A temperature-sensitive gel for mucosal antibacterial repair and a preparation method thereof

Abstract

This invention discloses a thermosensitive gel for antibacterial repair of mucous membranes and its preparation method, comprising: 3-8 parts of water-soluble chitosan, 18-28 parts of poloxamer 407, 0.0005-0.002 parts of nano-silver, 2-10 parts of plant polyphenols, 10-40 parts of propylene glycol, and deionized water. In the system, propylene glycol and poloxamer 407 form hydrogen bonds, prolonging the phase transition solidification time of the fluid and allowing it to penetrate into micro-folds before solidification. Simultaneously, the plant polyphenols utilize surface physical adsorption to form a coating layer on the nano-silver, and the steric hindrance buffers the physical compression of the nanoparticles caused by the gel phase transition shrinkage, reducing the aggregation of nano-silver during the phase transition process and ensuring the high monodispersity and strong antibacterial properties of the nano-silver. Furthermore, this invention also provides a preparation method for phase-separated independent sterilization and aseptic cold mixing, effectively reducing the apparent viscosity of the system before membrane filtration, avoiding membrane clogging caused by shear heating, and improving the filtration flux in industrial production.

Description

Technical Field

[0001] This invention relates to the fields of cavity-targeted drug delivery and polymer medical materials technology, and in particular to a thermosensitive gel for antibacterial repair of mucous membranes and its preparation method. Background Technology

[0002] The vaginal mucosa is an important physiological barrier in the human body. This area has a unique weakly acidic microecology and is constantly in a moist and warm environment. The anatomical microfolds on its inner wall easily become a breeding ground for pathogenic bacteria to form biofilms. When using temperature-sensitive in-situ gel as a drug delivery carrier, it has the characteristics of "easy drug delivery at room temperature and solidification at body temperature to prevent loss".

[0003] Under actual clinical application and production conditions, the conventional poloxamer compound system (such as the P407 and P188 compound) and the physical mixing of nano-antibacterial agents have the following technical limitations: In aseptic production environments, poloxamer-based polymers are prone to thermal damage to their micellar structure upon heating, typically requiring sterilization filtration using 0.22μm microporous membranes. If macromolecules such as chitosan are directly mixed with a poloxamer matrix at room temperature, intermolecular hydrogen bonding can easily occur, increasing the apparent viscosity of the mixed sol. During pumping through the membrane, the shear resistance and heat generated by the high-viscosity fluid passing through the hydrophilic membrane can easily trigger localized thermal gelation, leading to membrane clogging.

[0004] In targeted drug delivery scenarios, when a low-viscosity fluid comes into contact with a mucosal surface at 36°C, the rapid sol-gel phase transition causes a high-viscosity, high-modulus gel layer to form around the fluid. This physical layer easily seals the openings of micro-folds, hindering the penetration of the un-phase-transformed fluid into deeper layers. Furthermore, conventional methods often physically blend nano-silver into a temperature-sensitive matrix. When the hydrogel undergoes a large-scale physical phase transition, the dehydration and aggregation of its hydrophobic blocks cause the three-dimensional network to shrink, resulting in physical compression within the gel. This causes the originally monodisperse nanoparticles to aggregate, thereby reducing long-lasting antibacterial efficacy. The larger aggregated particles also increase the risk of triggering local mucosal irritation. Summary of the Invention

[0005] The primary objective of this invention is to provide a thermosensitive gel for antibacterial repair of mucous membranes.

[0006] Another objective of this invention is to provide a method for preparing the aforementioned gel. By specifically optimizing the phase separation sterilization and aseptic cold mixing processes, the apparent viscosity of the system before membrane filtration is effectively reduced, avoiding membrane clogging caused by shear heating and improving the filtration flux in industrial production.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: The applicant unexpectedly discovered that water-soluble chitosan with a specific molecular weight plays a "phase transition temperature anchoring" role in the propylene glycol-water system. The introduction of propylene glycol strips free water molecules, causing an upward shift in the critical micelle temperature (CMT). However, in the specific system of this invention, the free amino groups of water-soluble chitosan and the polyoxyethylene segments of poloxamer form a weak electrostatic compensation under a weakly acidic environment, neutralizing the thermodynamic equilibrium shift caused by the dehydration effect. This stabilizes the sol-gel phase transition point of the final system within the 35°C-37°C range, ensuring the accuracy of the body temperature-triggered phase transition.

