CN111298204B - Polyurethane composite film containing antibacterial layer and application thereof - Google Patents

Abstract

The invention belongs to the field of medical multilayer film materials, and particularly relates to a composite material which is wrapped outside a medical apparatus in an implant and has a protection and isolation effect. The antibacterial layer-containing polyurethane composite film is made into a bag, a sleeve, a sheath and other products, and the bag, the sleeve, the sheath and other products are coated outside an implanted medical apparatus device, so that the pollution and corrosion of the implanted apparatus device are prevented, and the risk and pain of a patient caused by the instability of the implanted apparatus device are reduced. Meanwhile, the direct contact between the implanted equipment and human tissues is prevented, the stimulation to the human body is reduced, the growth of bacteria is inhibited, and the infection occurrence probability is reduced.

Description

Polyurethane composite film containing antibacterial layer and application thereof

Technical Field

The invention belongs to the field of medical multilayer film materials, and particularly relates to a composite material which is wrapped outside a medical apparatus in an implant and plays a role in protection and isolation.

Background

The active implantable medical devices comprise cardiac pacemakers, cardioverter defibrillators, neurostimulators, spinal cord electrical stimulators, cardiac resynchronization therapy defibrillators, cardiac resynchronization therapy pacemakers and the like. The active implantable medical device is made of titanium alloy material.

Complications may occur in some patients during the implantation procedure. The more common complication is local infection, which is caused by hematemesis of embedded bursa cavity after implantation, inflammation infection or abscess.

Infection after the implantation operation is a complex process, the implantation instrument is corroded under the soaking of effusion, and corroded materials can further stimulate the human body to generate liquid; the bacterial growth environment is acidic, bacterial infection stimulates generation of more liquid, and a large amount of acidic liquid accelerates corrosion and deterioration of an implantation instrument. Liquid, especially acidic liquid and the like seeps into the device to pollute circuit elements and influence the normal work of the implantation instrument, so that the implantation operation fails and the life safety of a patient is threatened.

The common solution is to treat the surface of metal to increase the coating layer, so as to prevent the metal from contacting with human tissue and inhibit infection. The preparation method of the coating comprises the following steps of firstly carrying out surface treatment, and utilizing a mechanical method (turning, sand blasting and laser treatment), chemical treatment (acid and alkali etching), heat treatment or ion etching to enable the surface to be combined with a modified substance more easily; then the treated titanium and titanium alloy surfaces are soaked in a solution containing the medicine, so that the medicine or a carrier containing the medicine is grafted to the material surface. The method can also coat bacteriostatic material on the metal surface to further improve the anti-infection effect. However, this method has the agreed problem that the active implantation instrument has many material structures, more complex structures, irregular shapes including electronic units. The common physical and chemical surface treatment method can destroy important structural units and core functions of the instrument. The relatively mild treatment method is adopted, the preparation method is complex, the condition requirement is strict, the process cost is high, and the large-scale industrial production is difficult.

Aiming at the defects of the prior art, the invention provides a multilayer composite film which is made into products such as a bag, a jacket, a sheath and the like, and the products are coated outside an implanted medical apparatus device, so that the implanted equipment is prevented from being directly contacted with human tissues, the stimulation to the human body is reduced, and the infection occurrence rate is reduced. Meanwhile, the pollution and corrosion of the implantation instrument are prevented, and the risk and pain of the patient caused by the instability of the implantation instrument are reduced.

The invention content is as follows:

in order to solve the technical problems, the invention firstly provides a polyurethane composite film, which sequentially comprises a polyurethane antibacterial layer, a supporting layer and a bonding layer.

The polyurethane antibacterial layer, the supporting layer and the bonding layer can be connected with each other by bonding, coating, branching and crosslinking methods.

Wherein, the supporting layer is selected from one of polypropylene base film and polyurethane base film.

Wherein the bonding layer is a polydopamine layer.

Further, the polyurethane antibacterial layer is bonded with the supporting layer through the polydopamine layer.

Further, the polyurethane antibacterial layer contains polyurethane modified with an antibacterial agent.

Further, the modification method comprises blending, copolymerization and grafting methods.

Further, the antibacterial agent is one or more of chitosan, nano silver ions, nano zinc oxide, nano copper oxide, zirconium oxide, copper nitrate, zinc nitrate, ammonium dihydrogen phosphate or calcium carbonate.

Further, the amount of the antibacterial agent is 5 to 10 wt% of the polyurethane resin.

Further, the antibacterial agent contains 20-90wt% of calcium carbonate.

Further, the antibacterial agent comprises 10-40wt% of nano silver and 0-40wt% of nano zinc oxide.

The invention secondly provides a preparation method of the polyurethane composite film, which comprises the following specific contents:

1) the polydopamine layer is compounded with the supporting layer

Preparing a dopamine buffer solution; and immersing the support layer in a dopamine buffer solution to prepare the composite membrane A with poly-dopamine attached to two sides.

