Bioactive glass ointment and preparation method thereof

Abstract

The invention discloses bioactive glass ointment and a preparation method thereof. The method comprises the following steps: mixing and melting a first alcohol polymer and a second alcohol polymer to form a mobile phase matrix; carrying out high-speed shearing and constant-temperature stirring on the basic carrier, and crosslinking the interpenetrating structure carrier to obtain a crosslinked matrix; adding chitosan, tannic acid, vitamin E succinate and glutaraldehyde into the cross-linked matrix, and carrying out laminar stirring; preparing modified bioactive glass particles, and adding the modified bioactive glass particles into the response carrier to obtain a modified matrix; sequentially adding dimethyl sulfoxide, glycerol and trehalose into the modified matrix, and sequentially performing staged freezing, drying and grinding to obtain the bioactive glass ointment. The preparation has the advantages of low toxicity, stability, process controllability and clinical applicability, unification of targeted therapy, long-acting antibacterial property and clinical usability is realized, and an innovative solution is provided for wound repair.

Description

Technical Field

[0001] The present invention relates to the fields of biomedical materials, tissue engineering and regenerative medicine, and in particular to a bioactive glass ointment and a preparation method thereof. Background Art

[0002] Refractory wounds are those that fail to heal continuously or are incapable of healing. These wounds are caused by multiple factors that are impaired during the wound healing process. Common examples of refractory wounds include diabetic ulcers, burns, and bedsores.

[0003] Topical ointments are a class of semi-solid or near-solid preparations specifically formulated for external use, manufactured using a suitable process. As a classic and commonly used preparation, ointments effectively combine a base with an additive, offering characteristics such as high tolerance, portability, and excellent efficacy. With the development of the medical industry, ointments are frequently used in preoperative preparation and postoperative recovery. However, the current challenges in ointment preparation are how to select the appropriate base based on clinical needs, employ different manufacturing processes, and impart unique properties to the ointment to achieve optimal therapeutic effects.

[0004] Bioactive glass is an inorganic material with excellent bioactivity and biocompatibility. In terms of skin wound repair, bioactive glass exhibits excellent hemostatic, antibacterial, and pro-angiogenic properties. It can promote angiogenesis, inhibit scarring, suppress inflammation, and promote re-epithelialization, thereby actively promoting wound healing. It is effective in treating conditions such as oral ulcers, burns, and diabetic skin ulcers.

[0005] The existing creams for treating difficult-to-heal wounds have the problems of low activity, weak targeting, and poor recovery effect. Summary of the Invention

[0006] In view of the problems existing in the prior art, the present invention provides a bioactive glass ointment and a preparation method thereof.

[0007] A method for preparing a bioactive glass ointment, comprising the following steps: S1, mixing the first alcohol polymer and the second alcohol polymer, and melting them to form a mobile phase matrix to obtain a base carrier; S2. subjecting the base carrier to high-speed shearing and constant-temperature stirring to obtain an interpenetrating structure carrier, and cross-linking the interpenetrating structure carrier to obtain a cross-linked matrix; S3, adding chitosan, tannic acid, vitamin E succinate, and glutaraldehyde to the cross-linked matrix and stirring the mixture under laminar flow to obtain a response carrier; S4, preparing modified bioactive glass particles, and adding the modified bioactive glass particles to the response carrier to obtain a modified matrix; S5. Adding dimethyl sulfoxide, glycerol, and trehalose to the modified matrix in sequence, and performing stage-by-stage freezing, drying, and grinding in sequence to obtain the target bioactive glass ointment.

[0008] In addition, the method for preparing the bioactive glass ointment provided by the present invention may also have the following additional technical features: Preferably, step S1 is specifically as follows: The first alcohol polymer and the second alcohol polymer are mixed according to a preset mass ratio, and melted at 60° C.-90° C. to form a mobile phase matrix to obtain a basic carrier.

