CN107929819B

CN107929819B - Medical metal surface hydrophilic coating and preparation method thereof

Info

Publication number: CN107929819B
Application number: CN201711181454.3A
Authority: CN
Inventors: 张效凯; 成正辉; 林建国; 颜世平; 张德闯
Original assignee: APT MEDICAL Inc; Xiangtan University
Current assignee: APT MEDICAL Inc; Xiangtan University
Priority date: 2017-11-23
Filing date: 2017-11-23
Publication date: 2020-07-03
Anticipated expiration: 2037-11-23
Also published as: CN107929819A

Abstract

The invention provides a medical metal surface hydrophilic coating, which comprises the following components: a polymeric elastic precoat disposed on said metal surface; a hydrophilic cross-linked layer disposed on a surface of the polymer elastic precoat layer; the hydrophilic crosslinking layer is formed by a hydrophilic polymer, a binder and a crosslinking agent; the binder is a polymer that is reactive with the hydrophilic polymer and the crosslinker. Compared with the prior art, the polymer elastic precoating layer is arranged on the surface of the metal, so that the metal elastic precoating layer has excellent ultrathin elasticity and bonding performance, and can effectively ensure that the hydrophilic coating does not fall off or tear and does not influence the original flexibility of the metal when the metal is bent; meanwhile, the lubricating degree and the binding power of the hydrophilic crosslinking layer can be adjusted by adjusting the proportion of the hydrophilic polymer and the crosslinking agent in the hydrophilic crosslinking layer, and the adhesive is added in the hydrophilic crosslinking layer to form a crosslinking network with the hydrophilic polymer, so that the amount of the hydrophilic polymer dissolved in water or blood is reduced, and the durability of the hydrophilic coating is improved.

Description

Medical metal surface hydrophilic coating and preparation method thereof

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a medical metal surface hydrophilic coating and a preparation method thereof.

Background

The endovascular intervention diagnosis and treatment technology is widely applied to the aspects of clinical angiography, angioplasty, removal of thrombus or foreign matters in blood vessels and the like, compared with the traditional medical technology, the endovascular intervention diagnosis and treatment technology is convenient to operate, and can relieve the pain of patients due to low trauma of interventional therapy, has small treatment risk and relatively low treatment cost, so that the technology is widely popularized and applied in the medical field. The medical instruments adopted in the current interventional therapy operation are mainly class III medical instruments, and mainly comprise medical interventional polymer materials, medical interventional metal wires and medical interventional metal guide wire spring materials. The medical intervention high polymer material composed of the medical intervention inorganic non-metal material and the medical intervention composite material has the characteristics of low rigidity, good trafficability and the like, and the medical intervention metal wire has the characteristics of high strength, good fatigue property, good toughness, excellent processability and the like.

The medical intervention metal guide wire spring acts in a human body, and in the process of implantation or intervention in the human body, the medical intervention metal guide wire spring is usually in direct contact friction reaction with organs or tissues of the human body, such as blood vessels and the like, so that the performance requirement on the medical intervention metal guide wire spring is high, besides the raw materials and the processing and forming method of the medical intervention metal guide wire spring, the surface state of the biomedical intervention alloy, such as biocompatibility, such as anti-dissolving blood coagulation property, antibacterial property and the like, and the surface hydrophilicity and hydrophobicity are very important, and the reaction of the human body to the implanted or intervened biomedical intervention metal guide wire spring, such as mechanical injury, infection and inflammation and the like caused by friction is related. Therefore, it is necessary to lubricate the surface of the metal wire spring for medical intervention.

The hydrophilic coating is an effective means for improving the surface lubricity of the metal guide wire for medical intervention. The hydrophilic coating is utilized to lubricate the surface of the medical intervention metal guide wire spring, and when the surface of the spring is in contact with human tissues, a complex physical and chemical action is generated, so that the friction effect in the insertion process can be effectively reduced. The coating needs to meet high hydrophilic lubricating performance, and needs to pay attention to firmness and stability of the lubricating performance, the coating does not fall off after repeated friction and is not torn after repeated bending of the spring, and the coating cannot influence the flexibility of the spring.

