Antibacterial chemical gel for neonatal umbilical care and its synthesis process

Abstract

The application discloses an antibacterial chemical gel for umbilical cord nursing of newborns and a synthesis process thereof, relates to the technical field of medical preparations, and comprises the following steps: using active silver ions and benzalkonium chloride as an antibacterial agent, using propylene glycol and glycerol as a moisturizing agent, using honeysuckle extract and farnesol as a bacteriostatic additive, and using a gel matrix compounded by polylactic acid-glycolic acid copolymer (PLGA) and a temperature-sensitive poly-N-isopropyl acrylamide (PNIPAM) graft copolymer and modified diatomite, wherein the ratio range and performance parameters of the raw materials are determined, a temperature-sensitive degradable and liquid-permeable responsive gel system is constructed, and the technical problems of traditional products are effectively solved by realizing mild antibacterial property, liquid-permeable response, degradation without residue, and the functions of moisturizing and wound repair.

Description

Technical Field

[0001] This invention relates to the field of medical preparations technology, specifically to an antibacterial chemical gel for neonatal umbilical cord care and its synthesis process. Background Technology

[0002] The umbilical cord is a critical physiological site for newborns. The wound formed after the umbilical cord is cut after birth is an open wound. The mucous membrane in this area is delicate, rich in blood vessels, and connects to the abdominal cavity, making it an easy area for common pathogens such as Escherichia coli and Staphylococcus aureus to infect. If the umbilical cord is not properly cared for, pathogens can easily invade the wound and cause complications such as omphalitis and periumbilical redness and swelling. In severe cases, it can further develop into sepsis, directly threatening the newborn's life and health. Therefore, keeping the umbilical wound dry and clean, and achieving effective antibacterial protection and wound repair, is one of the core research directions in the field of neonatal care.

[0003] Currently, existing products in the field of neonatal umbilical cord care mainly include topical disinfectants such as povidone-iodine and alcohol, as well as various antibacterial ointments and traditional hydrogel care products. While povidone-iodine and alcohol possess basic antibacterial capabilities, they inherently have the drawback of being highly irritating, easily damaging the delicate skin and mucous membranes of newborns. Furthermore, their antibacterial effect is short-lived, requiring frequent reapplication. Traditional antibacterial ointments are viscous and have poor breathability, easily clogging the umbilical wound after application, hindering exudate drainage, and thus increasing the risk of infection. Some ointments also contain hormones, and long-term use may have adverse effects on the newborn's physical development. Existing antibacterial... Gel products often use a single antibacterial ingredient, resulting in a narrow antibacterial spectrum that makes it difficult to fully cover common pathogens in the umbilical cord area of ​​newborns. They also generally suffer from limited moisturizing and repairing effects, complex synthesis processes, and high production costs. In addition, most gel products use traditional hydrogel matrices such as carbomer and polyethylene glycol, or conventional temperature-sensitive matrices, which have drawbacks such as being sticky and difficult to clean after application, easily dissolving and becoming ineffective after contact with umbilical exudate, and failing to accurately respond to the needs of wound exudate. Furthermore, some matrices are non-degradable, which can easily cause secondary friction damage to the umbilical wound during cleaning, making them unsuitable for the special care needs of newborn umbilical wounds. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies and provide an antibacterial chemical gel for neonatal umbilical cord care and its synthesis process. This gel utilizes a combination of active silver ions and benzalkonium chloride as an antibacterial agent, propylene glycol and glycerin as a moisturizing agent, honeysuckle extract and bisabolol as an antibacterial adjuvant, and a gel matrix composed of polylactic-co-glycolic acid copolymer (PLGA), thermosensitive poly(N-isopropylacrylamide) graft copolymer (PNIPAM), and modified diatomaceous earth. By clearly defining the proportions and performance parameters of each raw material, a thermosensitive, biodegradable, and exudate-responsive gel system is constructed. This achieves gentle antibacterial action, exudate response, and residue-free degradation, while also providing moisturizing and wound repair benefits, effectively solving the technical challenges of traditional products.

[0005] To solve the above-mentioned technical problems, the present invention provides the following technical solution: On the one hand, an antibacterial chemical gel for neonatal umbilical cord care is composed of the following raw materials in weight percentage: antibacterial agent 0.01%-0.05%, gel matrix 1.0%-3.0%, moisturizer 2.0%-5.0%, pH adjuster 0.05%-0.2%, antibacterial adjuvant 0.1%-0.3%, and purified water balance; The antibacterial agent is a compound system of active silver ions and benzalkonium chloride, with a weight ratio of 1:2-4; The gel matrix is ​​a compound system of polylactic acid-glycolic acid copolymer (PLGA), thermosensitive poly(N-isopropylacrylamide) graft copolymer (PNIPAM), and modified diatomaceous earth. The weight ratio of the PLGA-PNIPAM graft copolymer to the modified diatomaceous earth is 4-6:1.

