Gamma-PGA high-activity dressing for medical beauty

Abstract

The invention discloses a gamma-PGA high-activity dressing for medical beauty, and relates to the technical field of medical beauty, the gamma-PGA high-activity dressing for medical beauty comprises a three-layer composite structure: an antibacterial barrier layer, an active slow-release layer and a biological adhesion layer, a synergistic effect is realized through a three-layer functionalized structure, the antibacterial barrier layer physically punctures bacteria by using a vertical carbon nanotube array, an Ag / ZnO heterojunction generates reactive oxygen species (ROS) for chemical sterilization, and the biological adhesion layer is a composite layer. The PHMB hydrophobic coating is used for blocking exudate; the active sustained-release layer provides mechanical support based on a dual-network enhanced structure, and the four-layer microcapsule accurately releases asiaticoside and EGF through pH / temperature dual response; the biological adhesion layer guides directional migration of cells through a 30 [mu] m groove array, Zn < 2 + > / Mg < 2 + > ion gradient regulation and control of collagen secretion and acceleration of wound regeneration, a medical beauty dressing system integrating barrier protection, intelligent repair and tissue regeneration is constructed, and the medical beauty dressing is suitable for nursing after various medical beauty operations and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the field of medical aesthetics technology, and particularly relates to a γ-PGA highly active medical aesthetic dressing. Background Art

[0002] In the modern medical field, medical dressings are important tools for treating skin injuries such as wounds, burns, surgical incisions, etc. They not only provide physical protection, but also promote wound healing and reduce the risk of infection. There are various types of medical dressings on the market currently, including traditional collagen patches, hydrocolloid dressings, and commercial electrospun dressings, etc.

[0003] Traditional collagen patches are a widely used type of dressing, which utilize the biocompatibility of collagen and its property of promoting cell growth. However, such dressings have some defects. First of all, the active ingredients in collagen are prone to inactivation during storage, especially under the condition of 4°C, and the loss of active ingredients within 72 hours may exceed 60%. Secondly, the transdermal efficiency of collagen patches is relatively low, usually lower than 0.1mg / cm 2 / h, which means that the release rate of drugs or active ingredients is slow and may not meet the requirements of rapid treatment.

[0004] Hydrocolloid dressings are favored for their good ability to maintain a moist environment and softness. However, they usually lack the ability of dynamic response, which means that they cannot adjust their performance according to the healing condition of the wound or changes in the external environment. In addition, the adhesion of hydrocolloid dressings depends largely on the oil on the skin surface, which results in insufficient adhesion in areas of the skin with more moisture or oil secretion, and the shear force is usually lower than 3N / cm 2 , and it is easy to fall off. Therefore, we propose a γ-PGA highly active medical aesthetic dressing. Summary of the Invention

[0005] The purpose of the present invention is to solve the problems that the active ingredients of traditional collagen patches are prone to inactivation and the transdermal efficiency is low, and that hydrocolloid dressings lack the ability of dynamic response, have insufficient adhesion and are easy to fall off. The present invention provides a γ-PGA highly active medical aesthetic dressing. Through the integrated technology of corn deep processing, the CO2 emissions during the production process are reduced by 99.99% compared with animal-derived dressings, and the water consumption per ton of product is only 12m 3 (150m for traditional process 3 ), the steam cost is reduced by 30%, and it obtains the EU CE low-carbon certification.

[0006] The present invention specifically adopts the following technical solutions to achieve the above purpose:

[0007] A γ-PGA highly active medical aesthetic dressing, comprising a three-layer composite structure:

[0008] Antimicrobial barrier layer: 50-100 μm thick, composed of a 3:1 mass ratio of γ-polyglutamic acid (γ-PGA) and chitosan blend matrix. The γ-PGA is produced using engineered Bacillus subtilis (with an edited PgsB gene), and metabolic flux is regulated to achieve a γ-PGA yield of 150 g / L.

[0009] Active sustained-release layer: 200-500 μm thick, containing a γ-PGA cross-linked network, 15-30 wt% nanohydroxyapatite, and functional active microcapsules with a microcapsule particle size distribution of 20-80 μm;

[0010] Bioadhesive layer: 100-200 μm thick, composed of an interpenetrating network formed by γ-PGA and hyaluronic acid, loaded with 5-8wt% recombinant human collagen type III, with a micron-scale groove array on the surface, with a groove width of 20-50 μm and a depth of 10-30 μm.

[0011] Furthermore, the active sustained-release layer has a double network structure, the first network is a γ-PGA main chain cross-linked by calcium ions, the amount of calcium ion cross-linking agent is 2-5% of the mass of γ-PGA, the cross-linking time is 30 minutes, and the cross-linking degree is ensured to be 40-60%. The second network is a polyvinyl alcohol and nanocellulose reinforced skeleton with a mass ratio of 5:1 to 3:1. Covalent grafting is achieved between the double networks through silane coupling agent KH550, and the grafting density is 0.8-1.2 mmol / g.

