Silicone gel for scar repair and preparation method thereof

Abstract

The invention discloses silicone gel for scar repair and a preparation method thereof, and belongs to the technical field of silicone gel for scar repair. The zein is thermally modified, the chlorella polysaccharide and the thermally modified whey protein are compounded, sulfate groups of the chlorella polysaccharide enable double-helix structures of the zein to be close to each other to form a stable gel network, ursolic acid has antibacterial, anti-inflammatory and antioxidant properties, and the chlorella polysaccharide and the ursolic acid have rich hydroxyl groups, so that the anti-inflammatory and anti-aging effects are achieved. Intermolecular hydrogen bonds are formed to promote the formation of a gel network, so that the silicone gel has hydrophilic water-retaining property and absorbs tissue fluid; a flexible three-dimensional network is formed between zein and chlorella polysaccharide, and a rigid network is formed by the chlorella polysaccharide, vinyltriethoxysilane and dihydroxyl-terminated polydimethylsiloxane through hydrosilylation, so that the ketone gel has a rigid and flexible synergistic dual-network structure; and the adhesive force is mild, the adhesive force is not adhered to a wound bed, the mechanical property is better, and the cytotoxicity is avoided.

Description

Technical Field

[0001] The invention belongs to the technical field of scar repair silicone gel, and in particular relates to a silicone gel for scar repair and a preparation method thereof. Background Art

[0002] Scars are an inevitable physiological phenomenon in the process of human wound healing. Wound repair is divided into two types: simple epithelialization healing of superficial wounds and scar repair after deep damage to the dermis and subcutaneous tissue. In the process of wound treatment, wound dressings play a key role, and gel dressings have attracted much attention due to their softness and water retention. With their high water content, hydrogel dressings can prevent tissue dehydration, promote autolysis and debridement of necrotic and exfoliated cells through rehydration, stimulate wound healing and reduce temperature and relieve pain, and can also create a moist environment, leave no residue and facilitate wound re-epithelialization.

[0003] However, existing hydrogel dressings have obvious defects. Their high water content leads to a serious lack of ability to absorb exudates, and they can only be applied to dry wounds or wounds with only a small amount of exudate. They cannot effectively deal with wounds with more exudate, which limits their scope of use in various trauma repair scenarios. Moreover, conventional hydrogel dressings have room for improvement in gel properties, such as gelling, flexibility and stability. Their structure is relatively simple, and it is difficult to achieve an ideal balance in mechanical properties, adhesion and other aspects. For example, there may be problems such as poor adhesion or adhesion to the wound bed. At the same time, the comprehensive performance of promoting wound healing, such as antibacterial, anti-inflammatory, antioxidant ability and hydrophilic water retention, needs to be further optimized, and cannot fully meet the various complex requirements for wound dressings in the scar repair process. Summary of the invention

[0004] In view of the above situation, in order to overcome the defects of the prior art, the present invention conducts thermal modification on zein to improve its gelation, flexibility and stability, and compound with Chlorella polysaccharide, and uses the negative charge of its sulfate group to make the double helix structure of zein interact to form a stable gel network, and then combines the antibacterial, anti-inflammatory and antioxidant properties brought by the pentacyclic triterpene structure of ursolic acid, and utilizes it to form intermolecular hydrogen bonds with the hydroxyl groups of Chlorella polysaccharide, so as to enhance the network and impart hydrophilic and water-retaining properties to absorb tissue fluid, thereby achieving the optimization of silicone gel performance and providing a more effective solution for scar repair.

