Sodium polyacrylate composite poloxamer gel and preparation process thereof

Abstract

The invention relates to a sodium polyacrylate composite poloxamer gel which comprises the following components in percentage by weight: a gel matrix component: 5-20% of poloxamer P407; 1% to 10% of poloxamer P188; an ionic thickening and enhancing component: 0.2%-1% of sodium polyacrylate; auxiliary functional components: 0.5%-2% of a humectant; 0.5%-2% of a water-soluble polyamino polysaccharide derivative; and a solvent: the balance of purified water. According to the invention, the thermo-sensitive nonionic polymer (poloxamer) and the ionic polymer (sodium polyacrylate) are creatively compounded, the biocompatibility is good, the application range is wide, the used raw materials have good biocompatibility, the pH value of the final gel is close to neutral (6-8), and the gel is non-irritant to skin or mucosa and is suitable for various medical and nursing fields.

Description

Technical Field

[0001] This invention relates to the field of polymer composite medical gel technology, specifically a sodium polyacrylate composite poloxamer gel, and also discloses its preparation process. Background Technology

[0002] Hydrogels, due to their high water content and good biocompatibility, have wide applications in medical dressings, drug carriers, and tissue engineering. Poloxamer, especially P407 and P188, is a class of amphiphilic nonionic polymers composed of a polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) triblock. Its aqueous solution exhibits unique reverse thermogelation properties, meaning it is a free-flowing sol at low temperatures and transforms into a semi-solid gel near body temperature. This property makes it ideal for in-situ gel formulations. However, single poloxamer gels suffer from drawbacks such as low strength, poor mechanical properties, and susceptibility to dilution and degradation under physiological conditions.

[0003] To enhance gel performance, it is often compounded with other polymeric materials. Sodium polyacrylate, as a strongly hydrophilic ionic polymer, is a highly efficient thickener that can form a dense and strong gel network. However, its gel is susceptible to electrolyte interference, leading to demulsification or a decrease in viscosity. Carbomer and sodium carboxymethyl cellulose (CMC-Na) are also commonly used gel matrices. However, the former is extremely sensitive to pH and requires neutralization under specific alkaline conditions to achieve optimal thickening effects, which involves complex processes and may introduce irritating substances. The latter suffers from problems such as easy viscosity decay (especially after irradiation sterilization, with viscosity decreasing by more than 70%) and poor long-term stability.

[0004] Therefore, developing a poloxamer composite gel with a reasonable formulation, simple process, and the ability to overcome the above-mentioned defects, especially one that can maintain high stability and ideal performance after sterilization, has important application value. Summary of the Invention

[0005] (a) Technical problems to be solved The aim is to overcome the shortcomings of existing technologies by providing a sodium polyacrylate composite poloxamer gel and its preparation method. This composite gel, through specific component selection and optimized preparation processes, solves the problems of insufficient poloxamer gel strength, susceptibility of sodium polyacrylate gel to electrolyte influences, and the tendency for clumping and uneven texture when the two are directly combined. Ultimately, a stable composite gel with uniform texture, high strength, moderate pH, and minimal performance degradation after irradiation sterilization is obtained.

[0006] (II) Technical Solution The technical solution adopted in this invention is as follows: A sodium polyacrylate composite poloxamer gel, comprising the following components by weight percentage: Gel matrix components: Poloxamer P407, 5%-20%; Poloxamer P188, 1%-10%; Ionic thickening and reinforcing component: Sodium polyacrylate: 0.2%-1%; Auxiliary functional components: Moisturizer: 0.5%-2% Water-soluble polyaminopolysaccharide derivatives: 0.5%-2%; Solvent: purified water, balance.

[0007] A method for preparing sodium polyacrylate composite poloxamer gel includes the following steps: S1. Preparation of gel stock solution: Add water-soluble polyamino polysaccharide derivatives to a portion of purified water and stir to dissolve; add humectant and mix well; add poloxamer P407 and P188 at a stirring speed of 100-200 rpm and continue stirring for 1 hour to fully impregnate the poloxamer; then let stand at a low temperature of 5-20℃ until the poloxamer is completely dissolved to obtain a clear and transparent gel stock solution for later use; S2. Preparation of sodium polyacrylate solution: In another container, at a stirring speed of 200-500 rpm, slowly and evenly disperse sodium polyacrylate powder in the remaining purified water, and continue stirring until it is completely dissolved to form a homogeneous sodium polyacrylate aqueous solution. S3. Combining: The sodium polyacrylate aqueous solution obtained in step S2 is slowly added dropwise or flowed into the gel stock solution obtained in step S1. The addition rate is controlled to avoid excessive local concentration leading to clumping. The volume mixing ratio of sodium polyacrylate solution to gel stock solution is 1-15:100.

