Intelligent responsive medical liquid dressing and preparation method thereof

Abstract

The application provides a smart response type medical liquid dressing and a preparation method thereof, and relates to the technical field of medical dressings.The liquid dressing is composed of a basic repair component, a natural antibacterial component, a plant active component, a smart carrier system and an auxiliary material.The application adopts a pH / temperature dual-response smart delivery system to realize accurate release of the active component, significantly improving the transdermal absorption rate;the synergistic effect of the composite protein and the plant extract accelerates wound healing;and the multi-modal sterilization process effectively retains the active component.The liquid dressing has the characteristics of strong antibacterial property, good environmental adaptability and excellent healing effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical dressings, in particular to an intelligent responsive medical liquid dressing and a preparation method thereof. BACKGROUND

[0002] The medical dressing industry refers to an industrial field of various dressing products for wound covering, protection, promotion of healing, absorption of exudates, prevention of infection, etc. produced by specific process technology based on medical materials. As an important branch of the medical device industry, medical dressing products are widely used in various departments of the clinic, including surgery, orthopedics, burn department, obstetrics and gynecology, etc. Their functions are not limited to physical protection, but also include promoting wound healing, controlling infection, and reducing pain, etc.

[0003] In terms of product classification system, medical dressings can be classified in multiple dimensions according to different standards.

[0004] From the perspective of product function and material, it can be divided into two categories: disposable dressing and reusable dressing. Disposable dressing mainly includes sterile transparent dressing, adhesive dressing, foam dressing, etc.; while reusable dressing includes elastic bandage, pressure dressing, etc. According to the sterilization state, it can be divided into sterile dressing such as sterile gauze, sterile cotton ball, sterile cotton swab, etc., mainly used for wound covering and cleaning in the early stage, and non-sterile dressing such as ordinary gauze, cotton swab, etc., suitable for daily wound care.

[0005] From the perspective of material composition, medical dressings can be divided into three categories: natural materials such as cotton, hemp, silk, etc., which have good air permeability and biocompatibility; synthetic materials such as polyethylene, polypropylene, etc., which have the characteristics of waterproof, breathable, antibacterial, etc.; composite materials, which combine the advantages of natural and synthetic materials, such as antibacterial dressing containing silver ions. According to the function, it can be divided into ordinary dressing mainly used for wound covering and protection, and functional dressing with specific therapeutic effect, such as antibacterial dressing, reduced pressure dressing, growth factor dressing, etc.

[0006] Modern high-end dressings have developed liquid dressings based on the "wet wound healing theory". As a new type of medical dressing, liquid dressing forms a protective film on the wound surface through liquid or gel-like material, replacing traditional gauze or adhesive tape dressing. Compared with traditional dressings, liquid dressings have the advantages of being sterile, transparent, comfortable, and having strong plasticity, etc., and can be accurately shaped according to the size and shape of the wound, better fitting the wound shape, and creating a microenvironment conducive to healing. This innovative product represents an important technological progress in the field of wound care and is changing the mode of clinical practice and home care.

[0007] However, the liquid dressing industry currently faces several challenges. First, traditional liquid dressings suffer from a significant problem with their limited ingredient diversity. These products often rely on a single antibacterial or repairing component, making it difficult to address the diverse treatment needs of complex wounds such as infected wounds and chronic ulcers. Furthermore, traditional liquid dressings suffer from low penetration efficiency, resulting in low transdermal absorption of active ingredients and limited drug accumulation, severely impacting treatment efficacy. Second, the sterilization methods for traditional liquid dressings are limited. High-temperature sterilization (such as moist heat sterilization) easily damages protein activity, while traditional irradiation sterilization (dose ≥25kGy) leads to the loss of effective ingredients. Finally, traditional liquid dressings lack environmental adaptability, preventing them from dynamically adjusting drug release based on the wound microenvironment (such as pH and temperature), leading to problems such as over-release or under-release. These technological limitations collectively restrict the further expansion of the clinical efficacy and application scope of liquid dressings. Summary of the Invention

[0008] In view of this, the present invention provides an intelligent responsive medical liquid dressing and its preparation method. The present invention adopts a pH / temperature dual-response intelligent delivery system, and through the synergistic effect of composite protein and plant extract, and through a multimodal sterilization process, improves the antibacterial properties, environmental adaptability and healing promotion effect of the liquid dressing, overcomes the shortcomings of traditional liquid dressings, and has good application prospects.

