CN111249538B

CN111249538B - Medical polyurethane composite membrane and application thereof

Info

Publication number: CN111249538B
Application number: CN202010182678.1A
Authority: CN
Inventors: 邢玥; 朱沛宁; 王广; 杨闯; 郭子源; 张依帆; 邓鹏飏
Original assignee: Jilin University
Current assignee: Jilin University
Priority date: 2020-03-16
Filing date: 2020-03-16
Publication date: 2022-04-19
Anticipated expiration: 2040-03-16
Also published as: CN111249538A

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 plays a role in protection and isolation. The medical polyurethane composite film is made into a bag, a jacket, a sheath and other products, and is 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

Medical polyurethane composite membrane 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.

On one hand, the metal material generates corrosion action under the immersion of effusion, so that the infection is worsened, the implantation operation fails, and on the other hand, cell sap, blood and the like penetrate into the device to pollute circuit elements, influence the normal work of implantation equipment and endanger the life safety of patients.

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 layer, a supporting layer and an antibacterial bonding layer.

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

Wherein the antibacterial adhesive layer is a polydopamine layer.

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

Further, the polyurethane layer is bonded with the support layer through the polydopamine layer.

Further, the polyurethane layer also comprises a dopamine modified polyurethane layer.

Further, the polyurethane layer comprises a polydopamine structure.

Secondly, the invention 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 uniformly distributing the 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 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; drying at room temperature after coating, and drying at 40-60 ℃ to obtain the required polyurethane composite film.

Further, the polyurethane emulsion is polyurethane emulsion, or dopamine modified polyurethane emulsion, or the polyurethane emulsion and the dopamine modified polyurethane emulsion are used together.

Further, step 2) is to coat the dopamine modified polyurethane emulsion on one surface of the composite membrane A, and then coat the polyurethane emulsion on the dopamine modified polyurethane layer. Further improve the barrier effect of the composite film and prolong the service life.

Further, selecting one surface of the composite membrane A in the step 2), uniformly coating the dopamine modified polyurethane emulsion on the surface, wherein the dip-coating time is 10-30s, and the dip-coating operation is repeated for 2-4 times, and the interval time is 20s each time; drying at room temperature after coating, and drying at 40-60 ℃ to obtain the required polyurethane composite film. The polyurethane emulsion is dopamine modified polyurethane.

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

adding diisocyanate and dihydric alcohol into a reactor according to a certain proportion, and adding a proper amount of solvent, wherein the molar ratio of the diisocyanate to the dihydric alcohol is (1.2-1.5):1, the reaction temperature is 60-80 ℃, and the reaction lasts for 2-4 h. Adding a chain extender, wherein the molar ratio of the chain extender to the dihydric alcohol is (0.2-0.5):1, reacting for 3-4h, adding a neutralizing agent, stirring for 0.5h, and adding triethylamine and dopamine, wherein the molar ratio of the dopamine to the diisocyanate is (0.2-1):1, and the molar ratio of the triethylamine to the dopamine is 1: (1-1.2). Stirring for 2-4 hours, and carrying out vacuum degassing treatment to obtain the dopamine modified polyurethane emulsion.

Further, the solvent is selected from one of tetrahydrofuran, dimethyl sulfoxide and acetone.

Further, the polymer dihydric alcohol is one or more of polyethylene glycol, polycaprolactone glycol, polypropylene glycol and polybutylene glycol with the molecular weight of 600-2000-.

Further, the diisocyanate is one or more of Hexamethylene Diisocyanate (HDI), Lysine Diisocyanate (LDI), isophorone diisocyanate (IPDI) and dicyclohexylmethane diisocyanate (HMDI).

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-sodium sulfonate, triethylene glycol, neopentyl glycol (NPG), sorbitol, Diethylaminoethanol (DEAE), N-dihydroxy (diisopropyl) aniline (HPA).

The invention secondly provides an application of the polyurethane composite film in a packaging material for implanted medical instruments, and the specific method comprises the following steps: the polyurethane composite film is used for wrapping medical instruments, wherein the polyurethane layer on the inner surface is in contact with the surface of the medical instrument, and the outer surface is a bonding layer. The adhesive layer on the external surface is contacted with human tissue after being implanted into 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 method has the advantages of milder reaction conditions, simpler operation, convenience, suitability for large-scale production and obvious cost advantage. 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 side of the medical liquid bag contacting with the human body has the functions of adhesion and antibiosis, and reduces infection risk while effectively preventing the liquid from flowing out. The dopamine layer on the other side is directly used as a bonding layer to adhere other functional layers, so that the bonding degree between the functional layers is improved, the working procedures are reduced, and the production efficiency is improved.