[0009] Preferably, the first alcohol polymer is a combination of one or more of polypropylene glycol 200, polypropylene glycol 400, polypropylene glycol 600, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600; and the second alcohol polymer is a combination of one or more of polypropylene glycol 2000, polypropylene glycol 4000, polypropylene glycol 6000, polypropylene glycol 8000, polyethylene glycol 1500, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 8000.

[0010] Preferably, the preset mass ratio is (1-5): (5-9).

[0011] Preferably, step S2 specifically includes: S21, high-speed shearing the base support at 1000 rpm-1500 rpm for 20 min-50 min until the first alcohol polymer and the second alcohol polymer are completely dispersed, and then stirring at a constant speed of 500 rpm-800 rpm for 50 min-70 min to obtain an interpenetrating structure support; S22, adding 1 wt%-5 wt% Pluronic F127 and 0.2%-1% photoinitiator to the interpenetrating structure support, slowly stirring at 300 rpm-500 rpm for 1 hour-3 hours, and simultaneously irradiating with 365 nm UV for 30 minutes at an intensity of 50 mW / cm² to obtain a dual-responsive gel network; S23, dissolving Pluronic F127 and a silane coupling agent KH-570 in a toluene solvent and reacting the mixture under reflux at 110° C. for 8 h to obtain a modified Pluronic F127, adding the modified Pluronic F127 to the dual-responsive gel network and cooling the mixture to 28° C. to obtain an intermediate cross-linked matrix; S24. Add 5 wt%-20 wt% of the polyol material and 1 wt%-2 wt% of the auxiliary component to the intermediate cross-linked matrix, and stir and mix at 60-80° C. and 300 rpm-500 rpm to obtain a cross-linked matrix.

[0012] Preferably, in step S24, the polyol material is a combination of one or more of ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and glycerol, and the auxiliary component is a combination of one or more of hyaluronic acid, silk fibroin, methyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, dextran, gelatin, chitosan, polylysine, and tannic acid.

[0013] Preferably, step S3 is specifically as follows: 1wt%-3wt% chitosan, 0.05wt%-0.2wt% tannic acid and 5wt%-10wt% vitamin E succinate are dissolved in 0.5%-2% acetic acid solution, ultrasonically dispersed for 10-20 minutes, 0.1%-0.5% glutaraldehyde is added dropwise, and the mixture is stirred at 150rpm-300rpm laminar flow for 10h-18h. After dialyzed and freeze-dried, the mixture is ground into powder to obtain an effective antibacterial powder, which is added to the cross-linked matrix to obtain a response carrier.

[0014] Preferably, step S4 is specifically as follows: Bioactive glass was prepared by a sol-gel method. The dispersed bioactive glass was placed in an atomic layer deposition chamber. TiCl4 / H2O and Al(CH3)3 / H2O precursors were alternately introduced for 45 to 60 cycles to form a TiO2 / Al2O3 double shell on the surface of the bioactive glass to obtain a modified product. The modified product was reacted with 3-aminopropyltriethoxysilane in anhydrous ethanol for 10 to 16 hours to perform surface amination treatment to obtain modified bioactive glass particles. The modified bioactive glass particles were Active glass particles were added to the response carrier in equal amounts in several batches. The initial batch was dispersed at 1200-1600 rpm for 15-30 minutes to break up hard agglomerates. The intermediate batches were pulsed stirred, alternating between 1200 rpm for 5 minutes and 800 rpm for 15 minutes, with a total dispersion time of 3-6 hours. The final batch was added with 0.05-0.1 wt% polylysine for surface charge modification, and the mixture was dispersed at 500-800 rpm for 1-3 hours to obtain a modified matrix.

[0015] Preferably, step S5 is specifically as follows: Dimethyl sulfoxide, glycerol, and trehalose were mixed and added dropwise to the modified matrix, followed by three-stage freezing: the first stage: pre-freezing at -25°C for 6 hours; the second stage: deep freezing at -50°C for 12 hours; the third stage: gradual temperature increase to 20°C, followed by supercritical CO2-assisted drying: pressure 15 MPa, temperature 40°C, maintained for 2 hours, with the CO2 flow rate controlled at 5 mL / min, to obtain a mixed paste. The mixed paste was then ground three times using a three-roll mill to obtain a bioactive glass ointment.

