CN111228580A - Multilayer polyurethane composite film 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 plays a role in protection and isolation. The multilayer 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, and the relative sliding is reduced through the elastic layer, so that the stimulation to the human body is further reduced, the growth of bacteria is inhibited, and the infection probability is reduced.

Description

Multilayer polyurethane composite film 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 material which can be made into products such as bags, envelopes, sheaths and the like, and the products are coated outside an implanted medical apparatus device to prevent the implanted equipment from directly contacting human tissues, reduce the stimulation to the human body, reduce the infection probability, prevent the pollution and the corrosion of the implanted apparatus, and reduce the risk and the pain of a patient caused by the instability of the implanted apparatus.

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, a polyurethane elastic layer and a bonding layer; or sequentially comprises a polyurethane antibacterial layer, a polyurethane elastic layer, a supporting layer and a bonding layer.

Wherein the bonding layer is a polydopamine layer.

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

And a polydopamine layer can be arranged between the polyurethane antibacterial layer and the supporting layer, or between the polyurethane antibacterial layer and the polyurethane elastic layer.

The polyurethane antibacterial layer, the supporting layer, the polyurethane elastic layer and the bonding layer are connected through bonding, coating and branching crosslinking methods.

Further, the polyurethane antibacterial layer is coated on the support layer or is adhered to the support layer through the polydopamine layer.

Further, the polyurethane antibacterial layer contains an antibacterial agent.

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 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%.

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

1) bonding the polyurethane elastic layer with the supporting layer by using a polyurethane adhesive to obtain a polyurethane elastic layer composite film A;

2) preparing a dopamine composite polyurethane elastic layer composite membrane A,

preparing a dopamine buffer solution; and immersing the composite membrane A in a dopamine buffer solution to prepare a composite membrane B with two sides attached with polydopamine.

3) Polyurethane layer composition

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

Further, the step 1) of preparing the polyurethane elastic layer comprises the following steps:

injecting preheated and melted polymer polyol, diisocyanate, a catalyst and an antioxidant into a reaction kettle according to a proportion, stirring for 2-4 hours, adding a chain extender, curing at the temperature of 110-.

Further, injecting preheated and melted polymer polyol, diisocyanate and a chain extender into a reactor according to a proportion, uniformly mixing, adding the chain extender, stirring for 2-4 hours at 60-90 ℃, extruding, curing and granulating at 110-130 ℃ to obtain a thermoplastic polyurethane elastomer material, blending and modifying the thermoplastic polyurethane elastomer material according to needs, and extruding into a film to obtain the polyurethane elastic layer.

Further, 44-79 parts by mass of polymer polyol, 16-33 parts by mass of diisocyanate, 4-7.8 parts by mass of chain extender, 0.2-0.6 part by mass of antioxidant and 0.02-0.04 part by mass of catalyst.

Further, 3-15 parts by mass of a modifier can be added.

Further, the polyalcohol is one or more of polytetramethylene ether glycol, polytetrahydrofuran glycol, polyethylene glycol adipate glycol and polycarbonate glycol; the relative molecular weight of the polyol is 1000-4000.

Further, the diisocyanate compound is selected from one or more of toluene diisocyanate, 4 '-diphenylmethane diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, dimethyl diphenyl diisocyanate, 1, 5-naphthalene diisocyanate, p-phenylene diisocyanate and 4,4' -dicyclohexylmethane diisocyanate;

further, the chain extender is one or more selected from dihydric alcohol selected from 1, 4-butanediol, ethylene glycol, 1, 3-propanediol, 2-methyl-1, 3-propanediol, 2, 3-butanediol, 1, 5-pentanediol, 3-methyl-1, 5-pentanediol, 2-ethyl-1, 3-hexanediol and N-methyldiethanolamine.

Further, the catalyst is an organic tin catalyst, preferably one or more of stannous octoate, dibutyltin diacetate, dibutyltin dilaurate and dibutyltin bis (dodecyl sulfur).

Further, the antioxidant comprises a main antioxidant and an auxiliary oxidant, wherein the main antioxidant is a hindered phenol antioxidant or an aromatic secondary amine antioxidant, and the auxiliary catalyst is a thioester antioxidant or a phosphite antioxidant, 2, 6-di-tert-butyl-4-methylphenol, pentaerythritol tetrakis [ β - (3, 5-di-tert-butyl-4-hydroxyphenyl) propionate ] and octadecyl 3, 5-di-tert-butyl-4-hydroxyphenylpropionate.