[0009] The first aspect of this invention is to provide a smart responsive medical liquid dressing, specifically comprising the following raw materials:

[0010] The ingredients include 10-50 parts by weight of basic repair components, 2-15 parts by weight of natural antibacterial components, 1-10 parts by weight of plant active ingredients, 5-30 parts by weight of the intelligent carrier system, 5-25 parts by weight of excipients, and 0.5-2 parts by weight of pH adjuster.

[0011] The basic repair components include the following raw materials: 5-12 parts by weight of complex protein, 5-20 parts by weight of high molecular weight sodium hyaluronate (HMW-HA), 2-10 parts by weight of hydrolyzed hyaluronic acid, 2-30 parts by weight of β-glucan, and 5-15 parts by weight of ectoin.

[0012] Further, the composite protein is composed of recombinant collagen and bird's nest protein peptides in a mass ratio of (1-2):(1-2); the natural antibacterial component includes the following raw materials: 3-8 parts by mass of chitosan quaternary ammonium salt and 1-5 parts by mass of 1,2-hexanediol; the plant active ingredient is Centella asiatica extract, and the content of asiaticoside in the Centella asiatica extract is not less than 20 wt.%; the intelligent carrier system includes the following raw materials: 8-25 parts by mass of pH-responsive liposomes encapsulating hyaluronic acid and 1-3 parts by mass of thermosensitive PNIPAM / PLGA nanofibers, the particle size of the pH-responsive liposomes encapsulating hyaluronic acid is 70-90 nm, and the molecular weight of HMW-HA is 1800-2400 kDa; the excipients include the following raw materials: 5-20 parts by mass of trehalose and 1-5 parts by mass of yeast β-glucan; the pH adjuster is triethanolamine.

[0013] The second aspect of this invention is to provide a method for preparing a smart responsive medical liquid dressing, specifically including the following steps:

[0014] Weigh the raw materials according to the proportions, prepare pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive PNIPAM / PLGA nanofibers, mix the basic repair ingredients, natural antibacterial ingredients, plant active ingredients and excipients, and then add the pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive nanofibers in sequence. Adjust the pH to 5.5-7.5 with a pH adjuster, disperse evenly and then sterilize to obtain a smart responsive medical liquid dressing.

[0015] Furthermore, the sterilization is multimodal sterilization, specifically involving first performing low-temperature plasma pretreatment to kill surface microorganisms, followed by dry ice irradiation sterilization; in the low-temperature plasma pretreatment, the Ar / O2 volume ratio is 9:1, the treatment temperature is -10℃, and the treatment time is 5min; in the dry ice irradiation sterilization, the material is first pre-cooled to -30℃ and then irradiated with cobalt-60 gamma rays (dose 20kGy).

[0016] Furthermore, the method for preparing the pH-responsive liposome-encapsulated hyaluronic acid is as follows:

[0017] Dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol were mixed in proportion and dissolved in a chloroform-methanol mixed solvent. The solvent was removed by rotary evaporation to form a uniform lipid film. The lipid film was hydrated with PBS buffer containing hyaluronic acid to form pH-responsive liposomes encapsulating hyaluronic acid. The liposomes were then extruded to obtain pH-responsive liposomes encapsulating hyaluronic acid.

[0018] Further, the molar ratio of dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol is (4.5-5.5):(3.5-4.5):(0.8-1.2), preferably 5:4:1; in the chloroform-methanol mixed solvent, the volume ratio of chloroform to methanol is (1.5-2.5):1; the pH of the PBS buffer is 7.4; the hydration temperature is 55℃-65℃, preferably 60℃; the hydration time is 20-40 min, preferably 30 min; appropriate shaking during hydration can accelerate the hydration process; the extrusion includes pre-extrusion and final extrusion. Pre-extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 200 nm three times at 60℃; final extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 50 nm seven times at 60℃.