[0006] Furthermore, the active silver ions are nano-silver ions modified by slow release of silver nitrate, with a particle size of 5-20 nm; the benzalkonium chloride has a purity of ≥99.5% and is a 10% aqueous solution.

[0007] Furthermore, in the gel matrix, the number-average molecular weight of the PLGA-PNIPAM graft copolymer is 10,000-30,000 Da, the molar ratio of lactic acid to glycolic acid in PLGA is 50-75:50-25, the grafting rate of PNIPAM is 15%-30%, the modified diatomaceous earth is diatomaceous earth modified with silane coupling agent KH-550, with a pore size of 50-200 nm and a specific surface area of ​​100-300 m² / g, PLGA has good biocompatibility and biodegradability, and can be slowly degraded into lactic acid and glycolic acid, which can be metabolized and absorbed by the human body without the need for additional cleaning, avoiding friction and irritation to the umbilical wound during the cleaning process; PNIPAM has good thermosensitivity, with a minimum critical dissolution temperature of 32-35℃, which matches the body temperature of newborns, allowing the PLGA-PNIPAM graft copolymer to... At room temperature, it is a fluid liquid, making it easy to apply precisely to umbilical folds and stumps. Upon contact with the newborn's body temperature, it quickly transforms into a semi-solid gel, adhering tightly to the wound and preventing it from falling off, while ensuring good breathability, without clogging the wound or hindering exudate drainage. Diatomaceous earth itself has a rich porous structure, and after modification with the silane coupling agent KH-550, its hydrophilicity and dispersibility are significantly improved, enabling it to quickly absorb exudate from the umbilical wound and keep the umbilical area dry. At the same time, when exudate comes into contact with the porous structure of the modified diatomaceous earth, it triggers the slow release of antibacterial components inside the gel, achieving responsive protection with stronger antibacterial properties the more exudate there is. This specifically addresses the increased risk of infection when there is umbilical exudate, further improving the precision and effectiveness of antibacterial care. In addition, the modified diatomaceous earth also enhances the mechanical strength of the gel, preventing it from dissolving upon contact with exudate and improving its stability.

[0008] Furthermore, the moisturizer is a compound system of propylene glycol and glycerin in a weight ratio of 1-2:1. Propylene glycol has good moisturizing and plasticizing effects, which can increase the flexibility and extensibility of the gel, while promoting the dissolution and release of antibacterial ingredients. Glycerin can form a moisturizing film on the skin surface, lock in moisture, relieve dryness and discomfort of the newborn's umbilical wound, and promote wound healing. The combination of the two has a better moisturizing effect, which can effectively avoid skin dryness after gel application. It has good compatibility with the temperature-sensitive and biodegradable matrix and does not affect the temperature sensitivity and biodegradability of the matrix. The pH adjuster is a buffer system of sodium hydroxide and hydrochloric acid, which is used to adjust the pH value of the gel to 5.5-6.5. This pH value is close to the acidity and alkalinity of the newborn's skin, which can reduce the irritation of the gel to the newborn's umbilical wound, reduce the risk of allergies, and at the same time help the antibacterial ingredients to play their role, improve the care effect, meet the care needs of the newborn's delicate skin, and does not affect the temperature sensitivity and degradation performance of the gel matrix.

[0009] Furthermore, the antibacterial adjuvant is a compound system of honeysuckle extract and bisabolol, with a weight ratio of 2-3:1. Honeysuckle extract has antibacterial, anti-inflammatory, and soothing effects, which can help inhibit the growth of pathogenic bacteria and relieve redness and discomfort of the umbilical wound. Bisabolol has good anti-inflammatory and repairing effects, which can promote the healing of the umbilical wound and reduce scar formation. The combination of the two can synergistically enhance the repairing effect of the gel, while further reducing the irritation of the gel, making it suitable for long-term use by newborns and in line with the development trend of natural and mild infant care products. The flavonoid content of honeysuckle extract is ≥10%, and the purity of bisabolol is ≥98%.

[0010] Furthermore, the preparation method of the PLGA-PNIPAM graft copolymer is as follows: PLGA is dissolved in dichloromethane, N-isopropylacrylamide monomer and initiator azobisisobutyronitrile are added, and the reaction is carried out at 60-70℃ for 8-12h. After the reaction is completed, the copolymer is precipitated, washed and vacuum dried to obtain the PLGA-PNIPAM graft copolymer. The preparation method of the modified diatomaceous earth is as follows: diatomaceous earth is dispersed in an ethanol aqueous solution, silane coupling agent KH-550 is added, and the mixture is stirred at 50-60℃ for 2-3h. After filtration and drying, the modified diatomaceous earth is obtained.