4. Through the modification of polyurethane layer resin, dopamine-like structures are added in molecules, the cohesion of a polyurethane layer is improved, the leveling and compacting degrees of the polyurethane layer are further improved, the blocking effect of the polyurethane layer is improved, and meanwhile the combination degree of polyurethane and other layers can also be improved.

Drawings

FIG. 1 is a schematic structural diagram of a medical polyurethane composite membrane according to the present invention.

In the figure, 1 is a polyurethane layer, 2 is a support layer, and 3 is an adhesive layer.

The specific implementation mode is as follows:

example 1

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 dopamine composite polyurethane composite film A.

Example 2

Preparing the aqueous polyurethane emulsion: 60.00g of polyethylene glycol (molecular weight 2000) is weighed into a reactor, 6.96g of hexamethylene diisocyanate and 300ml of tetrahydrofuran solvent are added into the reactor, and the mixture is mechanically stirred under the protection of nitrogen and reacted for 30min at 70 ℃. 1.5g dimethylolpropionic acid was added and reacted at 80 ℃ for 24 h. 1.2g triethylamine was added at 35 ℃ and a stirring speed of 1000rpm for 0.5 h. Adding the reactants into high-purity deionized water, stirring at high speed of 3000rpm for emulsifying for 0.5h, and concentrating the reaction product under reduced pressure until the solid content is 20%. Thus obtaining the aqueous polyurethane emulsion 1.

Example 3

Preparing a modified waterborne polyurethane emulsion: 60.00g of polyethylene glycol (molecular weight 2000) is weighed into a reactor, 6.96g of hexamethylene diisocyanate and 300ml of tetrahydrofuran solvent are added into the reactor, and the mixture is mechanically stirred under the protection of nitrogen and reacted for 30min at 70 ℃. 1.5g dimethylolpropionic acid was added and reacted at 80 ℃ for 24 h. 1.2g triethylamine was added at 35 ℃ and a stirring speed of 1000rpm for 0.5 h. 2.08g of triethylamine were added, the stirring speed was 1000rpm, 3.79g of dopamine hydrochloride was added, and stirring was continued for 2 hours. Adding the reactants into high-purity deionized water, stirring at high speed of 3000rpm for emulsifying for 0.5h, and concentrating the reaction product under reduced pressure until the solid content is 20%. To obtain the modified waterborne polyurethane emulsion 2.

Example 4

Preparing a modified waterborne polyurethane emulsion: 20.00g of polypropylene glycol (molecular weight 600) was weighed into a reactor, 9.78g of isophorone diisocyanate and 300ml of tetrahydrofuran solvent were added to the reactor, and the mixture was mechanically stirred under nitrogen protection and reacted at 70 ℃ for 30 min. 1.63g of dimethylolbutyric acid was added and reacted at 80 ℃ for 24 hours. 1.15g triethylamine was added at 35 ℃ and a stirring speed of 1000rpm for 0.5 h. 0.89g of triethylamine was added, the stirring speed was 1000rpm, 1.67g of dopamine hydrochloride was added, and stirring was continued for 2 hours. Adding the reactants into high-purity deionized water, stirring at high speed of 3000rpm for emulsifying for 0.5h, and concentrating the reaction product under reduced pressure until the solid content is 20%. To obtain the modified waterborne polyurethane emulsion 3.

Example 5

Preparing a modified waterborne polyurethane emulsion: 30.00g of polycaprolactone (molecular weight 1000) is weighed into a reactor, 10.40g of dicyclohexylmethane diisocyanate and 300ml of tetrahydrofuran solvent are added into the reactor, and the mixture is mechanically stirred under the protection of nitrogen and reacted for 30min at 70 ℃. 1.34g dimethylolpropionic acid was added and reacted at 80 ℃ for 24 h. 1.01g of triethylamine was added at a temperature of 35 ℃ and a stirring speed of 1000rpm for 0.5 h. 1.78g of triethylamine was added thereto, the stirring speed was 1000rpm, 3.04g of dopamine hydrochloride was added thereto, and the stirring was continued for 2 hours. Adding the reactants into high-purity deionized water, stirring at high speed of 3000rpm for emulsifying for 0.5h, and concentrating the reaction product under reduced pressure until the solid content is 20%. To obtain the modified waterborne polyurethane emulsion 4.