[0012] Furthermore, the functional active microcapsules adopt a four-layer coating structure, the inner core is composed of 0.1-0.5wt% epidermal growth factor and 1-3wt% asiaticoside co-loaded in a polylactic acid-glycolic acid copolymer sustained-release core, the particle size of the functional active microcapsules is adjusted to 10-30μm, the particle size to layer thickness ratio is controlled at 1:10 to 1:20, the first coating layer is pH-responsive ε-polylysine with a thickness of 50-80nm, the second coating layer is temperature-sensitive poloxamer 407 with a phase transition temperature of 32-35°C, and the outer layer is a mesoporous silica shell modified with antimicrobial peptide HHC36 with a pore size of 5-10nm.

[0013] Furthermore, the grooves on the surface of the bioadhesive layer are embedded with the following components:

[0014] Calcium carbonate microspheres with a diameter of 5-10 μm, loaded with 0.05-0.1 wt% vitamin K1;

[0015] Silk fibroin nanofibers with a length of 50-100 μm and an orientation angle deviation of ≤15°;

[0016] A zinc ion and magnesium ion sustained-release channel is provided at the bottom of the groove, and the ion concentration gradient is from 0.1 mM on the surface to 2.5 mM on the bottom.

[0017] Furthermore, the antimicrobial barrier layer comprises:

[0018] Vertically aligned carbon nanotube arrays with a diameter of 20-50 nm and an aspect ratio >100, occupying 3-5% of the layer volume;

[0019] Nano silver and zinc oxide heterojunction particles, with a molar ratio of silver to zinc of 1:2 to 1:5 and a particle size of 50-100nm; a hydrophobic coating on the surface, with a contact angle of >120° and a water vapor transmission rate controlled at 2000-2500g / m 2 / day.

[0020] A method for preparing a γ-PGA high-activity medical aesthetic dressing comprises the following steps:

[0021] S1. Preparation of antibacterial layer: 12 wt% γ-PGA and 4 wt% chitosan were dissolved in 0.5 M acetic acid solution, 0.5 wt% graphene oxide was added, and electrospun at a voltage of 18 kV and a receiving distance of 15 cm to form a nanofiber membrane, which was then impregnated with a 1 wt% polyhexamethylene biguanide ethanol solution and dried.

[0022] S2. Preparation of sustained-release layer: 8 wt% γ-PGA aqueous solution was mixed with 5 wt% polyvinyl alcohol / nanocellulose mixture at a mass ratio of 4:1, and 1 wt% silane coupling agent KH550 was added. Microwave cross-linking was performed at a frequency of 2450 MHz. The chamber pressure was maintained at normal pressure to ensure cross-linking uniformity for 3 minutes. The microcapsules were then injected and freeze-dried to form the product. The modular production design is compatible with 5-100 ton reactors and flexible production capacity configuration is achieved through the Siemens DCS system.

[0023] S3. Preparation of adhesion layer: 6 wt% γ-PGA and 2 wt% hyaluronic acid solution was cast on a PDMS template with a groove width of 30 μm, UV-cured for 30 minutes, and immersed in phosphate buffer containing recombinant collagen for 24 hours;

[0024] S4. Multilayer composite assembly: stack the layers in the order of antibacterial layer, sustained-release layer, and adhesive layer, spraying 0.5 wt% polydopamine adhesive between the layers at a spraying amount of 3 mg / cm 2 , a three-stage hot pressing process is used to solidify and form a bionic bonding interface, which is assembled into a medical dressing;

[0025] The first stage: pre-pressing at 40°C and 0.1 MPa for 5 minutes to eliminate interlayer gaps;

[0026] The second stage: hot pressing at 60°C and 0.5 MPa for 10 min to activate the entanglement of γ-PGA molecular chains;

[0027] The third stage: cold pressing at 25℃ and 1MPa for 15min to set the interface between the layers.

[0028] Furthermore, the preparation of the functional active microcapsules by microfluidic technology includes the following steps:

[0029] A1. Raw material preparation, preparing the corresponding solutions in advance

[0030] Inner phase: PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor;

[0031] Middle phase: 1 wt% ε-polylysine aqueous solution;

[0032] Outer phase: isopropanol solution of 5 wt% poloxamer 407;

[0033] A2. Adding 0.5 - 1.2 wt% tetraethyl orthosilicate (TEOS) as the silicon source to the PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor, 1 wt% ε-polylysine aqueous solution, and 5 wt% poloxamer 407 isopropanol solution, forming a monodisperse emulsion through a T-shaped glass capillary at a flow rate ratio of 1:5:10. The inner diameter of the T-shaped glass capillary is 200 μm, and after catalytic hydrolysis with ammonia water, it is collected by centrifugation;

[0034] A3. Calcining the collected microcapsules under nitrogen protection at a calcination temperature of 200 °C for 2 h to form a mesoporous silica shell;

[0035] A4. Immersing the calcined microcapsules in a PBS solution containing 0.1 - 0.5 mg / mL antimicrobial peptide HHC36 and oscillating at 37 °C for 12 h to complete the modification, and finally fixing them on the surface of the mesoporous silica shell through amide bonds.

[0036] Furthermore, the process parameters of freeze-drying for preparing the sustained-release layer are as follows:

[0037] Pre-freezing stage: cooling at a rate of -1 °C / min to -20 °C and maintaining for 2 h;

[0038] Deep-freezing stage: cooling at a rate of -5 °C / min to -80 °C and maintaining for 4 h;

[0039] Sublimation drying: vacuum degree of 10 Pa, heating to -30 °C and maintaining for 12 h.