[0011] On the other hand, a process for synthesizing an antibacterial chemical gel for neonatal umbilical cord care includes the following steps: S1: Pass the PLGA-PNIPAM graft copolymer and modified diatomaceous earth through an 80-mesh sieve to remove impurities; place the active silver ions, benzalkonium chloride, humectant, and antibacterial agent in a sterile environment and let them stand at room temperature for 30-60 minutes for later use. S2: Place purified water in a sterile reactor, control the temperature at 25-30℃, and the stirring speed at 100-150r / min. Add PLGA-PNIPAM graft copolymer and stir until completely dissolved. Then add modified diatomaceous earth and continue stirring for 30-40min. Let it stand for 1-2h to allow the modified diatomaceous earth to be fully dispersed and form a uniform matrix system with PLGA-PNIPAM graft copolymer. S3: Take active silver ions and benzalkonium chloride, add an appropriate amount of purified water, stir evenly to prepare an antibacterial mother liquor, and store it in an environment of 4-8℃ for later use. S4: Slowly add the antibacterial mother liquor, the prescribed amount of moisturizer, and the antibacterial adjuvant to the obtained matrix system, adjust the stirring speed to 300-400 r / min, stir for 30-60 min, and at the same time use a homogenizer to homogenize the mixture. The homogenization pressure is 10-15 MPa and the homogenization time is 10-15 min to obtain a mixed gel solution. S5: Slowly add the pH adjuster dropwise to the mixed gel solution while stirring. Monitor the pH value of the gel in real time until the pH value reaches 5.5-6.5. Stop adding the pH adjuster and continue stirring for 10-15 minutes to make the system homogeneous. S6: Place the obtained gel solution in a sterilizer and sterilize it using a low-temperature steam sterilization method. Control the temperature at 80-90℃ and the sterilization time at 15-20 minutes. After sterilization, allow it to cool naturally to room temperature. S7: Place the cooled gel liquid in a sterile filling device, fill it into a sterile container, seal and label it to obtain the antibacterial chemical gel for neonatal umbilical care.

[0012] Furthermore, in S4, the homogenization process is performed intermittently, with a 5-minute homogenization followed by a 2-minute pause, repeated 2-3 times. This ensures that the antibacterial components, moisturizers, antibacterial agents, and gel matrix are fully integrated, resulting in a smooth texture without any graininess, and without damaging the porous structure of the modified diatomaceous earth.

[0013] Furthermore, in step S6, the steam pressure for low-temperature steam sterilization is 0.1-0.15 MPa, and violent vibrations are avoided during the cooling process to prevent the gel matrix from gelling prematurely and to ensure that it is a fluid liquid at room temperature.

[0014] Compared with existing technologies, this antibacterial chemical gel for neonatal umbilical cord care and its synthesis process have the following beneficial effects: This invention utilizes an antibacterial system composed of active silver ions and benzalkonium chloride to synergistically exert a broad-spectrum antibacterial effect, achieving a sterilization rate of over 99.9% against common pathogens in the neonatal umbilical cord. The antibacterial effect is long-lasting, and the antibacterial components are released slowly upon contact with exudate, achieving responsive protection where the more exudate, the stronger the antibacterial effect. Furthermore, it employs a temperature-sensitive, biodegradable, exudate-responsive matrix composed of PLGA-PNIPAM graft copolymer and modified diatomaceous earth. At room temperature, it is a fluid liquid for precise application; upon contact with body temperature (37°C), it rapidly gels and adheres to the wound. The modified diatomaceous earth quickly absorbs the exudate. The liquid enhances gel stability, and PLGA is biodegradable and metabolized by the human body, eliminating the need for additional cleaning and preventing secondary friction damage. This solves the technical problems of traditional matrices being sticky, easily soluble, non-biodegradable, and unable to respond to exudation needs. The pH value is adjusted to 5.5-6.5, close to the acidity and alkalinity of newborn skin. Skin irritation tests have verified that it is non-irritating with a 0% sensitization rate, making it suitable for long-term use. It is supplemented with a moisturizing agent composed of propylene glycol and glycerin, and an antibacterial agent composed of honeysuckle extract and bisabolol, making it suitable for large-scale promotion. It has low production costs and combines the comprehensive advantages of safety, high efficiency, gentleness, and convenience.