[0008] A thermosensitive gel for antibacterial repair of mucous membranes, comprising, by weight: Water-soluble chitosan 3-8 parts; poloxamer 407 18-28 parts; nano silver 0.0005-0.002 parts; plant polyphenols 2-10 parts; propylene glycol 10-40 parts; deionized water balance; Among them, poloxamer 407 is the only thermosensitive hydrogel forming agent in the gel, and it and propylene glycol jointly construct a hydrogen bond competing phase transition system; The nano-silver exhibits a sterically hindered structure formed by in-situ surface modification of the plant polyphenols and dispersion in the propylene glycol.

[0009] Furthermore, by weight, the raw material components also include: 1-5 parts of cellulose derivative; The cellulose derivative is selected from one or both of methylcellulose and hydroxypropylcellulose.

[0010] Furthermore, by weight, the raw material components also include: 5-15 parts of transdermal absorption enhancer; The transdermal absorption enhancer is selected from one or more of laurocapram, clove volatile oil, Cnidium monnieri oil, or cinnamon oil.

[0011] Furthermore, the water-soluble chitosan is carboxymethyl chitosan with a degree of deacetylation of 85%-95% and an average molecular weight of 50-150 kDa.

[0012] Furthermore, the plant polyphenols are selected from tea polyphenols or grape seed proanthocyanidins; the particle size distribution D50 of the nano-silver is 10-50 nm.

[0013] Furthermore, the present invention also provides a method for preparing the thermosensitive gel for antibacterial repair of mucous membranes as described above, comprising the following steps: Step S1: Preparation of chitosan aqueous phase: The water-soluble chitosan is added to the first part of deionized water and stirred to dissolve, obtaining phase A; Step S2: Preparation of active alcohol phase: The plant polyphenols and the nano silver are added to the propylene glycol for incubation and dispersion to obtain phase B; Step S3: Preparation of the matrix aqueous phase: The poloxamer 407 is dispersed in the second part of deionized water and swollen at low temperature to obtain phase C; Step S4, Phase-by-phase sterilization filtration: Phase A, Phase B and Phase C are individually sterilized by using microporous filter membranes with a pore size of 0.22 μm. Step S5, Aseptic Cold Mixing: Under aseptic conditions at an ambient temperature of 22℃-25℃, the sterilized phase B is added to the sterilized phase C and stirred under low shear. Then, the sterilized phase A is added and mixed evenly to obtain the temperature-sensitive gel for antibacterial repair of the mucosa.

[0014] Further, in step S2, the specific preparation process is as follows: first, the plant polyphenols are completely dissolved in the propylene glycol, then the nano-silver is added, and under stirring conditions, the plant polyphenols are coated on the surface of the nano-silver to form a uniformly dispersed active alcohol phase.

[0015] Furthermore, in step S3, the temperature of the low-temperature environment is 4℃-10℃, and after the poloxamer 407 has fully swelled, the phase C is subjected to ultrasonic degassing treatment with a power of 100W-150W until no air bubbles remain in the solution.

[0016] Furthermore, it also includes step S6, terminal shaping: the temperature-sensitive gel for antibacterial repair of the mucosa obtained in step S5 is filled into the vaginal applicator under sterile conditions and sealed.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: Introducing a high concentration of propylene glycol into the system creates strong hydrogen bond competition between the polyoxyethylene segments of poloxamer 407 and water molecules. When the drug is applied to the mucosa at 36°C, propylene glycol preferentially captures interfacial moisture, delaying the rapid dehydration and accumulation of micelles and precisely providing a 10-15 second delayed penetration window. During this period, the gel maintains a low-modulus flow state, penetrating deeply into the bottom of folds under gravity and solidifying as a whole, achieving comprehensive physical coverage of deep, hidden lesions.

[0018] Utilizing the abundant phenolic hydroxyl groups in plant polyphenols, nano-silver surfaces were physically adsorbed and encapsulated in propylene glycol medium to form an elastic steric hindrance buffer layer. During the gel's phase transition and dehydration shrinkage, this steric hindrance layer buffered the physical compression of the nanoparticles caused by the gel's phase transition shrinkage, reducing the aggregation of nano-silver during the phase transition and forcibly anchoring the nano-silver in a highly monodisperse state of approximately 22 nm. This resulted in the gel maintaining an antibacterial rate of over 99.9% even after 8 hours of curing, reducing the aggregation rate of large heavy metal particles, and no obvious mucosal redness or irritation was observed.

