A high biocompatibility adhesive for medical supplies and a preparation method thereof

Abstract

This invention discloses a highly biocompatible adhesive for medical products and its preparation method. The adhesive comprises, by weight, 30-50 parts of oligomer, 10-30 parts of biocompatible tackifying resin, 15-35 parts of reactive diluent monomer, 0.5-5 parts of nano-silver powder, 100-200 parts of solvent, 5-15 parts of bioactive enhancer, and 0.5-2 parts of photoinitiator. The oligomer is preferably a specific acrylate copolymer, and the bioactive enhancer can be chitosan, hyaluronic acid, etc. The preparation method includes: first, premixing the oligomer, tackifying resin, and a portion of the solvent in a 60°C water bath; then, dissolving the ball-milled 40-50nm nano-silver powder and bioactive enhancer in the remaining solvent, and slowly adding the premixed adhesive solution at 35-50°C; finally, adding the photoinitiator and stirring for 1-3 hours, followed by cooling and filtration to obtain the final product. This invention introduces biocompatible tackifying resin and bioactive enhancer, combined with the antibacterial effect of nano silver powder, to make the adhesive have good biocompatibility, antibacterial properties and adhesive properties, making it particularly suitable for the field of medical products.

Description

[0001] In wound treatment and surgical procedures, natural and synthetic implantable materials are used to close or fix human tissues, such as surgical mesh, suture devices, and absorbable sutures, which are commonly used tools for wound closure. These techniques remain widely used because they are easy to operate and have high tensile strength. However, from a clinical perspective, they often fall short of the demands of modern surgery, especially in minimally invasive and laparoscopic procedures. This is because these methods are invasive, often requiring secondary intervention for removal, and may lead to fluid leakage. Furthermore, they can cause pain, scarring, or delayed healing due to poor tissue integration, and in severe cases, infection. These drawbacks directly conflict with key clinical goals such as reducing surgical trauma, improving postoperative recovery, and achieving seamless integration of biomaterials.

[0002] In this context, highly biocompatible adhesives are increasingly emerging as alternatives capable of overcoming these challenges. Highly biocompatible adhesives are non-invasive, easy to use, and easy to apply. Furthermore, some formulations also function as hemostatic agents, effectively controlling bleeding. Surgical adhesives, in particular, are designed to bind tissues together or fix implanted biomaterials. The physiological degradation of surgical adhesives is controlled by a combination of hydrolytic, oxidative, and enzymatic mechanisms, which act synergistically or sequentially, depending on the adhesive's chemical structure and the specific biological environment. Hydrolytic degradation primarily affects ester, amide, and urea bonds through nucleophilic reactions of water molecules, a process significantly influenced by local pH. Ester bonds are generally less stable in neutral to weakly alkaline environments. For example, amide hydrolysis is more pronounced in plasma in acidic environments (such as lysosomes). Simultaneously, oxidative degradation acts on sulfur-containing groups, such as thiol groups and thioesters, which undergo oxidation reactions with the participation of reactive oxygen species (such as hydrogen peroxide and superoxide radicals). Finally, enzymatic degradation involves the cleavage action of specific enzymes, including esterases, proteases, and ureases, which specifically hydrolyze functional groups such as urea, urea-formaldehyde, and peptide-like bonds. These enzymatic processes are organ- and tissue-specific, with higher activity in protease-rich environments, such as chronic wounds, the gastrointestinal tract, and the liver. These degradation pathways determine the biodegradation rate and biocompatibility characteristics of medical adhesives, making their carefully designed formulation crucial for safe and effective clinical application.

[0003] Bioadhesion is primarily achieved through three mechanisms: physiological, physical, and chemical. Since blood and body fluids may compete with adhesive functional groups, biocompatible adhesives must utilize multiple types of interactions simultaneously. Adhesion with biocompatible adhesives typically involves three stages: wetting, polymer swelling, interchain diffusion with the biofilm, and the formation of chemical bonds between entangled chains. From a clinical perspective, successful bioadhesives must provide strong and stable adhesion under the influence of tissue movement, blood, and moisture. To be considered an ideal bioadhesive, it must meet the following criteria: 1. Biocompatibility: The adhesive and its degradation products must be safe, non-toxic, and not trigger an immune response. 2. Ease of use and repositionability: The material needs to be easy to handle and repositionable shortly after use. 3. Rapid curing: Biocompatible adhesives must be able to rapidly solidify or cure in a moist environment containing biological fluids. After cross-linking and curing, it should possess good flexibility and maintain strong adhesion in physiological environments. 4. Physiological degradation: Ideally, this adhesive should be able to decompose into non-toxic byproducts through enzymatic or hydrolytic processes, which are then metabolized and excreted from the body through the kidneys or liver.