[0019] Furthermore, the average particle size of the hyaluronic acid encapsulated in the pH-responsive liposomes is 80±10 nm, and the PDI is <0.2.

[0020] Furthermore, the preparation method of the thermosensitive PNIPAM / PLGA nanofibers is as follows:

[0021] Lactic acid / glycolic acid copolymer (PLGA) was completely dissolved in chloroform solution to obtain solution A; N-isopropylacrylamide (PNIPAM) was dissolved in DMF solution to obtain solution B; solution A and solution B were mixed to obtain spinning solution; the spinning solution was electrospun to obtain thermosensitive PNIPAM / PLGA nanofibers.

[0022] Further, the molecular weight of PNIPAM is 20-50 kDa, and the LA:GA ratio in PLGA is 75:25; the concentration of the chloroform solution is 8%-12%, and the concentration of the DMF solution is 6%-10%; the mass ratio of PNIPAM to PLGA in the spinning solution is (1-2):(3-4); the viscosity of the spinning solution is 800-1500 cP; the electrospinning parameters are set as follows: voltage: 15-25 kV, receiving distance: 10-20 cm, feed rate: 0.5-1.5 mL / h, ambient temperature and humidity: temperature 25℃, humidity <40%.

[0023] Compared with the prior art, the beneficial technical effects of the present invention are as follows:

[0024] This invention constructs a dual antibacterial barrier using chitosan quaternary ammonium salt and 1,2-hexanediol to enhance the antibacterial rate. It achieves precise targeted delivery of antibacterial and repairing components through a pH / temperature dual-responsive liposome-nanofiber intelligent delivery system, increasing the accumulation of effective ingredients. The introduction of PNIPAM, a temperature-sensitive component, dynamically regulates wound humidity, releasing moisturizing factors at body temperature to maintain an ideal moist environment. Combined with the synergistic effects of complex proteins, hyaluronic acid, and Centella asiatica extract, wound healing time is shortened. Furthermore, the combined use of complex active ingredients, the intelligent delivery system, and temperature-sensitive PNIPAM / PLGA nanofibers prolongs the antibacterial duration of the liquid dressing, improves transdermal absorption, shortens wound healing time, and reduces scar formation. Additionally, the multimodal process combining raw material composition and low-temperature plasma pretreatment with dry ice irradiation sterilization improves the viscosity retention rate of the liquid dressing and reduces the loss of active ingredients. Detailed Implementation

[0025] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0026] The first aspect of this invention is to provide a smart responsive medical liquid dressing, specifically comprising the following raw materials:

[0027] The ingredients include 10-50 parts by weight of basic repair components, 2-15 parts by weight of natural antibacterial components, 1-10 parts by weight of plant active ingredients, 5-30 parts by weight of the intelligent carrier system, 1-10 parts by weight of excipients, 5-25 parts by weight of pH adjuster.

[0028] The basic repair components include the following raw materials: 5-12 parts by weight of complex protein, 5-20 parts by weight of HMW-HA, 2-10 parts by weight of hydrolyzed hyaluronic acid, 2-30 parts by weight of β-glucan, and 5-15 parts by weight of Ectoin.

[0029] The composite protein is composed of recombinant collagen and bird's nest protein peptide in a mass ratio of (1-2):(1-2); the natural antibacterial component includes the following raw materials: 3-8 parts by mass of chitosan quaternary ammonium salt and 1-5 parts by mass of 1,2-hexanediol; the plant active ingredient is Centella asiatica extract, and the content of asiaticoside in the Centella asiatica extract is not less than 20 wt.%; the intelligent carrier system includes the following raw materials: 8-25 parts by mass of pH-responsive liposomes encapsulating hyaluronic acid and 1-3 parts by mass of thermosensitive PNIPAM / PLGA nanofibers, the particle size of the pH-responsive liposomes encapsulating hyaluronic acid is 70-90 nm, and the molecular weight of HMW-HA is 1800-2400 kDa; the excipients include the following raw materials: 5-20 parts by mass of trehalose and 1-5 parts by mass of yeast β-glucan; the pH adjuster is triethanolamine.