[0019] Employing a phase-separation physical disintegration process, phases A, B, and C are maintained at an absolutely low viscosity (all ≤310 mPa·s) during the filtration stage. This avoids the high viscosity caused by hydrogen bonding entanglement after macromolecular mixing, ensuring a stable flux of 800 L / m² for the 0.22 μm filter membrane. 2 With a lifespan of over 1 hour, there is no shearing heating or pump blockage throughout the entire process, enabling a sterile, large-scale mass production channel. Attached Figure Description

[0020] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof.

[0021] Figure 1 A schematic diagram of the phase separation sterilization and aseptic cold mixing process of a thermosensitive gel for antibacterial repair of mucous membranes provided by the present invention. Figure 2 This is a schematic diagram of the state transition of the hydrogen bond competition system and the hysteresis permeation mechanism constructed by poloxamer 407 and propylene glycol according to the present invention. Figure 3 This is a schematic diagram of the microscopic anti-agglomeration mechanism of the present invention, which utilizes plant polyphenols to construct a sterically hindered confined structure to resist micelle extrusion stress. Detailed Implementation

[0022] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0023] To make the technical means, inventive features, objectives, and effects of this invention readily understandable, the invention is further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative and are not intended to limit the scope of protection of this invention.

[0024] like Figure 1-3As shown, the present invention provides a thermosensitive gel for antibacterial repair of mucous membranes, the raw material components of which, by weight, include: 3-8 parts of water-soluble chitosan, 18-28 parts of poloxamer 407, 0.0005-0.002 parts of nano silver, 2-10 parts of plant polyphenols, 10-40 parts of propylene glycol, and the balance of deionized water.

[0025] This invention employs poloxamer 407 as the sole thermosensitive hydrogel forming agent in the system and specifically introduces a high concentration of propylene glycol in a particular proportion. Propylene glycol, utilizing its abundant free hydroxyl groups, forms a strong hydrogen bond competition phase transition system with the polyoxyethylene segments of poloxamer 407 and free water molecules. When the gel is injected into the vagina and comes into contact with the human mucosa, propylene glycol preferentially captures interfacial moisture, effectively delaying the rapid dehydration and accumulation of poloxamer 407 micelles upon contact with body temperature. This provides the fluid with a delayed penetration window, overcoming the crusting and blocking effect of conventional thermosensitive gels that seal the natural microfolds of the vagina due to the instantaneous rapid solidification of the surface layer. During this window, the gel maintains a low-modulus flow state, deeply penetrating into the folds under the influence of injection pressure and gravity. Subsequently, environmental thermodynamics drives the breaking of the hydrogen bond equilibrium, and the system rapidly completes three-dimensional physical phase transition solidification within 30 seconds, achieving precise coverage and physical integration of deep lesions.

[0026] At the microscopic anti-agglomeration mechanism level, the nano-silver in this system is not added to the matrix through conventional direct physical blending, but rather pre-incubated with plant polyphenols under specific conditions in a propylene glycol medium. The numerous phenolic hydroxyl groups in the plant polyphenol molecules, through coordination and multiple hydrogen bonds in the liquid phase, physically adsorb and encapsulate the surface of the nano-silver particles, forming a dense and elastic physical buffer layer. When the gel undergoes phase transition and dehydration shrinkage in vivo, this steric structure acts as a physical buffer layer to resist micelle extrusion stress, forcibly anchoring the nano-silver in a monodisperse state of 10-50 nm. This prevents irreversible physical agglomeration of the nanomaterials under polymer network extrusion, ensuring the extremely high antibacterial specific surface area and long-lasting silver ion slow-release channels of the cured nano-silver.

[0027] Furthermore, to optimize the mechanical modulus and mucosal adhesion of the cured gel, the raw material components may further include 1-5 parts by weight of a cellulose derivative and 5-15 parts by weight of a transdermal absorption promoter. The cellulose derivative is selected from one or both of methylcellulose and hydroxypropylcellulose; the transdermal absorption promoter is selected from one or more of laurocapram, clove volatile oil, Cnidium monnieri oil, or cinnamon oil.