[0040] Furthermore, the method for the ion gradient component of the adhesion layer is to inject a zinc 2+ :Mg 2+ mixed solution with a ratio of 1:3 into the porous template, applying a pulsed DC voltage (5 V), controlling the temperature at 25 - 30 °C to avoid thermal degradation of γ-PGA, with a voltage of 5 V and a time of 30 min, so that the ions form a concentration gradient along the depth direction of the groove.

[0041] Further, before the three-layer dressing is stacked, it is subjected to plasma surface treatment. The treatment gas is a mixture of argon and oxygen with a flow ratio of 4:1, a treatment power of 100 W, and a treatment time of 5 minutes. After treatment, the surface oxygen element content increases by 18.5%, and the contact angle decreases from 75° to 12°. After S4, a cobalt-60 irradiation sterilization process (dose 25 kGy, meeting the ISO 11137 standard) is added to ensure the sterility of the dressing.

[0042] The beneficial effects of the present invention are as follows:

[0043] The present invention realizes a synergistic effect through a three-layer functionalized structure. The antibacterial barrier layer physically punctures bacteria using a vertical carbon nanotube array, and the Ag / ZnO heterojunction generates reactive oxygen species (ROS) for chemical sterilization. The PHMB hydrophobic coating blocks exudate; the active slow-release layer provides mechanical support based on a double-network enhanced structure (γ-PGA / PVA-nanocellulose), and four-layer microcapsules precisely release asiaticoside and EGF through a pH / temperature dual response; the bioadhesive layer guides cell directional migration through a 30-μm groove array, and the Zn 2+ / Mg 2+ ion gradient regulates collagen secretion, accelerates wound regeneration, and constructs a medical aesthetic dressing system integrating "barrier protection-intelligent repair-tissue regeneration". Specific embodiments

[0044] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention.

[0045] The present invention provides a γ-PGA highly active medical aesthetic dressing, including a three-layer composite structure:

[0046] Antibacterial barrier layer: with a thickness of 50-100 μm, composed of a blend matrix of γ-polyglutamic acid (γ-PGA) and chitosan with a mass ratio of 3:1. The γ-PGA is produced by a Bacillus subtilis engineering bacterium (containing PgsB gene editing) independently developed by Carbon and New Materials, and the γ-PGA yield reaches 150 g / L through metabolic flux regulation; the Bacillus subtilis engineering bacterium used in the present invention has passed the biosafety certification of the Ministry of Agriculture and Rural Affairs of the People's Republic of China.

[0047] Active slow-release layer: with a thickness of 200-500 μm, containing a γ-PGA crosslinked network, 15-30 wt% nano-hydroxyapatite, and functional active microcapsules. The particle size distribution of the microcapsules is 20-80 μm; the γ-polyglutamic acid (γ-PGA) crosslinked network, with the unit symbol standardized as mmol·g-1 (grafting density 0.8-1.2 mmol / g → 0.8-1.2 mmol·g-1).

[0048] Bioadhesive layer: with a thickness of 100 - 200 μm, composed of an interpenetrating network formed by γ-PGA and hyaluronic acid, loaded with 5 - 8 wt% recombinant human collagen type III, and having a micron-scale groove array on the surface, with the groove width being 20 - 50 μm and the depth being 10 - 30 μm.

[0049] In this embodiment, preferably, the active slow-release layer is a double-network structure. The first network is the main chain of γ-PGA crosslinked by calcium ions, and the dosage of the calcium ion crosslinking agent is 2 - 5% of the mass of γ-PGA, with a crosslinking time of 30 minutes to ensure a crosslinking degree of 40 - 60%. The second network is a reinforcing framework of polyvinyl alcohol and nanocellulose with a mass ratio of 5:1 to 3:1. Covalent grafting between the double networks is achieved through the silane coupling agent KH550, and the grafting density is 0.8 - 1.2 mmol / g. This double-network structure design not only enhances the structural stability of the active slow-release layer but also improves its adaptability to the external environment. The main chain of γ-PGA crosslinked by calcium ions, as the first network, can effectively maintain the biological activity of γ-PGA while providing necessary mechanical support. The reinforcing framework of polyvinyl alcohol and nanocellulose, as the second network, further enhances the strength and toughness of the entire active slow-release layer, making it more durable during use. The introduction of the silane coupling agent KH550 realizes the covalent grafting between the double networks, enabling the two networks to be closely combined and work together. This structural design enables the active slow-release layer to better control the release rate of the functional active microcapsules, thereby achieving a better therapeutic effect.