2) Polyurethane layer composition

And (3) uniformly distributing the antibacterial polyurethane emulsion on one surface of the composite film A to obtain the required polyurethane composite film.

Further, in the preparation method of the dopamine buffer solution in the step 1), firstly, the preparation concentration is as follows: adjusting the pH value to 8.0-8.6 with 8-12mmol/L Tris-HCl buffer solution, and adding dopamine with the concentration of 0.5-1.6 mg/mL.

Further, the supporting layer in the step 1) is immersed in a dopamine buffer solution, immersed for 4 hours at normal temperature and taken out, washed by deionized water, and dried in an oven at 40-60 ℃.

Further, the antibacterial polyurethane emulsion in the step 2) adopts a coating method, the dip-coating time is 10-30s, the dip-coating operation is repeated for 2-4 times, and the interval time is 20s each time; and drying at room temperature after coating, and drying to obtain the required polyurethane composite membrane.

Further, the antibacterial polyurethane emulsion contains one or more of chitosan, nano silver, nano zinc oxide, nano copper oxide, zirconium oxide, copper nitrate, zinc nitrate, ammonium dihydrogen phosphate or calcium carbonate as an antibacterial agent.

Further, the amount of the antibacterial agent added is 5 to 10 wt% of the polyurethane resin.

Further, the antibacterial agent is a mixture of calcium carbonate and other antibacterial agents. Preferably, the calcium carbonate content of the antimicrobial agent is from 20 to 90 wt%.

Further, the antibacterial agent comprises 10-40wt% of nano silver and 0-40wt% of nano zinc oxide.

Further, the preparation of the antibacterial polyurethane emulsion comprises the following steps:

adding the dehydrated diisocyanate and the dehydrated dihydric alcohol into a reactor according to a proportion, and adding a proper amount of solvent. Wherein the molar ratio of diisocyanate to diol is (1.2-1.5) 1; the temperature is 60-90 ℃, and the reaction lasts 2-4 h.

Adding an antibacterial agent under the condition of full stirring; adding chain extender, the mol ratio of the chain extender to the dihydric alcohol is (0.1-0.5):1, the temperature is 60-90 ℃, and reacting for 2-4 h. And cooling and concentrating to obtain the antibacterial polyurethane material.

Further, the solvent is selected from one of acetone, N-Dimethylformamide (DMF) and tetrahydrofuran.

Furthermore, the polyether diol mainly selects polytetramethylene glycol and polypropylene glycol, and the polyethylene glycol is preferably diol with the relative molecular weight of 600-2000.

Further, the isocyanate is mainly selected from aliphatic isocyanates, and the following can be selected: isophorone diisocyanate (IPDI), dicyclohexylmethane diisocyanate (HMDI), hexamethylene diisocyanate (HMDI), Lysine Diisocyanate (LDI).

Furthermore, catalysts in an amount of 0.1 to 2 wt.% based on the theoretical mass of the polyurethane can be added, the catalysts being selected from stannous octoate, dibutyltin dilaurate, Triethylenediamine (TEDA), N-dimethylethanolamine, triethylamine, trimethylbenzylamine, dimethylethanolamine, morpholine.

Further, the chain extender is selected from: 1, 4-Butanediol (BDO), 1, 6-hexanediol, 2-dimethylolpropionic acid (DMPA), 2-dimethylolbutyric acid (DMBA), diethylene glycol (DEG), Isophoronediamine (IPDA), 1, 4-butanediol-2-sulfonic acid sodium salt, triethylene glycol, neopentyl glycol (NPG), sorbitol, Diethylaminoethanol (DEAE), N-dihydroxy (diisopropyl) aniline (HPA).

Further, the antibacterial agent may be added directly, or may be added in the form of a mixture such as a solution, emulsion or suspension.

Wherein, chitosan, copper nitrate, zinc nitrate, ammonium dihydrogen phosphate or calcium carbonate can be directly added.

Further, the preparation of the antimicrobial solution or suspension comprises the steps of:

under the condition of high-speed stirring, adding 5-10 parts by mass of silane coupling agent into 100 parts by mass of solvent, adding 10-20 parts by mass of inorganic antibacterial agent particles or powder in batches, and violently stirring for 1-3 hours to obtain an antibacterial agent mixture.

Further, the silane coupling agent is selected from one of gamma-aminopropyl triethoxysilane, gamma- (methacryloyloxy) propyl triethoxysilane, gamma-mercaptopropyl triethoxysilane, or gamma-mercaptopropyl triethoxysilane.

Further, the solvent is selected from one of acetone, N-Dimethylformamide (DMF) and tetrahydrofuran.