[0028] Regarding the selection of raw materials, the water-soluble chitosan is carboxymethyl chitosan with a deacetylation degree between 85% and 95% and an average molecular weight of 50-150 kDa. This specific parameter selection ensures its absolutely low viscosity in a pure aqueous phase at room temperature, providing a technological basis for industrial microporous membrane filtration and sterilization. Furthermore, it can rapidly undergo amino protonation in the weakly acidic microecological environment of the vagina, forming strong electrostatic cross-links with mucosal epithelial cells. The plant polyphenols are selected from tea polyphenols or grape seed proanthocyanidins with a purity ≥98%.

[0029] Based on the aforementioned unique microstructure formulation, this invention provides a preparation method that can solve the problems of high-temperature thermal damage and high-viscosity micropore shear blockage in polymeric thermosensitive gels. The specific steps are as follows: Step S1, preparing the chitosan aqueous phase: add water-soluble chitosan to the first part of deionized water, and stir at low speed at room temperature until completely dissolved to obtain phase A with extremely low viscosity.

[0030] Step S2, Preparation of the active alcohol phase: Plant polyphenols are completely dissolved in propylene glycol, followed by the addition of silver nanoparticles. The mixture is stirred and incubated at 30℃-35℃ at 500-800 r / min for 40-60 minutes. During this process, the phenolic hydroxyl groups of the plant polyphenols fully adsorb and physically encapsulate the surface of the silver nanoparticles, resulting in a uniformly dispersed golden-yellow phase B. If the formulation contains a transdermal absorption enhancer, it should be dissolved in the propylene glycol system before adding the silver nanoparticles.

[0031] Step S3, Preparation of the matrix aqueous phase: Disperse poloxamer 407 and optional cellulose derivatives in the second part of deionized water, and allow it to swell in a low-temperature cold storage at 4℃-10℃ for 12-24 hours. After the polymer is completely hydrated to form a clear sol, subject phase C to ultrasonic degassing at a power of 100W-150W for 15-20 minutes to remove hydrated microbubbles.

[0032] Step S4, Phase-separated sterilization filtration: Phases A, B, and C are independently filtered and sterilized using industrial-grade microporous membranes with a pore size of 0.22 μm. Through the phase-separation physical disassembly in the preparation process, each phase is in an extremely low viscosity state, thereby avoiding the extremely high apparent viscosity caused by the hydrogen bonding entanglement of macromolecules, ensuring high-throughput filtration and sterilization.

[0033] Step S5, Aseptic Cold Mixing: In a Class 10,000 aseptic mixing tank where the ambient temperature is strictly controlled at 22℃-25℃, start the anchor-type agitator for low-shear mixing. First, slowly pump the sterilized phase B into the sterilized phase C and stir for 15-20 minutes to allow propylene glycol molecules to fully penetrate into the intercellular spaces of the poloxamer micelles and establish a stable hydrogen bond competition system; then slowly add the sterilized phase A and continue stirring for 30 minutes until a semi-transparent homogeneous fluid is formed, obtaining a temperature-sensitive gel for antibacterial repair of mucous membranes.

[0034] Step S6, Terminal Forming: On the aseptic filling line, the gel obtained in step S5 is quantitatively filled into a vaginal applicator and sealed to protect it from light.

[0035] Example 1

[0036] The raw material components of this embodiment include, by weight, the following: 5 parts carboxymethyl chitosan (degree of deacetylation 90%, Mw 100kDa), 22 parts poloxamer 407, 0.001 parts nano silver, 4 parts tea polyphenols, 1 part methylcellulose, 2 parts hydroxypropylcellulose, 5 parts laurocapram, 2 parts clove volatile oil, 25 parts propylene glycol, and 33.999 parts deionized water.

[0037] Preparation process: Phase A was prepared by dissolving 5 parts chitosan in 15 parts deionized water; Phase B was prepared by dissolving 4 parts tea polyphenols, 5 parts lauryl azedarone, and 2 parts clove volatile oil in 25 parts propylene glycol, adding 0.001 parts nano silver, and incubating at 35℃ for 50 minutes; Phase C was prepared by dispersing 22 parts poloxamer 407 and 3 parts cellulose derivative in the remaining 18.999 parts deionized water, swelling at 4℃ for 24 hours, and then ultrasonically degassing at 120W for 15 minutes. After sterilization by passing each of the three phases through a 0.22μm microporous membrane, they were mixed under aseptic conditions at 25℃ with low-shear anchoring stirring at 40r / min in the order of adding Phase B to Phase C, followed by Phase A. The mixture was then filled into a delivery device.

