Liquid dressing with nano antibacterial and antioxidant functions and synthesis method thereof

Abstract

The invention relates to the technical field of biological medicine, in particular to a liquid dressing with nano antibacterial and antioxidant functions and a synthesis method thereof, and the liquid dressing is prepared from the following raw materials in percentage by weight: 10%-25% of chitosan quaternary ammonium salt, 5%-15% of metal organic framework nano material, 3%-8% of plant polyphenol antioxidant, 1%-5% of natural essential oil emulsion and the balance of water. The preparation comprises the following components in percentage by weight: 0.5 to 3 percent of sodium alginate, 0.1 to 1.0 percent of controlled release microspheres, 5 to 10 percent of glycerol and the balance of sterile purified water. Wherein the metal organic framework nano material is HKUST-1 type copper-based nano particles loaded with quercetin; the chitosan quaternary ammonium salt and the quercetin-loaded HKUST-1 nanoparticles have a synergistic effect, and through dual mechanisms of bacterial cell membrane destruction and copper ion release, the chitosan quaternary ammonium salt / quercetin-loaded HKUST-1 nanoparticles show excellent antibacterial activity on gram-positive bacteria, gram-negative bacteria and drug-resistant bacteria. And the natural essential oil emulsion further enhances the antibacterial effect and reduces the generation of drug-resistant strains.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a nano liquid dressing with antibacterial and antioxidant functions and a synthesis method thereof. Background Art

[0002] With the increasing global bacterial resistance and the growing demand for chronic wound management, traditional antibiotic treatments and single-function dressings are no longer able to meet clinical needs. In existing technologies, the overuse of antibiotics has led to the widespread spread of drug-resistant strains (such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacteria), while traditional dressings (such as gauze and silver ion dressings) generally have the following problems:

[0003] Narrow antimicrobial spectrum and easy to develop drug resistance: Long-term use of metal antimicrobial agents such as silver ions can easily induce drug resistance and have limited effect on Gram-negative bacteria (such as Escherichia coli);

[0004] Insufficient antioxidant capacity: Chronic wounds are often accompanied by oxidative stress damage, and traditional dressings lack the ability to effectively scavenge free radicals;

[0005] Poor controlled-release properties: active ingredients (such as growth factors and antimicrobial agents) are released too quickly, making it difficult to maintain long-term therapeutic effects;

[0006] Existing technology urgently needs a new liquid dressing that has broad-spectrum antibacterial, long-lasting antioxidant, controlled release function and biocompatibility to meet the challenges of drug-resistant bacterial infection and chronic wound repair. Summary of the Invention

[0007] In view of the above, it is necessary to provide a new type of liquid dressing that can combine broad-spectrum antibacterial, long-lasting antioxidant, controlled release function and biocompatibility, a nano-antibacterial and antioxidant liquid dressing and its synthesis method.

[0008] The present invention provides a nano liquid dressing with antibacterial and antioxidant functions and a synthesis method thereof, which is prepared from the following raw materials in percentage by weight:

[0009] Chitosan quaternary ammonium salt 10% to 25%,

[0010] Metal-organic framework nanomaterials 5% to 15%,

[0011] Plant polyphenol antioxidants 3% to 8%,

[0012] Natural essential oil emulsion 1% to 5%,

[0013] Sodium alginate 0.5% to 3%,

[0014] Controlled release microspheres 0.1% to 1.0%,

[0015] Glycerin 5% to 10%,

[0016] The balance is sterile purified water;

[0017] The metal organic framework nanomaterial is HKUST-1 type copper-based nanoparticles loaded with quercetin.

[0018] In a possible implementation, the chitosan quaternary ammonium salt has a degree of substitution of ≥40% and a molecular weight of 10 kDa to 50 kDa.

[0019] In a possible implementation, the particle size of the quercetin-loaded HKUST-1 copper-based nanoparticles is 50 nm to 200 nm, and the quercetin loading amount is 15% to 30%.

[0020] In a possible implementation, the plant polyphenol antioxidant is at least one of tea polyphenols, rosmarinic acid or resveratrol.

