CN106880876A - A kind of preparation method of the antimicrobial coating of Implantable Medical Device - Google Patents

Abstract

The invention provides a method for preparing an antibacterial coating of an implantable medical device, comprising the following steps: soaking the implantable medical device in a solution containing dopamine for treatment, taking it out and blowing it dry with nitrogen at room temperature for later use to obtain surface treatment The implanted medical device that has been processed; the mask is placed on the metal part of the surface-treated implanted medical device, and then the coating solution is sprayed on the surface of the implanted medical device; the mask is removed, and the The solvent is completely volatilized to obtain an implantable medical device with an antibacterial coating; wherein, the shape of the mask plate matches the shape of the metal parts of the implantable medical device, and holes are opened on the surface of the mask plate. The preparation method of the antibacterial coating of the implantable medical device provided by the present invention overcomes the limitation of coating treatment only on the surface of the titanium sheet in the prior art, and solves the problem of performing antimicrobial coating on the surface of the active implantable medical device with a complex structure. The problem with antimicrobial coating treatments.

Description

A kind of preparation method of the antibacterial coating of implantable medical device

technical field

The invention belongs to the field of medical equipment, and relates to a preparation method of an antibacterial coating of an implantable medical equipment.

Background technique

Implantable medical devices (IMD: implantable medical devices) are used in the human body to treat a large number of patients on the one hand, but at the same time there are some negative effects, the most typical being infection.

When a typical IMD such as a pacemaker is implanted, a pouch is created under the skin. Although the pacemaker will be packaged aseptically before implantation, and the implantation is also performed in a sterile environment, it is difficult to avoid the entry of microorganisms pouch. Therefore, preoperative doctors will use disinfectants or antibacterial agents (such as chlorhexidine, gluconate, iodophor, isopropanol, ethanol, etc.) on the skin of the surgical incision, and will directly use disinfection before the incision is closed Orally absorbed drugs (such as gentamicin, rifamycin, vancomycin, etc.) will be used to prevent infection during the recovery period after surgery , despite this, infections can still occur. According to statistics, after taking these measures, the incidence of clinical infection reaches 2%. Although the incidence of infection is low, once the pouch is infected, the infection will migrate along the electrodes or catheters to the heart, brain, spinal canal or other positions that electrodes or catheters can reach, which will aggravate the pain of the patient and bring harm to the family members. A huge economic burden, even life-threatening in severe cases. When infection occurs, even if antibiotic treatment is taken, the treatment effect is not obvious because biofilm has formed on the surface of the infected implanted device, which is difficult to be killed by antibiotics. Therefore, we should find ways to avoid the occurrence of infection in the early stage of implantation.

Local drug release is the most effective way to avoid infection. On the one hand, it can reduce the dosage of drugs and avoid drug toxicity to other tissues in non-lesional parts; It is widely concerned by developers in the field of medical devices. If antibacterial treatment can be carried out on the surface of the pacemaker, so that the pacemaker itself has an antibacterial effect after implantation, the probability of capsular bag infection can be reduced, thereby reducing treatment costs and patient pain.

Titanium is often used in existing medical devices, the most common of which are titanium implants (such as parts of bone, teeth, joints or other soft tissue implants) and some active implantable medical devices (including cardiac pacemaker, cardioverter defibrillator, nerve stimulator, spinal cord electrical stimulator, cardiac resynchronization therapy defibrillator, cardiac resynchronization therapy pacemaker, etc.). When the surface of these medical devices is antibacterially treated by the method of local drug release, the method of antibacterial coating modification is generally used.

There are many ways to modify the surface of titanium implants with antibacterial coatings. The first is to treat the surface of titanium metal to make it easier to combine with active substances. Surface treatment methods include mechanical methods, chemical treatments, heat treatments, and anodic oxidation methods. , micro-arc oxidation method, etc.; and then soaked in the coating solution containing the drug to attach or graft the drug and the drug carrier on the surface of the titanium metal. Compared with orthopedic implants, joint implants, dental implants, etc. made of titanium sheets or titanium-based materials, active implantable medical devices have the characteristics of complex structure, irregular shape, and many types of materials. Take a pacemaker as an example. The main material on the surface is a titanium shell and electrode wire connectors made of silicone and polyurethane. There are also complex circuits and various components inside. Therefore, the only way to modify the surface of a pacemaker with an antibacterial coating Mild surface treatment and coating methods to avoid damage to the important structural units and functions of the pacemaker.