[0038] Example 2

[0039] The raw material components of this embodiment, by weight, include: 8 parts carboxymethyl chitosan (degree of deacetylation 85%, Mw 50kDa), 28 parts poloxamer 407, 0.002 parts nano silver, 8 parts grape seed proanthocyanidins, 5 parts hydroxypropyl cellulose, 5 parts Cnidium monnieri oil, 15 parts propylene glycol, and 30.998 parts deionized water. The preparation process is the same as in Example 1, with the ultrasonic degassing power set to 150W.

[0040] Example 3

[0041] The raw material components of this embodiment, by weight, include: 3 parts carboxymethyl chitosan (degree of deacetylation 95%, Mw 150kDa), 18 parts poloxamer 407, 0.0005 parts nano silver, 10 parts tea polyphenols, 8 parts cinnamon oil, 40 parts propylene glycol, and 20.9995 parts deionized water. The preparation process is the same as in Example 1.

[0042] Comparative Example 1 The formulation components are completely identical to those in Example 1. The preparation process is changed as follows: at room temperature, deionized water and propylene glycol are mixed, and then chitosan, tea polyphenols, nano silver, excipients and poloxamer 407 are added directly in sequence. The mixture is then mixed evenly using a conventional high-shear mixer, and then the whole mixture is sterilized by passing it through a 0.22μm filter membrane.

[0043] Comparative Example 2 Propylene glycol was removed from the raw material components and replaced with an equal amount of deionized water by weight. Simultaneously, a composite system of poloxamer 407 (20 parts) and poloxamer 188 (5 parts) replaced the single poloxamer 407 matrix to maintain the phase transition temperature. The remaining components and the phase separation cold preparation process were the same as in Example 1.

[0044] Comparative Example 3 The raw material composition is completely identical to that of Example 1. The preparation process is changed as follows: when preparing the active alcohol phase B, the plant polyphenols are not added for pre-incubation; instead, the nano-silver is dispersed in propylene glycol. The plant polyphenols are added to the aqueous matrix phase C instead. The remaining independent sterilization and mixing processes are the same as in Example 1.

[0045] Performance testing and verification The permeation flux and apparent viscosity of each system on a 0.22 μm hydrophilic polyethersulfone filter membrane were tested at 25℃. The test results are shown in Table 1.

[0046] The test environment was 25℃, and a hydrophilic polyethersulfone microporous filter membrane with a pore size of 0.22μm was used to test the permeation flux and apparent viscosity of the phase-separated fluid of Example 1 and the globally mixed fluid of Comparative Example 1. The test results are shown in Table 1.

[0047] Table 1. Test results of filtration efficiency of industrial-grade 0.22μm microporous membranes

[0048] As verified by the test data in Table 1, the viscosity of the globally mixed system increases dramatically due to strong hydrogen bonding entanglement of macromolecules. Forced passage through the membrane would trigger significant shear resistance and shear heating, ultimately leading to pump blockage and membrane rupture. The phase separation sterilization and cold mixing process of this invention can maintain extremely low viscosity in each phase fluid, representing an effective way to overcome the bottleneck in the aseptic mass production process of polymeric temperature-sensitive gels.

[0049] Two-stage cascaded phase change and deep permeability testing A silicone artificial vaginal mucosa model with biomimetic micro-folds 5 mm deep on its surface was used. It was placed in a 36℃ constant temperature water bath to simulate the clinical injection process, and the phase transition and permeation of the gel were recorded using a staining tracer method. The test results are shown in Table 2.

[0050] Table 2. Results of Phase Transition and Deep Permeability Tests in the Vaginal Mucosal Model

[0051] In Example 1, after administration, the fluid maintained good rheological permeability for the first ten seconds upon contact with a 36°C surface, penetrating to the bottom of the folds under gravity before solidifying completely. In Comparative Example 2 (excluding the propylene glycol hydrogen bond competing system), a violent phase transition occurred in less than 3 seconds at the contact interface, and the high-viscosity gel skin formed on the periphery directly blocked the fold openings, preventing further permeation of the remaining fluid. The formulation system of this invention effectively solves the instantaneous skin-forming blocking effect of traditional formulations.

[0052] Microscopic resistance to compression agglomeration and long-lasting antibacterial test The gels from Example 1 and Comparative Example 3 were allowed to cure statically at 36°C. The internal microstructure was observed using transmission electron microscopy, and the antibacterial rate and mucosal irritation after 8 hours of curing were tested according to pharmacopoeia standards. The test results are shown in Table 3.