[0021] The present invention also provides a method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions, comprising the following steps:

[0022] S1. Preparation of controlled-release microspheres:

[0023] a) dissolving poly(lactic acid-co-glycolic acid) in dichloromethane, adding an aqueous solution of epidermal growth factor, and performing ultrasonic emulsification using a probe to form a W / O emulsion;

[0024] b) injecting the W / O emulsion into an aqueous phase containing 2% polyvinyl alcohol and homogenizing to form a W / O / W double emulsion;

[0025] c) after volatilizing the organic solvent, collecting the microspheres by centrifugation, and freeze-drying to obtain controlled-release microspheres with a particle size of 10 μm to 50 μm;

[0026] S2. Nanoparticle Synthesis:

[0027] The HKUST-1 precursor and quercetin were ultrasonically mixed in an ethanol aqueous solution, reacted at 60°C with constant temperature shaking for 2 to 4 hours, and centrifugally dried to prepare quercetin-loaded HKUST-1 nanoparticles;

[0028] S3. Construction of nano-dispersion system:

[0029] The nanoparticles obtained in S2 are dispersed in glycerol, a plant polyphenol antioxidant is added, and the mixture is subjected to high-pressure homogenization to form a nanodispersion liquid;

[0030] S4. Preparation of matrix solution:

[0031] Dissolve chitosan quaternary ammonium salt in sterile purified water, stir and hydrate at 40°C to 50°C, and add sodium alginate to form solution A;

[0032] S5. Final product synthesis:

[0033] The S1 controlled-release microspheres, the S3 nanodispersion, and the natural essential oil emulsion are added to the solution A, and are homogenized and emulsified under low temperature under inert gas protection. After the pH is adjusted to 5.5 to 6.5, sterile filling is performed.

[0034] In a possible implementation manner, the natural essential oil is at least one of tea tree oil, eucalyptus oil, or thyme oil.

[0035] In a possible implementation manner, the pH adjustment in the step S5 adopts a citric acid-sodium citrate buffer system.

[0036] In a possible implementation manner, the ultrasonic power in the step S2 is 300 W to 500 W, and the frequency is 20 kHz to 40 kHz.

[0037] In a possible implementation manner, the homogenization and emulsification in the step S5 is performed under a low-temperature environment of 4°C to 10°C, and the homogenization pressure is 50 MPa to 100 MPa.

[0038] In a possible implementation manner, the probe ultrasonic power in the step S1a is 100 W to 150 W, and the emulsification time is 3 min to 5 min.

[0039] In the step S1b, the molar ratio of lactic acid / hydroxyacetic acid of the polylactic acid-hydroxyacetic acid copolymer is 75:25 to 85:15.

[0040] In the above-mentioned liquid dressing with nanometer antibacterial and antioxidant functions and the synthesis method thereof, the quaternary ammonium salt of chitosan and the HKUST-1 nanoparticles loaded with quercetin synergistically act, through a double mechanism of destroying the bacterial cell membrane and releasing copper ions, to exhibit excellent antibacterial activity on gram-positive bacteria, gram-negative bacteria, and drug-resistant bacteria. The natural essential oil emulsion further enhances the antibacterial effect and reduces the generation of drug-resistant strains.

[0041] Highly efficient antioxidant and anti-inflammatory: the plant polyphenol antioxidant significantly reduces oxidative stress damage and accelerates wound healing by scavenging free radicals and inhibiting the expression of inflammatory factors. The controlled-release microspheres realize the sustained release of epidermal growth factor, promote angiogenesis and fibroblast proliferation, and improve the efficiency of tissue regeneration.

[0042] Long-acting controlled release and stable release: the nanodispersion system construction ensures the uniform dispersion of the HKUST-1 nanoparticles and the plant polyphenols, and in combination with the gelation characteristics of sodium alginate, the residence time of the active ingredients in the wound site is prolonged. The low-temperature homogenization and emulsification process and the citric acid-sodium citrate buffer system maintain the stability of the dressing and avoid the degradation of the active ingredients.

[0043] Biocompatibility and safety: Chitosan quaternary ammonium salt and sodium alginate form a moist healing environment, reducing scarring and being non-toxic to normal tissue. Sterile purified water is used as the solvent to avoid organic solvent residues, meeting clinical aseptic filling requirements. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0045] Figure 1 The figure is a flow chart of a method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions in one embodiment of the present invention. DETAILED DESCRIPTION

[0046] In order to make the purpose, 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 drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0047] Example 1

[0048] See also Figure 1 This embodiment provides a technical solution: a nano-antibacterial and antioxidant liquid dressing and a synthesis method thereof, which is prepared from the following raw materials in percentage by weight:

[0049] Chitosan quaternary ammonium salt: 20% (degree of substitution 45%, molecular weight 30kDa);

[0050] Quercetin-loaded HKUST-1 nanoparticles: 12% (particle size 100 nm, quercetin loading 25%);

[0051] Tea polyphenols (plant polyphenol antioxidants): 6%;

[0052] Natural essential oil emulsion (tea tree oil): 3%;

[0053] Sodium alginate: 2%;

[0054] Controlled-release microspheres (particle size 30 μm): 0.8%;

[0055] Glycerol: 8%;

[0056] Sterile purified water: balance.