Among the above-mentioned surface treatment methods for titanium implants, mechanical methods such as grinding and polishing will cause damage to the structure of the medical device itself, and are not suitable for active implantable medical devices that have been formed and assembled or can no longer be tested. Structurally processed implantable devices; although chemical treatment such as treatment in hot lye can effectively improve the activity of the metal surface, it is not suitable for active implantable medical devices that have already been formed and assembled, and there is damage to the internal circuit or The risk of corrosion of other plastic parts; heat treatment will also bring similar problems to chemical treatment; both anodizing and micro-arc oxidation methods require complex equipment and high processing costs.

In the prior art, when preparing antibacterial coatings for medical equipment, a method for inhibiting the growth of microorganisms on the surface of medical equipment using a composition is provided. The antibacterial composition is mainly composed of a polypeptide and a polyurea-silicone resin copolymer. binding to inhibit biofilm growth. The specific method is as follows: firstly, APTES (3-aminopropyltriethoxysilane) is used to coat the surface of the titanium sheet, and after curing, glucose oxidase is fixed on the surface of the titanium sheet with glutaraldehyde, and then polyurea dissolved in tetrahydrofuran is -Silicone polymer coated on the surface of the titanium sheet. However, the above scheme has the problem that the coating material cannot be degraded.

There are also many existing coating methods, such as dipping, spraying, rolling, brushing, etc. The bonding force of the coating will be the primary consideration, and dipping, rolling, and brushing are more suitable for regular shapes and substrates. Uniform material, coating onto a surface with a complex structure will result in uneven localized areas and the presence of hanging droplets. In addition, it is necessary to choose a suitable surface treatment method to make the coating better bond with the complex surface and improve the coating adhesion. Therefore, it is a great challenge to find a suitable method to treat the metal surface of active implantable medical devices.

Contents of the invention

The purpose of the present invention is to provide the preparation method of the antibacterial coating of implantable medical device, overcome the limitation that coating treatment is only carried out on the surface of titanium sheet in the prior art, solve the active implanted medical device surface with complex structure Problems with antimicrobial coating treatments.

In order to solve the above-mentioned technical problems, the invention provides a method for preparing an antibacterial coating of an implantable medical device, comprising the steps of:

S1: Soak the implantable medical device in a solution containing dopamine for treatment, take it out and dry it with nitrogen at room temperature for later use, and obtain a surface-treated implantable medical device;

S2: Put a mask on the surface-treated metal part of the implantable medical device, and then spray the coating solution on the surface of the implantable medical device;

S3: remove the mask, and wait until the solvent is completely volatilized to obtain an implantable medical device with an antibacterial coating;

Wherein, the shape of the mask plate matches the shape of the metal part of the implantable medical device, and holes are opened on the surface of the mask plate.

Optionally, the implantable medical device (IMD) may be a cardiac pacemaker, cardioverter defibrillator, nerve stimulator, spinal cord electrical stimulator, cardiac resynchronization therapy defibrillator or cardiac resynchronization therapy pacemaker etc.

Further, the solution containing dopamine is a Tris-HCl solution of dopamine. In the S1, the implantable medical device is soaked in a Tris-HCl solution of dopamine for 4-24 hours.

Optionally, in the Tris-HCl solution of dopamine, the concentration of dopamine is 0.02-0.05 mol/L, and the pH of the solution is 8.5.

Further, the mask plate is made of polydimethylsiloxane (PDMS).

Optionally, the shape of the hole is circular or polygonal, and the polygonal shape can be triangular, square, rhombus and/or pentagonal, the thickness of the mask plate is 0.1-2mm, and the porosity is 60%-90% , the pores are uniformly distributed.

Further, the coating solution is composed of medicine, polymer and solvent, the quality of the medicine accounts for 0.1%-3% of the mass of the coating solution, and the mass of the polymer accounts for 0.1%-3% of the mass of the coating solution. 1%-5%, the mass of the solvent accounts for 92%-98.9% of the mass of the coating solution.