[0004] Every year, tens of millions of people suffer from tissue trauma or various diseases requiring surgical procedures. Traditional wound suturing techniques, such as surgical mesh, suture devices, and absorbable sutures, are somewhat invasive. For wounds in certain fragile areas requiring tight and rapid sealing, these traditional treatments have limitations. This patent develops a highly biocompatible medical surgical adhesive. Compared to traditional treatment methods, this biocompatible medical adhesive offers advantages such as ease of use, good biocompatibility, and meeting adhesion requirements under physiological conditions.

[0005] Objective: Traditional wound closure methods have limitations and require highly skilled operators. Therefore, medical tissue adhesives are increasingly favored as a non-invasive treatment method. To meet the bonding requirements under physiological conditions, this patent develops a highly biocompatible medical tissue adhesive that can rapidly bond tissue in a moist environment while maintaining bonding strength. This adhesive possesses hemostatic and antibacterial properties, significantly reducing the risks of bleeding and infection during surgery.

[0006] This patent aims to overcome the shortcomings of existing technologies and provide a medical adhesive that integrates high adhesion, excellent biocompatibility, long-lasting antibacterial activity, and bioactivity enhancement.

[0007] (i) A highly biocompatible adhesive for medical products, comprising the following components by weight: Runao DEC5B bio-based oligomer: 30-50 parts; Runao DEC6B bio-based oligomer: 30-50 parts, serving as the main body of the adhesive, providing cohesive strength and basic viscoelasticity. Preferred embodiment: The oligomer is an acrylate copolymer, copolymerized from monomers including isooctyl acrylate (providing flexibility), acrylic acid (providing polarity), hydroxyethyl methacrylate (providing reactive hydroxyl groups), and vinyl acetate. Its weight-average molecular weight is controlled between 500,000 and 1,500,000 to ensure suitable initial tack and holding power.

[0008] Biocompatible tackifying resin: 10-30 parts. Used to improve the wettability of adhesives on skin or tissues.

[0009] Preferred option: The resin is selected from at least one of hydrogenated rosin glycerol esters, hydrogenated petroleum resins, terpene resins, and polyisobutylene. These resins undergo hydrogenation treatment, exhibiting stable chemical properties, resistance to oxidation and discoloration, and good biocompatibility.

[0010] Reactive diluent monomer: 15-35 parts. Used to adjust the viscosity of the system and participate in the photocuring crosslinking reaction to form a three-dimensional network structure.

[0011] Preferred option: The monomer is selected from at least one of cyanoacrylate monomers, n-butyl-2-cyanoacrylate, and 2-ethylhexyl acrylate.

[0012] Nano silver powder: 0.5-5 parts. As a broad-spectrum, long-lasting antibacterial agent, it imparts excellent antibacterial properties to adhesives, preventing wound infection.

[0013] Bioactivity enhancer: 5-15 parts. Used to improve the cell affinity of adhesives or to provide biological functions such as hemostasis and promoting healing.

[0014] Preferred option: at least one of chitosan and its derivatives, hyaluronic acid, collagen, hydroxyapatite, and silk fibroin.

[0015] Photoinitiator: 0.5-2 parts. Used to initiate the polymerization and crosslinking of unsaturated bonds in reactive diluted monomers and oligomers under ultraviolet light irradiation.

[0016] Preferred option: at least one of (2,4,6-trimethylbenzoyl)bis(p-tolyl)phosphine oxide (TMO), camphorquinone (CQ), and 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0017] Optional components: The adhesive may also contain 0.1-2 parts of antioxidants (such as vitamin E, BHT, etc.) to improve storage stability.

[0018] (II) Preparation method of the highly biocompatible adhesive Includes the following steps: (1) Premixing: At a water bath temperature of 60°C, the oligomer and biocompatible tackifying resin are added to the reaction vessel and stirred until completely dissolved to obtain a uniform premixed adhesive solution.

