducive to wound healing, have good biocompatibility and anti-infection ability, and play a role in protecting the skin by covering the damaged skin to form a wound healing environment. It is a common medical device with broad prospects and research space.

[0003] There are many types of medical dressings. Currently, the applied dressings are classified into fibers, films, sponges, hydrogels, hydrocolloids, and medical adhesives in terms of form. Among them, hydrogel dressings have the advantages of soft texture, can keep the wound surface moist, and have good biocompatibility. They are not easy to adhere to the wound tissue, avoiding secondary damage. Moreover, the environmentally responsive hydrogel dressings loaded with active drugs can achieve controlled release of drugs, improve the drug efficacy, thus preventing infection and eliminating the inflammatory response, and promoting wound healing.

[0004] Chinese Patent CN104906625A discloses a preparation method of a medical hydrogel, including the following steps: Pour deionized water into a reactor, heat the reactor, and then slowly add lemon peel pectin and gelatin while mechanically stirring. After adding lemon peel pectin and gelatin, continue to stir, and then add chitosan, soybean oligosaccharide, polycaprolactone, and chlorhexidine acetate to the reactor, and also stir evenly while adding. After the above materials are mixed, cool the hydrogel to room temperature to obtain the medical hydrogel. This medical hydrogel has good biocompatibility and air permeability, but its antibacterial effect is general and its mechanical properties are poor, and it is easy to break during use.

[0005] Chinese Patent CN108030954A discloses a medical wound dressing containing nano-polysaccharides, including a wet dressing. The wet dressing is a hydrocolloid dressing, a hydrogel dressing, a silicone gel dressing, or an alginate dressing, and also adds a nano-polysaccharide compound or derivative. Mix the nano-polysaccharide with the wet dressing, so that the wound dressing can quickly absorb the wound exudate, has good moisture retention performance, and at the same time helps to enhance the mechanical properties of the dressing, but the antibacterial effect of the medical wound dressing is poor.

[0006] Therefore, it has important practical significance to develop a medical gel dressing with excellent mechanical properties and excellent antibacterial effect. Summary of the Invention

[0007] In view of the problems existing in the prior art, the present invention provides a nano medical gel dressing and its preparation method, which not only solves the problem of poor antibacterial effect of medical dressings, but also has good mechanical properties, excellent water absorption and storage efficacy, and strong drug loading capacity.

[0008] In order to achieve the above invention purposes, the technical scheme adopted by the present invention is as follows:

[0009] A preparation method of a nano medical gel dressing includes the following steps:

[0010] S1. Disperse nano titanium dioxide into anhydrous ethanol. After uniform dispersion, add γ-glycidyl ether oxypropyltrimethoxysilane, mix, heat up, and react in a nitrogen atmosphere. After the reaction ends, filter, wash, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide.

[0011] S2. Ultrasonically disperse the epoxidized titanium dioxide into deionized water, then add polyhexamethylene biguanide, stir and mix to react. After the reaction ends, filter, wash, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide.

[0012] S3. Ultrasonically disperse the amino-modified titanium dioxide into deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide, stir and mix to react. After the reaction ends, filter and freeze-dry to obtain modified titanium dioxide.

[0013] S4. Stir and mix gelatin and deionized water for 1 h. After uniform mixing, add polyethylene glycol, modified titanium dioxide, and sodium alginate, stir and mix for 2 - 4 h. After stirring and mixing, let stand for 12 h, and sterilize to obtain the nano medical gel dressing.

[0014] In the present invention, γ-glycidyl ether oxypropyltrimethoxysilane is used to modify nano titanium dioxide, introducing epoxy groups on the surface of nano titanium dioxide to obtain epoxidized titanium dioxide. The amino groups on polyhexamethylene biguanide and the epoxy groups on epoxidized titanium dioxide undergo ring-opening reactions, introducing a large number of hydroxyl groups, amino groups, and flexible long chains to obtain amino-modified titanium dioxide. The amino groups on the amino-modified titanium dioxide and sodium hyaluronate react under the action of 1-ethyl-(-3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to obtain modified titanium dioxide, introducing carboxyl groups and hydroxyl groups. Stir and mix gelatin, modified titanium dioxide, polyethylene glycol, sodium alginate, and deionized water to obtain the nano medical gel dressing.