At present, a plurality of patents are related to hydrophilic coatings, but the hydrophilic coatings are mainly applied to the surfaces of high molecular polymers, such as U.S. Pat. Nos. US6042876, US4875287, US5509899, US5331027 and US5620738, which disclose a hydrophilic coating containing polyvinylpyrrolidone (PVP), wherein the coating is divided into two layers, but because no cross-linking structure is introduced into the two layers of the coating, the hydrophilic coating prepared by the method is easy to fall off after water absorption and expansion, and the firmness of the coating is poor. Also, for example, U.S. Pat. nos. US4666437, US5179174, US8287890B2, US6299980B1 and US5160790 disclose a coating layer incorporating a crosslinking agent, which is isocyanate as a base coating layer, wherein the top coating layer contains hydrophilic polymers such as PVP or polyethylene oxide (PEO), and polyols or polyamines which can react with the crosslinking agent, but since the hydrophilic polymers do not participate in the crosslinking reaction in the system, the hydrophilic polymers are still easily released from the coating matrix by friction after water absorption and expansion. Also, for example, U.S. Pat. nos. US8513320B2, US7534495B2, US 8039524B2, US 7696259B2, US8378011B2, and US 8512795B2 all disclose a coating formed by ultraviolet curing, which comprises a double bond compound and a hydrophilic polymer, and is uniformly coated on the surface of an instrument under the mixing action of a solvent, and then ultraviolet curing is performed to obtain a crosslinked structure, but the coating still has the problem of poor durability after swelling due to water absorption.

Zhao Lei in his doctor's thesis "preparation and relevant research of novel hydrophilic coating coronary artery stent" has set forth the method for preparing hydrophilic coating on the surface of metal stent, use and hydroxylate on the surface of stainless steel, then carry on the silanization treatment, react with different silane coupling agents, thus form the silane derivative material combining different hydrophilic groups on the surface of coronary artery stent, but the hydrophilic coating can't form the complete gel water film in the case of water, can't reach good lubricating effect.

Chinese patent publication No. CN106634389A discloses a method for preparing a hydrophilic coating on the surface of an aluminum foil, but the method is used for the surface of an aluminum foil of an air-conditioning heat exchange fin, is not biomedical, has limited lubricity when meeting water, and cannot meet the use requirements of interventional products. Chinese patents CN107213530A and CN107158484A both disclose a method for preparing a hydrophilic antibacterial coating on the surface of a stainless steel medical device, which solves the problem that the surface of the current medical device is easy to breed bacteria, resulting in secondary infection at the implanted part, but the coating does not use a cross-linking agent or a sub-cross-linking agent, and the binding force between the simple hydrophilic polymer and the surface of the device is limited, so that good durability and smoothness of the coating cannot be provided.

In conclusion, the current hydrophilic coating at home is mainly applied to the surface of a polymer macromolecule, cannot be well applied to the surface of a medical intervention metal material, and particularly is not ideal in flexibility, durability, smoothness and tear resistance when the hydrophilic coating is prepared on the surface of a medical intervention metal guide wire spring.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a hydrophilic coating on a medical metal surface and a preparation method thereof, wherein the hydrophilic coating has good flexibility, durability and smoothness.

The invention provides a medical metal surface hydrophilic coating, which comprises the following components:

a polymeric elastic precoat disposed on said metal surface;

a hydrophilic cross-linked layer disposed on a surface of the polymer elastic precoat layer; the hydrophilic crosslinking layer is formed by a hydrophilic polymer, a binder and a crosslinking agent; the binder is a polymer that is reactive with the hydrophilic polymer and the crosslinker.

Preferably, the thickness of the polymer elastic precoat layer is 0.005-0.01 mm.

Preferably, the polymeric elastic pre-coat layer is formed from one or more of parylene, phosphorylcholine polymer and poly-n-butyl methacrylate.

Preferably, the thickness of the hydrophilic crosslinking layer is 0.005-0.01 mm.

Preferably, the hydrophilic polymer is selected from one or more of polypropylene oxide, polyether vinyl alcohol, polyether ethyl acetate, polyvinyl pyrrolidone, polyethylene oxide, carboxymethyl chitosan, polyvinyl alcohol, polyethylene oxide and polyethylene glycol.