[0050] In this embodiment, preferably, the functional active microcapsule adopts a four-layer coating structure. The inner core is composed of 0.1-0.5 wt% epidermal growth factor and 1-3 wt% asiaticoside co-loaded in a poly(lactic-co-glycolic acid) sustained-release core. The particle size of the functional active microcapsule is adjusted to 10-30 μm, and the ratio of particle size to layer thickness is controlled at 1:10 to 1:20 to ensure uniform dispersion and avoid the risk of aggregation. The first coating layer is pH-responsive ε-polylysine with a thickness of 50-80 nm. The second coating layer is temperature-sensitive poloxamer 407 with a phase transition temperature of 32-35 °C. The outer layer is a mesoporous silica shell modified with antibacterial peptide HHC36, with a pore size of 5-10 nm. The design of the four-layer coating structure aims to achieve effective controlled release and targeted release of functional active ingredients. Epidermal growth factor and asiaticoside in the inner core, as the main active ingredients, can continuously provide the driving force for skin repair and regeneration through the sustained-release effect of poly(lactic-co-glycolic acid). The pH-responsive ε-polylysine in the first coating layer can adjust the release rate according to the changes in the skin microenvironment, ensuring the release of active ingredients under appropriate pH conditions and improving bioavailability. The temperature-sensitive poloxamer 407 in the second coating layer can undergo a phase transition within a specific temperature range, further regulating the release behavior and achieving intelligent release. The mesoporous silica shell modified with antibacterial peptide HHC36 on the outer layer not only provides good antibacterial performance but also realizes the micro-nano scale encapsulation of active ingredients through its mesoporous structure, enhancing stability and sustained-release effect.

[0051] In this embodiment, preferably, the following components are embedded in the surface grooves of the bioadhesive layer.

[0052] Calcium carbonate microspheres with a diameter of 5-10 μm, loaded with 0.05-0.1 wt% vitamin K1;

[0053] Silk fibroin nanofibers with a length of 50-100 μm, and the deviation of the orientation angle ≤ 15°;

[0054] Slow-release channels for zinc ions and magnesium ions are provided at the bottom of the groove, and the ion concentration gradient is 0.1 mM on the surface layer to 2.5 mM at the bottom layer.

[0055] In this embodiment, preferably, the antibacterial barrier layer comprises:

[0056] Vertically aligned carbon nanotube arrays with a diameter of 20-50 nm, a length-to-diameter ratio > 100, accounting for 3-5% of the layer volume;

[0057] Nanoscale silver and zinc oxide heterojunction particles with a molar ratio of silver to zinc of 1:2 to 1:5 and a particle size of 50-100 nm;

[0058] A surface hydrophobic coating with a contact angle > 120° for the surface hydrophobic coating, and the water vapor transmission rate is controlled at 2000-2500 g / m 2 / day.

[0059] The antibacterial barrier layer is uniquely designed to provide efficient antibacterial performance and good physical barrier effect. The vertically aligned carbon nanotube arrays not only enhance the mechanical strength of the material, but also effectively hinder the penetration of microorganisms due to their unique nanostructure. The introduction of silver nanowire and zinc oxide heterojunction particles utilizes the synergistic antibacterial effect of the two, broadens the antibacterial spectrum, and improves the antibacterial efficiency. The surface hydrophobic coating further enhances the waterproof performance of the material, reduces the erosion of moisture on the internal structure, and also increases the cleanliness of the material surface, which is beneficial to maintaining the aseptic state of the dressing.

[0060] A preparation method of a γ-PGA highly active medical aesthetic dressing, comprising the following steps:

[0061] S1. Preparation of antibacterial layer: Dissolve 12 wt% γ-PGA and 4 wt% chitosan in 0.5 M acetic acid solution, add 0.5 wt% graphene oxide, and perform electrospinning at a voltage of 18 kV and a receiving distance of 15 cm to form a nanofiber membrane, impregnate it with 1 wt% polyhexamethylene biguanide ethanol solution and then dry it; The corn steep liquor generated during the preparation of the antibacterial layer is recycled with 100% water resource utilization rate by ultrafiltration, creating an additional income of 200 yuan per ton of raw material.

[0062] S2. Preparation of sustained-release layer: Mix 8 wt% γ-PGA aqueous solution with 5 wt% polyvinyl alcohol / nanocellulose mixture (the existing 400 tons / year γ-PGA production capacity of Carbon and New Materials Chifeng Pharmaceutical supports), with a mass ratio of 4:1, add 1 wt% silane coupling agent KH550, and perform microwave crosslinking. The microwave crosslinking uses a frequency of 2450 MHz, the chamber pressure is maintained at atmospheric pressure to ensure crosslinking uniformity, the crosslinking time is 3 minutes, then inject microcapsules, and freeze-dry and mold. Adopt modular production design, which can be compatible with 5-100 ton reaction tanks, and realize flexible production capacity configuration through Siemens DCS system;

[0063] S3. Preparation of adhesion layer: Cast 6 wt% γ-PGA and 2 wt% hyaluronic acid solution on a PDMS template with a groove width of 30 μm, cure it under ultraviolet light for 30 minutes, and soak it in a phosphate buffer solution containing recombinant collagen for 24 hours;

[0064] S4. Multilayer composite assembly: Stack in the order of antibacterial layer - sustained-release layer - adhesion layer, spray 0.5 wt% polydopamine adhesive between layers, with a spraying amount of 3 mg / cm 2 , and adopt a three-stage hot pressing process to cure and form a bionic bonding interface, and assemble it into a medical dressing;

[0065] The first stage: Pre-press at 40 °C and 0.1 MPa for 5 min to eliminate the interlayer gap;

[0066] The second stage: hot press at 60 °C and 0.5 MPa for 10 min to activate the entanglement of γ-PGA molecular chains;

[0067] The third stage: cold press at 25 °C and 1 MPa for 15 min to shape the interlayer interface.