[0015] In the present invention, sodium hyaluronate is a natural glycosaminoglycan present in the extracellular matrix of most tissues. It contains abundant carboxyl and hydroxyl groups, which can promote the migration and proliferation of fibroblasts and prevent the formation of scars. At the same time, sodium hyaluronate can adsorb and retain skin moisture, providing a long-lasting moisturizing effect. It has extremely strong water absorption capacity, can penetrate deep into the bottom layer of the skin, provide long-lasting moisture nourishment for the skin, and has excellent moisturizing efficacy.

[0016] Sodium alginate is non-toxic, has good biocompatibility, can be gelated, and has good thermal stability. It is widely used in fields such as medical dressings. Sodium alginate has good moisturizing performance, can maintain a moist environment at the wound surface, promote cell proliferation and tissue regeneration, thus accelerating wound healing, and has certain antibacterial and anti-inflammatory effects, which helps to reduce the risk of bacterial infection, relieve the inflammatory reaction around the wound surface, regulate the permeability of the liquid in the wound surface, reduce the loss of exudate, protect the wound surface environment, and accelerate the repair of the tissue at the bottom of the wound surface.

[0017] Gelatin is a product of partial hydrolysis of collagen. It is an amphoteric substance with both acidic and basic properties and has the characteristics of no antigenicity and easy absorption. As a carrier material, gelatin provides good biocompatibility and biodegradability in medical gel dressings. It helps the targeted delivery of drugs and improves the bioavailability of drugs in the body.

[0018] Polyethylene glycol can play the roles of wound protection, wound surface protection, promoting wound healing, relieving pain, and reducing scar formation in medical gel dressings. It can isolate bacteria and prevent infection. At the same time, the polyethylene glycol dressing has certain water absorption capacity, can keep the wound surface moist, and is beneficial to promoting healing.

[0019] Preferably, in the step S1, the mass ratio of nano-titanium dioxide, absolute ethanol, and γ-glycidoxypropyltrimethoxysilane is 100: 1500 - 1800: 45 - 65.

[0020] Preferably, in the step S1, the reaction temperature is 65 - 75 °C, and the reaction time is 12 - 18 h.

[0021] Preferably, in the step S2, the mass ratio of epoxidized titanium dioxide, deionized water, and polyhexamethylene biguanide is 100: 4000 - 4800: 210 - 250.

[0022] Preferably, in the step S2, the reaction temperature is 25 - 35 °C, and the reaction time is 24 - 36 h.

[0023] Preferably, in the step S3, the mass ratio of the amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide is 100: 5000-5500: 90-105: 82-100: 72-86.

[0024] Preferably, in the step S3, the reaction temperature is 25-35 °C and the reaction time is 18-24 h.

[0025] Preferably, in the step S4, the mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide and sodium alginate is 2-3: 100: 0.5-1.2: 1.5-3: 1.2-2.

[0026] Preferably, in the step S4, the stirring temperature is 50-55 °C.

[0027] The present invention also provides a nano medical gel dressing prepared by the above preparation method.

[0028] The beneficial effects of the present invention are as follows:

[0029] (1) Nano titanium dioxide is added to the nano medical gel dressing in the present invention, which has excellent antibacterial and mechanical properties; in the water and air system, electrons of nano titanium dioxide are excited from the valence band to the conduction band, corresponding holes are generated in the valence band, electron-hole pairs are formed, under the action of an electric field, electrons and holes are separated and migrate to the surface of titanium dioxide, the superoxide radicals formed react with the organic matter in bacteria, thus killing the bacteria and causing the decomposition of bacteria. Due to the quantum size effect of nano titanium dioxide, the migration speed is very fast and the bactericidal speed is fast; the guanidine group on polyhexamethylene guanidine has good biocompatibility, similar to the structure of natural antibacterial peptides. After the guanidine group is protonated, a positive charge is obtained, which can adsorb and bind various negatively charged bacteria, viruses and other microorganisms, form hydrogen bonds with the phosphates on bacteria, and destroy the structure of bacterial cells, resulting in the death of bacteria; after modification of nano titanium dioxide, the agglomeration of nano titanium dioxide is avoided, and at the same time, through the synergistic antibacterial effect between nano titanium dioxide and polyhexamethylene guanidine, the antibacterial efficiency and persistence are improved, and the purpose of rapid sterilization is achieved.