[0057] The synthesis method of a nanometer liquid dressing with antibacterial and antioxidant functions comprises the following steps:

[0058] S1. Preparation of controlled-release microspheres:

[0059] Poly(lactic acid-glycolic acid) copolymer (lactic acid / glycolic acid molar ratio 80:20) was dissolved in dichloromethane, and an aqueous solution of epidermal growth factor was added. Ultrasonic emulsification was performed at a probe power of 120 W for 3 minutes to form a W / O emulsion.

[0060] Aqueous phase containing 2% polyvinyl alcohol was injected and homogenized to form a W / O / W emulsion. After the solvent was evaporated, the microspheres were collected by centrifugation and freeze-dried to obtain controlled-release microspheres.

[0061] S2. Nanoparticle Synthesis:

[0062] HKUST-1 precursor and quercetin were mixed in an ethanol aqueous solution (volume ratio 1:1) at a mass ratio of 1:0.3, and ultrasonically shaken at a constant temperature of 60°C for 3 hours at a power of 300 W and a frequency of 30 kHz. Nanoparticles were then centrifuged and dried.

[0063] S3. Construction of nano-dispersion system:

[0064] The nanoparticles were dispersed in glycerol, tea polyphenols were added, and high-pressure homogenization was performed at a pressure of 80 MPa for 10 minutes to form a nano-dispersion liquid.

[0065] S4. Preparation of matrix solution:

[0066] Chitosan quaternary ammonium salt was dissolved in sterile purified water, stirred and hydrated at 45°C, and sodium alginate was added to form solution A.

[0067] S5. Final product synthesis:

[0068] Controlled-release microspheres, nanodispersion, and tea tree oil emulsion were added to solution A, homogenized and emulsified at a low temperature of 4°C (homogenization pressure 80 MPa), the pH was adjusted to 6.0 with a citric acid-sodium citrate buffer system, and the solution was aseptically filled.

[0069] Beneficial Effects: Tea polyphenols and HKUST-1 copper-based nanoparticles work synergistically, achieving 99.2% and 98.5% inhibition rates against Staphylococcus aureus and Escherichia coli, respectively. Tea polyphenols are 3.5 times more efficient at scavenging free radicals than vitamin C, effectively reducing inflammation. Controlled-release microspheres continuously release epidermal growth factor over 72 hours, accelerating wound healing by 40%. Quaternary ammonium chitosan and sodium alginate work together to maintain a moist environment and reduce scarring.

[0070] Example 2

[0071] See also Figure 1This embodiment provides a technical solution: a nano-antibacterial and antioxidant liquid dressing and a synthesis method thereof, which is prepared from the following raw materials in percentage by weight:

[0072] Chitosan quaternary ammonium salt: 25% (degree of substitution 50%, molecular weight 50kDa);

[0073] Quercetin-loaded HKUST-1 nanoparticles: 15% (particle size 150 nm, quercetin loading 30%);

[0074] Rosmarinic acid (plant polyphenol antioxidant): 5%;

[0075] Natural essential oil emulsion (eucalyptus oil): 2%;

[0076] Sodium alginate: 1.5%;

[0077] Controlled-release microspheres (particle size 40 μm): 0.5%;

[0078] Glycerol: 7%;

[0079] Sterile purified water: balance.

[0080] The synthesis method of a nanometer liquid dressing with antibacterial and antioxidant functions comprises the following steps:

[0081] S1. Preparation of controlled-release microspheres:

[0082] Poly(lactic acid-glycolic acid copolymer) (lactic acid / glycolic acid molar ratio 85:15) was dissolved in dichloromethane, and an aqueous solution of epidermal growth factor was added. The probe ultrasonic power was 150 W for 4 minutes to form a W / O emulsion.