Preferably, the coating solution in the S2 includes at least two kinds, namely a first coating solution and a second coating solution, and the first coating solution is composed of a drug, a polymer and a solvent; the The second coating solution includes at least a polymer and a solvent; the S2 specifically includes: placing a mask on the surface-treated metal part of the implantable medical device, and then respectively applying the first coating solution and the second coating solution are sequentially sprayed on the surface of the implantable medical device.

Further, in the first coating solution, the mass of the drug accounts for 0.1%-3% of the mass of the first coating solution, and the mass of the polymer accounts for 0.1%-3% of the mass of the first coating solution. 1%-5%, the mass of the solvent accounts for 92%-98.9% of the mass of the first coating solution.

Optionally, in the second coating solution, the second coating solution is composed of a polymer and a solvent, wherein the mass of the polymer accounts for 1%-5% of the mass of the second coating solution. %, the mass of the solvent accounts for 95%-99% of the mass of the second coating solution.

Optionally, the second coating solution is composed of a drug, a polymer and a solvent, wherein the drug accounts for 0.1%-3% of the second coating solution, and the polymer accounts for 1%-5% of the mass of the second coating solution, and the mass of the solvent accounts for 92%-98.9% of the mass of the second coating solution.

Optionally, the drug is selected from one or more combinations of analgesics, antibacterials, anti-inflammatory drugs and anesthetics.

Preferably, the analgesic is selected from one or more combinations of aspirin, ibuprofen, bupivacaine and celecoxib.

Preferably, the antibacterial agent is selected from rifampicin, minocycline, gentamicin, macrolide, penicillin, tetracycline, chloramphenicol, vancomycin, fusidic acid, trimethoprim , clindamycin, triclosan, chlorhexidine, cephalosporins, aztreonam, cefotetan, loracarbef, cefaclor, ceftizoxime, cefixime, cefazolin, cephalexin, One or more combinations of penicillin, neomycin and colistin, or one or more combinations selected from the salts of these compounds.

Preferably, the anti-inflammatory drug is selected from naproxen, tyroprofen, ibuprofen, diclofenac, celecoxib, sulindac, diflunisal, piroxicam, indomethacin, meloxicam , flurbiprofen, mefenamic acid, nabumetone, toluoyl pyridine acetic acid, ketorolac, choline magnesium, aspirin, salicylic acid and acetylsalicylate, or one or more combinations of One or more combinations of salts from these compounds.

Preferably, the anesthetic is selected from the group consisting of lidocaine, bupivacaine, carbocaine, paracetamol, clonine, benzodiazepine, flumazenil, carbamazepine, pethidine, zalidine One or more combinations of Pron, Trimethazine Maleate, Buprenorphine, Nalbuphine, Methadone, Hydromorphone, Hydrocodone, and Morphine.

Further, the polymer is selected from one of polyglutamic acid, polylysine, polyaspartic acid, polyethylene glycol, polylactic acid, polycaprolactone, polyglycolide and polycarbonate or multiple combinations, or one or more combinations selected from the copolymers of these compounds.

Further, the solvent is selected from water, ethanol, methanol, tetrahydrofuran, hexafluoroisopropanol, trifluoroethanol, trifluoroacetic acid, methylene chloride, chloroform, dimethylformamide, ethyl acetate and acetone one or more combinations of .

Optionally, in step S2, the coating solution is sprayed on the surface of the implantable medical device by means of electrostatic spraying, ultrasonic spraying or air spraying.

Further, the area of the antibacterial coating accounts for 60%-90% of the surface area of the implantable medical device, and the mass of the antibacterial coating accounts for 0.1% of the total mass of the implantable medical device containing the antibacterial coating. %-0.8%.

In the implantable medical device prepared by the preparation method provided by the invention, the bacteriostatic rate of the antibacterial coating to Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa reaches more than 98%, and the antibacterial coating has a The release time is 3-14 days.