[0005] In order to achieve the above object, the following technical scheme is adopted: the present invention provides a method for preparing silicone gel for scar repair and a preparation method thereof, the preparation method comprising the following steps:

[0006] S1, adding chlorella polysaccharide to deionized water, then heating to 50-80°C, stirring to dissolve, to obtain a chlorella polysaccharide solution, dispersing zein in deionized water, stirring at 40°C for 2h, and then heating at 90°C for 20min to obtain a zein dispersion, separating the supernatant by centrifugation, freeze-drying at -20°C for 12h to obtain heat-modified zein, adding the heat-modified zein to deionized water, adding glycerol, and stirring to obtain a heat-modified zein solution;

[0007] S2, adding ursolic acid oil solution to the heat-modified zein solution for pre-emulsification, and then adding chlorella polysaccharide solution to obtain a mixed solution, and then adding vinyl triethoxysilane to the mixed solution, heating to 80-100° C., reacting for 24-36 hours, adding 2 times the volume of anhydrous ethanol to the mixed solution, stirring evenly and then centrifuging, washing the obtained precipitate with anhydrous ethanol three times, and drying at 60-80° C. for 12-24 hours to obtain a modified chlorella polysaccharide / zein complex;

[0008] S3. Add the modified Chlorella polysaccharide / zein complex into deionized water, disperse it by ultrasonic, add dihydroxy-terminated polydimethylsiloxane and Custer catalyst, heat to 80-100° C. to react for 1-3 hours, apply film with a coating machine, and cure at room temperature to obtain the silicone gel.

[0009] Furthermore, the mass concentration of the Chlorella polysaccharide solution is 5-10%.

[0010] Furthermore, the mass concentration of the zein dispersion is 10-20%.

[0011] Furthermore, in the heat-modified zein solution, the mass concentration of the heat-modified zein is 5-15%, and the mass concentration of the glycerol is 1-3%.

[0012] Furthermore, the mass concentration of the ursolic acid oil solution is 1-5%.

[0013] Furthermore, the solvent of the ursolic acid oil solution is one of epoxidized soybean oil, sunflower seed oil, linseed oil and palm oil.

[0014] Furthermore, in step S2, the mass ratio of the heat-modified zein solution, the ursolic acid oil solution, the Chlorella polysaccharide solution and the vinyl triethoxysilane is 4:1.5-3:3-5:0.1-0.5.

[0015] Furthermore, in step S3, the mass ratio of vinyl triethoxysilane, deionized water, dihydroxy-terminated polydimethylsiloxane and Custer catalyst is 1:40-60:2-4.5:1.2-3.

[0016] Furthermore, the ultrasonic dispersion in step S3 is performed for 30-60 minutes at a power of 100-400W.

[0017] The beneficial effects of the present invention are:

[0018] (1) The present invention improves the gelling property of the protein by heat-modifying zein, thereby increasing the flexibility and stability of the protein molecules. Chlorella polysaccharide and heat-modified whey protein are compounded. The sulfate group of chlorella polysaccharide carries a negative charge, so that the double helix structures of zein are close to each other and interact with each other, thereby forming a stable gel network. Ursolic acid has a pentacyclic triterpene structure and has antibacterial, anti-inflammatory and antioxidant properties. Chlorella polysaccharide and ursolic acid have abundant hydroxyl groups on their surfaces, forming intermolecular hydrogen bonds, promoting the formation of a gel network, and making the silicone gel hydrophilic and water-retaining, thereby absorbing tissue fluid.

[0019] (2) The present invention forms a flexible three-dimensional network between zein and Chlorella polysaccharide, and forms a rigid network with Chlorella polysaccharide, vinyl triethoxysilane and dihydroxy-terminated polydimethylsiloxane by the hydrosilylation method, so that the prepared silicone gel has a double network structure with synergistic rigidity and flexibility. The silicone gel prepared by the present invention has mild adhesion, does not adhere to the wound bed, has good mechanical properties, is non-cytotoxic, and can effectively promote wound healing. It is a good wound dressing for scar repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The mechanical properties test results of the silicone gel prepared by the present invention;

[0021] Figure 2 The swelling test results of the silicone gel prepared in the present invention are as follows;

[0022] Figure 3 The peel strength test results of the silicone gel prepared in the present invention are as follows;

[0023] Figure 4 The cytotoxicity test results of the silicone gel prepared in the present invention are shown.