[0016] The present invention also provides a bioactive glass ointment, which is prepared by the above-mentioned method for preparing the bioactive glass ointment.

[0017] The beneficial effects of the present invention include at least: according to the preparation method of the bioactive glass ointment proposed by the present invention, the responsive carrier is modified by modifying the bioactive glass particles, so that the molecules of the modified matrix have nano-scale micropores and a high specific surface area, and the mineralization activity in the simulated body fluid is significantly improved. By preparing the responsive carrier, the bioactive glass ointment undergoes a phase change at 32°C-36°C, that is, under conditions close to body temperature, and combined with ultraviolet light cross-linking, the drug is released on demand. At the same time, in a weakly alkaline wound environment, such as an infected area, the relevant effective ingredients are quickly released, so that the bioactive glass ointment has better drug controlled release and targeting. At the same time, the bioactive glass ointment has a high antibacterial effect by destroying the bacterial membrane structure and electrostatic adsorption. At the same time, the bioactive glass ointment has low toxicity, stability, process controllability and clinical applicability, realizing the unity of targeted therapy, long-term antibacterial and clinical ease of use, and providing an innovative solution for wound repair.

[0018] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. DETAILED DESCRIPTION

[0019] To make the objects, features, and advantages of the present invention more readily apparent, the following detailed description of the specific embodiments of the present invention is provided in conjunction with the following examples. Several embodiments of the present invention are provided in the examples. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these examples are provided to provide a more thorough and comprehensive understanding of the present invention.

[0020] Example 1 A method for preparing a bioactive glass ointment, comprising the following steps: S1, mixing the first alcohol polymer and the second alcohol polymer, and melting them to form a mobile phase matrix to obtain a base carrier; Wherein, the step S1 is specifically as follows: The first alcohol polymer and the second alcohol polymer are mixed in a preset mass ratio and melted at 60°C-90°C to form a mobile phase matrix to obtain a basic carrier, preferably at 80°C.

[0021] Among them, the first alcohol polymer is a combination of one or more of polypropylene glycol 200, polypropylene glycol 400, polypropylene glycol 600, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600; the second alcohol polymer is a combination of one or more of polypropylene glycol 2000, polypropylene glycol 4000, polypropylene glycol 6000, polypropylene glycol 8000, polyethylene glycol 1500, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 8000.

[0022] Among them, the preset mass ratio is (1-5): (5-9), and the preset mass ratio is preferably 3:7.

[0023] S2. subjecting the base carrier to high-speed shearing and constant-temperature stirring to obtain an interpenetrating structure carrier, and cross-linking the interpenetrating structure carrier to obtain a cross-linked matrix; Wherein, the step S2 includes: S21, high-speed shearing the base support at 1000 rpm-1500 rpm for 20 min-50 min until the first alcohol polymer and the second alcohol polymer are completely dispersed, and then stirring at a constant speed of 500 rpm-800 rpm for 50 min-70 min to obtain an interpenetrating structure support; Preferably, the speed of high-speed shearing is 1200 rpm, the time is 30 min, and the speed of constant stirring is 600 rpm, the time is 60 min.

[0024] S22, adding 1 wt%-5 wt% Pluronic F127 and 0.2%-1% photoinitiator to the interpenetrating structure support, slowly stirring at 300 rpm-500 rpm for 1 hour-3 hours, and simultaneously irradiating with 365 nm UV for 30 minutes at an intensity of 50 mW / cm² to obtain a dual-responsive gel network; The addition amount of Pluronic F127 is preferably 3 wt %, the addition amount of the photoinitiator is preferably 0.5%, and the photoinitiator is specifically a photoinitiator corresponding to UV light. The slow stirring speed is 400 rpm and the time is 2 h.