[0015] Other advantages, objectives and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination or study, or may be learned from the practice of the invention. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0017] Figure 1 A flowchart illustrating the synthesis process of an antibacterial chemical gel for neonatal umbilical cord care; Figure 2 This is a flowchart illustrating the preparation of a PLGA-PNIPAM graft copolymer antibacterial chemical gel for neonatal umbilical cord care. Detailed Implementation

[0018] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0019] Example 1 An antibacterial chemical gel for neonatal umbilical cord care comprises the following raw materials in weight percentages: 0.01% antibacterial agent (0.0025% active silver ions, 0.0075% benzalkonium chloride), 1.0% gel matrix (0.8% PLGA-PNIPAM graft copolymer, 0.2% modified diatomaceous earth), 2.0% humectant (1.0% propylene glycol, 1.0% glycerin), 0.05% pH adjuster (0.02% sodium hydroxide, 0.03% hydrochloric acid), 0.1% antibacterial adjuvant (0.067% honeysuckle extract, 0.033% bisabolol), and 96.84% purified water.

[0020] The PLGA-PNIPAM graft copolymer has a number average molecular weight of 10,000 Da, the molar ratio of lactic acid to glycolic acid in PLGA is 50:50, and the grafting rate of PNIPAM is 15%. The modified diatomaceous earth is modified with silane coupling agent KH-550, with a pore size of 50-100 nm and a specific surface area of ​​100-150 m² / g.

[0021] like Figure 1 As shown, its synthesis process includes: PLGA-PNIPAM graft copolymer and modified diatomaceous earth were passed through an 80-mesh sieve to remove impurities; active silver ions, benzalkonium chloride, propylene glycol, glycerin, honeysuckle extract and bisabolol were placed in a sterile environment and left at room temperature for 30 minutes for later use. Among them, such as Figure 2 As shown, the preparation process of PLGA-PNIPAM graft copolymer is as follows: PLGA is dissolved in dichloromethane, N-isopropylacrylamide monomer and initiator azobisisobutyronitrile are added, and the reaction is carried out at 60℃ for 8 hours. After the reaction is completed, the copolymer is precipitated, washed and vacuum dried to obtain PLGA-PNIPAM graft copolymer. Preparation of modified diatomaceous earth: diatomaceous earth was dispersed in an ethanol aqueous solution, silane coupling agent KH-550 was added, and the mixture was stirred at 50°C for 2 hours. After filtration and drying, modified diatomaceous earth was obtained. Take 96.84% purified water and place it in a sterile reactor. Control the temperature at 25℃ and the stirring speed at 100r / min. First, add 0.8% of PLGA-PNIPAM graft copolymer and stir until completely dissolved. Then, add 0.2% of modified diatomaceous earth and continue stirring for 30min. Let it stand for 1h to form a uniform matrix system. Take 0.0025% active silver ions and 0.0075% benzalkonium chloride, add an appropriate amount of purified water, stir evenly to prepare an antibacterial stock solution, and store it in an environment of 4℃ for later use. The antibacterial stock solution, 1.0% propylene glycol, 1.0% glycerol, 0.067% honeysuckle extract, and 0.033% bisabolol were slowly added to the obtained matrix system. The stirring speed was adjusted to 300 r / min and stirred for 30 min. At the same time, the mixture was intermittently homogenized using a homogenizer at a pressure of 10 MPa. The homogenization was repeated twice, with a 2-min pause after every 5 min of homogenization, to obtain a mixed gel solution. Slowly add a 0.02% sodium hydroxide and 0.03% hydrochloric acid buffer system to the obtained mixed gel solution while stirring. Monitor the pH value of the gel in real time until the pH value reaches 5.5. Stop adding the solution and continue stirring for 10 minutes to make the system homogeneous. The obtained gel solution was placed in a sterilizer and sterilized using a low-temperature steam sterilization method. The temperature was controlled at 80℃, the steam pressure at 0.1MPa, and the sterilization time at 15min. After sterilization, the solution was allowed to cool naturally to room temperature, avoiding violent vibrations during the cooling process. The cooled gel solution is placed in a sterile filling device, filled into a sterile container, sealed, and labeled to obtain an antibacterial chemical gel for neonatal umbilical cord care.

[0022] Example 2 An antibacterial chemical gel for neonatal umbilical cord care comprises the following raw materials in weight percentages: 0.03% antibacterial agent (0.0075% active silver ions, 0.0225% benzalkonium chloride), 2.0% gel matrix (1.6% PLGA-PNIPAM graft copolymer, 0.4% modified diatomaceous earth), 3.5% humectant (2.0% propylene glycol, 1.5% glycerin), 0.12% pH adjuster (0.05% sodium hydroxide, 0.07% hydrochloric acid), 0.2% antibacterial adjuvant (0.133% honeysuckle extract, 0.067% bisabolol), and 94.15% purified water.

[0023] The PLGA-PNIPAM graft copolymer has a number average molecular weight of 20,000 Da, the molar ratio of lactic acid to glycolic acid in PLGA is 60:40, and the grafting rate of PNIPAM is 22%. The modified diatomaceous earth is modified with silane coupling agent KH-550, with a pore size of 100-150 nm and a specific surface area of ​​150-220 m² / g.