[0024] The accompanying drawings are used to provide further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention. DETAILED DESCRIPTION

[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0026] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.

[0027] The experimental methods in the following examples are conventional methods unless otherwise specified, and the experimental materials used in the following examples are purchased from commercial channels unless otherwise specified.

[0028] Example 1

[0029] A preparation method of silicone gel for scar repair and a preparation method thereof, the preparation method comprising the following steps:

[0030] S1, adding chlorella polysaccharide to deionized water, then heating to 50°C, stirring to dissolve, to obtain a chlorella polysaccharide solution, dispersing zein in deionized water, stirring at 40°C for 2h, and then heating at 90°C for 20min to obtain a zein dispersion, separating the supernatant by centrifugation, freeze-drying at -20°C for 12h to obtain heat-modified zein, adding the heat-modified zein to deionized water, adding glycerol, and stirring to obtain a heat-modified zein solution;

[0031] S2, adding ursolic acid oil solution to the heat-modified zein solution for pre-emulsification, and then adding chlorella polysaccharide solution to obtain a mixed solution, and then adding vinyl triethoxysilane to the mixed solution, heating to 80°C, reacting for 24-36h, adding 2 times the volume of anhydrous ethanol to the mixed solution, stirring evenly and then centrifuging, washing the obtained precipitate with anhydrous ethanol three times, and drying at 60°C for 12h to obtain a modified chlorella polysaccharide / zein complex;

[0032] S3. Add the modified Chlorella polysaccharide / zein complex into deionized water, disperse it by ultrasonic, add dihydroxy-terminated polydimethylsiloxane and Custer catalyst, heat to 80-100° C. to react for 1-3 hours, apply film with a coating machine, and cure at room temperature to obtain the silicone gel.

[0033] The mass concentration of the chlorella polysaccharide solution is 5%; the mass concentration of the zein dispersion is 10%; the mass concentration of the heat-modified zein solution is 5%, and the mass concentration of glycerol is 1%; the mass concentration of the ursolic acid oil solution is 1%; the solvent of the ursolic acid oil solution is epoxidized soybean oil; the mass ratio of the heat-modified zein solution, the ursolic acid oil solution, the chlorella polysaccharide solution and vinyl triethoxysilane in the step S2 is 4:1.5:3:0.1; the mass ratio of vinyl triethoxysilane, deionized water, dihydroxy-terminated polydimethylsiloxane and Custer catalyst in the step S3 is 1:40:2:1.2; the ultrasonic dispersion time in the step S3 is 30 minutes, and the power is 100W.

[0034] Example 2

[0035] A preparation method of silicone gel for scar repair and a preparation method thereof, the preparation method comprising the following steps:

[0036] S1, adding chlorella polysaccharide to deionized water, then heating to 80°C, stirring to dissolve, to obtain a chlorella polysaccharide solution, dispersing zein in deionized water, stirring at 40°C for 2h, and then heating at 90°C for 20min to obtain a zein dispersion, separating the supernatant by centrifugation, freeze-drying at -20°C for 12h to obtain heat-modified zein, adding the heat-modified zein to deionized water, adding glycerol, and stirring to obtain a heat-modified zein solution;

[0037] S2, adding ursolic acid oil solution to the heat-modified zein solution for pre-emulsification, and then adding chlorella polysaccharide solution to obtain a mixed solution, and then adding vinyl triethoxysilane to the mixed solution, heating to 100 ° C, reacting for 36 hours, adding 2 times the volume of anhydrous ethanol to the mixed solution, stirring evenly and then centrifuging, washing the obtained precipitate with anhydrous ethanol three times, and drying at 80 ° C for 24 hours to obtain a modified chlorella polysaccharide / zein complex;

[0038] S3. Add the modified Chlorella polysaccharide / zein complex into deionized water, disperse it by ultrasonic, add dihydroxy-terminated polydimethylsiloxane and Custer catalyst, heat to 100° C. to react for 3 hours, apply film by a coating machine, and cure at room temperature to obtain the silicone gel.