[0008] It also includes step S4. Maturation: The mixture obtained in step S3 is continuously stirred until it is completely homogeneous, and then left to stand for at least 2 hours.

[0009] The ripening process includes the following two stages: S41. Low-temperature winding: The homogeneous mixture obtained in step S3 is stirred at low speed for 1-2 hours at 10-15℃, and then allowed to stand at this temperature for 1-3 hours. S42. Heating and curing: Slowly heat the system that has undergone S41 first-stage curing to 25-37℃ and let it stand at this temperature for 2-6 hours.

[0010] It also includes step S5. Terminal pH equilibration: After the gel has fully formed, a small amount of acid-base regulator is used to precisely adjust the pH of the final gel product to a neutral value of 6.5-7.5 with gentle stirring, and then it is allowed to stand briefly again for equilibration.

[0011] In step S1, a water-soluble polyamino polysaccharide derivative is added to a portion of purified water and stirred to dissolve. A humectant is added and mixed thoroughly. Poloxamer P407 and P188 are added at a stirring speed of 100-200 rpm, and stirring is continued for 1 hour to fully impregnate the poloxamer. After the poloxamer is fully impregnated, it is then allowed to stand at a low temperature of 2-8°C for 6-24 hours until the poloxamer is completely dissolved, resulting in a clear and transparent gel stock solution. The temperature of the gel stock solution is stabilized at 10-15°C for later use.

[0012] In step S2, which involves preparing a sodium polyacrylate solution, sodium polyacrylate powder is slowly and uniformly dispersed in the remaining purified water in another container under high-speed stirring at 200-500 rpm. After initial dispersion, the pH of the system is adjusted to 8.0-9.0 using a dilute alkaline solution. Stirring continues under this weakly alkaline environment until the sodium polyacrylate is completely dissolved and its molecular chains are fully extended, forming a homogeneous, transparent, viscous solution. The temperature of this solution is then adjusted to 10-15°C for later use.

[0013] Under constant temperature and stirring conditions of 10-15℃, the pre-stabilized sodium polyacrylate solution obtained in step S2 is slowly added to the low-temperature gel stock solution obtained in step S1 using a constant-speed peristaltic pump or a dropping device. The addition rate is controlled so that the mixing process lasts for at least 30 minutes. The final volume mixing ratio of sodium polyacrylate solution to gel stock solution is 1-15:100.

[0014] The application of the sodium polyacrylate composite poloxamer gel in the preparation of medical dressings, drug sustained-release carriers, or coupling agents for medical devices.

[0015] (III) Beneficial Effects The beneficial effects of this invention are as follows: 1. Synergistic Reinforcement and Defect Complementarity: This invention creatively combines a thermosensitive nonionic polymer (poloxam) with an ionic polymer (sodium polyacrylate). Poloxamer provides the thermosensitive and gelling framework, while the ionic segments of sodium polyacrylate can penetrate and reinforce this framework, forming an interpenetrating or semi-interpenetrating network structure. This significantly improves the mechanical strength and elastic modulus of the gel, while the stability disadvantage of sodium polyacrylate is buffered by the nonionic properties of poloxamer.

[0016] 2. Excellent sterilization stability: Through experimental comparison (see the performance comparison in the examples), the composite gel of the present invention showed the least change in appearance and pH value after sterilization by Co-60 γ-ray irradiation, and the highest viscosity retention rate (>56%), which is far superior to the poloxamer / carbomer composite gel (viscosity retention rate of about 30%) and poloxamer / sodium carboxymethyl cellulose composite gel (viscosity retention rate <2%) prepared under the same conditions, demonstrating excellent irradiation stability.