Preferably, the binder is a polyurethane and/or a derivative thereof.

Preferably, the crosslinking agent is selected from one or more of carbodiimide, aziridine, epoxy crosslinking agent, polyisocyanate and siloxane crosslinking agent.

Preferably, the mass ratio of the hydrophilic polymer to the cross-linking agent is (10-100): 1.

preferably, the mass ratio of the hydrophilic polymer to the binder is (10-100): 1.

The invention also provides a preparation method of the medical metal surface hydrophilic coating, which comprises the following steps:

s1) coating the elastic polymer solution on the metal surface, drying and curing to form a polymer elastic precoat;

s2) coating the hydrophilic cross-linked layer solution on the surface of the polymer elastic precoat, and drying and curing to form a hydrophilic cross-linked layer; the hydrophilic cross-linking layer solution comprises a hydrophilic polymer, a binder and a cross-linking agent; the binder is a polymer that is reactive with the hydrophilic polymer and the crosslinker.

Drawings

FIG. 1 is a schematic structural diagram of a medical metal surface hydrophilic coating provided by the present invention;

FIG. 2 is a photograph of a medical intervention metal guide wire lubrication durability test device;

FIG. 3 is a photograph of a test sample;

fig. 4 is a photograph of a sample compliance test.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

a polymeric elastic precoat disposed on said metal surface;

Referring to fig. 1, fig. 1 is a schematic structural diagram of a medical metal surface hydrophilic coating provided by the present invention, wherein 1 is a metal, 2 is a hydrophilic polymer, 3 is an adhesive, 4 is a cross-linking agent, and 5 is a polymer elastic precoat.

The metal is not particularly limited as long as it is a metal used for medical devices, which is well known to those skilled in the art, and a medical intervention metal guide wire is preferable in the present invention.

The medical metal surface hydrophilic coating provided by the invention comprises a polymer elastic precoat layer arranged on the metal surface; the thickness of the polymer elastic precoat layer is preferably 0.005-0.01 mm; the polymeric elastic precoat layer is formed of a polymer having elastic properties, which is well known to those skilled in the art, without particular limitation; in the present invention, the polymeric elastic precoat is preferably formed from one or more of parylene, phosphorylcholine polymer, and poly-n-butyl methacrylate.

The surface of the polymer elastic precoat layer is provided with a hydrophilic crosslinking layer; the thickness of the hydrophilic crosslinking layer is preferably 0.005-0.01 mm; the hydrophilic crosslinking layer is formed by a hydrophilic polymer, a binder and a crosslinking agent; the hydrophilic polymer is not particularly limited as long as it is a hydrophilic polymer known to those skilled in the art, and in the present invention, one or more of polypropylene oxide, polyether vinyl alcohol, polyether ethyl acetate, polyvinyl pyrrolidone, polyethylene oxide, carboxymethyl chitosan, polyvinyl alcohol, polyethylene oxide, and polyethylene glycol are preferable; the crosslinking agent is a crosslinking agent well known to those skilled in the art, and is not particularly limited, and in the present invention, one or more of carbodiimide, aziridine, epoxy crosslinking agent, polyisocyanate, and siloxane crosslinking agent are preferable; the binder is a polymer which is well known to those skilled in the art to be reactive with the hydrophilic polymer and the crosslinking agent, and is not particularly limited, and in the present invention, a polymer containing amino groups and carboxyl groups is preferable, and polyurethane and/or a polyurethane derivative is more preferable; the mass ratio of the hydrophilic polymer to the cross-linking agent is preferably (10-100): 1; in some embodiments provided herein, the mass ratio of the hydrophilic polymer to the crosslinking agent is preferably 10: 1; in some embodiments provided herein, the mass ratio of the hydrophilic polymer to the crosslinking agent is preferably 80: 1; in some embodiments provided herein, the mass ratio of the hydrophilic polymer to the crosslinking agent is preferably 20: 1; in other embodiments provided herein, the mass ratio of the hydrophilic polymer to the crosslinking agent is preferably 100: 1. the mass ratio of the hydrophilic polymer to the adhesive is preferably (10-100): 1, more preferably (20 to 80): 1, and preferably (30-50): 1, and preferably (30-40): 1, most preferably 30: 1. The degree of lubrication and the bonding force of the hydrophilic crosslinked layer can be adjusted by adjusting the ratio of the hydrophilic polymer, the crosslinking agent and the binder in the present invention.