[0039] The mass concentration of the chlorella polysaccharide solution is 10%; the mass concentration of the zein dispersion is 20%; the mass concentration of the heat-modified zein in the heat-modified zein solution is 15%, and the mass concentration of glycerol is 3%; the mass concentration of the ursolic acid oil solution is 5%; the solvent of the ursolic acid oil solution is sunflower oil; in the step S2, the mass ratio of the heat-modified zein solution, the ursolic acid oil solution, the chlorella polysaccharide solution and vinyl triethoxysilane is 4:3:5:0.5; in the step S3, the mass ratio of vinyl triethoxysilane, deionized water, dihydroxy-terminated polydimethylsiloxane and Custer catalyst is 1:60:4.5:3; the ultrasonic dispersion time in the step S3 is 60 minutes, and the power is 400W.

[0040] Example 3

[0041] A preparation method of silicone gel for scar repair and a preparation method thereof, the preparation method comprising the following steps:

[0042] S1, adding chlorella polysaccharide to deionized water, then heating to 60°C, stirring to dissolve, to obtain a chlorella polysaccharide solution, dispersing zein in deionized water, stirring at 40°C for 2h, and then heating at 90°C for 20min to obtain a zein dispersion, separating the supernatant by centrifugation, freeze-drying at -20°C for 12h to obtain heat-modified zein, adding the heat-modified zein to deionized water, adding glycerol, and stirring to obtain a heat-modified zein solution;

[0043] S2, adding ursolic acid oil solution to the heat-modified zein solution for pre-emulsification, and then adding chlorella polysaccharide solution to obtain a mixed solution, and then adding vinyl triethoxysilane to the mixed solution, heating to 90°C, reacting for 30 hours, adding 2 times the volume of anhydrous ethanol to the mixed solution, stirring evenly and then centrifuging, washing the obtained precipitate with anhydrous ethanol three times, and drying at 60-80°C for 18 hours to obtain a modified chlorella polysaccharide / zein complex;

[0044] S3. Add the modified Chlorella polysaccharide / zein complex into deionized water, disperse it by ultrasonic, add dihydroxy-terminated polydimethylsiloxane and Custer catalyst, heat to 90° C. to react for 2 h, apply film with a coating machine, and cure at room temperature to obtain the silicone gel.

[0045] The mass concentration of the chlorella polysaccharide solution is 8%; the mass concentration of the zein dispersion is 15%; the mass concentration of the heat-modified zein in the heat-modified zein solution is 10%, and the mass concentration of glycerol is 2%; the mass concentration of the ursolic acid oil solution is 2%; the solvent of the ursolic acid oil solution is linseed oil; in the step S2, the mass ratio of the heat-modified zein solution, the ursolic acid oil solution, the chlorella polysaccharide solution and vinyl triethoxysilane is 4:2:4:0.2; in the step S3, the mass ratio of vinyl triethoxysilane, deionized water, dihydroxy-terminated polydimethylsiloxane and Custer catalyst is 1:50:3:1.5; the ultrasonic dispersion time in the step S3 is 50 minutes, and the power is 300W.

[0046] Comparative Example 1

[0047] In this comparative example, no zein was used in the process of preparing silicone gel. That is, an equal amount of the chlorella polysaccharide solution prepared in step S1 was used instead of the heat-modified zein solution to mix with the ursolic acid oil solution. The remaining raw materials, mass ratios, and preparation methods were the same as those in Example 3.

[0048] Comparative Example 2

[0049] In this comparative example, no ursolic acid oil solution was added in the preparation of silicone gel, and the remaining raw materials, mass ratio and preparation method were the same as those in Example 3.