[0025] S23, dissolving Pluronic F127 and a silane coupling agent KH-570 in a toluene solvent and reacting the mixture under reflux at 110° C. for 8 h to obtain a modified Pluronic F127, adding the modified Pluronic F127 to the dual-responsive gel network and cooling the mixture to 28° C. to obtain an intermediate cross-linked matrix; The mass ratio of Pluronic F127 to the silane coupling agent KH-570 is 1:0.2, and the amount of modified Pluronic F127 added to the dual-responsive gel network is 4 wt%. After the reflux reaction, Fourier transform infrared spectroscopy (FTIR) is used to verify the double bond grafting rate. When the double bond grafting rate is not less than 85%, the responsive modified Pluronic F127 can be obtained. After step S23, the second stage cross-linking can be completed, thereby improving the energy storage capacity.

[0026] S24, adding 5 wt%-20 wt% of a polyol material and 1 wt%-2 wt% of an auxiliary component to the intermediate cross-linked matrix, and stirring and mixing at 60-80° C. and 300 rpm-500 rpm to obtain a cross-linked matrix; Among them, the addition amount of polyol material is preferably 10wt%, and the addition amount of auxiliary components is preferably 1.5wt%, and stirring and mixing at 70°C and 400rpm can obtain a cross-linked matrix. The cross-linked matrix is a uniform viscous matrix that can enhance wound coverage and moisturizing ability.

[0027] Preferably, the polyol material is a combination of one or more of ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and glycerol, and the auxiliary component is a combination of one or more of hyaluronic acid, silk fibroin, methyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, dextran, gelatin, chitosan, polylysine, and tannic acid.

[0028] S3, adding chitosan, tannic acid, vitamin E succinate, and glutaraldehyde to the cross-linked matrix and stirring the mixture under laminar flow to obtain a response carrier; Wherein, step S3 is specifically as follows: 1wt%-3wt% chitosan, 0.05wt%-0.2wt% tannic acid and 5wt%-10wt% vitamin E succinate are dissolved in 0.5%-2% acetic acid solution, ultrasonically dispersed for 10-20 minutes, 0.1%-0.5% glutaraldehyde is added dropwise, and the mixture is stirred at 150rpm-300rpm laminar flow for 10h-18h. After dialyzed and freeze-dried, the mixture is ground into powder to obtain an effective antibacterial powder, which is added to the cross-linked matrix to obtain a response carrier.

[0029] Among them, the addition amount of chitosan is preferably 2wt%, the addition amount of tannic acid is preferably 0.1wt%, the addition amount of vitamin E succinate is preferably 8wt%, the acetic acid solution is preferably 1% acetic acid solution, the parameters of ultrasonic dispersion are 15min, 40kHz, 300W, glutaraldehyde is preferably 0.3% glutaraldehyde, the laminar stirring speed is preferably 200rpm, and the time is preferably 12h.

[0030] S4, preparing modified bioactive glass particles, and adding the modified bioactive glass particles to the response carrier to obtain a modified matrix; Wherein, step S4 is specifically as follows: Bioactive glass was prepared by a sol-gel method. The dispersed bioactive glass was placed in an atomic layer deposition chamber. TiCl4 / H2O and Al(CH3)3 / H2O precursors were alternately introduced for 45 to 60 cycles to form a TiO2 / Al2O3 double shell on the surface of the bioactive glass to obtain a modified product. The modified product was reacted with 3-aminopropyltriethoxysilane in anhydrous ethanol for 10 to 16 hours to perform surface amination treatment to obtain modified bioactive glass particles. The modified bioactive glass particles were Active glass particles were added to the response carrier in equal amounts in several batches. The initial batch was dispersed at 1200-1600 rpm for 15-30 minutes to break up hard agglomerates. The intermediate batches were subjected to pulsed stirring, alternating cycles of 1200 rpm for 5 minutes to 800 rpm for 15 minutes, for a total dispersion time of 3-6 hours. The final batch was added with 0.05-0.1 wt% polylysine for surface charge modification, and the mixture was dispersed at 500-800 rpm for 1-3 hours to obtain a modified matrix. Specifically, the number of cycles of alternately introducing TiCl4 / H2O and Al(CH3)3 / H2O precursors is limited to 50 times, and after the TiO2 / Al2O3 double shell is formed, the specific surface area can be increased and the mineralization activity can be improved. The reaction time of the modified product and 3-aminopropyltriethoxysilane in anhydrous ethanol is preferably 12 hours. Surface amination treatment can enhance the interfacial binding force with the modified product. The obtained modified bioactive glass particles are then added to the response carrier in equal amounts in 5 batches. The first batch is dispersed at 1400 rpm for 20 minutes to break up hard agglomerates; batches 2-4 use pulse stirring, alternating cycles of 1200 rpm×5min→800 rpm×15min, and the total dispersion time is 5 hours; the fifth batch adds 0.08 wt% polylysine for surface charge modification, and steady-state dispersion is performed at 600 rpm for 2 hours to obtain a modified matrix.