[0030] In the intelligent responsive medical liquid dressing of this invention, the composite protein can promote cell proliferation and collagen synthesis, thereby improving wound healing rate. Recombinant collagen, as a major component of the skin's extracellular matrix, possesses a unique triple helix structure and RGD sequence that can directly activate fibroblast proliferation signals (FAK-ERK pathway). Meanwhile, bird's nest protein peptides can significantly accelerate keratinocyte migration and prolong the half-life of growth factors. The collagen fiber network and high-molecular-weight hyaluronic acid form a mechanically enhanced interpenetrating structure, increasing the energy storage modulus, and the bird's nest protein peptides can enhance the moisturizing effect of the dressing. Compared to other composite proteins such as fibronectin or elastin, collagen / bird's nest protein peptides have better efficacy and lower production costs. Therefore, this invention uses recombinant collagen and bird's nest protein peptides as the basic repair components.

[0031] HMW-HA forms a denser three-dimensional network structure, and its zero-shear viscosity is significantly higher than that of ordinary sodium hyaluronate (LMW-HA), which can significantly improve the mechanical strength of the dressing and effectively isolate external microbial invasion. Simultaneously, HMW-HA has a higher hydroxyl exposure rate and a significantly higher water-binding capacity than LMW-HA, which helps maintain long-term water retention and eliminates the need for frequent reapplication. Furthermore, HMW-HA activates the TSG-6 pathway through the CD44 receptor, reducing IL-6 levels in the wound. Its free radical scavenging ability is also higher than that of LMW-HA, which can more effectively neutralize excess ROS in the wound and promote healing. Finally, the HMW-HA matrix has a low burst release rate, achieving a sustained-release cycle of 7-10 days. In synergy with pH-responsive liposomes, it can trigger intelligent release in infected wounds, maintaining a high local antibiotic concentration for a prolonged period, a level that LMW-HA struggles to achieve. Therefore, this invention chooses HMW-HA to prepare the liquid dressing, rather than LMW-HA.

[0032] Beta-glucan can activate the beta-glucan receptor (Dectin-1) on keratinocytes, promoting the expression of tight junction proteins (such as Claudin) and reducing transepidermal water loss; it can inhibit the release of inflammatory factors (such as IL-6 and TNF-α), relieving sensitivity symptoms such as redness and stinging; and it can stimulate fibroblast proliferation, accelerating epidermal repair. Furthermore, beta-glucan can neutralize ROS (reactive oxygen species), reducing oxidative stress damage to form a breathable hydrating film for long-lasting moisturization.

[0033] Ectoin protects proteins, lipids, and DNA through a "hydration shell" mechanism, combating environmental damage such as ultraviolet (UV) radiation, high temperatures, and pollution. It also reduces epidermal permeability, preventing the invasion of external irritants. Ectoin can block the NF-κB pathway, reducing the release of inflammatory factors (such as IL-8), decreasing the activity of matrix metalloproteinases (MMPs), and protecting collagen and elastin fibers. Finally, Ectoin enhances stratum corneum hydration through osmotic pressure regulation.

[0034] Chitosan quaternary ammonium salt (hydroxypropyltrimethylammonium chloride chitosan) forms a synergistic antibacterial network with 1,2-hexanediol, which can also inhibit bacteria and suppress microbial growth.

[0035] The asiaticoside in the Centella asiatica extract of this invention can enhance collagen synthesis rate by activating the TGF-β / Smad signaling pathway, increase capillary density in the wound by regulating VEGF expression levels, and reduce IL-6 levels in the wound by inhibiting NF-κB nuclear translocation, thereby promoting wound healing. However, experimental data show that when the asiaticoside content is too low, the wound healing speed is not significantly different from the control group; when the asiaticoside content is too high, the improvement in technical effect is not significant and the cost increases. In addition, 20% asiaticoside can form an optimal cascade effect of repair factors with recombinant collagen in the formula, thereby improving transdermal absorption rate; however, excessively high asiaticoside content is not conducive to the realization of these synergistic effects. In the product development process, this invention also tried other types of plant extracts, including aloe vera extract, green tea polyphenols, and calendula extract. However, the results showed that aloe vera extract performed well in moisturizing and anti-inflammatory effects, green tea polyphenols performed well in antioxidant effects, and calendula extract performed well in antibacterial effects. However, these extracts did not perform well in directly activating repair pathways and promoting wound repair.