[0068] By using gradient hot pressing technology and precisely controlling the temperature at different stages, progressive entanglement of molecular chains is achieved. The detection results of differential scanning calorimetry (DSC) show that the glass transition temperature (Tg) at the interface increases from 45 °C to 58 °C, which directly reflects the improvement of material interface bonding. Tested under ASTM D1876 standard, the peel strength of the material reaches 18 N / cm, showing excellent adhesive performance.

[0069] The polydopamine adhesion technology realizes strong adhesion between materials through covalent bonding between catechol groups and γ-PGA amino groups. Fourier transform infrared spectroscopy (FTIR) detects characteristic peaks at 1540 cm -1 This further confirms the formation of covalent bonds. In addition, this adhesion technology also endows the material with excellent hydrothermal stability. After being placed in an environment of 85 °C and 85% relative humidity for 48 hours, no delamination phenomenon appears on the material surface, ensuring the long-term reliability of the material.

[0070] In this embodiment, preferably, the functional active microcapsules are prepared by microfluidic technology, including the following steps:

[0071] A1. Raw material preparation, pre-configure the corresponding solutions

[0072] Inner phase: PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor;

[0073] Middle phase: 1 wt% ε-polylysine aqueous solution;

[0074] Outer phase: 5 wt% poloxamer 407 isopropanol solution;

[0075] A2. Add 0.5 - 1.2 wt% tetraethyl orthosilicate (TEOS) as a silicon source to the PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor, 1 wt% ε-polylysine aqueous solution, and 5 wt% poloxamer 407 isopropanol solution, and form a monodisperse emulsion through a T-shaped glass capillary at a flow rate ratio of 1:5:10. The inner diameter of the T-shaped glass capillary is 200 μm, and after being catalyzed and hydrolyzed by ammonia water, it is centrifuged and collected;

[0076] A3. Calcinate the collected microcapsules under nitrogen protection, with a calcination temperature of 200 °C and a calcination time of 2 h to form a mesoporous silica shell;

[0077] A4. The calcined microcapsules were immersed in a PBS solution containing 0.1 - 0.5 mg / mL of antibacterial peptide HHC36 and shaken at 37 °C for 12 hours to complete the modification, and finally fixed on the surface of the mesoporous silica shell through amide bonds.

[0078] During the surface modification process of the microcapsules, first, the calcined microcapsules were placed in an anhydrous toluene solution containing 1% APTES (3-aminopropyltriethoxysilane), and then refluxed at 80 °C for 6 hours to achieve the amination of the microcapsule surface. After amination, the microcapsules were immersed in a 2.5% glutaraldehyde solution for cross-linking reaction. The pH value of this solution was adjusted to 7.4, and the cross-linking time was 4 hours. After cross-linking, the microcapsules were washed with phosphate buffer solution (PBS), and the washing process was repeated 3 times to remove the unreacted glutaraldehyde. Next, the microcapsules were mixed with a 10 mg / mL HHC36 solution containing 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), and reacted at 4 °C for 12 hours to promote the covalent binding of HHC36 to the microcapsule surface. After the reaction, the microcapsules were dried by freeze-drying. To detect the modification efficiency, the modified microcapsules were observed using a confocal microscope, and the results showed that the uniformity of peptide distribution exceeded 90%.

[0079] During the modification process, a short-chain cross-linking agent, glutaraldehyde, with a carbon chain length of This enabled the antibacterial active center of HHC36 (i.e., the amino acid residues at positions 6 - 15 in the peptide chain) to face the outside of the microcapsule pores, thus enabling more effective bactericidal action when in contact with bacteria. Through this modification method, the bactericidal efficiency of the microcapsules was significantly improved, specifically by 3.2 times. After the modified microcapsules were immersed in phosphate buffer solution (PBS) for 7 days and detected by high-performance liquid chromatography (HPLC), the residual rate of HHC36 was still higher than 95%, while that of the control group without immobilization treatment was only 21%. This result indicates that after the immobilization treatment of antibacterial peptide HHC36, its stability and persistence on the surface of the mesoporous silica shell were significantly enhanced, effectively preventing rapid elution during use. In addition, by optimizing the cross-linking conditions, it was ensured that the antibacterial peptide still maintained high antibacterial activity after modification, enabling the microcapsules to rapidly kill bacteria when in contact with the wound surface, thus effectively reducing the risk of infection.

[0080] In this example, preferably, the freeze-drying process parameters for preparing the sustained-release layer are:

[0081] Pre-freezing stage: Cool down to -20 °C at a rate of -1 °C / min and maintain for 2 hours;

[0082] Deep freezing stage: Cool down to -80°C at a rate of -5°C / min and maintain for 4 hours;

[0083] Sublimation drying: The vacuum degree is 10 Pa, heat up to -30°C and hold for 12 hours.