The invention secondly provides an application of the polyurethane composite film in implanting medical appliances, which specifically comprises the following steps: the polyurethane composite film is used for wrapping and implanting medical instruments, wherein the polydopamine layer on the inner surface is adhered to the surface of the medical instrument, and the antibacterial polyurethane layer is arranged on the outer surface. The antibacterial polyurethane layer on the external surface is contacted with human tissue after being implanted in the body.

Compared with the prior art, the invention has the beneficial effects that:

1. utilize the polyurethane complex film can effectively protect implantation medical instrument, the human body fluid infiltration of polyurethane layer separation prevents to implant medical instrument and is corroded by internal material, increase of service life, reduces the risk because of the instrument is malfunctioning brings for the patient.

2. Compared with coating and film plating processes, the reaction conditions are milder, the operation is simpler and more convenient, the method is suitable for large-scale production, and the cost advantage is obvious. The adoption of the polymer film material is more beneficial to modification processing and improvement of the overall performance of the device.

3. Two poly dopamine layers are formed on the supporting layer through a one-step method, so that the operation steps are reduced. The poly-dopamine adhesive is utilized to moderately adhere to the surface of the device and simultaneously has the function of inhibiting bacteria on the surface of the device. The binding force between the layers is improved by utilizing the affinity of polydopamine and high polymer materials.

4. Through the modification of the polyurethane layer resin, the antibacterial property is increased in the polyurethane layer, and the infection risk is reduced. The antibacterial agent is added with alkaline substances, and the synergistic antibacterial and anti-infection effects are realized by adjusting the pH value of the microenvironment.

Drawings

FIG. 1 is a schematic view of a composite membrane according to an embodiment of the present invention;

in fig. 1, 1 is an antibacterial polyurethane layer, 2 is a support layer, and 3 is an adhesive layer.

The specific implementation mode is as follows:

example 1

Under the protection of nitrogen, 200g of acetone is added with 5g of gamma-aminopropyltriethoxysilane under high-speed stirring, 5g of nano-silver is respectively added, and the mixture is stirred for 10 min.

Preparation of polyurethane emulsion: 60.00g of polytetramethylene glycol (molecular weight 2000) is weighed into a reactor, 5.30g of hexamethylene diisocyanate and 200ml of acetone solvent are added into the reactor, the mixture is mechanically stirred for 30min under the protection of nitrogen, 1g of dibutyltin dilaurate is added, and the temperature is raised to 90 ℃ for reaction for 2 h. Adding 0.77g of 1, 6-hexanediol, adding 60g of the nano silver-acetone mixed solution for three times, and reacting for 20 hours at the temperature of 80 ℃. At a temperature of 35 ℃ 4.1g of calcium carbonate were added with a stirring speed of 2000rpm for 1 h. The stirring speed is 1000rpm, the solid content is controlled according to the requirement, and partial acetone is removed under the reduced pressure condition to obtain the polyurethane material 1.

Example 2

Under the protection of nitrogen, stirring at a high speed, adding 10g of gamma- (methacryloyloxy) propyl triethoxysilane into 200g of acetone, respectively adding 2g of nano silver, and stirring for 10 min; 4g of nano zinc oxide, and stirring for 10 min.

Preparation of polyurethane emulsion: weighing 50.00g of polypropylene glycol (molecular weight 800) into a reactor, adding 20.84g of isophorone diisocyanate and 200ml of acetone solvent into the reactor, mechanically stirring for 30min under the protection of nitrogen, adding 0.8g of stannous octoate, and heating to 90 ℃ for reaction for 4 h. Adding 100g of nano silver/nano zinc oxide acetone mixed solution for four times, adding 2.82g of 1, 4-butanediol, and reacting for 20 hours at 80 ℃. The reaction temperature was reduced to 35 ℃ and 4.1g of calcium carbonate was added with stirring at 1000rpm for 2 h. Controlling the solid content according to the requirement, and removing part of acetone under the reduced pressure condition to obtain the polyurethane material 2.

Example 3

Under the protection of nitrogen, stirring at a high speed, adding 8g of gamma- (methacryloyloxy) propyl triethoxysilane into 200g of acetone, respectively adding 1g of nano-silver, and stirring for 10 min; 2g of nano zinc oxide, and stirring for 10 min.

Preparation of polyurethane emulsion: 30.00g of polyethylene glycol (molecular weight 1000) is weighed into a reactor, 9.44g of dicyclohexylmethane diisocyanate and 200ml of acetone solvent are added into the reactor, mechanically stirred for 30min under the protection of nitrogen, 0.5g of stannous octoate is added, and the temperature is raised to 90 ℃ for reaction for 2 h. Adding 0.54g of 1, 4-butanediol, adding 90g of nano silver/nano zinc oxide acetone mixed solution for three times, and reacting for 20 hours at 80 ℃. The reaction temperature was reduced to 35 ℃ and 5g of calcium carbonate were added with stirring at 1000rpm for 2 h. Controlling the solid content according to the requirement, and removing part of acetone to obtain the antibacterial polyurethane material 3.