According to the invention, the polymer elastic precoating layer is arranged on the metal surface, so that the metal elastic precoating layer has excellent ultrathin elasticity and bonding property, and the hydrophilic coating layer can be effectively ensured not to fall off or tear and influence the original flexibility of the metal when the metal is bent; meanwhile, the lubricating degree and the binding power of the hydrophilic crosslinking layer can be adjusted by adjusting the proportion of the hydrophilic polymer and the crosslinking agent in the hydrophilic crosslinking layer, and the adhesive is added in the hydrophilic crosslinking layer to form a crosslinking network with the hydrophilic polymer, so that the amount of the hydrophilic polymer dissolved in water or blood is reduced, and the durability of the hydrophilic coating is improved.

The invention also provides a preparation method of the medical metal surface hydrophilic coating, which comprises the following steps: s1) coating the elastic polymer solution on the metal surface, drying and curing to form a polymer elastic precoat; s2) coating the hydrophilic cross-linked layer solution on the surface of the polymer elastic precoat, and drying and curing to form a hydrophilic cross-linked layer; the hydrophilic cross-linking layer solution comprises a hydrophilic polymer, a binder and a cross-linking agent; the binder is a polymer that is reactive with the hydrophilic polymer and the crosslinker.

In the present invention, the sources of all raw materials are not particularly limited, and they may be commercially available.

The polymeric elastic precoat and the hydrophilic coating are as described above and will not be described in detail herein.

Coating the elastic polymer solution on the metal surface, drying and curing to form a polymer elastic precoat; the concentration of the solvent in the elastic polymer solution is preferably 0.005-0.5 g/ml, more preferably 0.01-0.5 g/ml, still more preferably 0.05-0.3 g/ml, and most preferably 0.05-0.1 g/ml; the solvent in the elastic polymer solution is not particularly limited, but is preferably one or more selected from acetone, ethyl acetate, chloroform, toluene, xylene, Dimethylformamide (DMF) and Tetrahydrofuran (THF); the coating method is a method well known to those skilled in the art, and is not particularly limited, and dip coating, spray coating or painting is preferred in the present invention; the drying and curing temperature is preferably 50-150 ℃, more preferably 60-130 ℃, and further preferably 90-120 ℃; the drying and curing time is preferably 10min to 2 hours, more preferably 0.5 to 2 hours, and still more preferably 1 to 2 hours.

Coating the hydrophilic cross-linked layer solution on the surface of the polymer elastic precoat, and drying and curing to form a hydrophilic cross-linked layer; the hydrophilic cross-linking layer solution comprises a hydrophilic polymer, a binder and a cross-linking agent; the adhesive is a polymer that can react with a hydrophilic polymer and a cross-linking agent; the hydrophilic polymer, binder and cross-linking agent are the same as described above and will not be described herein. In the present invention, the hydrophilic crosslinked layer solution is preferably prepared according to the following steps: preparing a binder solution; and then adding the adhesive solution into the solution of the hydrophilic compound, finally adding the cross-linking agent, and uniformly stirring to obtain the hydrophilic cross-linked layer solution. The concentration of the adhesive in the adhesive solution is preferably 5-30 wt%; the solvent in the binder solution is not particularly limited, but is preferably one or more selected from acetone, ethyl acetate, chloroform, toluene, xylene, Dimethylformamide (DMF) and Tetrahydrofuran (THF); the concentration of the hydrophilic polymer in the hydrophilic polymer solution is preferably 2-10 wt%; the solvent in the hydrophilic polymer solution is not particularly limited as long as it is well known to those skilled in the art, and in the present invention, one or more of ethyl acetate, diacetone alcohol, dimethylformamide, methyl ethyl ketone and glycerol are preferable. The coating method is a method known to those skilled in the art, and is not particularly limited, and dip coating, spray coating or painting is preferred in the present invention; the drying and curing temperature is preferably 50-150 ℃, more preferably 60-130 ℃, and further preferably 60-100 ℃; the drying and curing time is preferably 10min to 2h, more preferably 10min to 60min, and still more preferably 30min to 60 min.