[0024] Its synthesis process includes: PLGA-PNIPAM graft copolymer and modified diatomaceous earth were passed through an 80-mesh sieve to remove impurities. Active silver ions, benzalkonium chloride, propylene glycol, glycerin, honeysuckle extract, and bisabolol were placed in a sterile environment and left at room temperature for 45 minutes for later use. Specifically, the PLGA-PNIPAM graft copolymer was prepared by dissolving PLGA in dichloromethane, adding N-isopropylacrylamide monomer and the initiator azobisisobutyronitrile, and reacting at 65°C for 10 hours. After the reaction, the copolymer was precipitated, washed, and vacuum dried to obtain the PLGA-PNIPAM graft copolymer. The modified diatomaceous earth was prepared by dispersing diatomaceous earth in an ethanol-water solution, adding silane coupling agent KH-550, stirring at 55°C for 2.5 hours, filtering, and drying to obtain the modified diatomaceous earth. Take 94.15% purified water and place it in a sterile reactor. Control the temperature at 28℃ and the stirring speed at 120r / min. First, add 1.6% of PLGA-PNIPAM graft copolymer and stir until completely dissolved. Then, add 0.4% of modified diatomaceous earth and continue stirring for 35min. Let it stand for 1.5h to form a uniform matrix system. Take 0.0075% active silver ions and 0.0225% benzalkonium chloride, add an appropriate amount of purified water, stir evenly to prepare an antibacterial stock solution, and store it in an environment of 6℃ for later use. The antibacterial stock solution, 2.0% propylene glycol, 1.5% glycerol, 0.133% honeysuckle extract, and 0.067% bisabolol were slowly added to the matrix system. The stirring speed was adjusted to 350 r / min and stirred for 45 min. At the same time, the mixture was intermittently homogenized using a homogenizer at a pressure of 12 MPa. The homogenization was repeated 3 times, with a 2-min pause after every 5 min of homogenization, to obtain a mixed gel solution. Slowly add a 0.05% sodium hydroxide and 0.07% hydrochloric acid buffer system to the mixed gel solution while stirring. Monitor the pH value of the gel in real time until the pH value reaches 6.0. Stop adding the solution and continue stirring for 12 minutes to make the system homogeneous. The gel solution was placed in a sterilizer and sterilized using a low-temperature steam sterilization method. The temperature was controlled at 85℃, the steam pressure at 0.12MPa, and the sterilization time at 18min. After sterilization, the solution was allowed to cool naturally to room temperature, avoiding violent vibrations during the cooling process. The cooled gel solution is placed in a sterile filling device, filled into a sterile container, sealed, and labeled to obtain an antibacterial chemical gel for neonatal umbilical cord care.

[0025] Example 3 An antibacterial chemical gel for neonatal umbilical cord care comprises the following raw materials in weight percentages: 0.05% antibacterial agent (0.0125% active silver ions, 0.0375% benzalkonium chloride), 3.0% gel matrix (2.5% PLGA-PNIPAM graft copolymer, 0.5% modified diatomaceous earth), 5.0% humectant (3.0% propylene glycol, 2.0% glycerin), 0.2% pH adjuster (0.08% sodium hydroxide, 0.12% hydrochloric acid), 0.3% antibacterial adjuvant (0.2% honeysuckle extract, 0.1% bisabolol), and 91.45% purified water.

[0026] The PLGA-PNIPAM graft copolymer has a number average molecular weight of 30,000 Da, the molar ratio of lactic acid to glycolic acid in PLGA is 75:25, and the grafting rate of PNIPAM is 30%. The modified diatomaceous earth is modified with silane coupling agent KH-550, with a pore size of 150-200 nm and a specific surface area of ​​220-300 m² / g.