[0017] 3. Stable process and uniform product: Through a specific process of "dissolving separately first and then slowly mixing at low temperature", the instantaneous aggregation and clumping caused by differences in solubility and polarity when poloxamer and sodium polyacrylate are directly mixed are effectively avoided, ensuring that the final gel texture is uniform and delicate.

[0018] 4. Good biocompatibility and wide range of applications: All raw materials used have good biocompatibility, and the final gel pH value is close to neutral (6-8), which is non-irritating to the skin or mucous membranes and is suitable for a variety of medical and nursing fields. Attached Figure Description

[0019] Figure 1 The effects of each drug group on the healing of scalded wounds in rats; Figure 2 This study compares the healing rates of scalded wounds in rats from different groups on day 21 of the experiment. The healing rate is calculated as the healing area divided by the wound area. Figure 3 Comparative images of the pathological morphology (HE staining) of scalded skin tissue from different groups of rats in the experiment were obtained using a hematoxylin and eosin (HE) staining kit (catalog number: G1120). Figure 4 Comparative images of the pathological morphology (Masson staining) of scalded skin tissue from different groups of rats in the experiment were obtained using the Masson staining kit (catalog number: G1340). Detailed Implementation

[0020] To better explain and facilitate understanding of this invention, the following description is provided in conjunction with the appendix. Figures 1-4 The present invention will be described in detail through specific embodiments.

[0021] Example 1. This embodiment provides a sodium polyacrylate composite poloxamer gel, which comprises the following components by weight percentage: poloxamer P407, 10%; poloxamer P188, 5%; sodium polyacrylate: 0.5% (based on the effective content in the final gel); glycerin as a humectant, 1%; carboxymethyl chitosan, 1%; and purified water as the solvent, balance.

[0022] The preparation method of the above-mentioned sodium polyacrylate composite poloxamer gel includes the following steps: S1. Preparation of gel stock solution: Add carboxymethyl chitosan to a portion of purified water and stir to dissolve; add glycerol and mix well; add poloxamer P407 and P188 at a stirring speed of 100-200 rpm and continue stirring for 1 hour to fully impregnate the poloxamer; then let it stand at a low temperature of 15±2℃ until the poloxamer is completely dissolved to obtain a clear and transparent gel stock solution for later use. S2. Preparation of sodium polyacrylate solution: In another container, at a stirring speed of 300-350 rpm, slowly and evenly disperse sodium polyacrylate powder in the remaining purified water, and continue stirring until it is completely dissolved to form a homogeneous sodium polyacrylate aqueous solution. S3. Composite: Under stirring, the sodium polyacrylate aqueous solution obtained in step S2 is slowly added dropwise or flowed into the gel stock solution obtained in step S1. The addition rate is controlled to avoid excessive local concentration leading to clumping. The volume mixing ratio of sodium polyacrylate solution to gel stock solution is 10:100.

[0023] S4. Maturation: The mixture obtained in step S3 is continuously stirred until it is completely homogeneous, and then left to stand for 3 hours to allow the PEO-PPO-PPO micelles of poloxamer to fully entangle and crosslink with the molecular chains of sodium polyacrylate, forming a dense and stable three-dimensional network gel structure.

[0024] The sodium polyacrylate composite poloxamer gel prepared in this embodiment is a colorless to pale yellow gel with a pH of 7.64 and a viscosity (25°C) of 11685 mPa·s.

[0025] Example 2. This embodiment provides a sodium polyacrylate composite poloxamer gel, comprising the following components by weight percentage: poloxamer P407, 20%; poloxamer P188, 1%; Sodium polyacrylate: 1% (based on effective content in the final gel); propylene glycol as humectant, 2%; carboxymethyl chitosan as water-soluble polyaminopolysaccharide derivative, 0.5%; solvent: purified water, balance.

[0026] The preparation method of the above-mentioned sodium polyacrylate composite poloxamer gel includes the following steps: S1. Preparation of gel stock solution: Add carboxymethyl chitosan to a portion of purified water and stir to dissolve; add propylene glycol and mix evenly; add poloxamer P407 and P188 at a stirring speed of 100-200 rpm and continue stirring for 1 hour to fully impregnate the poloxamer; after the poloxamer is fully impregnated, let it stand at a low temperature of 5°C for 20 hours until the poloxamer is completely dissolved to obtain a clear and transparent gel stock solution. Stabilize the temperature of the gel stock solution at 10-15°C (below the micelle conversion temperature of poloxamer) for later use.