[0030] (2) In the present invention, gelatin, modified titanium dioxide, polyethylene glycol, and sodium alginate are used as raw materials, and a medical dressing gel is obtained through crosslinking. The raw materials used are non-toxic and harmless, and have good biocompatibility and degradability. The preparation process is simple and the production cost is low. The prepared gel dressing has excellent comprehensive properties. The prepared medical gel dressing can form a film to cover the wound surface, playing a physical protection role, reducing external stimulation to the wound surface, providing a more suitable microenvironment for the wound, and promoting cell growth and repair. Among them, both sodium alginate and sodium hyaluronate have high water absorption. The gel dressing contains hydrophilic groups such as carboxyl groups, hydroxyl groups, amide bonds, and amino groups, and can be significantly swollen by water but not dissolved in water. Electrostatic interactions occur between the amino and carboxyl groups on the gelatin molecule and the carboxyl groups on sodium alginate and the carboxyl groups on modified titanium dioxide, and hydrogen bonds are formed with the hydroxyl groups on polyethylene glycol at the same time, forming a three-dimensional network structure with good flexibility and good structural stability, having excellent effects of absorbing and storing moisture, having good drug loading capacity, and at the same time, the overall density of the gel increases, the polymer entanglement is more compact, the compressive strength is improved, and at the same time, the tensile strength and elongation at break are improved, and the mechanical properties are excellent. The nano-medical gel prepared by the present invention is not easy to adhere to the wound during dressing change, avoiding secondary damage caused by wound tearing.

[0031] (3) The nano-medical gel prepared by the present invention has a high swelling ratio, has excellent effects of absorbing and storing moisture, quickly and largely absorbs the exudate at the wound, and keeps the wound clean and dry. The present invention is particularly important for treating wounds with more exudate. By absorbing the exudate, the dressing can reduce the risk of wound infection and promote wound healing. After absorbing the exudate, the dressing will form a gel-like substance, and this gel can serve as a natural physical barrier to effectively block the invasion of external bacteria. Further, the dressing can fit the wound bed, minimizing the dead zone for bacterial reproduction, locking the bacteria in the exudate, inhibiting bacterial reproduction, and preventing wound infection. Specific embodiments

[0032] The technical solutions of the present invention will be further specifically described below through examples. These examples are for the purpose of illustrating the present invention and are not intended to limit the present invention. Based on the examples in this application, all other examples obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of this application.

[0033] The experimental methods described in the examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, can be obtained from commercial channels.

[0034] Example 1

[0035] A preparation method of a nano-medical gel dressing includes the following steps:

[0036] S1. Disperse nano-titanium dioxide into absolute ethanol. After uniform dispersion, add γ-glycidoxypropyltrimethoxysilane. The mass ratio of nano-titanium dioxide, absolute ethanol, and γ-glycidoxypropyltrimethoxysilane is 100:1500:45. Mix them, heat up, and react at 65 °C in a nitrogen atmosphere for 18 h. After the reaction, filter, wash with deionized water, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide;

[0037] S2. Ultrasonically disperse epoxidized titanium dioxide into deionized water, then add polyhexamethylene biguanide and stir to mix. The mass ratio of epoxidized titanium dioxide, deionized water, and polyhexamethylene biguanide is 100:4000:210. React at 25 °C for 36 h. After the reaction, filter, wash with deionized water, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide;

[0038] S3. Ultrasonically disperse amino-modified titanium dioxide into deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide. The mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is 100:5500:105:100:86. Stir to mix and react at 35 °C for 18 h. After the reaction, filter and freeze-dry to obtain modified titanium dioxide;

[0039] S4. Stir and mix gelatin and deionized water for 1 h at a stirring temperature of 50 °C. After uniform mixing, add polyethylene glycol, modified titanium dioxide, and sodium alginate. The mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate is 2:100:0.5:1.5:1.2. Stir and mix for 2 h, then let it stand for 12 h and sterilize to obtain a nano-medical gel dressing.

[0040] Example 2

[0041] A preparation method of a nano-medical gel dressing, comprising the following steps:

[0042] S1. Disperse nano-titanium dioxide into absolute ethanol. After uniform dispersion, add γ-glycidoxypropyltrimethoxysilane. The mass ratio of nano-titanium dioxide, absolute ethanol, and γ-glycidoxypropyltrimethoxysilane is 100:1650:55. Mix them, heat up, and react at 70 °C in a nitrogen atmosphere for 15 h. After the reaction, filter, wash with deionized water, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide;

[0043] S2. Ultrasonically disperse the epoxidized titanium dioxide in deionized water, then add polyhexamethylene biguanide and stir to mix. The mass ratio of epoxidized titanium dioxide, deionized water, and polyhexamethylene biguanide is 100:4200:225. React at 30 °C for 32 h. After the reaction, filter, wash with deionized water, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide.