Example 4

Preparation of polyurethane emulsion: 30.00g of polyethylene glycol (molecular weight 1000) is weighed into a reactor, 9.44g of dicyclohexylmethane diisocyanate and 200ml of acetone solvent are added into the reactor, mechanically stirred for 30min under the protection of nitrogen, 0.5g of stannous octoate is added, and the temperature is raised to 90 ℃ for reaction for 2 h. 0.54g of 1, 4-butanediol and 1.5g of chitosan were added and reacted at 80 ℃ for 20 hours. The reaction temperature was reduced to 35 ℃ and 0.5g of calcium carbonate was added with stirring at 1000rpm for 2 h. Controlling the solid content according to the requirement, controlling the stirring speed to be 1000rpm, and removing part of acetone under the reduced pressure condition to obtain the antibacterial polyurethane material 4.

Examples 5 to 8

Preparing a composite membrane A by using a support membrane and dopamine: preparing a Tris-HCl buffer solution with the concentration of 8mmol/L, adjusting the pH value of the buffer solution to 8 by using hydrochloric acid with the concentration of 0.1mol/L, and then dissolving a dopamine monomer in the Tris-HCl buffer solution to obtain a dopamine buffer solution with the initial concentration of 1.2 mg/mL; soaking the polyurethane support membrane in dopamine buffer solution for 4h, taking out, washing with deionized water, and drying in a 50 ℃ oven. And obtaining the polydopamine composite polyurethane composite membrane A.

Uniformly coating the antibacterial polyurethane material 1-4 on one surface of the polydopamine composite polyurethane composite membrane A, wherein the dip-coating time is 10s, and the dip-coating operation is repeated for 4 times, and the interval time is 20s each time; and drying at room temperature after coating, and drying to obtain the corresponding polyurethane composite membrane.

Claims (5)

1. A polyurethane composite film containing an antibacterial layer is characterized in that: sequentially comprises a polyurethane antibacterial layer, a supporting layer and a bonding layer;

the polyurethane antibacterial layer, the supporting layer and the bonding layer can be connected with each other by bonding, coating and branching crosslinking methods;

wherein the bonding layer is a polydopamine layer;

the supporting layer is selected from one of a polypropylene base film and a polyurethane base film;

the polyurethane antibacterial layer comprises antibacterial agent modified polyurethane;

the antibacterial agent comprises 20-90wt% of calcium carbonate, 10-40wt% of nano silver and 0-40wt% of nano zinc oxide.

2. The polyurethane composite film comprising an antibacterial layer according to claim 1, wherein: the polyurethane antibacterial layer is bonded with the supporting layer through the polydopamine layer.

3. A preparation method of a polyurethane composite film containing an antibacterial layer is characterized by comprising the following steps: the method comprises the following steps:

1) the polydopamine layer is compounded with the supporting layer

Preparing a dopamine buffer solution: immersing the supporting layer in a dopamine buffer solution to prepare a composite membrane A with poly-dopamine attached to two sides;

2) polyurethane layer composition

Uniformly distributing the antibacterial polyurethane emulsion on one surface of the composite film A to obtain a required polyurethane composite film;

the specific operation of immersing the supporting layer in the dopamine buffer solution in the step 1) is as follows: soaking for 4h at normal temperature;

the preparation method of the antibacterial polyurethane emulsion comprises the following steps:

adding the dehydrated diisocyanate and the dehydrated dihydric alcohol into a reactor in proportion, and adding a proper amount of solvent; wherein the molar ratio of diisocyanate to dihydric alcohol is (1.2-1.5) to 1, the temperature is 60-90 ℃, and the reaction is carried out for 2-4 h;

adding an antibacterial agent under the condition of full stirring; adding a chain extender, wherein the molar ratio of the chain extender to the dihydric alcohol is (0.1-0.5) to 1, the temperature is 60-90 ℃, and reacting for 2-4 h; cooling and concentrating to obtain the antibacterial polyurethane emulsion.

4. A method of preparing a polyurethane composite film comprising an antimicrobial layer according to claim 3, wherein: the antibacterial agent is added in a mixture form, and the specific steps are as follows:

under the condition of high-speed stirring, adding 5-10 parts by mass of silane coupling agent into 100 parts by mass of solvent, adding 10-20 parts by mass of inorganic antibacterial agent particles or powder in batches, and violently stirring for 1-3 hours to obtain an antibacterial agent mixture.

5. Use of the polyurethane composite film comprising the antibacterial layer according to claim 1 or 2 in a packaging material for an implanted medical device.

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