[0027] S2. Preparation of sodium polyacrylate solution: In another container, slowly and evenly disperse sodium polyacrylate powder in the remaining purified water at a stirring speed of 200-300 rpm. After initial dispersion, adjust the pH of the system to 8.0-9.0 using a dilute alkaline solution (such as 0.1M NaOH). Continue stirring in this weakly alkaline environment until the sodium polyacrylate is completely dissolved and its molecular chains are fully extended to form a homogeneous, transparent, viscous solution. Adjust the temperature of the solution to 10-15℃ and set aside for later use. Pre-dissolving sodium polyacrylate under weakly alkaline conditions allows for the complete dissociation and full hydration of its carboxylate ions (-COO⁻), resulting in the molecular chains reaching their most extended state. This provides the optimal conformation for its subsequent effective intercalation with poloxamer. At the same time, this step avoids the potentially violent local reactions that may be caused by directly adding the alkaline regulator to the final gel system.

[0028] S3. Composite: Under stirring, the sodium polyacrylate aqueous solution obtained in step S2 is slowly added dropwise or flowed into the gel stock solution obtained in step S1. The addition rate is controlled to avoid excessive local concentration leading to clumping. The volume mixing ratio of sodium polyacrylate solution to gel stock solution is 15:100.

[0029] S4. Maturation: The mixture obtained in step S3 is continuously stirred until it is completely homogeneous, and then left to stand for 3 hours to allow the PEO-PPO-PPO micelles of poloxamer to fully entangle and crosslink with the molecular chains of sodium polyacrylate, forming a dense and stable three-dimensional network gel structure.

[0030] The sodium polyacrylate composite poloxamer gel prepared in this embodiment has the following characteristics: appearance: colorless to pale yellow gel; obvious temperature sensitivity; pH ​​value: 7.42; viscosity (25℃): 253559 mPa·s.

[0031] Example 3. This embodiment provides a sodium polyacrylate composite poloxamer gel, comprising the following components by weight percentage: poloxamer P407, 15%; poloxamer P188, 5%; Sodium polyacrylate: 0.6% (based on effective content in the final gel); glycerin as humectant, 1.5%; carboxymethyl chitosan as water-soluble polyaminopolysaccharide derivative, 1.5%; solvent: purified water, balance.

[0032] The preparation method of the above-mentioned sodium polyacrylate composite poloxamer gel includes the following steps: S1. Preparation of gel stock solution: Add carboxymethyl chitosan to a portion of purified water and stir to dissolve; add glycerol and mix evenly; add poloxamer P407 and P188 at a stirring speed of 150±10 rpm and continue stirring for 1 hour to fully impregnate the poloxamer; after the poloxamer is fully impregnated, let it stand at a low temperature of 8℃ for 6-12 hours until the poloxamer is completely dissolved to obtain a clear and transparent gel stock solution. Stabilize the temperature of the gel stock solution at 10-12℃ for later use.

[0033] S2. Preparation of sodium polyacrylate solution: In another container, slowly and evenly disperse sodium polyacrylate powder in the remaining purified water at a stirring speed of 200-300 rpm. After initial dispersion, adjust the pH of the system to 8.0-9.0 using a dilute alkaline solution. Continue stirring in this weakly alkaline environment until the sodium polyacrylate is completely dissolved and its molecular chains are fully extended to form a homogeneous, transparent, viscous solution. Adjust the temperature of the solution to 10-15℃ and set aside for later use. S3. Composite: Under stirring, the sodium polyacrylate aqueous solution obtained in step S2 is slowly added dropwise or flowed into the gel stock solution obtained in step S1. The addition rate is controlled to avoid excessive local concentration leading to clumping. The volume mixing ratio of sodium polyacrylate solution to gel stock solution is 5:100.

[0034] S4. Maturation: The mixture obtained in step S3 is continuously stirred until it is completely homogeneous, and then left to stand for 3 hours to allow the PEO-PPO-PPO micelles of poloxamer to fully entangle and crosslink with the molecular chains of sodium polyacrylate, forming a dense and stable three-dimensional network gel structure.