[0084] The selection of these parameters is aimed at ensuring that during the freeze-drying process, the antimicrobial peptide HHC36 and γ-PGA can maintain their biological activity and structural integrity. The slow cooling in the pre-freezing stage helps to reduce the formation of ice crystals in the solution, thereby protecting the active ingredients from mechanical damage. The deep freezing stage further reduces the temperature to ensure that all moisture exists in a solid state, preparing for the subsequent sublimation drying process. The sublimation drying stage is carried out in a vacuum environment. The low vacuum degree helps to promote the direct sublimation of ice and avoid the denaturation or degradation of the active ingredients caused by the presence of liquid water. At the same time, the temperature of -30°C and the holding time of 12 hours ensure the thoroughness of the sublimation process, as well as the stability and activity of the final product. Through the optimization of this series of process parameters, the obtained medical aesthetic dressing not only ensures high antibacterial activity but also has good stability and durability, and is suitable for various application scenarios in the medical aesthetic field.

[0085] In this embodiment, preferably, the method for the ion gradient component of the adhesion layer is to inject a zinc 2+ :magnesium 2+ mixed solution with a ratio of 1:3 into the porous template, apply a pulsed DC voltage (5 V), control the temperature at 25 - 30°C to avoid thermal degradation of γ-PGA, with a voltage of 5 V and a time of 30 min, so that the ions form a concentration gradient along the depth direction of the groove.

[0086] This method not only ensures that zinc ions and magnesium ions in the adhesion layer can be evenly and orderly distributed in the pores of the template, but also enhances the binding force between the ions and the template material through the action of the electric field, thereby improving the stability and durability of the adhesion layer. In addition, by precisely controlling the voltage and time, the distribution of the ion gradient can be further adjusted to meet the specific requirements of different medical aesthetic dressings for adhesion performance. The application of this ion gradient component method enables the γ-PGA high-activity medical aesthetic dressing to not only maintain high antibacterial activity but also have excellent adhesion performance, and can better fit the wound surface and promote wound healing.

[0087] In this embodiment, preferably, before the three-layer dressing is stacked, it undergoes plasma surface treatment. The treatment gas is a mixture of argon and oxygen with a flow ratio of 4:1, a treatment power of 100 W, and a treatment time of 5 minutes. After treatment, the oxygen element content on the surface increases by 18.5%, and the contact angle decreases from 75° to 12°. After S4, a cobalt-60 irradiation sterilization process (dose 25 kGy, meeting the ISO 11137 standard) is added to ensure the sterility of the dressing. Through surface activation treatment, -OH and -COOH groups are introduced onto the material surface using oxygen plasma technology, which significantly increases the surface energy of the material, reducing its contact angle from the original 105 degrees to 28 degrees, thus achieving a high surface energy level of 72 mN / m. This treatment not only improves the wettability of the material but also greatly enhances the interfacial bonding strength, specifically showing a 210% increase.

[0088] Through a carefully designed three-layer functional structure, the present invention realizes the synergistic effect of materials to achieve a more efficient treatment effect. First, the antibacterial barrier layer uses a vertically arranged carbon nanotube array to physically puncture the cell wall of bacteria, thereby achieving the purpose of inhibiting bacterial growth. In addition, the Ag / ZnO heterojunction can generate reactive oxygen species (ROS) when contacting bacteria, which is a powerful chemical bactericide that can further eliminate bacteria. The PHMB hydrophobic coating effectively blocks exudate, protects the wound from external contamination, and provides a clean and safe healing environment for the wound.

[0089] Secondly, the active slow-release layer is based on a double-network enhanced structure composed of γ-PGA and PVA-nanocellulose, which provides the necessary mechanical support to ensure the stability and durability of the material during use. In addition, the design of four-layer microcapsules can accurately release asiaticoside and epidermal growth factor (EGF) according to changes in pH value and temperature. Asiaticoside is a known ingredient that promotes skin repair, while EGF is a protein that can stimulate cell growth and division. Their synergistic effect can significantly accelerate the wound healing process.

[0090] Finally, the bioadhesive layer guides cell migration in a specific direction through a 30-micron deep groove array, thereby promoting tissue regeneration. The formation of Zn 2+ and Mg 2+ ion gradients can regulate the secretion of collagen, which is the main protein constituting the skin and tissues. The increase in its secretion helps to accelerate the regeneration and repair of the wound surface. This interaction and synergistic effect between layers make the entire material perform excellently in medical applications, providing new possibilities for wound treatment.

[0091] The dressing of the present invention has achieved triple innovation in materials, structure and process. Firstly, it has highly effective antibacterial properties, with an inhibition rate of over 99.99% against methicillin-resistant Staphylococcus aureus (MRSA). This antibacterial effect can last up to 7 days, effectively preventing the occurrence of secondary infection. According to the test of China Certification and Inspection Group (report number: CTI2024-0789), the oxygen permeability of this dressing is 1350cc / m 2 / day(Industry standard YY / T 0471-2022 requires>500cc / m 2 / day), cytotoxicity level 0 (in line with ISO 10993-5 standard), and methicillin-resistant Staphylococcus aureus (MRSA) inhibition rate > 99.99%.

[0092] Secondly, the dressing system possesses intelligent repair capabilities, with its active ingredients capable of sustained release over 72 hours, achieving a sustained-release rate exceeding 80%. This intelligent release mechanism significantly accelerates wound healing. According to animal research, the healing rate within 14 days reached an astonishing 98%, a 40% improvement over traditional methods.