[0036] Furthermore, pH-responsive liposomes encapsulating hyaluronic acid allow for rapid release at inflamed sites (pH < 6.5), enhancing transdermal absorption. Thermosensitive PNIPAM / PLGA nanofibers swell at body temperature, releasing moisturizing factors and dynamically regulating the humid environment. Trehalose protects cells and active ingredients, enhancing radiation resistance, while yeast β-glucan activates immune cells and accelerates wound repair. The pH adjuster regulates the patch's pH to 5.5-7.5, adapting to the skin's slightly acidic environment. The various ingredients work synergistically to improve the retention rate of the liquid patch's components, achieving targeted delivery and enhancing its antibacterial and repair effects, thus solving the problems existing in traditional liquid patches.

[0037] The second aspect of this invention is to provide a method for preparing a smart responsive medical liquid dressing, specifically including the following steps:

[0038] Weigh the raw materials according to the proportions, prepare pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive PNIPAM / PLGA nanofibers, mix the basic repair ingredients, natural antibacterial ingredients, plant active ingredients and excipients, and then add the pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive nanofibers in sequence. Adjust the pH to 5.5-7.5 with a pH adjuster, disperse evenly and then sterilize to obtain a smart responsive medical liquid dressing.

[0039] The sterilization is a multimodal sterilization, specifically, it involves first performing low-temperature plasma pretreatment to kill surface microorganisms, and then performing dry ice irradiation sterilization; in the low-temperature plasma pretreatment, the volume ratio of Ar / O2 is 9:1, the treatment temperature is -10℃, and the treatment time is 5min; in the dry ice irradiation sterilization, the material is first pre-cooled to -30℃ and then irradiated with cobalt-60 gamma rays (dose 20kGy).

[0040] The method for preparing pH-responsive liposomes encapsulating hyaluronic acid according to the present invention is as follows:

[0041] Dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol were mixed in proportion and dissolved in a chloroform-methanol mixed solvent. The solvent was removed by rotary evaporation to form a uniform lipid film. The lipid film was hydrated with PBS buffer containing hyaluronic acid to form pH-responsive liposomes encapsulating hyaluronic acid. The liposomes were then extruded to obtain pH-responsive liposomes encapsulating hyaluronic acid.

[0042] The molar ratio of dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol is (4.5-5.5):(3.5-4.5):(0.8-1.2), preferably 5:4:1; the volume ratio of chloroform to methanol in the chloroform-methanol mixed solvent is (1.5-2.5):1; the pH of the PBS buffer is 7.4; the hydration temperature is 55℃-65℃, preferably 60℃; the hydration time is 20-40 min, preferably 30 min; appropriate shaking during hydration can accelerate the hydration process; the extrusion includes pre-extrusion and final extrusion. Pre-extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 200 nm three times at 60℃; final extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 50 nm seven times at 60℃.

[0043] The average particle size of the pH-responsive liposomes encapsulating hyaluronic acid was 80±10 nm, and the PDI was <0.2.

[0044] The method for preparing the thermosensitive PNIPAM / PLGA nanofibers of this invention is as follows:

[0045] Lactic acid / glycolic acid copolymer (PLGA) was completely dissolved in chloroform solution to obtain solution A; N-isopropylacrylamide (PNIPAM) was dissolved in DMF solution to obtain solution B; solution A and solution B were mixed to obtain spinning solution; the spinning solution was electrospun to obtain thermosensitive PNIPAM / PLGA nanofibers.