[0035] In this embodiment, the ripening process includes the following two stages: S41. Low-temperature entanglement: The homogeneous mixture obtained in step S3 is stirred at low speed for 1.5 hours at 10-15℃, and then left to stand at this temperature for 2 hours. During this stage, the molecular chains are further entangled with each other at low temperature to form a preliminary, uniform interpenetrating network precursor. S42. Heating and Curing: The system, after S41 primary curing, is slowly heated to 25-37℃ (physiological temperature range) and left to stand at this temperature for 3 hours. As the temperature rises, poloxamer molecules self-assemble to form a regular micelle network. At this point, the sodium polyacrylate long chains, which have been uniformly distributed and partially "anchored" at low temperature, are in situ encapsulated and locked within the forming micelle network. Simultaneously, the electrostatic repulsion between the ionic chain segments and the physical cross-linking points of the micelles mutually restrain each other, thus forming a unique "ion-micelle interlocking" three-dimensional network structure. This structure is much denser and stronger than networks formed by simple physical mixing.

[0036] The sodium polyacrylate composite poloxamer gel prepared in this embodiment has the following characteristics: appearance: pale yellow gel; temperature sensitive; pH value: 7.56; viscosity (25℃): 18598 mPa·s.

[0037] Example 4. The composition ratio and preparation process steps of this embodiment are the same as those of Embodiment 3. The difference is that this embodiment also includes step S5. Terminal pH equilibration: After the gel is completely formed, a small amount of acid-base regulator (such as very dilute citric acid or sodium hydroxide solution) is used to precisely adjust the pH value of the final gel product to the neutral optimal range of 6.5-7.5 under gentle stirring, and then let it stand for 10 minutes again to equilibrate.

[0038] The sodium polyacrylate composite poloxamer gel prepared in this embodiment has the following characteristics: appearance: pale yellow gel; temperature sensitive; pH value: 7.45; viscosity (25℃): 21647 mPa·s.

[0039] Example 5. The composition and preparation process of this embodiment are the same as those in Embodiment 3. The difference lies in that, under constant temperature and stirring conditions of 10-15℃, the pre-stabilized sodium polyacrylate solution obtained in step S2 is slowly added to the low-temperature gel stock solution obtained in step S1 using a constant-speed peristaltic pump or a dropping device. The addition rate is controlled to ensure that the mixing process lasts for at least 30 minutes, and the final volume mixing ratio of the sodium polyacrylate solution to the gel stock solution is 10:100. At an environment of 10-15℃, which is far below the formation temperature of poloxamer micelles (typically >20℃), poloxamer exists in the form of monomolecules or loose pre-micelles. At this time, the fully extended long chains of sodium polyacrylate are slowly added, and the two can be mixed uniformly and smoothly at the molecular level. The anionic segments of sodium polyacrylate are initially "anchored" to the PPO segments of poloxamer through hydrogen bonding and hydrophobic interactions, achieving pre-assembly and completely avoiding the problem of agglomeration and clumping caused by direct collision with the already formed dense micelles at high temperatures.

[0040] The sodium polyacrylate composite poloxamer gel prepared in this embodiment has the following characteristics: appearance: pale yellow gel; temperature sensitive; pH value: 7.53; viscosity (25℃): 19974 mPa·s.

[0041] Example 6. The sodium polyacrylate composite poloxamer gel from Example 1 can be used as a sprayable antibacterial liquid wound dressing. Healing-promoting factors, such as recombinant human epidermal growth factor (rhEGF) at 10 μg / g, can be added as needed. Under aseptic conditions, the cooled gel is filled into a specially designed container equipped with a sterile spray pump. After cleaning the wound, the container is shaken well and sprayed onto the wound. Within seconds, a transparent, flexible gel dressing forms at body temperature. It has good conformability and is particularly suitable for irregular areas such as the ears, nose, and joints.

[0042] Example 7. The gel prepared using the process described in Example 2 of this invention can be used as an ultrasonic coupling agent. During the preparation of the sodium polyacrylate solution in S2, some glycerol and propylene glycol can be added for co-dissolution to optimize acoustic properties. After curing in S4 and cooling of the gel, phenoxyethanol, ethylhexylglycerin, and an antifoaming agent are added, and the mixture is stirred at low speed until homogeneous. Degassing is then performed: the gel is placed in a vacuum drying oven, and a vacuum is slowly applied at a low temperature (e.g., 10°C) to completely remove air bubbles introduced during stirring. The gel is then filled into tubing or bottles in a clean environment.