[0031] S5. Adding dimethyl sulfoxide, glycerol, and trehalose to the modified matrix in sequence, and performing stage-by-stage freezing, drying, and grinding in sequence to obtain the target bioactive glass ointment.

[0032] Wherein, step S5 is specifically as follows: Dimethyl sulfoxide, glycerol, and trehalose were mixed and added dropwise to the modified matrix, followed by three-stage freezing: the first stage: pre-freezing at -25°C for 6 hours; the second stage: deep freezing at -50°C for 12 hours; the third stage: gradual temperature increase to 20°C, followed by supercritical CO2-assisted drying at a pressure of 15 MPa and a temperature of 40°C for 2 hours, with a CO2 flow rate controlled at 5 mL / min, to obtain a mixed paste. The mixed paste was then ground three times using a three-roll mill to obtain a bioactive glass ointment. Specifically, the volume ratio of dimethyl sulfoxide to glycerol is 3:7, and the amount of trehalose added is 1.5wt%. After the first stage, ice crystals grow along the mesopore axis. After the second stage, the vacuum degree is ≤10Pa to remove free water. After the third stage, the final product has a water content of ≤0.2% and a porosity of >85%. The temperature gradient of the third stage is 0.5℃ / min. After supercritical CO2-assisted drying, a multimodal pore size distribution can be formed. The mixed paste is then ground three times using a three-roll mill (roller spacing 50μm) to ensure that the particle size is ≤10μm and improve the smoothness of the paste, thereby obtaining a bioactive glass ointment.

[0033] By modifying the responsive carrier with bioactive glass particles, the molecules of the modified matrix have nanoscale micropores and a high specific surface area. At the same time, the mineralization activity in simulated body fluids is significantly improved. By preparing the responsive carrier, the bioactive glass ointment undergoes a phase change at 32°C-36°C, that is, under conditions close to body temperature. Combined with ultraviolet light cross-linking, the drug is released on demand. At the same time, in a weakly alkaline wound environment, such as an infected area, the relevant active ingredients are quickly released, making the bioactive glass ointment have better drug controlled release and targeting. At the same time, the bioactive glass ointment has a high antibacterial effect by destroying the bacterial membrane structure and electrostatic adsorption. At the same time, the bioactive glass ointment has low toxicity, stability, process controllability and clinical applicability, realizing the unity of targeted therapy, long-term antibacterial and clinical ease of use, and providing an innovative solution for wound repair.

[0034] Comparative Example 1 This control example provides a method for preparing a bioactive glass ointment. The difference between this control example and the method for preparing a bioactive glass ointment provided in Example 1 is that: Control Example 1 does not undergo step S2 in Example 1, but directly performs step S3 based on the basic carrier, that is, chitosan, tannic acid, vitamin E succinate, and glutaraldehyde are added to the basic carrier and laminar stirring is performed to obtain a response carrier.