[0044] S3. Ultrasonically disperse the amino-modified titanium dioxide in deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide. The mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is 100:5200:95:90:78. Stir to mix and react at 30 °C for 20 h. After the reaction, filter and freeze-dry to obtain modified titanium dioxide.

[0045] S4. Stir and mix gelatin and deionized water for 1 h at a stirring temperature of 52 °C. After mixing evenly, add polyethylene glycol, modified titanium dioxide, and sodium alginate. The mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate is 2.4:100:0.8:2:1.5. Stir and mix for 3 h, then let stand for 12 h and sterilize to obtain the nano medical gel dressing.

[0046] Example 3

[0047] A preparation method of a nano medical gel dressing, comprising the following steps:

[0048] S1. Disperse nano titanium dioxide in absolute ethanol. After dispersing evenly, add γ-glycidoxypropyltrimethoxysilane. The mass ratio of nano titanium dioxide, absolute ethanol, and γ-glycidoxypropyltrimethoxysilane is 100:1650:55. Mix, heat up, and react in a nitrogen atmosphere at 70 °C for 15 h. After the reaction, filter, wash with deionized water, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide.

[0049] S2. Ultrasonically disperse the epoxidized titanium dioxide in deionized water, then add polyhexamethylene biguanide and stir to mix. The mass ratio of epoxidized titanium dioxide, deionized water, and polyhexamethylene biguanide is 100:4600:240. React at 30 °C for 35 h. After the reaction, filter, wash with deionized water, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide.

[0050] S3. Ultrasonically disperse amino-modified titanium dioxide in deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, where the mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide is 100:5400:102:95:82. Stir and mix, react at 30 °C for 22 h. After the reaction, filter and freeze-dry to obtain modified titanium dioxide;

[0051] S4. Stir and mix gelatin and deionized water for 1 h at a stirring temperature of 52 °C. After mixing evenly, add polyethylene glycol, modified titanium dioxide and sodium alginate, where the mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide and sodium alginate is 2.8:100:1:2.5:1.8. Stir and mix for 3.5 h, then let stand for 12 h and sterilize to obtain the nano medical gel dressing.

[0052] Example 4

[0053] A preparation method of a nano medical gel dressing, comprising the following steps:

[0054] S1. Disperse nano titanium dioxide in absolute ethanol. After dispersing evenly, add γ-glycidoxypropyltrimethoxysilane, where the mass ratio of nano titanium dioxide, absolute ethanol and γ-glycidoxypropyltrimethoxysilane is 100:1800:65. Mix, heat up, and react at 75 °C in a nitrogen atmosphere for 12 h. After the reaction, filter, wash with deionized water, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide;

[0055] S2. Ultrasonically disperse epoxidized titanium dioxide in deionized water, then add polyhexamethylene biguanide and stir and mix. The mass ratio of epoxidized titanium dioxide, deionized water and polyhexamethylene biguanide is 100:4800:250. React at 35 °C for 24 h. After the reaction, filter, wash with deionized water, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide;

[0056] S3. Ultrasonically disperse amino-modified titanium dioxide in deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, where the mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide is 100:5500:105:100:86. Stir and mix, react at 35 °C for 18 h. After the reaction, filter and freeze-dry to obtain modified titanium dioxide;

[0057] S4. Stir and mix gelatin and deionized water for 1 h at a temperature of 55 °C. After mixing evenly, add polyethylene glycol, modified titanium dioxide, and sodium alginate. The mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate is 3:100:1.2:3:2. Stir and mix for 4 h. After stirring and mixing, let it stand for 12 h, sterilize, and obtain the nano medical gel dressing.

[0058] Comparative Example 1

[0059] A preparation method of a medical gel dressing includes the following steps:

[0060] S1. Disperse nano titanium dioxide into absolute ethanol. After dispersing evenly, add γ-aminopropyltriethoxysilane. The mass ratio of nano titanium dioxide, absolute ethanol, and γ-aminopropyltriethoxysilane is 100:1650:55. Mix, heat up, and react at 70 °C in a nitrogen atmosphere for 15 h. After the reaction is completed, filter, wash with deionized water, and vacuum dry at 60 °C for 12 h to obtain amino-functionalized titanium dioxide.