[0019] (2) Addition of active substances and nano silver powder: The nano silver powder is pre-ball-milled to a particle size of 40-50 nm. The treated nano silver powder is dispersed in the premixed gel. Under stirring, vacuum is applied to maintain the system temperature at 35-50℃, and the mixture is homogeneous.

[0020] (3) Initiator addition: Add the photoinitiator to the mixture obtained in step (2) and stir continuously for 1-3 hours to ensure that the initiator is completely dissolved and mixed evenly.

[0021] (4) Post-processing: After stirring, cool the premixed adhesive to room temperature, and then filter it (e.g., a 200-400 mesh filter) to remove any possible impurities or undispersed particles, thus obtaining the final high biocompatibility adhesive product.

[0022] The advantages of this invention are: it is a highly biocompatible adhesive for medical supplies, with simple and widely available raw materials, high bonding strength, significantly extended service life, and is safe and non-toxic, posing no harm to the human body. Example Example

[0023] Formula: 40 parts of acrylate copolymer (Mw≈800,000), 20 parts of hydrogenated rosin glycerol ester, 25 parts of cyanoacrylate monomer (reactive diluent monomer), 2 parts of nano silver powder (50nm), 8 parts of chitosan (bioactivity enhancer), 1 part of 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator), and 0.5 parts of vitamin E (antioxidant).

[0024] Preparation: In a 60°C water bath, acrylate copolymer, hydrogenated rosin glycerol ester and 100 parts of ethyl acetate were added to a three-necked flask and stirred to dissolve for 2 hours to obtain a premixed adhesive solution.

[0025] Nano-silver powder and chitosan were dissolved in 50 parts of ethyl acetate. The solution was then slowly added dropwise to the premixed gel solution while stirring at 40°C for 1 hour. A photoinitiator and vitamin E were then added, and the mixture was stirred in the dark for another 2 hours.

[0026] After cooling, pass through a 300-mesh sieve to obtain adhesive A.

[0027] Application: Apply adhesive A onto a medical PET film to form an adhesive layer of approximately 50 μm, then cover with another PET film. After bonding, it will be fully cured by irradiation with UV light (365nm, 500mJ / cm²) for 5 seconds. Example

[0028] Formulation: 40 parts of acrylate copolymer (Mw≈800,000), 20 parts of hydrogenated rosin glycerol ester, 25 parts of n-butyl-2-cyanoacrylate monomer (reactive diluent monomer), 2 parts of nano silver powder (50nm), 8 parts of silk fibroin (bioactivity enhancer), 1 part of TMO, and 0.5 parts of vitamin E (antioxidant). Preparation method is as described in Example 1. Example

[0029] Formulation: 40 parts acrylate copolymer (Mw≈1000,000), 20 parts hydrogenated rosin glycerol ester, 25 parts cyanoacrylate monomer (reactive diluent monomer), 2 parts silver nanoparticles (50nm), 8 parts chitosan (bioactivity enhancer), 1 part 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator), and 0.5 parts vitamin E (antioxidant). Preparation method is as described in Example 1. Example

[0030] Formulation: 40 parts acrylate copolymer (Mw≈1,000,000), 20 parts hydrogenated rosin glycerol ester, 25 parts n-butyl-2-cyanoacrylate monomer (reactive diluent monomer), 2 parts silver nanoparticles (50nm), 8 parts silk fibroin (bioactivity enhancer), 1 part TMO, and 0.5 parts vitamin E (antioxidant). Preparation method is as described in Example 1.

[0031] Comparative Example 1: Formulation: 40 parts acrylate copolymer (Mw≈1000,000), 20 parts hydrogenated rosin glycerol ester, 25 parts cyanoacrylate monomer (reactive diluent monomer), 2 parts silver nanoparticles (50nm), 8 parts 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator), 1 part vitamin E (antioxidant). Preparation method as in Example 1. Chitosan (bioactivity enhancer) is not included to compare biocompatibility.

[0032] Comparative Example 2: Formulation: 40 parts acrylate copolymer (Mw≈1,000,000), 25 parts n-butyl-2-cyanoacrylate monomer (reactive diluent monomer), 2 parts silver nanoparticles (50nm), 1 part TMO, and 0.5 parts vitamin E (antioxidant). Preparation method is as described in Example 1. It does not contain silk fibroin, to compare the adhesive strength of the adhesive on pigskin.