[0046] The PNIPAM of this invention has a molecular weight of 20-50 kDa, and the PLGA has an LA:GA ratio of 75:25; the concentration of the chloroform solution is 8%-12%, and the concentration of the DMF solution is 6%-10%; the mass ratio of PNIPAM to PLGA in the spinning solution is (1-2):(3-4); the viscosity of the spinning solution is 800-1500 cP; the electrospinning parameters are set as follows: voltage: 15-25 kV, receiving distance: 10-20 cm, feed rate: 0.5-1.5 mL / h, ambient temperature and humidity: temperature 25℃, humidity <40%.

[0047] The amount of PNIPAM used needs to be strictly controlled. When its mass ratio with PLGA is (1-2):(3-4), the fiber has good temperature sensitivity and spinnability. If the content is too high, the solution viscosity will be too high and the fiber diameter will be coarsened. If the content is too low, the temperature sensitivity of the fiber cannot be guaranteed.

[0048] To further illustrate the present invention, the following embodiments are provided for detailed description. All raw materials used in the following embodiments of the present invention are commercially available.

[0049] Unless otherwise specified, all experiments were repeated three times. Analysis of variance (ANOVA) and Duncan's multiple comparison analysis were performed using SPSS 21.0. Results are expressed as mean ± standard deviation, and p < 0.05 was considered statistically significant.

[0050] Example 1: A smart responsive medical liquid dressing, composed of the following raw materials:

[0051] The composition includes 27 parts by weight of basic repair ingredients, 8.5 parts by weight of natural antibacterial ingredients, 3 parts by weight of Centella asiatica extract (containing 22 wt.%), 18.5 parts by weight of the intelligent carrier system, 15.5 parts by weight of excipients, and 1.25 parts by weight of triethanolamine.

[0052] The basic repair components include the following raw materials: 8.5 parts by weight of complex protein, 22.5 parts by weight of HMW-HA (2000kDa), 6 parts by weight of hydrolyzed hyaluronic acid, 16 parts by weight of β-glucan, and 10 parts by weight of Ectoin;

[0053] The composite protein is composed of recombinant collagen (Hubei Xinyuhong Biomedical Technology Co., Ltd.) and bird's nest protein peptide in a mass ratio of 1:1; the natural antibacterial components are composed of: 5.5 parts by mass of chitosan quaternary ammonium salt and 3 parts by mass of 1,2-hexanediol; the intelligent carrier system is composed of: 16.5 parts by mass of pH-responsive liposomes encapsulating hyaluronic acid and 2 parts by mass of thermosensitive PNIPAM / PLGA nanofibers; the excipients are composed of: 22.5 parts by mass of trehalose and 3 parts by mass of yeast β-glucan.

[0054] The preparation method of the intelligent responsive medical liquid dressing includes the following steps:

[0055] Raw materials were weighed according to the proportions, and pH-responsive liposomes encapsulating hyaluronic acid and thermosensitive PNIPAM / PLGA nanofibers were prepared. The basic repair ingredients, natural antibacterial ingredients, Centella asiatica extract, and excipients were mixed and then added to the pH-responsive liposomes encapsulating hyaluronic acid and thermosensitive nanofibers in sequence. Triethanol was added to adjust the pH. After being dispersed evenly, the mixture was pretreated with low-temperature plasma at a volume ratio of 9:1 (Ar / O2) and a temperature of -10℃ for 5 minutes. Then, the material was pre-cooled to -30℃ and irradiated with cobalt-60 gamma rays (dose 20kGy) to obtain a smart responsive medical liquid dressing.

[0056] The method for preparing pH-responsive liposomes encapsulating hyaluronic acid is as follows:

[0057] Dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol were mixed in proportion and dissolved in a chloroform-methanol mixed solvent. The solvent was removed by rotary evaporation to form a uniform lipid film. The lipid film was hydrated by shaking with PBS buffer containing hyaluronic acid to form pH-responsive liposomes encapsulating hyaluronic acid. The liposomes were then extruded to obtain pH-responsive liposomes encapsulating hyaluronic acid.