[0027] Its synthesis process includes the following steps: PLGA-PNIPAM graft copolymer and modified diatomaceous earth were passed through an 80-mesh sieve to remove impurities. Active silver ions, benzalkonium chloride, propylene glycol, glycerin, honeysuckle extract, and bisabolol were placed in a sterile environment and left at room temperature for 60 minutes for later use. Specifically, the PLGA-PNIPAM graft copolymer was prepared by dissolving PLGA in dichloromethane, adding N-isopropylacrylamide monomer and the initiator azobisisobutyronitrile, and reacting at 70°C for 12 hours. After the reaction, the copolymer was precipitated, washed, and vacuum dried to obtain the PLGA-PNIPAM graft copolymer. The modified diatomaceous earth was prepared by dispersing diatomaceous earth in an ethanol-water solution, adding silane coupling agent KH-550, stirring at 60°C for 3 hours, filtering, and drying to obtain the modified diatomaceous earth. Take 91.45% purified water and place it in a sterile reactor. Control the temperature at 30℃ and the stirring speed at 150r / min. First, add 2.5% of PLGA-PNIPAM graft copolymer and stir until completely dissolved. Then, add 0.5% of modified diatomaceous earth and continue stirring for 40min. Let it stand for 2h to form a uniform matrix system. Take 0.0125% active silver ions and 0.0375% benzalkonium chloride, add an appropriate amount of purified water, stir evenly to prepare an antibacterial stock solution, and store it in an 8℃ environment for later use. The antibacterial stock solution, 3.0% propylene glycol, 2.0% glycerin, 0.2% honeysuckle extract, and 0.1% bisabolol were slowly added to the matrix system. The stirring speed was adjusted to 400 r / min and stirred for 60 min. At the same time, the mixture was intermittently homogenized using a homogenizer at a pressure of 15 MPa. The homogenization was repeated 3 times, with a 2-min pause after every 5 min of homogenization, to obtain a mixed gel solution. Slowly add a 0.08% sodium hydroxide and 0.12% hydrochloric acid buffer system to the mixed gel solution while stirring. Monitor the pH value of the gel in real time until the pH value reaches 6.5. Stop adding the solution and continue stirring for 15 minutes to make the system homogeneous. The gel solution was placed in a sterilizer and sterilized using a low-temperature steam sterilization method. The temperature was controlled at 90℃, the steam pressure at 0.15MPa, and the sterilization time at 20min. After sterilization, the solution was allowed to cool naturally to room temperature, avoiding violent vibrations during the cooling process. The cooled gel solution is placed in a sterile filling device, filled into a sterile container, sealed, and labeled to obtain an antibacterial chemical gel for neonatal umbilical cord care.

[0028] Comparative Example 1 An antibacterial chemical gel for neonatal umbilical cord care has the same raw material composition and synthesis process as in Example 2. The only difference is that the gel matrix is ​​replaced with a traditional carbomer matrix (carbomer 940), and the amount is still 2.0%. PLGA-PNIPAM graft copolymer and modified diatomaceous earth are not added.

[0029] Comparative Example 2 An antibacterial chemical gel for neonatal umbilical cord care has the same raw material composition and synthesis process as in Example 2, except that the antibacterial agent is replaced with a single active silver ion, the dosage is still 0.03%, and benzalkonium chloride is not added.

[0030] Comparative Example 3 An antibacterial chemical gel for neonatal umbilical cord care has the same raw material composition and synthesis process as in Example 2. The only difference is that the modified diatomaceous earth is replaced with ordinary diatomaceous earth that has not been modified by silane coupling agent KH-550, and the amount is still 0.4%. The other raw materials and processes remain unchanged.

[0031] Comparative Example 4 An antibacterial chemical gel for neonatal umbilical cord care has the same raw material composition and synthesis process as in Example 2. The only difference is that the gel matrix is ​​only PLGA-PNIPAM graft copolymer, and the amount is still 2.0%, without the addition of modified diatomaceous earth.

[0032] Performance testing Antibacterial efficacy test: A quantitative suspension bactericidal test was used to test the bactericidal rate of the gel against Escherichia coli and Staphylococcus aureus. Simultaneously, the sustained-release effect of the antibacterial component after contact with exudate was tested. The results showed that the gels in Examples 1-3, after 5 minutes of contact, achieved a bactericidal rate of ≥99.9% against Escherichia coli and Staphylococcus aureus. After contact with simulated umbilical exudate, the sustained-release rate of the antibacterial component increased by 30%-50%, achieving stronger antibacterial activity with more exudate and a duration of antibacterial activity of 12-16 hours. (Comparative Example 1) The sterilization rate was 98.2%, with no antibacterial sustained-release effect after exudate contact, and the antibacterial duration was only 6-8 hours; Comparative Example 2 had a sterilization rate of 97.8%, an antibacterial duration of 7-9 hours, and no exudate-responsive sustained-release function; Comparative Example 3 had a sterilization rate of 99.0%, a slow exudate absorption rate, and the antibacterial sustained-release rate was only increased by 10%-15%, with an antibacterial duration of 9-11 hours; Comparative Example 4 had a sterilization rate of 99.1%, no exudate absorption capacity, a weak antibacterial sustained-release effect, and an antibacterial duration of 8-10 hours.

[0033] Skin irritation test: Ten healthy New Zealand rabbits were selected and multiple complete skin irritation tests were conducted. At the same time, ten families with newborns aged 0-3 months were selected for actual testing. The results showed that the gels of Examples 1-3 and Comparative Examples 2-4 were not irritating to the skin, and no discomfort such as redness, allergy, or dryness was observed in the newborns after use. However, Comparative Example 1 was sticky after application, and some newborns experienced slight skin dryness.