Further, in the preparation method of the dopamine buffer solution in the step 2), 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 2) 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 3) is uniformly distributed on the surface of the polydopamine layer on one side, close to the support layer, of the composite film.

Further, the antibacterial polyurethane emulsion in the step 3) 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 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 10-30 wt% of nano silver and 0-20 wt% 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. Cooling and concentrating to obtain the antibacterial polyurethane emulsion.

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).

Further, a catalyst in an amount of 0.1 to 2 wt% based on the weight of the polyurethane may be added, and the catalyst is selected from stannous octoate, dibutyltin dilaurate, Triethylenediamine (TEDA), N-dimethylethanolamine, triethylamine, trimethylbenzylamine, dimethylethanolamine, and 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.

Further, the preparation of the antibacterial agent mixture comprises the following steps:

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 solution or suspension.

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 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 composite membrane 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. The risk of infection is reduced by the antimicrobial polyurethane layer. Alkaline substances are added in the bacteriostatic agent, and the synergistic anti-infection and antibacterial effects are realized by adjusting the pH value of the microenvironment.

5. The polyurethane elastic layer can effectively absorb the relative slippage energy of the implanted device, thereby reducing the slippage damage to human tissues and reducing the possibility of secondary damage.

Drawings

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

in the figure, 1 is an antibacterial polyurethane layer, 2 is a polydopamine bonding layer, 3 is a support layer, and 4 is a polyurethane elastic 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, mechanical stirring is carried out 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.

Example 5

Fully stirring preheated and melted 70 parts by mass of polytetramethylene ether glycol (with the molecular weight of 3000), slowly adding preheated and melted 30 parts by mass of hexamethylene diisocyanate, adding 15 parts by mass of 1, 4-butanediol, fully mixing, heating to 70 ℃, and stirring for 1 hour. Slowly heating to 110 ℃, and stirring for 5 h. Film extrusion to obtain the polyurethane elastomer layer.

Examples 6 to 9

And (3) bonding the supporting layer and the polyurethane elastomer layer by using a polyurethane adhesive, and drying at 70 ℃. A first intermediate composite film is obtained.

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; and soaking the first intermediate composite membrane in a dopamine buffer solution for 4 hours, taking out, washing with deionized water, and drying in a 50 ℃ oven. A second intermediate composite film is obtained.

Uniformly coating the antibacterial polyurethane emulsion 1-4 on a polydopamine layer on one side, close to a support layer, of a second intermediate composite film, 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 corresponding polyurethane composite membrane.

Claims (8)

1. A multilayer polyurethane composite film characterized by: sequentially comprises a polyurethane antibacterial layer, a supporting layer, a polyurethane elastic layer and a bonding layer; or sequentially comprises a polyurethane antibacterial layer, a polyurethane elastic layer, a supporting layer and a bonding layer;

wherein the bonding layer is a polydopamine layer;

the polyurethane antibacterial layer, the supporting layer, the polyurethane elastic layer and the bonding layer are connected through bonding, coating and branching crosslinking methods.

2. The multilayer polyurethane composite film of claim 1, wherein: the supporting layer is selected from one of a polypropylene base film and a polyurethane base film.

3. The multilayer polyurethane composite film of claim 1, wherein: a polydopamine layer can be arranged between the polyurethane antibacterial layer and the supporting layer, or a polydopamine layer can be arranged between the polyurethane antibacterial layer and the polyurethane elastic layer.

4. The multilayer polyurethane composite film of claim 1, wherein: the polyurethane antibacterial layer contains an antibacterial agent, wherein 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.

5. A preparation method of a multilayer polyurethane composite film is characterized by comprising the following steps: the method comprises the following steps:

1) bonding the polyurethane elastic layer with the supporting layer by using a polyurethane adhesive to obtain a polyurethane elastic layer composite film A;

2) preparing a dopamine composite polyurethane elastic layer composite membrane A,

preparing a dopamine buffer solution; immersing the composite membrane A in a dopamine buffer solution to prepare a composite membrane B with two sides attached with polydopamine;

3) polyurethane layer composition

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

6. A method of preparing a multilayer polyurethane composite film according to claim 5, wherein: 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 diol is (1.2-1.5) 1; reacting for 2-4h at the temperature of 60-90 ℃; 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.

7. A method of preparing a multilayer polyurethane composite film according to claim 6, wherein: the antibacterial agent is added in a mixture form, and the preparation method of the mixture comprises the following steps:

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 solution or suspension.

8. Use of the multilayer polyurethane composite film according to claims 1-4 for implanting medical device packaging material.

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