[0035] Comparative Example 2 This control example provides a method for preparing a bioactive glass ointment. The difference between this control example and the method for preparing a bioactive glass ointment provided in Example 1 is that: Control Example 1 does not undergo step S3 in Example 1, but directly performs step S4 based on the cross-linked matrix, i.e., preparing modified bioactive glass particles, and adding the modified bioactive glass particles to the cross-linked matrix to obtain a modified matrix.

[0036] Comparative Example 3 This control example provides a method for preparing a bioactive glass ointment. The difference between this control example and the method for preparing a bioactive glass ointment provided in Example 1 is that: Control Example 1 does not undergo step S4 in Example 1, but directly performs step S5 based on the response carrier, that is, dimethyl sulfoxide, glycerol, and trehalose are added to the response carrier in sequence and staged freezing, drying, and grinding are performed in sequence to obtain the target bioactive glass ointment.

[0037] The bioactive glass ointment prepared by the methods of preparing the bioactive glass ointment provided in the above examples and control examples was prepared. The bioactive glass ointment was used as a sample and human umbilical vein endothelial cells were selected for cytotoxicity experiments. Live / Dead cell staining was used for evaluation. Human umbilical vein endothelial cells without sample were used as a blank group. The results of the cytotoxicity experiments are shown in Table 1 below: Table 1

[0038] According to Table 1, the samples corresponding to Example 1 and Comparative Examples 1-3 all have good biocompatibility and no cytotoxicity.

[0039] Afterwards, human umbilical vein endothelial cells were used for angiogenesis experiments and characterized using tubule formation experiments. The test results are shown in Table 2:

[0040] According to the contents of Table 2, the bioactive glass ointment prepared in Example 1 has good angiogenic properties, thereby improving the repair ability of the wound surface. The bioactive glass ointments prepared in Control Examples 1-3 also have certain angiogenic properties, and the angiogenic properties of Control Example 2 are poor. This is because the responsive carrier is modified by modifying the bioactive glass particles, so that the molecules of the modified matrix have nanoscale micropores and a high specific surface area, and the mineralization activity in simulated body fluids is significantly improved. At the same time, the prepared responsive carrier allows the bioactive glass ointment to undergo a phase transition at 32°C-36°C, i.e., under conditions close to body temperature. Combined with ultraviolet crosslinking, it achieves on-demand drug release. At the same time, in a weakly alkaline wound environment, such as an infected area, the relevant active ingredients are rapidly released, giving the bioactive glass ointment good drug controlled release and targeting. The change in activity, drug controlled release, and targeting can slightly affect the angiogenic properties within a limited time. However, the degree of impact of Control Examples 1 and 3 is less than that of Control Example 2. This is because the ingredients in the bioactive glass ointment, chitosan, tannic acid, and vitamin E succinate, can effectively affect the angiogenic properties.

[0041] Afterwards, the preparation methods of the bioactive glass ointments provided in the above examples and control examples were used to prepare corresponding bioactive glass ointments, and the bioactive glass ointments were used as samples for animal experiments. The experimental process was as follows: Thirty C57BL / 6 male mice (weighing 18-20 g) were selected for this experiment. Mice that appeared normal after one week of adaptive feeding were selected for the experiment. After fasting for 12 hours, the mice were intraperitoneally injected with 50 mg / kg of streptozotocin diluted in 0.05 mol / L citric acid-sodium citrate buffer to induce a type 1 diabetic mouse model. Mice with blood glucose levels exceeding 16.67 mmol / L for one week and exhibiting typical diabetic symptoms (three excesses and one deficiency) were selected for subsequent experiments. Successfully induced diabetic mice were anesthetized with a dose of 45 mg / kg. After anesthesia, the back hair of the mice was shaved with a razor and routinely disinfected. An 8 mm diameter hole punch was used to create a uniform circular hole on the back of each mouse. Mice were divided into five groups: a, b, c, d, and e. The wounds of mice in group a were smeared with the ointment prepared in Example 1, the wounds of mice in group b were smeared with the ointment prepared in Control Example 1, the wounds of mice in group c were smeared with the ointment prepared in Control Example 2, and the wounds of mice in group d were smeared with the ointment prepared in Control Example 3. The mice in group e were a blank group. Physiological saline was added dropwise, and the wounds were wrapped with gauze after treatment. The dressings were changed once a day, and the wound healing was observed. The specific experimental results are shown in Table 3 below: Table 3