[0034] Stability test: The gels were stored in a constant temperature environment of 37℃ for 3 months. The changes in gel texture and color were observed, and the content of antibacterial components and temperature sensitivity were tested. The results showed that the gels of Examples 1-3 had a uniform texture, without layering, clumping, or discoloration. They maintained good fluidity at room temperature and could quickly gel within 30-60 seconds at 37℃. The content of active silver ions and benzalkonium chloride decreased by ≤4.8%, indicating good stability. Comparative Example 1 showed slight layering, and the content of antibacterial components decreased by 8.5%, with no temperature sensitivity. The gels of Comparative Examples 2-4 had good stability, but Comparative Examples 1 and 4 had no exudate absorption or sustained-release function, and Comparative Example 3 had weak exudate absorption capacity.

[0035] Temperature sensitivity test: The changes in gel state were observed at 25℃, 30℃, 37℃ and 40℃ respectively. The results showed that Examples 1-3 and Comparative Examples 2-4 (containing PLGA-PNIPAM graft copolymer) were free-flowing liquids at 25-30℃, rapidly gelled within 30-60s at 37℃, and remained in a semi-solid state at 40℃. Comparative Example 1 had no temperature sensitivity, was a semi-solid gel at room temperature, was inconvenient to apply, and easily dissolved after contact with exudate.

[0036] Exudate absorption test: Simulated umbilical exudate (a mixture of physiological saline and serum) was used to test the exudate absorption volume and absorption rate of the gel. The results showed that the exudate absorption volume of gels in Examples 1-3 reached 150%-200% of their own weight within 10 minutes, with a fast absorption rate; the exudate absorption volume of Comparative Example 1 was only 50%-70% of its own weight within 10 minutes, and it was easily dissolved; the exudate absorption volume of Comparative Example 3 was 90%-120% of its own weight within 10 minutes, with a slow absorption rate; and Comparative Example 4 had no obvious exudate absorption capacity.

[0037] Degradability test: The gel was placed in a simulated human body fluid environment and incubated at a constant temperature of 37°C. The degradation was observed. The results showed that the gels of Examples 1-3 and Comparative Examples 2-4 degraded slowly within 7-14 days. PLGA was decomposed into lactic acid and glycolic acid with no residue. Comparative Example 1 was not degradable, required additional cleaning, and was prone to causing friction damage to the wound.

[0038] In summary, the antibacterial chemical gel for neonatal umbilical cord care prepared in Examples 1-3 of this invention relies on a thermosensitive, biodegradable, exudate-responsive gel matrix composed of PLGA-PNIPAM graft copolymer and modified diatomaceous earth, combined with an antibacterial system composed of active silver ions and benzalkonium chloride, and an antibacterial adjuvant composed of honeysuckle extract and bisabolol. It exhibits excellent comprehensive performance, possessing not only broad-spectrum and long-lasting antibacterial effects, but also responsive protection where the more exudate, the stronger the antibacterial effect. Furthermore, it has advantages such as being mild and non-irritating, easy to form a thermosensitive gel, rapid exudate absorption, and biodegradable with no residue. It is well-suited to the special care needs of neonatal umbilical wounds. Compared to the comparative examples, this invention effectively solves the technical defects of traditional matrices, such as non-degradability, lack of exudate-responsive function, poor antibacterial effect of single antibacterial agents, and insufficient exudate absorption and sustained-release performance of unmodified diatomaceous earth. Moreover, the synthesis process is simple and controllable, making it suitable for large-scale production.

[0039] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An antibacterial chemical gel for neonatal umbilical cord care, characterized in that, It is composed of the following raw materials in weight percentage: antibacterial agent 0.01%-0.05%, gel matrix 1.0%-3.0%, humectant 2.0%-5.0%, pH adjuster 0.05%-0.2%, antibacterial adjuvant 0.1%-0.3%, and purified water balance; The antibacterial agent is a compound system of active silver ions and benzalkonium chloride, with a weight ratio of 1:2-4; The gel matrix is ​​a compound system of polylactic acid-glycolic acid copolymer (PLGA), thermosensitive poly(N-isopropylacrylamide) graft copolymer (PNIPAM), and modified diatomaceous earth. The weight ratio of the PLGA-PNIPAM graft copolymer to the modified diatomaceous earth is 4-6:

1.

2. The antibacterial chemical gel for neonatal umbilical cord care according to claim 1, characterized in that, The active silver ions are nano-silver ions modified by slow release of silver nitrate, with a particle size of 5-20 nm; the benzalkonium chloride has a purity of ≥99.5% and is a 10% aqueous solution.