According to the invention, the steps of coating the hydrophilic cross-linking layer solution and drying and curing can be repeated according to the requirement of the smoothness of the hydrophilic coating on the surface of the medical metal.

The preparation method of the medical metal surface hydrophilic coating provided by the invention is simple to operate and low in cost, and the prepared hydrophilic coating has lasting lubricity, good biocompatibility, good flexibility and excellent tear resistance.

In order to further illustrate the present invention, the following will describe a medical metal surface hydrophilic coating and a preparation method thereof in detail with reference to the following examples.

The reagents used in the following examples are all commercially available.

Example 1

1.1 preparing an ethyl acetate elastic polymer solution with the content of poly-n-butyl methacrylate of 0.1 g/ml.

1.2 uniformly coating the elastic polymer solution in the step 1.1 on the surface of a medical intervention metal guide wire spring in a spraying mode, drying for 2h at 90 ℃, and curing to form a polymer elastic precoat (the thickness is 0.005 mm).

1.3 preparation of a polyurethane solution with a solute content of 5% by weight as a sub-binder (solvent is tetrahydrofuran).

1.4, adding the polyurethane solution into a polyvinylpyrrolidone solution (3 wt%, the solvent is ethyl acetate and diacetone alcohol, the mass ratio of polyvinylpyrrolidone to polyurethane is 30:1), stirring for 1h, adding a carbodiimide crosslinking agent (the mass ratio of polyvinylpyrrolidone to carbodiimide crosslinking agent is 10:1), and stirring for 2h to obtain a hydrophilic crosslinked layer A solution.

1.5 uniformly coating the hydrophilic coating A solution obtained in the step 1.4 on the surface of the polymer elastic precoat, and drying and curing at the high temperature of 60 ℃ for 30min to form a first hydrophilic crosslinked layer (the thickness is 0.005 mm).

The following steps can be continued as required:

1.6 changing the mass ratio of the polyvinylpyrrolidone solution to the carbodiimide crosslinking agent in the step 1.4 to 80:1, and stirring for 1h to form a hydrophilic crosslinked layer B solution.

1.7 uniformly coating the hydrophilic crosslinked layer B solution obtained in the step 1.6 on the surface of the first hydrophilic crosslinked layer obtained in the step 1.5, and drying and curing at a high temperature of 60 ℃ for 30min to form a second hydrophilic crosslinked layer (the thickness is 0.005 mm).

The experimental result shows that the lubricity of the surface of the medical intervention metal guide wire spring coated with the hydrophilic coating prepared according to the steps is improved by 75%, the coating has good durability, the bent coating of the spring is not torn or shed, and the coating has no influence on the flexibility of the spring.

The method for testing the lubrication durability of the medical intervention metal guide wire comprises the following steps:

the test equipment comprises a constant temperature water tank, a digital display dynamometer and a friction force test tool, wherein a sheath pipe joint is fixed in the water tank, a test sample is a 0.025' metal guide wire, the test sample is fixed on the digital display dynamometer by a clamp, the sample and the friction force test tool are kept on the same horizontal line, the speed of the dynamometer is adjusted to be 300mm/min, the test distance is +/-50 mm, the digital display dynamometer returns to zero before each test, each sample slides back and forth for 50 times, the tension value before each tension coating is recorded to be 24.5g, the tension of the 1 st test is 5.6g, the tension of the 50 th test is 6.5g, the friction force difference between the 50 th test and the 1 st test is very small, and the coating has good durability; the average tensile value after formation of the first hydrophilic coating was 8.2g and the average tensile value after formation of the second hydrophilic coating was 6.1 g.

FIG. 2 is a photograph of a medical intervention metal guide wire lubrication durability test device; fig. 3 is a photograph of a test sample, and fig. 4 is a photograph of a sample compliance test.

Example 2

2.1A toluene elastomeric polymer solution having a parylene content of 0.05g/ml was prepared.