[0053] Table 3. Results of internal microstructure and antibacterial properties after gel phase transition.

[0054] During the curing and dehydration process of the gel in Comparative Example 3, due to the lack of a physical coating layer formed by the pre-adsorption of plant polyphenols in the alcohol phase, the silver nanoparticles underwent severe physical aggregation under the intense shrinkage and extrusion stress of the poloxamer micelles. This resulted in a sharp decrease in specific surface area, leading to a significant reduction in the long-lasting antibacterial rate. Furthermore, the large metal aggregates caused local mucosal irritation in the experimental model. In contrast, the silver nanoparticles in Example 1 maintained a good monodisperse state within the polymer network, ensuring the system's potent antibacterial properties and excellent biosafety.

[0055] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A temperature-sensitive gel for antibacterial repair of mucous membranes, characterized in that, By weight, its raw material components include: 3-8 parts of water-soluble chitosan; Polosham 407, 18-28 copies; Nano silver 0.0005-0.002 parts; 2-10 parts of plant polyphenols; 10-40 parts of propylene glycol; Deionized water balance; Among them, poloxamer 407 is the only thermosensitive hydrogel forming agent in the gel; The plant polyphenols are adsorbed on the surface of the nano-silver and dispersed and suspended in the propylene glycol.

2. The thermosensitive gel for antibacterial repair of mucosa according to claim 1, characterized in that, By weight, the raw material components also include: 1-5 parts of cellulose derivative; The cellulose derivative is selected from one or both of methylcellulose and hydroxypropylcellulose.

3. The thermosensitive gel for antibacterial repair of mucous membranes according to claim 1, characterized in that, By weight, the raw material components also include: 5-15 parts of transdermal absorption enhancer; The transdermal absorption enhancer is selected from one or more of laurocapram, clove volatile oil, Cnidium monnieri oil, or cinnamon oil.

4. The thermosensitive gel for antibacterial repair of mucous membranes according to claim 1, characterized in that, The water-soluble chitosan is carboxymethyl chitosan with a degree of deacetylation of 85%-95% and an average molecular weight of 50-150 kDa.

5. The thermosensitive gel for antibacterial repair of mucous membranes according to claim 1, characterized in that, The plant polyphenols are selected from tea polyphenols or grape seed proanthocyanidins; the particle size distribution D50 of the nano-silver is 10-50 nm.

6. A method for preparing a thermosensitive gel for antibacterial repair of mucous membranes as described in any one of claims 1-5, characterized in that, Includes the following steps: Step S1: Preparation of chitosan aqueous phase: The water-soluble chitosan is added to the first part of deionized water and stirred to dissolve, obtaining phase A; Step S2: Preparation of active alcohol phase: The plant polyphenols and the nano silver are added to the propylene glycol for incubation and dispersion to obtain phase B; Step S3: Preparation of the matrix aqueous phase: The poloxamer 407 is dispersed in the second part of deionized water and swollen at low temperature to obtain phase C; Step S4, Phase-by-phase sterilization filtration: Phase A, Phase B and Phase C are individually sterilized by using microporous filter membranes with a pore size of 0.22 μm. Step S5, Aseptic Cold Mixing: Under aseptic conditions at an ambient temperature of 22℃-25℃, the sterilized phase B is added to the sterilized phase C and stirred under low shear. Then, the sterilized phase A is added and mixed evenly to obtain the temperature-sensitive gel for antibacterial repair of the mucosa.

7. The preparation method according to claim 6, characterized in that, In step S2, the specific preparation process is as follows: first, the plant polyphenols are completely dissolved in the propylene glycol, and then the nano silver is added. Under stirring conditions, the plant polyphenols are coated on the surface of the nano silver to form a uniformly dispersed active alcohol phase.

8. The preparation method according to claim 6, characterized in that, In step S3, the temperature of the low-temperature environment is 4℃-10℃, and after the poloxamer 407 has fully swelled, phase C is subjected to ultrasonic degassing treatment with a power of 100W-150W until no bubbles remain in the solution.

9. The preparation method according to claim 6, characterized in that, It also includes step S6, terminal shaping: the temperature-sensitive gel for antibacterial repair of the mucosa obtained in step S5 is filled into the vaginal applicator under sterile conditions and sealed.

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