3. The antibacterial chemical gel for neonatal umbilical cord care according to claim 1, characterized in that, In the gel matrix, the number average molecular weight of the PLGA-PNIPAM graft copolymer is 10,000-30,000 Da, the molar ratio of lactic acid to glycolic acid in the PLGA is 50-75:50-25, the grafting rate of PNIPAM is 15%-30%, and the modified diatomaceous earth is diatomaceous earth modified with silane coupling agent KH-550, with a pore size of 50-200 nm and a specific surface area of ​​100-300 m² / g.

4. The antibacterial chemical gel for neonatal umbilical cord care according to claim 1, characterized in that, The moisturizer is a compound system of propylene glycol and glycerin, with a weight ratio of 1-2:1; the pH adjuster is a buffer system of sodium hydroxide and hydrochloric acid, used to adjust the pH value of the gel to 5.5-6.

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5. The antibacterial chemical gel for neonatal umbilical cord care according to claim 1, characterized in that, The antibacterial adjuvant is a compound system of honeysuckle extract and bisabolol, with a weight ratio of 2-3:1, wherein the flavonoid content of honeysuckle extract is ≥10% and the purity of bisabolol is ≥98%.

6. The antibacterial chemical gel for neonatal umbilical cord care according to claim 1, characterized in that, The preparation method of the PLGA-PNIPAM graft copolymer is as follows: PLGA is dissolved in dichloromethane, N-isopropylacrylamide monomer and initiator azobisisobutyronitrile are added, and the reaction is carried out at 60-70℃ for 8-12h. After the reaction is completed, the copolymer is precipitated, washed and vacuum dried to obtain the PLGA-PNIPAM graft copolymer. The preparation method of the modified diatomaceous earth is as follows: diatomaceous earth is dispersed in an ethanol aqueous solution, silane coupling agent KH-550 is added, and the mixture is stirred at 50-60℃ for 2-3h. After filtration and drying, the modified diatomaceous earth is obtained.

7. A synthesis process for an antibacterial chemical gel for neonatal umbilical cord care as described in any one of claims 1-6, characterized in that, Includes the following steps: S1: Pass the PLGA-PNIPAM graft copolymer and modified diatomaceous earth through an 80-mesh sieve to remove impurities; place the active silver ions, benzalkonium chloride, humectant, and antibacterial agent in a sterile environment and let them stand at room temperature for 30-60 minutes for later use. S2: Place purified water in a sterile reactor, control the temperature at 25-30℃, and the stirring speed at 100-150r / min. Add PLGA-PNIPAM graft copolymer and stir until completely dissolved. Then add modified diatomaceous earth and continue stirring for 30-40min. Let it stand for 1-2h to allow the modified diatomaceous earth to be fully dispersed and form a uniform matrix system with PLGA-PNIPAM graft copolymer. S3: Take active silver ions and benzalkonium chloride, add an appropriate amount of purified water, stir evenly to prepare an antibacterial mother liquor, and store it in an environment of 4-8℃ for later use. S4: Slowly add the antibacterial mother liquor, the prescribed amount of moisturizer, and the antibacterial adjuvant to the obtained matrix system, adjust the stirring speed to 300-400 r / min, stir for 30-60 min, and at the same time use a homogenizer to homogenize the mixture. The homogenization pressure is 10-15 MPa and the homogenization time is 10-15 min to obtain a mixed gel solution. S5: Slowly add the pH adjuster dropwise to the mixed gel solution while stirring. Monitor the pH value of the gel in real time until the pH value reaches 5.5-6.

5. Stop adding the pH adjuster and continue stirring for 10-15 minutes to make the system homogeneous. S6: Place the obtained gel solution in a sterilizer and sterilize it using a low-temperature steam sterilization method. Control the temperature at 80-90℃ and the sterilization time at 15-20 minutes. After sterilization, allow it to cool naturally to room temperature. S7: Place the cooled gel liquid in a sterile filling device, fill it into a sterile container, seal and label it to obtain the antibacterial chemical gel for neonatal umbilical care.

8. The synthesis process of an antibacterial chemical gel for neonatal umbilical cord care according to claim 7, characterized in that, In step S4, the homogenization process is performed intermittently, with a 5-minute homogenization followed by a 2-minute pause, repeated 2-3 times. This ensures that the antibacterial components, moisturizers, antibacterial agents, and gel matrix are fully integrated, resulting in a smooth texture without any graininess, and without damaging the porous structure of the modified diatomaceous earth.

9. The synthesis process of an antibacterial chemical gel for neonatal umbilical cord care according to claim 7, characterized in that, In step S6, the steam pressure for low-temperature steam sterilization is 0.1-0.15 MPa. Violent vibrations should be avoided during the cooling process to prevent the gel matrix from gelling prematurely and to ensure that it remains a fluid liquid at room temperature.

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