Example 6

Uniformly coating the aqueous polyurethane emulsion 1 on one surface of the dopamine 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 at 60 ℃ to obtain the polyurethane composite film 1.

Example 7

Uniformly coating the aqueous polyurethane emulsion 2 on one surface of the dopamine composite polyurethane composite membrane A, wherein the dip-coating time is 20s, and repeating the dip-coating operation for 2 times, wherein the interval time is 20s each time; standing at room temperature for 30s after coating; coating the water-borne polyurethane emulsion 1 on the surface coated with the water-borne polyurethane emulsion 2, wherein the dip-coating time is 30s, 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 at 60 ℃ to obtain the required polyurethane composite membrane 2.

Example 8

Uniformly coating the aqueous polyurethane emulsion 3 on one surface of the dopamine composite polyurethane composite membrane A, wherein the dip-coating time is 30s, and the dip-coating operation is repeated for 3 times, and the interval time is 20s each time; standing at room temperature for 30s after coating; coating the water-borne polyurethane emulsion 1 on the surface coated with the water-borne polyurethane emulsion 3, wherein the dip-coating time is 20s, and the dip-coating operation is repeated for 3 times, and the interval time is 20s each time; and drying at room temperature after coating, and drying at 40-60 ℃ to obtain the required polyurethane composite membrane 3.

Example 9

Uniformly coating the aqueous polyurethane emulsion 4 on one surface of the dopamine composite polyurethane composite membrane A, wherein the dip-coating time is 30s, and the dip-coating operation is repeated for 3 times, and the interval time is 20s each time; standing at room temperature for 30s after coating; coating the water-borne polyurethane emulsion 1 on the surface coated with the water-borne polyurethane emulsion 4, wherein the dip-coating time is 30s, 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 at 50 ℃ to obtain the required polyurethane composite film 4.

Example 10

Uniformly coating the aqueous polyurethane emulsion 3 on one surface of the dopamine composite polyurethane composite membrane A, wherein the dip-coating time is 30s, and the dip-coating operation is repeated for 3 times, and the interval time is 20s each time; and drying at room temperature after coating, and drying at 60 ℃ to obtain the required polyurethane composite film 5.

Claims

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

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

wherein the antibacterial bonding layer is a polydopamine layer;

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

2. The medical polyurethane composite film of claim 1, wherein said polyurethane layer is bonded to said support layer by a polydopamine layer.

3. A medical polyurethane composite film according to claim 1, wherein said polyurethane layer comprises a dopamine modified polyurethane layer.

4. A medical polyurethane composite film according to claim 1, wherein said polyurethane layer comprises a polydopamine structure.

5. A preparation method of a medical polyurethane composite film 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 polyurethane emulsion on one surface of the composite membrane A to obtain a required polyurethane composite membrane;

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;

step 2) firstly coating dopamine modified polyurethane emulsion on one surface of the composite membrane A, and then coating polyurethane emulsion on the dopamine modified polyurethane layer;

the preparation method of the dopamine modified polyurethane emulsion comprises the following steps:

adding diisocyanate and dihydric alcohol into a reactor according to a certain proportion, and adding a proper amount of solvent, wherein the molar ratio of the diisocyanate to the dihydric alcohol is (1.2-1.5) to 1, the reaction temperature is 60-80 ℃, and the reaction time is 2-4 h; adding a chain extender, wherein the molar ratio of the chain extender to the dihydric alcohol is (0.2-0.5):1, reacting for 3-4h, adding a neutralizing agent, stirring for 0.5h, adding triethylamine and dopamine, stirring for 2-4h, and carrying out reduced pressure degassing treatment to obtain a dopamine modified polyurethane emulsion;

wherein the molar ratio of dopamine to diisocyanate is (0.2-1) to 1, and the molar ratio of triethylamine to dopamine is 1 (1-1.2).

6. Use of the medical polyurethane composite film according to any one of claims 1 to 4 for implanting a medical device coating material.