[0083] S2. Nanoparticle Synthesis:

[0084] HKUST-1 precursor and quercetin were mixed in an ethanol aqueous solution (volume ratio 2:1) at a mass ratio of 1:0.4, and ultrasonically shaken at a constant temperature of 60°C for 4 hours at a power of 400 W and a frequency of 35 kHz. Nanoparticles were obtained by centrifugation and drying.

[0085] S3. Construction of nano-dispersion system:

[0086] The nanoparticles were dispersed in glycerol, rosmarinic acid was added, and high-pressure homogenization was performed at a pressure of 90 MPa for 15 minutes to form a nanodispersion liquid.

[0087] S4. Preparation of matrix solution:

[0088] Chitosan quaternary ammonium salt and sodium alginate are hydrated at 50°C to form solution A.

[0089] S5. Final product synthesis:

[0090] Controlled-release microspheres, nanodispersion, eucalyptus oil emulsion are added to solution A, and homogenized at low temperature of 8℃ (homogenization pressure 90MPa), and the pH is adjusted to 5.8, and then sterilized and filled.

[0091] Beneficial effects: Rosmarinic acid inhibits COX-2 enzyme activity, and reduces the expression of inflammatory factor IL-6 by 60%. HKUST-1 nanoparticles synergize with copper ions, and the antibacterial effect lasts for more than 7 days. The controlled-release microspheres with a particle size of 40μm prolong the release period of the active ingredients to 96 hours. Rosmarinic acid promotes collagen deposition, and the wound healing rate is increased by 50%.

[0092] Example 3

[0093] See Figure 1 The embodiment provides a technical solution: a nanometer antibacterial and antioxidant functional liquid dressing and a synthesis method thereof, which are prepared from the following raw materials in percentage by weight:

[0094] Chitosan quaternary ammonium salt: 10% (degree of substitution 40%, molecular weight 10kDa);

[0095] Quercetin-loaded HKUST-1 nanoparticles: 5% (particle size 200nm, quercetin loading capacity 15%);

[0096] Resveratrol (plant polyphenol antioxidant): 3%;

[0097] Natural essential oil emulsion (thyme oil): 1%;

[0098] Sodium alginate: 0.5%;

[0099] Controlled-release microspheres (particle size 50μm): 1.0%;

[0100] Glycerol: 5%;

[0101] Sterile purified water: the balance.

[0102] The synthesis method of the nanometer antibacterial and antioxidant functional liquid dressing comprises the following steps:

[0103] S1, preparation of controlled-release microspheres:

[0104] Poly (lactic-co-glycolic acid) (lactic acid / hydroxyacetic acid molar ratio 75:25) is dissolved in dichloromethane, and an aqueous epidermal growth factor solution is added, and a W / O emulsion is formed by probe ultrasonic power 100W emulsification for 5 minutes.

[0105] S2, synthesis of nanoparticles:

[0106] HKUST-1 precursor and quercetin were mixed in ethanol aqueous solution (volume ratio 3:1) at mass ratio 1:0.2, ultrasonic power 500 W, frequency 40 kHz, constant temperature 60℃, oscillation for 2 hours, centrifugal drying to obtain nanoparticles.

[0107] S3, Nanodispersion system construction:

[0108] The nanoparticles were dispersed in glycerol, resveratrol was added, and high-pressure homogenization pressure was 100 MPa for 20 minutes to form a nanodispersion.

[0109] S4, Preparation of matrix solution:

[0110] Chitosan quaternary ammonium salt and sodium alginate were hydrated in water at 40℃ to form solution A.

[0111] S5, Synthesis of final product:

[0112] The controlled-release microspheres, nanodispersion, and thyme oil emulsion were added to solution A, homogenized at low temperature of 10℃ (homogenization pressure 100 MPa), the pH was adjusted to 6.5, and sterilely filled.

[0113] Beneficial effects: The ROS (reactive oxygen species) scavenging efficiency of resveratrol is 2 times that of tea polyphenols, significantly reducing oxidative stress damage. The HKUST-1 nanoparticles have a bacteriostatic rate of 97% on methicillin-resistant Staphylococcus aureus (MRSA) by destroying the permeability of the bacterial membrane. The controlled-release microspheres with a particle size of 50μm achieve sustained release of active ingredients for 120 hours, reducing the frequency of replacement. Resveratrol activates the VEGF signaling pathway, increasing the number of new blood vessels by 35%, accelerating tissue regeneration.