[0042] According to Table 3, the bioactive glass ointment prepared in Example 1 has a good therapeutic effect on difficult-to-heal wounds, can significantly shorten the healing period of the wound, and no scars appear on the wound after healing. The bioactive glass ointments prepared in Control Examples 1-3 also have certain therapeutic effects, and the therapeutic effect of Control Example 2 is poor. This is because the responsive carrier is modified by modifying the bioactive glass particles, so that the molecules of the modified matrix have nano-scale micropores and high specific surface area, and the mineralization activity in the simulated body fluid is significantly improved. At the same time, the responsive carrier prepared makes the bioactive glass ointment at 32°C-36°C, that is, close to Phase change occurs at body temperature, combined with ultraviolet light cross-linking, to achieve on-demand drug release. At the same time, in a weakly alkaline wound environment, such as an infected area, the relevant active ingredients are quickly released, giving the bioactive glass ointment good drug controlled release and targeting. The change in activity and the controlled release and targeting of the drug can slightly affect the treatment of difficult-to-heal wounds within a limited time. Compared with control example 2, control examples 1 and 3 can shorten the healing period, but the degree of impact of control examples 1 and 3 is less than that of control example 2. This is because the ingredients in the bioactive glass ointment, chitosan, tannic acid, and vitamin E succinate, can effectively affect the treatment of difficult-to-heal wounds.

[0043] Throughout this specification, reference to terms such as "one embodiment," "some embodiments," "examples," "specific examples," or "some examples" means that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0044] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A method for preparing a bioactive glass ointment, characterized in that: The method comprises the following steps: S1, mixing the first alcohol polymer and the second alcohol polymer, and melting them to form a mobile phase matrix to obtain a base carrier; S2. subjecting the base carrier to high-speed shearing and constant-temperature stirring to obtain an interpenetrating structure carrier, and cross-linking the interpenetrating structure carrier to obtain a cross-linked matrix; S3, adding chitosan, tannic acid, vitamin E succinate, and glutaraldehyde to the cross-linked matrix and stirring the mixture under laminar flow to obtain a response carrier; S4, preparing modified bioactive glass particles, and adding the modified bioactive glass particles to the response carrier to obtain a modified matrix; S5. Adding dimethyl sulfoxide, glycerol, and trehalose to the modified matrix in sequence, and performing stage-by-stage freezing, drying, and grinding in sequence to obtain a bioactive glass ointment.

2. The method for preparing the bioactive glass ointment according to claim 1, wherein: Step S1 is specifically as follows: The first alcohol polymer and the second alcohol polymer are mixed according to a preset mass ratio, and melted at 60° C.-90° C. to form a mobile phase matrix to obtain a basic carrier.

3. The method for preparing the bioactive glass ointment according to claim 1, wherein: The first alcohol polymer is a combination of one or more of polypropylene glycol 200, polypropylene glycol 400, polypropylene glycol 600, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 600; the second alcohol polymer is a combination of one or more of polypropylene glycol 2000, polypropylene glycol 4000, polypropylene glycol 6000, polypropylene glycol 8000, polyethylene glycol 1500, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 8000.

4. The method for preparing the bioactive glass ointment according to claim 2, wherein: The preset mass ratio is (1-5): (5-9).