[0061] S2. Ultrasonically disperse the amino-functionalized titanium dioxide into deionized water, and add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide. The mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is 100:5400:102:95:82. Stir and mix, and react at 30 °C for 22 h. After the reaction is completed, filter and freeze-dry to obtain modified titanium dioxide.

[0062] S3. Stir and mix gelatin and deionized water for 1 h at a temperature of 52 °C. After mixing evenly, add polyethylene glycol, modified titanium dioxide, and sodium alginate. The mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate is 2.8:100:1:2.5:1.8. Stir and mix for 3.5 h. After stirring and mixing, let it stand for 12 h, sterilize, and obtain the medical gel dressing.

[0063] Comparative Example 2

[0064] A preparation method of a medical gel dressing includes the following steps:

[0065] S1. Stir and mix gelatin and deionized water for 1 h at a stirring temperature of 52 °C. After mixing evenly, add polyethylene glycol, nano-titanium dioxide, polyhexamethylene biguanide, and sodium alginate. The mass ratio of gelatin, deionized water, polyethylene glycol, nano-titanium dioxide, polyhexamethylene biguanide, and sodium alginate is 2.8:100:1:0.7:1.8:1.8. Stir and mix for 3.5 h. After stirring and mixing, let it stand for 12 h and sterilize to obtain a medical gel dressing.

[0066] In the examples and comparative examples of the present invention, nano-titanium dioxide was purchased from Xuancheng Jingrui New Materials Co., Ltd., with the model JR05 and an average particle size of 5 nm; sodium alginate and sodium hyaluronate were both purchased from Shanghai Macklin Biochemical Co., Ltd.; polyethylene glycol was purchased from Nantong Jiaxian International Trade Co., Ltd.; other undisclosed reagents were all commercially available.

[0067] Take the medical gel dressings prepared in Examples 1-4 and Comparative Examples 1-2 as samples, denoted as Samples 1-6 respectively, and conduct corresponding tests on the samples. The test methods and test results are as follows:

[0068] (1) Mechanical property test

[0069] 1) Compressive strength test: At room temperature, use a twelve-well plate to prepare a cylindrical gel with a diameter of 20 mm and a height of 5 mm. Use a physical property analyzer to conduct a compression test on the sample until it is broken, and set the compression rate to 0.5 mm / s. Each group of specimens is subjected to five compression tests;

[0070] 2) Cut the sample into a dumbbell shape with a total length of 75 cm, a test part length of 40 mm, and a width of 4 mm. Clamp the upper and lower ends of the specimen to a tensile testing machine and stretch it at a tensile speed of 100 mm / min to measure the tensile strength and elongation at break when it breaks. Each sample is tested three times and the average value is taken;

[0071] (2) Swelling property test: Place the sample in a vacuum freeze dryer and dry it to a constant weight. Take dry gel discs with similar size and mass, and record the mass as M0. Immerse the dried gel discs in deionized water, take them out at regular intervals, dry the surface moisture and then weigh, and record the mass at this time as Mt. Calculate the swelling ratio SR. The calculation method of the swelling ratio is as follows: SR = (Mt - M0) / Mt × 100%, where M0 and Mt are the masses of the dry gel and the hydrogel at time t respectively;

[0072] (3)Antibacterial performance test: 0.1 g of the sample was taken and mixed with 10 mL of Escherichia coli bacterial solution and Staphylococcus aureus bacterial solution at a concentration of 1×10⁷ CFU / mL in a test tube, and then placed on a constant temperature shaking incubator and cultured at 37 °C at a rotation speed of 120 r / min for 4 h. Then, it was incubated in a shaking incubator under natural indoor light conditions for 24 h. The antibacterial rate was calculated by the plate colony counting method. The calculation method of the antibacterial rate is as follows: Antibacterial rate = (M1 - M2) / M1×100%, where M1 and M2 are the initial colony count and the colony count after culture, respectively;

[0073] The above test results are shown in Table 1:

[0074] Table 1

[0075]

[0076] According to the test results in Table 1, it can be seen that the medical gel dressings prepared in Examples 1-4 have excellent mechanical properties, swelling properties and antibacterial properties. In Comparative Example 1, nano-titanium dioxide was directly aminized to obtain aminized titanium dioxide. Aminized titanium dioxide reacted with sodium hyaluronate to obtain modified titanium dioxide, and then it was mixed with gelatin, polyethylene glycol and sodium alginate to obtain a medical gel dressing. Since polyhexamethylene biguanide was not introduced, the antibacterial property was greatly reduced, and the mechanical properties and swelling ratio decreased. In Comparative Example 2, nano-titanium dioxide was not modified, the dispersibility of nano-titanium dioxide was greatly reduced, the compatibility with raw materials became poor, and the crosslinking degree became poor. As a result, the comprehensive performance of the prepared medical gel dressing was greatly reduced.