[0058] The molar ratio of dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol is 5:4:1; the volume ratio of chloroform to methanol in the chloroform-methanol mixed solvent is 2:1; the pH of the PBS buffer is 7.4; the hydration temperature is 60℃, and the hydration time is 30 min; the extrusion includes pre-extrusion and final extrusion, wherein the pre-extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 200 nm three times at 60℃, and the final extrusion refers to passing the pH-responsive liposomes encapsulated with hyaluronic acid through a polycarbonate membrane with a pore size of 50 nm seven times at 60℃; the average particle size of the hyaluronic acid encapsulated in the pH-responsive liposomes is 80 nm, and the PDI < 0.2.

[0059] The method for preparing the thermosensitive PNIPAM / PLGA nanofibers is as follows:

[0060] PLGA was completely dissolved in chloroform solution to obtain solution A, and PNIPAM was dissolved in DMF solution to obtain solution B; solution A and solution B were mixed to obtain spinning solution; the spinning solution was electrospun to obtain thermosensitive PNIPAM / PLGA nanofibers;

[0061] The PNIPAM has a molecular weight of 50 kDa, and the PLGA has an LA:GA ratio of 75:25. The chloroform solution has a concentration of 10%, and the DMF solution has a concentration of 8%. The mass ratio of PNIPAM to PLGA in the spinning solution is 2:4. The viscosity of the spinning solution is 1200 cP. The electrospinning parameters are set as follows: voltage: 20 kV, receiving distance: 15 cm, feed rate: 1 mL / h, ambient temperature and humidity: temperature 25℃, humidity 35%.

[0062] Example 2: A smart responsive medical liquid dressing, composed of the following raw materials:

[0063] The ingredients include 10 parts by weight of basic repair components, 2 parts by weight of natural antibacterial components, 1 part by weight of Centella asiatica extract (with a content of 22 wt.%), 5 parts by weight of the intelligent carrier system, 5 parts by weight of excipients, and 0.5 parts by weight of triethanolamine.

[0064] The basic repair components include the following raw materials: 5 parts by weight of complex protein, 5 parts by weight of HMW-HA (2000kDa), 2 parts by weight of hydrolyzed hyaluronic acid, 2 parts by weight of β-glucan, and 5 parts by weight of Ectoin;

[0065] The rest is the same as in Example 1.

[0066] The preparation method of the intelligent responsive medical liquid dressing is the same as in Example 1.

[0067] Example 3: A smart responsive medical liquid dressing, composed of the following raw materials:

[0068] The ingredients include 50 parts by weight of basic repair components, 15 parts by weight of natural antibacterial components, 10 parts by weight of Centella asiatica extract (with a content of 22 wt.%), 30 parts by weight of the intelligent carrier system, 25 parts by weight of excipients, and 2 parts by weight of triethanolamine.

[0069] The basic repair components include the following raw materials: 12 parts by weight of complex protein, 20 parts by weight of HMW-HA (2000kDa), 10 parts by weight of hydrolyzed hyaluronic acid, 30 parts by weight of β-glucan, and 15 parts by weight of Ectoin;

[0070] The rest is the same as in Example 1.

[0071] The preparation method of the intelligent responsive medical liquid dressing is the same as in Example 1.

[0072] Comparative Example 1

[0073] Same as Example 1, except that: ① the complex protein is replaced with an equal amount of recombinant collagen; ② the complex protein is replaced with an equal amount of bird's nest protein peptides.

[0074] Comparative Example 2

[0075] Same as Example 1, except that HMW-HA (2000kDa) is replaced with an equal amount of LMW-HA (200kDa).

[0076] Comparative Example 3

[0077] Same as Example 1, except that pH-responsive liposomes were not used to encapsulate hyaluronic acid.

[0078] Comparative Example 4

[0079] Same as Example 1, except that: ① thermosensitive PNIPAM / PLGA nanofibers were not used; ② the thermosensitive PNIPAM / PLGA nanofibers were replaced with an equal amount of PNIPAM; ③ the thermosensitive PNIPAM / PLGA nanofibers were replaced with an equal amount of PLGA.

[0080] The liquid dressing performance of Examples 1-3 and Comparative Examples 1-4 was tested, and the results are shown in Table 1.

[0081] Table 1 Results of Liquid Adhesive Performance Tests

[0082]

[0083] Note: Different lowercase letters in the same column in the table indicate a significant difference between the two (P < 0.05).