[0033] Comparative Example 3: The mixture consisted of 40 parts of acrylate copolymer (Mw≈800,000), 20 parts of hydrogenated rosin glycerol ester, 25 parts of n-butyl-2-cyanoacrylate monomer (reactive diluent monomer), 8 parts of silk fibroin (bioactivity enhancer), 1 part of TMO, and 0.5 parts of vitamin E (antioxidant). The preparation method was as described in Example 1. Silver powder was not included to compare antibacterial properties.

[0034] Comparative Example 4: The mixture consisted of 40 parts of acrylate copolymer (Mw≈800,000), 20 parts of hydrogenated rosin glycerol ester, 25 parts of n-butyl-2-cyanoacrylate monomer (reactive diluent monomer), 8 parts of silk fibroin (bioactivity enhancer), 1 part of CQ, and 0.5 parts of vitamin E (antioxidant). The preparation method was as described in Example 1. The initiator was varied to compare the photoinitiation effect.

[0035] 7. Performance Testing: 180° peel strength test, sweat and blood interfacial adhesion stability test (PET substrate immersed in simulated sweat for 72 hours), cytotoxicity test (MTT method, ISO 10993-5), and pigskin adhesion test.

[0036] The performance test results of the examples and comparative examples show that the adhesive of the examples, after being soaked in simulated sweat, exhibits a peel strength attenuation rate of ≤15%, which is significantly better than that of the comparative examples. The effect of the adhesive on mouse fibroblasts was detected using the MTT assay. The cell viability of the examples was ≥70%, and the adhesion strength to pigskin was greater than or equal to 25 kPa, indicating that the medical adhesive provided by this invention has excellent biocompatibility and adhesion.

Claims

1. A highly biocompatible adhesive for use in medical products, characterized in that, By weight, it includes the following components: Oligomers: 30-50 parts; Biocompatible tackifying resin: 10-30 parts; Reactive dilution monomer: 15-35 parts; Nano silver powder: 0.5-5 parts; Solvent: 100-200 parts; Bioactivity enhancer: 5-15 parts; Photoinitiator: 0.5-2 parts.

2. The highly biocompatible adhesive according to claim 1, characterized in that, The oligomer is an acrylate copolymer, which is copolymerized from monomers including isooctyl acrylate, acrylic acid, hydroxyethyl methacrylate, and vinyl acetate, and has a weight-average molecular weight of 500,000-1,500,000.

3. The highly biocompatible adhesive according to claim 1, characterized in that, The biocompatible tackifying resin is selected from at least one of hydrogenated rosin glycerol ester, hydrogenated petroleum resin, terpene resin, and polyisobutylene.

4. The highly biocompatible adhesive according to claim 1, characterized in that, The bioactivity enhancer is at least one of chitosan and its derivatives, hyaluronic acid, collagen, hydroxyapatite, and silk fibroin.

5. The highly biocompatible adhesive according to claim 1, characterized in that, The solvent is at least one of ethyl acetate, ethanol, acetone, and deionized water.

6. The highly biocompatible adhesive according to any one of claims 1-5, characterized in that, The adhesive also contains 0.1-2 parts of an antioxidant.

7. A method for preparing a highly biocompatible adhesive as described in any one of claims 1-6, characterized in that, Includes the following steps: (1) Premixing: At a water bath temperature of 60°C, the oligomer, biocompatible tackifying resin and part of the solvent are added to a flask and stirred to dissolve, so as to obtain a uniform premixed adhesive solution. (2) Addition of active substances and nano silver powder: The nano silver powder is ball-milled to 40-50nm, dissolved with the bioactive enhancer in the remaining solvent, and slowly added to the premixed adhesive obtained in step (1) under stirring, keeping the temperature at 35-50℃, and mixed evenly. (3) Initiator addition: Add the photoinitiator to the mixture obtained in step (2) and stir continuously for 1-3 hours; (4) Post-processing: After stirring, cool to room temperature and filter to obtain the highly biocompatible adhesive.

8. The preparation method according to claim 7, characterized in that, In step (2), the bioactivity enhancer is added in the form of a solution with a mass fraction of 1-5%, and the addition rate is controlled at 1-5% of the total mass per minute.