[0050] Comparative Example 3

[0051] In this comparative example, zein was not thermally modified, that is, an equal amount of zein was used instead of modified zein to be mixed with glycerol, and the remaining raw materials, mass ratio, and preparation method were the same as those in Example 3.

[0052] Results Analysis

[0053] Test Example 1

[0054] Silicone gel mechanical properties test

[0055] The tensile strength of silicone gel was tested using an Instron 68TM-5 tensile testing machine in accordance with GB / T 528-2009. The results are shown in Figure 1 .

[0056] Depend on Figure 1It can be seen that the silicone gel of Examples 1-3 has good mechanical properties, which is due to its unique double network structure, namely the flexible three-dimensional network formed by zein and Chlorella polysaccharide and the rigid network formed by Chlorella polysaccharide, vinyl triethoxysilane and dihydroxy-terminated polydimethylsiloxane. This synergistic double network structure allows the silicone gel to have a certain flexibility to adapt to different usage scenarios and wound shapes, while also having good mechanical properties, and can maintain structural integrity in wound dressing applications, effectively resist external pulling and other forces, prevent the gel from rupturing or deformation, thereby better playing its role in protecting wounds and promoting healing.

[0057] Test Example 2

[0058] Silicone gel swelling test

[0059] The swelling rate and water absorption of silicone gel were measured according to the standard YY / T 0471.1-2004. The results are shown in Figure 2 .

[0060] Depend on Figure 2 It can be seen that the swelling property of the modified silicone gel is improved. This is because the abundant hydroxyl groups on the surface of Chlorella polysaccharide and ursolic acid form intermolecular hydrogen bonds, which promote the formation of the gel network and make the silicone gel hydrophilic and water-retaining, and able to absorb tissue fluid. During the wound healing process, good swelling properties can enable the silicone gel to better interact with the tissue fluid secreted by the wound. On the one hand, it maintains a moist environment for the wound, which is beneficial to cell migration and proliferation and promotes wound healing; on the other hand, it can absorb excess tissue fluid to prevent problems such as infection caused by wound accumulation of fluid.

[0061] Test Example 3

[0062] Silicone gel peel strength test

[0063] The silicone gels prepared in each embodiment and comparative example were tested for peel strength using an Instron 68TM-5 tensile testing machine according to the standard of GB / T 22396. The results are shown in Figure 3 .

[0064] Depend on Figure 3 It can be seen that the smaller peel strength is very important in the application of silicone gel for wound dressings for scar repair. When the silicone gel is removed from the wound surface, the lower peel strength can avoid secondary damage to the wound bed, especially for new scar tissue or more sensitive wound areas. The tissue being repaired will not be torn due to excessive adhesion, thereby ensuring the smooth progress of the wound healing process. Compared with Comparative Examples 1-3, Examples 1-3 perform better in peel strength and are more in line with the requirements of being an ideal wound dressing.

[0065] Test Example 4

[0066] Cytotoxicity test

[0067] After the silicone gel prepared in each embodiment and comparative example was sterilized for 24 hours, it was sterilized under aseptic conditions at a temperature of 1.25 cm 2 / mL extraction ratio to prepare the extract, the mouse fibroblast L-929 cells in the logarithmic growth phase were digested with trypsin, and the cell culture medium was added to adjust the cell concentration to 1×10 4 The prepared cell suspension was inoculated into a 96-well plate, 100 μL per well, and placed in a 5% CO 2 Incubator at 37°C for 24 hours, discard the original culture medium, add fresh MEM cell culture medium to the blank control group, add sample extract to the test group, add high-density polyethylene extract to the negative control group, and add culture medium containing 5% dimethyl sulfoxide to the positive control group, 100 μL per well, and place in CO 2 The cells were cultured in the incubator for 72 h. After the culture medium was replaced for 72 h, the above groups were placed under a microscope to observe the cell morphology. 20 μL of 5 g / L MTT solution was added to each well. After 4 h of culture, the liquid in the well was discarded and 150 μL of DMSO was added. After oscillation for 10 min, the absorbance was measured at 570 nm and 630 nm using an enzyme marker. The relative proliferation rate was calculated as absorbance of the test group / absorbance of the blank control group × 100%. The results are shown in Table 1. Figure 4 .