[0043] Comparative Example 1. Preparation of Poloxamer-Carbomer Composite Gel T1. The preparation of the gel stock solution is the same as in Example 1, and is ready for use.

[0044] T2. In addition, carbomer (0.5-3%) is evenly dispersed in purified water, allowed to stand, and stirred until completely dissolved after it has swollen sufficiently. T3. Under high-speed stirring (200-500 rpm), slowly add the above carbomer aqueous solution to the gel stock solution at a ratio of 1:15 to avoid excessive local concentration and clumping due to rapid addition.

[0045] T4. Continue stirring until the mixture is homogeneous, and let it stand for 2 hours to obtain poloxamer-carbomer gel.

[0046] Comparative Example 2. Preparation of poloxamer combined with sodium carboxymethyl cellulose gel P1. Add polycarboxymethylamino polysaccharide to purified water, stir to dissolve, and form a pale yellow clear solution.

[0047] P2. Add glycerin, stir, and mix well.

[0048] P3. While stirring (100-200 rpm), slowly add poloxamer P407, P188 and sodium carboxymethyl cellulose (0.5-2.5%) to avoid excessive local concentration and clumping due to rapid addition.

[0049] P4. Continue stirring until the mixture is homogeneous, and let it stand for 2 hours to obtain poloxamer-based sodium carboxymethyl cellulose gel.

[0050] Comparison of performance indicators: ; Through the analysis of the gels prepared by the above three different schemes and the test results, the poloxamer composite sodium polyacrylate gel is better; the poloxamer composite carbomer gel is sensitive to the pH value of the system during the preparation process, significantly affecting the texture strength and viscosity value of the gel; the poloxamer composite sodium carboxymethylcellulose gel has a relatively high initial viscosity value, but is easily affected by the irradiation energy, resulting in a sharp decrease in viscosity, and stratification occurs after sterilization, and the gel is unstable.

[0051] Rat experiment on preparing gel by using the preparation process of the present invention: 1.1 Experimental animals: 80 SPF-grade male SD rats aged 6 - 8 weeks with a body weight of 220 - 260 g were selected. They were purchased from Jiangxi University of Traditional Chinese Medicine, and the production license number of experimental animals is: SCXK(Gan)2023 - 0001. The rats were housed in cages in the SPF laboratory on the 3rd floor of the Experimental Animal Science and Technology Center of Jiangxi University of Traditional Chinese Medicine. The feeding conditions were a room temperature of 23 - 25°C, a humidity of 55% - 65%, a 12h / 12h day-night cycle, normal diet and drinking water. After 5 days of quarantine, they entered the SPF laboratory and were used for the experiment after 7 days of adaptive feeding. Ethical number: TEMPOR20240128.

[0052] 1.2 Method for establishing a second-degree burn model in rats and grouping: Model establishment method: The rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (30 mL / kg). The back was depilated and disinfected at a distance of 2 cm from the scapula. A 50 g weight (with a diameter of 2 cm) was placed in boiling water and boiled for 10 min, then taken out and applied to the disinfected area of the rat for 10 s. Two wounds were evenly made on the back of each rat to construct a second-degree burn model rat. When the skin at the depilated area of the rat turned white and the skin in the burn area was hardened and scabbed the next day, it indicated that the model establishment was successful.

[0053] After 7 days of adaptive feeding, 48 rats were randomly selected and randomly divided into four groups, with 12 rats in each group, namely the model group, the positive drug group (wound healing gel), the test group, and the blank group. Except for the blank group, the other groups were modeled according to the above method.

[0054] 1.3 Test method Blank group: Depilation treatment was carried out, no model was established, no drug treatment was given, and the rats were fed freely with conventional feed; For the following groups, the corresponding drugs of each group were evenly applied to the affected area with cotton swabs twice a day, once in the morning and once in the afternoon. Before drug administration, the rats could be anesthetized with sodium pentobarbital, and the rats were fed freely with conventional feed at other times.

[0055] Model group: physiological saline was applied to the affected area twice a day for 21 consecutive days.

[0056] Experimental group: The gel from Example 1 of this case was used twice a day for 21 consecutive days.