[0093] In addition, the medical beauty dressing of the present invention also performs well in terms of safety and fit. Its 180° peel strength reaches 15.4N / cm, which means that the dressing can be firmly attached to the wound surface and is not easy to fall off. At the same time, its oxygen permeability exceeds 1200cc / m 2 / day, ensuring the breathing needs of the wound, and the cytotoxicity test result is level 0, indicating that it is harmless to human cells and safe to use.

[0094] Traditional collagen patches have the disadvantages of rapid inactivation of active ingredients (loss > 60% in 72 hours) and low transdermal efficiency (< 0.1 mg / cm 2 / h) and other problems, the performance of this patented dressing is significantly better than the existing technology, and the performance comparison table is as follows:

[0095]

[0096]

[0097] This invention also offers significant advantages in terms of process. The microcapsule encapsulation efficiency reaches 92% ± 3%, ensuring effective preservation and release of the active ingredient. The interlayer bonding strength reaches 2.8 MPa, ensuring the dressing's structural stability. Furthermore, its wet-heat stability exceeds 500 hours, meaning the dressing maintains its performance even in humid and high-temperature environments.

[0098] The medical aesthetic dressing system constructed by the present invention integrates three major functions: barrier protection, intelligent repair and tissue regeneration. Its technical indicators are significantly better than the current industry standards (YY / T 0471-2022), so it has great value and broad prospects in clinical applications.

[0099] The dressing of the present invention is suitable for supporting degradable surgical sutures (closed loop of carbon and new bio-based materials industry), with a tensile strength of 40MPa (traditional PU dressing 25MPa), and has passed EU REACH certification (technical field), specifically but not limited to the following fields:

[0100] Laser / minimally invasive postoperative wound care helps patients effectively care for and recover their wounds after laser or minimally invasive surgery.

[0101] Repair of chronic wounds such as burns and ulcers. This product can provide effective repair and care for chronic wounds such as burns and ulcers.

[0102] Anti-infection care after plastic surgery and filling surgery is applicable to patients after plastic surgery and filling surgery to help them prevent and control infection.

[0103] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A γ-PGA high-activity medical beauty dressing, characterized in that: Comprising three-layer composite structure: Antimicrobial barrier layer: 50-100 μm thick, composed of a 3:1 mass ratio of γ-polyglutamic acid (γ-PGA) and chitosan blend matrix. The γ-PGA is produced using engineered Bacillus subtilis (with an edited PgsB gene), and metabolic flux is regulated to achieve a γ-PGA yield of 150 g / L. Active sustained-release layer: 200-500 μm thick, containing a γ-PGA cross-linked network, 15-30 wt% nanohydroxyapatite, and functional active microcapsules with a microcapsule particle size distribution of 20-80 μm; Bioadhesive layer: 100-200 μm thick, composed of an interpenetrating network formed by γ-PGA and hyaluronic acid, loaded with 5-8wt% recombinant human collagen type III, with a micron-scale groove array on the surface, with a groove width of 20-50 μm and a depth of 10-30 μm.

2. The γ-PGA high-activity medical aesthetic dressing according to claim 1, wherein: The active sustained-release layer has a double-network structure. The first network is a γ-PGA main chain cross-linked by calcium ions. The amount of calcium ion cross-linking agent used is 2-5% of the mass of γ-PGA. The cross-linking time is 30 minutes, ensuring a cross-linking degree of 40-60%. The second network is a polyvinyl alcohol and nanocellulose reinforced skeleton with a mass ratio of 5:1 to 3:

1. Covalent grafting is achieved between the double networks through silane coupling agent KH550, and the grafting density is 0.8-1.2 mmol / g.

3. The γ-PGA high-activity medical aesthetic dressing according to claim 1, characterized in that: The functional active microcapsules adopt a four-layer coating structure, wherein the inner core is composed of 0.1-0.5wt% epidermal growth factor and 1-3wt% asiaticoside co-loaded in a polylactic acid-glycolic acid copolymer sustained-release core, the particle size of the functional active microcapsules is adjusted to 10-30 μm, and the particle size to layer thickness ratio is controlled at 1:10 to 1:

20. The first coating layer is pH-responsive ε-polylysine with a thickness of 50-80 nm, the second coating layer is temperature-sensitive poloxamer 407 with a phase transition temperature of 32-35°C, and the outer layer is a mesoporous silica shell modified with the antimicrobial peptide HHC36 with a pore size of 5-10 nm.

4. The γ-PGA highly active medical aesthetic dressing according to claim 1, wherein: The following components are embedded in the grooves on the surface of the bioadhesive layer: Calcium carbonate microspheres with a diameter of 5-10 μm, loaded with 0.05-0.1 wt% vitamin K1; Silk fibroin nanofibers with a length of 50-100 μm and an orientation angle deviation of ≤15°; A zinc ion and magnesium ion sustained-release channel is provided at the bottom of the groove, and the ion concentration gradient is from 0.1 mM on the surface to 2.5 mM on the bottom.

5. The γ-PGA high-activity medical aesthetic dressing according to claim 1, wherein: The antimicrobial barrier layer comprises: Vertically aligned carbon nanotube arrays with a diameter of 20-50 nm and an aspect ratio >100, occupying 3-5% of the layer volume; Nanosilver and zinc oxide heterojunction particles, with a molar ratio of silver to zinc of 1:2 to 1:5 and a particle size of 50-100 nm; Surface hydrophobic coating, the contact angle of the surface hydrophobic coating > 120°, and the water vapor transmission rate is controlled at 2000 - 2500 g / m 2 / day.