[0084] Comparative Example 5

[0085] Same as Example 1, except that the low-temperature plasma pretreatment time is 10 min.

[0086] Accelerated stability tests (40°C / 75%RH, 3 months) were conducted on the liquid dressings of Examples 1-3 and Comparative Examples 1-5, and the results are shown in Table 2.

[0087] Table 2 Results of Accelerated Stability Tests

[0088]

[0089] Note: Different lowercase letters in the same column in the table indicate a significant difference between the two (P < 0.05).

[0090] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A smart responsive medical liquid dressing, characterized in that, Including the following raw materials: Basic repair ingredients 10-50 parts by weight, natural antibacterial ingredients 2-15 parts by weight, plant active ingredients 1-10 parts by weight, intelligent carrier system 5-30 parts by weight, excipients 5-25 parts by weight, pH adjuster 0.5-2 parts by weight; The basic repair components include the following raw materials: 5-12 parts by weight of complex protein, 5-20 parts by weight of high molecular weight sodium hyaluronate, 2-10 parts by weight of hydrolyzed hyaluronic acid, 2-30 parts by weight of β-glucan, and 5-15 parts by weight of ectoine. The composite protein is composed of recombinant collagen and bird's nest protein peptides in a mass ratio of (1-2):(1-2); The natural antibacterial component includes the following raw materials: 3-8 parts by weight of chitosan quaternary ammonium salt and 1-5 parts by weight of 1,2-hexanediol; The plant active ingredient is Centella asiatica extract; The intelligent carrier system comprises the following raw materials: 8-25 parts by weight of pH-responsive liposomes encapsulating hyaluronic acid, and 1-3 parts by weight of thermosensitive PNIPAM / PLGA nanofibers.

2. The intelligent responsive medical liquid dressing according to claim 1, characterized in that, The content of asiaticoside in the Centella asiatica extract is not less than 20 wt.%.

3. The intelligent responsive medical liquid dressing according to claim 1, characterized in that, The method for preparing pH-responsive liposomes encapsulating hyaluronic acid is as follows: Dioleoylphosphatidylethanolamine, cholesterol hemisuccinate, and cholesterol were mixed in proportion and dissolved in a chloroform-methanol mixed solvent. The solvent was removed by rotary evaporation to form a uniform lipid film. The lipid film was hydrated with PBS buffer containing hyaluronic acid to form pH-responsive liposomes encapsulating hyaluronic acid. The liposomes were then extruded to obtain pH-responsive liposomes encapsulating hyaluronic acid.

4. The intelligent responsive medical liquid dressing according to claim 1, characterized in that, The average particle size of the pH-responsive liposomes encapsulating hyaluronic acid was 80±10 nm, and the PDI was <0.

2.

5. The intelligent responsive medical liquid dressing according to claim 1, characterized in that, The method for preparing the thermosensitive PNIPAM / PLGA nanofibers is as follows: Lactic acid / glycolic acid copolymer was completely dissolved in chloroform solution to obtain solution A; poly(N-isopropylacrylamide) was dissolved in DMF solution to obtain solution B; solution A and solution B were mixed to obtain spinning solution; the spinning solution was electrospun to obtain thermosensitive PNIPAM / PLGA nanofibers.

6. The method for preparing the intelligent responsive medical liquid dressing according to any one of claims 1-5, characterized in that, Includes the following steps: Weigh the raw materials according to the proportions, prepare pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive PNIPAM / PLGA nanofibers, mix the basic repair ingredients, natural antibacterial ingredients, plant active ingredients and excipients, and then add the pH-responsive liposomes to encapsulate hyaluronic acid and thermosensitive nanofibers in sequence. Adjust the pH to 5.5-7.5 with a pH adjuster, disperse evenly and then sterilize to obtain a smart responsive medical liquid dressing.

7. The preparation method according to claim 6, characterized in that, The sterilization process is multimodal sterilization, specifically involving first performing low-temperature plasma pretreatment to kill surface microorganisms, followed by dry ice irradiation sterilization.

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