[0057] Positive drug group: Purilon Gel hydrogel dressing (National Medical Device Registration Certificate No. 20163142356), product batch number 107438 was used.

[0058] 1.4 Analysis of Experimental Results: Wound healing was observed and photographed at 3, 7, 14, and 21 days after drug administration. ImageJ software was used for standardized analysis of wound area reduction during healing to calculate the wound healing rate. Rats were anesthetized with sodium pentobarbital, and wound healing was observed and photographed. Skin specimens were then collected, cleaned with physiological saline, fixed in 4% paraformaldehyde, embedded in paraffin for 24-48 hours, and stained with hematoxylin and eosin (HE) and Masson's stain. Pathological changes in the burned skin tissue of rats were observed under a microscope.

[0059] Experimental data were statistically analyzed using Graphpad Prism 10.0.

[0060] Depend on Figure 1 It was observed that on day 7 of drug administration, the burn wounds of rats in the model group were dry, thick, and brownish-red; the wounds of rats in the positive control group all showed scab formation and were yellowish-brown; the experimental group rats showed improvement, with their wounds becoming moist, softer, and smaller in area. On day 14 of drug administration, except for the model group, the wound area of ​​rats in all other groups significantly decreased, and the wounds in the experimental group healed considerably. On day 21 of drug administration, except for the model group, the wound area of ​​rats in all other groups significantly decreased, and the experimental group had achieved a great deal of healing by day 21, exhibiting the best healing condition.

[0061] Depend on Figure 2 It can be seen that on day 21, except for the model group, the wounds of rats in the other groups all healed to a certain extent, and the healing rate of the experimental group was the highest and closest to that of the blank group.

[0062] Depend on Figure 3 It was observed that the epidermal structure of the control group rats was intact and clear, with a distinct stratum corneum, a thinner epithelial layer, and neatly and tightly arranged cells. Collagen fibers in the dermis were interwoven and relatively dense, with no obvious pathological changes. In the model group rats, the skin tissue was significantly thinner, with epidermal necrosis, cell nucleus dissolution or disappearance, and extensive degeneration and necrosis of dermal fibrous tissue. The necrotic areas were accompanied by significant inflammatory cell infiltration, with only a small amount of connective tissue and neovascularization. On day 21 after drug administration, a thicker new epidermal layer was visible in the skin tissue of both the positive control group and the experimental group. Connective tissue and neovascularization in the dermis were significantly increased, with the experimental group showing the best recovery.

[0063] Depend on Figure 4 It was observed that in the model group, skin damage and necrosis occurred, collagen fibers broke, and the gaps between them increased. The necrotic collagen fibers were red, a significant difference from the blue collagen fibers in the control group. Vascular dilation was observed, and the epithelial cells of sebaceous glands, sweat glands, and hair follicles swelled, dissolved, and decreased in number. The epidermis and dermis became thinner, and the width of collagen fibers in the dermis also decreased relatively. During the wound healing process in each group, the area of ​​collagen deposition (blue) increased, and the collagen fibers became increasingly dense. Ultimately, the experimental group showed the best recovery state, most closely resembling the morphology of the control group.

[0064] Based on the treatment results of a rat model of deep second-degree burns, the sodium polyacrylate composite poloxamer gel (experimental group) prepared in this case showed a significant effect in promoting wound healing. Its superiority is specifically reflected in the following aspects: Faster healing process: On day 7 of administration, the wounds in the experimental group showed a favorable trend of "moistening, softening, and shrinking area," indicating that the gel created a moist environment conducive to healing and may have accelerated the initiation of inflammation control and tissue repair through its physical barrier and active ingredients. Superior healing effect: By day 21 of administration, the experimental group had the highest wound healing rate, closest to the state of healthy (blank) skin. Both visual and quantitative data demonstrated that its final healing effect was superior to the model group and the positive control group. More complete histological repair: HE staining showed that the newly formed epidermis in the experimental group was thicker and the structure was well restored. Dermal reconstruction: Masson staining showed that the collagen fiber deposition in the dermis of the experimental group was denser and more orderly, with abundant new blood vessels and connective tissue. Its histological morphological restoration was the best, closest to the normal skin structure.