2.2 the elastic polymer solution in the step 2.1 is evenly coated on the surface of the medical intervention metal guide wire spring in a dip-coating mode, dried for 1h at 120 ℃, and cured to form a polymer elastic precoat (with the thickness of 0.005 mm).

2.3 preparation of a polyurethane solution with a solute content of 30% by weight as a sub-binder (solvent dimethylformamide).

2.4 adding the polyurethane solution into a polyethylene glycol solution (with the concentration of 5 wt% and the solvent of diacetone alcohol and butanone; the mass ratio of the polyethylene glycol to the polyurethane is 30:1) with hydrophilic groups, stirring for 1h, adding an isophorone diisocyanate crosslinking agent (with the mass ratio of the polyethylene glycol to the isophorone diisocyanate crosslinking agent being 20:1), and stirring for 0.5h to obtain a hydrophilic crosslinking layer A solution.

2.5 uniformly coating the hydrophilic crosslinked layer A solution obtained in the step 2.4 on the surface of the polymer elastic precoat, and drying and curing at the high temperature of 60 ℃ for 30min to form a first hydrophilic crosslinked layer (the thickness is 0.005 mm).

The following steps can be continued as required:

2.6 changing the mass ratio of the polyethylene glycol solution to the isophorone diisocyanate crosslinking agent in the step 2.5 to be 100:1, and stirring for 0.5h to form a hydrophilic crosslinking layer B solution.

2.7 uniformly coating the solution B of the hydrophilic coating in the step 2.6 on the surface of the first hydrophilic coating after the step 2.5, and drying and curing at the high temperature of 60 ℃ for 30min to form a second hydrophilic crosslinked layer (the thickness is 0.005 mm).

The test method is the same as that of the first embodiment, and the experimental result shows that the lubricity of the metal surface coated with the hydrophilic coating prepared according to the steps is improved by 79%, the coating has good durability, the bent coating of the spring is not torn or shed, and the coating has no influence on the flexibility of the spring: the test specimen was bent at the tip end to the specified position before the elastic precoat, with a tip holding force of 0.331g, 0.338g after the elastic precoat, and 0.351g after the second hydrophilic crosslinked layer was provided.

Claims

1. A medical metal surface hydrophilic coating, comprising:

a polymeric elastic precoat disposed on said metal surface; the polymer elastic precoat layer is formed by one or more of parylene, phosphorylcholine polymer and poly n-butyl methacrylate;

a hydrophilic cross-linked layer disposed on a surface of the polymer elastic precoat layer; the hydrophilic crosslinking layer is formed by hydrophilic polymer, adhesive and crosslinking agent in solvent;

the hydrophilic polymer is selected from one or more of polypropylene oxide, polyether vinyl alcohol, polyether ethyl acetate, polyvinylpyrrolidone, polyethylene oxide, carboxymethyl chitosan, polyvinyl alcohol, polyethylene oxide and polyethylene glycol;

the adhesive is polyurethane and/or a derivative thereof;

the cross-linking agent is selected from one or more of carbodiimide, aziridine, epoxy cross-linking agent and polyisocyanate;

the thickness of the polymer elastic precoat layer is 0.005-0.01 mm;

the mass ratio of the hydrophilic polymer to the cross-linking agent is (10-100): 1;

the mass ratio of the hydrophilic polymer to the adhesive is (10-100): 1;

the solvent is selected from one or more of acetone, ethyl acetate, chloroform, toluene, xylene, dimethylformamide and tetrahydrofuran.

2. The medical metal surface hydrophilic coating according to claim 1, wherein the thickness of the hydrophilic crosslinked layer is 0.005-0.01 mm.

3. A method for preparing the hydrophilic coating on the surface of the medical metal according to claim 1, which comprises the following steps:

s2) coating the hydrophilic cross-linked layer solution on the surface of the polymer elastic precoat, and drying and curing to form a hydrophilic cross-linked layer; the hydrophilic cross-linking layer solution comprises a hydrophilic polymer, a binder and a cross-linking agent; the adhesive is a polymer that can react with a hydrophilic polymer and a cross-linking agent; the solvent in the hydrophilic crosslinking layer solution is selected from one or more of acetone, ethyl acetate, chloroform, toluene, xylene, dimethylformamide and tetrahydrofuran.