[0077] In the present invention, gelatin, deionized water, polyethylene glycol, modified titanium dioxide and sodium alginate are used as raw materials. After mixing, a medical dressing gel is obtained through crosslinking. The raw materials used in the present invention are non-toxic and harmless and have good biocompatibility. They can form a film to cover the wound surface, playing a physical protection role, reducing external stimulation to the wound surface, and then promoting tissue repair. The formed three-dimensional network structure has good stability, excellent water absorption and storage effects, strong drug loading capacity. Nano-titanium dioxide and polyhexamethylene guanidine improve the antibacterial efficiency and persistence through synergistic antibacterial effects, achieving the purpose of rapid sterilization. At the same time, the overall density of the gel increases, the polymer entanglement becomes more compact, the compressive strength is improved, and at the same time, the tensile strength and elongation at break are improved, and the mechanical properties are excellent.

[0078] Finally, it should also be noted that although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirits of the present invention. All equivalent changes and improvements made within the scope of the application of the present invention should still fall within the scope covered by the present invention.

Claims

1. A preparation method of a nano medical gel dressing, characterized in that: It includes the following steps: S1. Disperse nano-titanium dioxide in absolute ethanol. After uniform dispersion, add γ-glycidoxypropyltrimethoxysilane, mix, heat up, and react in a nitrogen atmosphere. After the reaction is completed, filter, wash, and vacuum dry at 60 °C for 12 h to obtain epoxidized titanium dioxide; S2. Ultrasonically disperse the epoxidized titanium dioxide in deionized water, then add polyhexamethylene biguanide, stir and mix to react. After the reaction is completed, filter, wash, and dry at 60 °C for 24 h to obtain amino-modified titanium dioxide; S3. Ultrasonically disperse the amino-modified titanium dioxide in deionized water, add sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide, and N-hydroxysuccinimide, stir and mix to react. After the reaction is completed, filter and freeze-dry to obtain modified titanium dioxide; S4. Stir and mix gelatin and deionized water for 1 h. After uniform mixing, add polyethylene glycol, modified titanium dioxide, and sodium alginate, stir and mix for 2 - 4 h. After stirring and mixing, let it stand for 12 h and sterilize to obtain a nano medical gel dressing; In step S1, the mass ratio of nano-titanium dioxide, absolute ethanol, and γ-glycidoxypropyltrimethoxysilane is 100:1500 - 1800:45 - 65; In step S2, the mass ratio of epoxidized titanium dioxide, deionized water, and polyhexamethylene biguanide is 100:4000 - 4800:210 - 250; In step S3, the mass ratio of amino-modified titanium dioxide, deionized water, sodium hyaluronate, 1-ethyl-(-3-dimethylaminopropyl) carbodiimide, and N-hydroxysuccinimide is 100:5000 - 5500:90 - 105:82 - 100:72 - 86; In step S4, the mass ratio of gelatin, deionized water, polyethylene glycol, modified titanium dioxide, and sodium alginate is 2 - 3:100:0.5 - 1.2:1.5 - 3:1.2 - 2; 2. The preparation method of a nano medical gel dressing according to claim 1, characterized in that: In step S1, the reaction temperature is 65 - 75 °C and the reaction time is 12 - 18 h; 3. The preparation method of a nano medical gel dressing according to claim 1, characterized in that: In step S2, the reaction temperature is 25 - 35 °C and the reaction time is 24 - 36 h; 4. The preparation method of a nano medical gel dressing according to claim 1, characterized in that: In step S3, the reaction temperature is 25 - 35 °C and the reaction time is 18 - 24 h; 5. The preparation method of a nano medical gel dressing according to claim 1, characterized in that: In step S4, the stirring temperature is 50 - 55 °C; 6. A nano medical gel dressing prepared by using the preparation method of the nano medical gel dressing according to any one of claims 1 - 5.

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