[0065] In conclusion, animal experiments have strongly demonstrated that the gel of this invention, as a wound dressing, has a clear effect on accelerating healing and improving healing quality, providing key experimental evidence for its medical value.

[0066] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A sodium polyacrylate complex poloxamer gel characterized in that, By weight percentage, it comprises the following components: Gel base component: poloxamer P407, 5%-20%; poloxamer P188, 1%-10%; Ionic thickening and reinforcing component: sodium polyacrylate: 0.2%-1%; Humectant: 0.5%-2% Water-soluble polyamino polysaccharide derivative: 0.5%-2%; Solvent: purified water, balance.

2. The preparation method of a sodium polyacrylate composite poloxamer gel according to claim 1, comprising the following steps: S1. Preparation of gel stock solution: add water-soluble polyamino polysaccharide derivative to part of purified water, stir to dissolve; add humectant, mix evenly; under the stirring speed of 100-200 rpm, add poloxamer P407 and P188, continue to stir for 1 hour to make poloxamer fully infiltrate; then stand at low temperature of 5-20℃ until poloxamer is completely dissolved, obtain clear and transparent gel stock solution, and reserve; S2. Preparation of sodium polyacrylate solution: in another container, under the stirring speed of 200-500 rpm, slowly and evenly disperse sodium polyacrylate powder in the remaining purified water, continue to stir until it is completely dissolved to form a uniform sodium polyacrylate aqueous solution; S3. Compound: slowly drop or flow the sodium polyacrylate aqueous solution obtained in step S2 into the gel stock solution obtained in step S1, control the adding speed to avoid local concentration too high leading to caking, the volume mixing ratio of sodium polyacrylate solution to gel stock solution is 1-15:

100.

3. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 2, wherein, Also includes step S4. Curing: continue to stir the mixture obtained in step S3 until it is completely uniform, then stand for at least 2 hours.

4. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 3, wherein, The curing includes the following two stages: S41. Low temperature winding: continue to stir the uniform mixture obtained in step S3 at 10-15℃ for 1-2 hours, then stand at this temperature for 1-3 hours; S42. Temperature rising solidification: slowly raise the system after S41 primary curing to 25-37℃, and stand at this temperature for 2-6 hours.

5. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 3, wherein, Also includes step S5. Terminal pH balance: after the gel is completely formed, use a small amount of acid-base regulator to accurately adjust the pH value of the final gel product to neutral 6.5-7.5 under gentle stirring, then stand again for a short time to balance.

6. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 2, wherein, In step S1, add water-soluble polyamino polysaccharide derivative to part of purified water, stir to dissolve; add humectant, mix evenly; under the stirring speed of 100-200 rpm, add poloxamer P407 and P188, continue to stir for 1 hour to make poloxamer fully infiltrate; after poloxamer fully infiltrates, then stand at low temperature of 2-8℃ for 6-24 hours until poloxamer is completely dissolved, obtain clear and transparent gel stock solution, and stabilize the temperature of the gel stock solution at 10-15℃, reserve.

7. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 2, wherein, In the step of preparing the sodium polyacrylate solution in step S2, in another container, under high-speed stirring at 200-500 rpm, the sodium polyacrylate powder is slowly and uniformly dispersed in the remaining purified water. After initial dispersion, the pH value of the system is adjusted to 8.0-9.0 using a dilute alkali solution. Under this weak alkaline environment, the stirring is continued until the sodium polyacrylate is completely dissolved and the molecular chain is fully stretched, forming a uniform, transparent, viscous solution. The temperature of the solution is adjusted to 10-15°C, and it is ready for use.

8. A process for the preparation of a sodium polyacrylate complexed poloxamer gel as claimed in claim 2, wherein: Under the conditions of constant low temperature at 10-15°C and continuous stirring, the pre-stabilized sodium polyacrylate solution obtained in step S2 is slowly added to the low-temperature gel stock solution obtained in step S1 using a constant-speed peristaltic pump or a dropping device. The addition speed is controlled so that the mixing process lasts for at least 30 minutes or more. The final volume mixing ratio of the sodium polyacrylate solution to the gel stock solution is 1-15:

100.

9. Use of the sodium polyacrylate composite poloxamer gel according to any one of claims 1 to 8 in the preparation of a medical dressing, a drug release carrier, or a coupling agent for medical devices.

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