[0068] From the above results, it can be seen that the relative proliferation rate of cells is higher than 95%, indicating that the silicone gel prepared in Examples 1-3 has no obvious cytotoxicity. Therefore, during the use of the silicone gel, when it comes into direct or indirect contact with cells, it will not inhibit or damage the normal growth, proliferation and other physiological activities of the cells, thereby ensuring that in the process of promoting wound healing, the silicone gel has good biocompatibility with the surrounding cell tissues, can provide cells with a safe and suitable microenvironment, and is conducive to the cells participating in the wound repair process, such as fibroblasts synthesizing collagen and other related activities that promote scar repair.

[0069] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0070] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.

Claims

1. A method for preparing a silicone gel for scar repair, characterized in that: The steps include: S1, adding chlorella polysaccharide to deionized water, then heating to 50-80°C, stirring to dissolve, to obtain a chlorella polysaccharide solution, dispersing zein in deionized water, stirring at 40°C for 2h, and then heating at 90°C for 20min to obtain a zein dispersion, separating the supernatant by centrifugation, freeze-drying at -20°C for 12h to obtain heat-modified zein, adding the heat-modified zein to deionized water, adding glycerol, and stirring to obtain a heat-modified zein solution; S2, adding ursolic acid oil solution to the heat-modified zein solution for pre-emulsification, and then adding chlorella polysaccharide solution to obtain a mixed solution, and then adding vinyl triethoxysilane to the mixed solution, heating to 80-100° C., reacting for 24-36 hours, adding 2 times the volume of anhydrous ethanol to the mixed solution, stirring evenly and then centrifuging, washing the obtained precipitate with anhydrous ethanol three times, and drying at 60-80° C. for 12-24 hours to obtain a modified chlorella polysaccharide / zein complex; S3. Add the modified Chlorella polysaccharide / zein complex into deionized water, disperse it by ultrasonic, add dihydroxy-terminated polydimethylsiloxane and Custer catalyst, heat to 80-100° C. to react for 1-3 hours, apply film with a coating machine, and cure at room temperature to obtain the silicone gel.

2. The heat-modified zein according to claim 1, characterized in that: The mass concentration of the chlorella polysaccharide solution is 5-10%.

3. The heat-modified zein according to claim 2, characterized in that: The mass concentration of the zein dispersion is 10-20%.

4. The heat-modified zein according to claim 3, characterized in that: The mass concentration of the heat-modified zein in the heat-modified zein solution is 5-15%, and the mass concentration of the glycerol is 1-3%.

5. The heat-modified zein according to claim 4, characterized in that: The mass concentration of the ursolic acid oil solution is 1-5%.

6. The heat-modified zein according to claim 5, characterized in that: The solvent of the ursolic acid oil solution is one of epoxidized soybean oil, sunflower seed oil, linseed oil and palm oil.

7. The heat-modified zein according to claim 6, characterized in that: In the step S2, the mass ratio of the heat-modified zein solution, the ursolic acid oil solution, the Chlorella polysaccharide solution and the vinyl triethoxysilane is 4:1.5-3:3-5:0.1-0.

5.

8. The heat-modified zein according to claim 7, characterized in that: In the step S3, the mass ratio of vinyl triethoxysilane, deionized water, dihydroxy-terminated polydimethylsiloxane and Custer catalyst is 1:40-60:2-4.5:1.2-3.

9. The heat-modified zein according to claim 8, characterized in that: The ultrasonic dispersion in step S3 is performed for 30-60 minutes at a power of 100-400W.

10. A silicone gel for scar repair, characterized in that: It is prepared by the preparation method according to any one of claims 1 to 9.

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