5. The method for preparing the bioactive glass ointment according to claim 1, wherein: Step S2 specifically includes: S21, high-speed shearing the base support at 1000 rpm-1500 rpm for 20 min-50 min until the first alcohol polymer and the second alcohol polymer are completely dispersed, and then stirring at a constant speed of 500 rpm-800 rpm for 50 min-70 min to obtain an interpenetrating structure support; S22, adding 1 wt%-5 wt% Pluronic F127 and 0.2%-1% photoinitiator to the interpenetrating structure support, slowly stirring at 300 rpm-500 rpm for 1 hour-3 hours, and simultaneously irradiating with 365 nm UV for 30 minutes at an intensity of 50 mW / cm² to obtain a dual-responsive gel network; S23, dissolving Pluronic F127 and a silane coupling agent KH-570 in a toluene solvent and reacting the mixture under reflux at 110° C. for 8 h to obtain a modified Pluronic F127, adding the modified Pluronic F127 to the dual-responsive gel network and cooling the mixture to 28° C. to obtain an intermediate cross-linked matrix; S24. Add 5 wt%-20 wt% of the polyol material and 1 wt%-2 wt% of the auxiliary component to the intermediate cross-linked matrix, and stir and mix at 60-80° C. and 300 rpm-500 rpm to obtain a cross-linked matrix.

6. The method for preparing the bioactive glass ointment according to claim 5, characterized in that: In step S24, the polyol material is a combination of one or more of ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and glycerol, and the auxiliary component is a combination of one or more of hyaluronic acid, silk fibroin, methyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, dextran, gelatin, chitosan, polylysine, and tannic acid.

7. The method for preparing the bioactive glass ointment according to claim 1, characterized in that: Step S3 is specifically as follows: 1wt%-3wt% chitosan, 0.05wt%-0.2wt% tannic acid and 5wt%-10wt% vitamin E succinate are dissolved in 0.5%-2% acetic acid solution, ultrasonically dispersed for 10-20 minutes, 0.1%-0.5% glutaraldehyde is added dropwise, and the mixture is stirred at 150rpm-300rpm laminar flow for 10h-18h. After dialyzed and freeze-dried, the mixture is ground into powder to obtain an effective antibacterial powder, which is added to the cross-linked matrix to obtain a response carrier.

8. The method for preparing the bioactive glass ointment according to claim 6, characterized in that: Step S4 is specifically as follows: Bioactive glass was prepared by a sol-gel method. The dispersed bioactive glass was placed in an atomic layer deposition chamber. TiCl4 / H2O and Al(CH3)3 / H2O precursors were alternately introduced for 45 to 60 cycles to form a TiO2 / Al2O3 double shell on the surface of the bioactive glass to obtain a modified product. The modified product was reacted with 3-aminopropyltriethoxysilane in anhydrous ethanol for 10 to 16 hours to perform surface amination treatment to obtain modified bioactive glass particles. The modified bioactive glass particles were Active glass particles were added to the response carrier in equal amounts in several batches. The initial batch was dispersed at 1200-1600 rpm for 15-30 minutes to break up hard agglomerates. The intermediate batches were pulsed stirred, alternating between 1200 rpm for 5 minutes and 800 rpm for 15 minutes, with a total dispersion time of 3-6 hours. The final batch was added with 0.05-0.1 wt% polylysine for surface charge modification, and the mixture was dispersed at 500-800 rpm for 1-3 hours to obtain a modified matrix.

9. The method for preparing the bioactive glass ointment according to claim 1, wherein: Step S5 is specifically as follows: Dimethyl sulfoxide, glycerol, and trehalose were mixed and added dropwise to the modified matrix, followed by three-stage freezing: the first stage: pre-freezing at -25°C for 6 hours; the second stage: deep freezing at -50°C for 12 hours; the third stage: gradual temperature increase to 20°C, followed by supercritical CO2-assisted drying: pressure 15 MPa, temperature 40°C, maintained for 2 hours, with the CO2 flow rate controlled at 5 mL / min, to obtain a mixed paste. The mixed paste was then ground three times using a three-roll mill to obtain a bioactive glass ointment.

10. A bioactive glass ointment, characterized in that: The bioactive glass ointment is prepared by the preparation method of the bioactive glass ointment according to any one of claims 1 to 9.

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