6. A preparation method of a γ-PGA high-activity medical aesthetic dressing, characterized in that: The following steps are involved: S1. Preparation of antibacterial layer: 12 wt% γ-PGA and 4 wt% chitosan were dissolved in 0.5 M acetic acid solution, 0.5 wt% graphene oxide was added, and electrospun at a voltage of 18 kV and a receiving distance of 15 cm to form a nanofiber membrane, which was then impregnated with a 1 wt% polyhexamethylene biguanide ethanol solution and dried. S2. Preparation of the sustained-release layer: Mix an 8 wt% γ-PGA aqueous solution with a 5 wt% polyvinyl alcohol / nanocellulose mixture in a mass ratio of 4:1, add 1 wt% silane coupling agent KH550, and perform microwave crosslinking. The microwave crosslinking uses a frequency of 2450 MHz, the chamber pressure is maintained at atmospheric pressure to ensure crosslinking uniformity, the crosslinking time is 3 minutes, then inject microcapsules, and freeze-dry to form a shape. Adopt modular production design, which can be compatible with reaction tanks of 5-100 tons, and realize flexible configuration of production capacity through the Siemens DCS system; S3. Preparation of the adhesion layer: Cast a 6 wt% γ-PGA and 2 wt% hyaluronic acid solution onto a PDMS template with a groove width of 30 μm in the PDMS template, and perform UV curing for 30 minutes, and soak it in a phosphate buffer solution containing recombinant collagen for 24 hours; S4. Multilayer composite assembly: Stack in the order of antibacterial layer - sustained-release layer - adhesion layer, spray 0.5 wt% polydopamine adhesive between layers, and the spraying amount is 3 mg / cm 2 , adopt a three-stage hot pressing process to cure and form a bionic bonding interface, and assemble it into a medical dressing; The first stage: Pre-press at 40 °C and 0.1 MPa for 5 min to eliminate the interlayer gap; The second stage: Hot-press at 60 °C and 0.5 MPa for 10 min to activate the entanglement of γ-PGA molecular chains; The third stage: Cold-press at 25 °C and 1 MPa for 15 min to shape the interlayer interface.

7. The method for preparing a γ-PGA high-activity medical aesthetic dressing according to claim 6, characterized in that: The functional active microcapsules are prepared by microfluidic technology and include the following steps: A1. Raw material preparation, pre-configure the corresponding solutions Inner phase: PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor; Intermediate phase: 1 wt% ε-polylysine aqueous solution; Outer phase: 5 wt% poloxamer 407 isopropanol solution; A2. Add 0.5-1.2 wt% tetraethyl orthosilicate (TEOS) as a silicon source to the PLGA / dichloromethane solution containing 0.3 wt% epidermal growth factor, 1 wt% ε-polylysine aqueous solution, and 5 wt% poloxamer 407 isopropanol solution, and form a monodisperse emulsion through a T-shaped glass capillary at a flow rate ratio of 1:5:

10. The inner diameter of the T-shaped glass capillary is 200 μm, and after catalytic hydrolysis with ammonia water, centrifuge and collect; A3. Calcinate the collected microcapsules under nitrogen protection, with a calcination temperature of 200 °C and a calcination time of 2 h to form a mesoporous silica shell; A4. Immerse the calcined microcapsules in a PBS solution containing 0.1-0.5 mg / mL antimicrobial peptide HHC36, and oscillate at 37 °C for 12 hours to complete the modification, and finally fix them on the surface of the mesoporous silica shell through amide bonds.

8. The preparation method of a γ-PGA highly active medical aesthetic dressing according to claim 6, characterized in that: The process parameters of freeze-drying during the preparation of the sustained-release layer are as follows: Pre-freezing stage: Cool down to -20 °C at a rate of -1 °C / min and maintain for 2 hours; Deep-freezing stage: Cool down to -80 °C at a rate of -5 °C / min and maintain for 4 hours; Sublimation drying: The vacuum degree is 10 Pa, heat up to -30 °C and keep for 12 hours.

9. The preparation method of a γ-PGA highly active medical aesthetic dressing according to claim 6, characterized in that: The method for constructing the ion gradient component of the adhesion layer is to inject a zinc-magnesium mixed solution with Zn2+:Mg2+ of 1:3 into a porous template, use a pulsed DC voltage (5 V), control the temperature at 25-30 °C to avoid thermal degradation of γ-PGA, with a voltage of 5 V and a time of 30 min, so that the ions form a concentration gradient along the depth direction of the groove.

10. The preparation method of a γ-PGA highly active medical aesthetic dressing according to claim 6, wherein: Before the three-layer dressings are stacked in S4, they are subjected to plasma surface treatment. The treatment gas is a mixture of argon and oxygen with a flow rate ratio of 4:1, a treatment power of 100 W, and a treatment time of 5 minutes. After the treatment, the oxygen element content on the surface increases by 18.5%, and the contact angle decreases from 75° to 12°. After S4, a cobalt-60 irradiation sterilization process (dose 25 kGy, meeting the ISO 11137 standard) is added to ensure the sterility of the dressings.

Images