[0114] In this article, the front, back, up, down, and other orientation words are defined by the position of the parts in the drawing and the position of the parts relative to each other in the drawing, only to express the clarity and convenience of the technical solution. It should be understood that the use of orientation words should not limit the scope of the invention claimed.

[0115] Obviously, the above-mentioned embodiments are only part of the embodiments of the present application, not all embodiments, and the present application is not limited to the details of the above-mentioned embodiments. Any appropriate changes or modifications made by those skilled in the art are considered not to deviate from the patent scope of the present application.

Claims

1. A nanometer liquid dressing with antibacterial and antioxidant functions, characterized in that: It is prepared from the following raw materials by weight percentage: Chitosan quaternary ammonium salt 10% to 25%, Metal-organic framework nanomaterials 5% to 15%, Plant polyphenol antioxidants 3% to 8%, Natural essential oil emulsion 1% to 5%, Sodium alginate 0.5% to 3%, Controlled release microspheres 0.1% to 1.0%, Glycerin 5% to 10%, The balance is sterile purified water; The metal organic framework nanomaterial is HKUST-1 type copper-based nanoparticles loaded with quercetin.

2. The nanometer antibacterial and antioxidant liquid dressing according to claim 1, characterized in that: The substitution degree of the chitosan quaternary ammonium salt is greater than or equal to 40%, and the molecular weight is 10 kDa to 50 kDa.

3. The nano-antibacterial and antioxidant liquid dressing according to claim 1, characterized in that: The particle size of the quercetin-loaded HKUST-1 type copper-based nanoparticles is 50 nm to 200 nm, and the quercetin loading amount is 15% to 30%.

4. The nano-antibacterial and antioxidant liquid dressing according to claim 1, characterized in that: The plant polyphenol antioxidant is at least one of tea polyphenols, rosmarinic acid or resveratrol.

5. A method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1. Preparation of controlled-release microspheres: a) dissolving poly(lactic acid-co-glycolic acid) in dichloromethane, adding an aqueous solution of epidermal growth factor, and performing ultrasonic emulsification using a probe to form a W / O emulsion; b) injecting the W / O emulsion into an aqueous phase containing 2% polyvinyl alcohol and homogenizing to form a W / O / W double emulsion; c) evaporating the organic solvent, collecting the microspheres by centrifugation, and freeze-drying to produce controlled-release microspheres with a particle size of 10 μm to 50 μm; S2. Nanoparticle Synthesis: The HKUST-1 precursor and quercetin were ultrasonically mixed in an ethanol aqueous solution, reacted at 60°C with constant temperature shaking for 2 to 4 hours, and centrifugally dried to prepare quercetin-loaded HKUST-1 nanoparticles; S3. Construction of nano-dispersion system: The nanoparticles obtained in S2 are dispersed in glycerol, a plant polyphenol antioxidant is added, and the mixture is subjected to high-pressure homogenization to form a nanodispersion liquid; S4. Preparation of matrix solution: Dissolve chitosan quaternary ammonium salt in sterile purified water, stir and hydrate at 40°C to 50°C, and add sodium alginate to form solution A; S5. Final product synthesis: Add S1 controlled-release microspheres, S3 nanodispersion, and natural essential oil emulsion to solution A, homogenize and emulsify at low temperature under the protection of inert gas, adjust the pH to 5.5 to 6.5, and then aseptically fill.

6. The method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to claim 5, characterized in that: The natural essential oil is at least one of tea tree oil, eucalyptus oil or thyme oil.

7. The method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to claim 5, characterized in that: In step S5, the pH is adjusted using a citric acid-sodium citrate buffer system.

8. The method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to claim 5, characterized in that: The ultrasonic power in step S2 is 300W to 500W, and the frequency is 20kHz to 40kHz.

9. The method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to claim 5, characterized in that: The homogenization and emulsification in step S5 is carried out in a low temperature environment of 4° C. to 10° C., and the homogenization pressure is 50 MPa to 100 MPa.

10. The method for synthesizing a nanometer liquid dressing with antibacterial and antioxidant functions according to claim 5, characterized in that: In step S1a, the probe ultrasonic power is 100W to 150W, and the emulsification time is 3min to 5min; In step S1b, the molar ratio of lactic acid to glycolic acid of the poly(lactic acid-glycolic acid) copolymer is 75:25 to 85:15.

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