Compared with prior art, the advantage of the preparation method of the antibacterial coating of implantable medical device provided by the present invention is:

1. The antibacterial coating has good coating adhesion to metal parts on the surface of implantable medical devices, silicone connectors or other plastic parts;

2. There are uncoated hole areas on the surface of the metal parts of implantable medical devices. On the one hand, it is conducive to the direct contact between the pacemaker and the tissue fluid, which is conducive to its normal work in the unipolar state; on the other hand, it increases The contact area between the drug and the tissue fluid can promote the degradation of the coating material and the release of the drug;

3. The preparation process provided by the present invention is simple, and the antibacterial coating on the surface of implantable medical devices can be realized with only simple operations, which is easy for large-scale production.

Description of drawings

Fig. 1 is a schematic structural view of the implantable medical device in the preparation method of the antibacterial coating of the implantable medical device provided by the embodiment of the present invention;

Fig. 2 is a schematic structural view of the surface-treated implantable medical device in the preparation method of the antibacterial coating of the implantable medical device provided by the embodiment of the present invention;

3 is a schematic structural view of the mask used in the method for preparing the antibacterial coating of the implantable medical device provided by the embodiment of the present invention;

4 is a schematic diagram of the overall structure after the mask is placed on the surface-treated metal part of the implantable medical device in the method for preparing the antibacterial coating of the implantable medical device provided by the embodiment of the present invention;

Fig. 5 is a schematic structural view of an implantable medical device containing an antibacterial coating obtained in the preparation method of the antibacterial coating of the implantable medical device provided by the embodiment of the present invention;

Fig. 6 is a flow chart of the preparation method of the antibacterial coating of the implantable medical device provided by the embodiment of the present invention.

Wherein, 1-implantable medical device; 2-implantable medical device with surface treatment; 3-mask; 4-antibacterial coating.

detailed description

The preparation method of the antibacterial coating of the implantable medical device proposed by the present invention will be further described in detail below in conjunction with the accompanying drawings and specific examples. Advantages and features of the present invention will be apparent from the following description and claims. It should be noted that all the drawings are in a very simplified form and use imprecise scales, and are only used to facilitate and clearly assist the purpose of illustrating the embodiments of the present invention.

Example 1

As shown in Fig. 1-Fig. 6, the present invention provides the preparation method of the antibacterial coating of implantable medical device, comprises the steps:

S1: Soak the implantable medical device 1 in a solution containing dopamine for treatment, take it out and dry it with nitrogen at room temperature for later use, and obtain a surface-treated implantable medical device 2;

S2: Put the mask plate 3 on the surface-treated metal part of the implantable medical device 2, and then spray the coating solution on the surface of the implantable medical device;

S3: remove the mask, wait until the solvent is completely volatilized, and obtain an implantable medical device containing an antibacterial coating 4;

Wherein, the shape of the mask 3 matches the shape of the metal part of the implantable medical device 1 , and holes are opened on the surface of the mask 3 . Preferably, the mask plate 3 is made of polydimethylsiloxane (PDMS).

In the above scheme, the implantable medical device (IMD) 1 can be a cardiac pacemaker, cardioverter defibrillator, nerve stimulator, spinal cord electrical stimulator, cardiac resynchronization therapy defibrillator or cardiac resynchronization therapy Treat pacemakers, etc.

Wherein, the solution containing dopamine is a Tris-HCl solution of dopamine, and in the S1, the implantable medical device 1 is soaked in the Tris-HCl solution of dopamine for 4-24 hours. In the Tris-HCl solution of dopamine, the pH value of the solution is 8.5, the concentration of dopamine is 0.02-0.05mol/L, preferably 0.02mol/L, and the implantable medical device is in the Tris-HCl solution of dopamine Soak for 4h.

Optionally, the shape of the hole on the surface of the mask 3 is circular or polygonal, and the polygon can be triangular, square, rhombus and/or pentagonal, and the porosity of the mask 3 is 60%-90%. , the pores are uniformly distributed. Preferably, the holes on the surface of the mask 3 are circular holes with a diameter of 2mm and a porosity of 60%, and the thickness of the mask 3 is 0.1-2mm.

Further, the coating solution is composed of medicine, polymer and solvent, the quality of the medicine accounts for 0.1%-3% of the mass of the coating solution, and the mass of the polymer accounts for 0.1%-3% of the mass of the coating solution. 1%-5%, the mass of the solvent accounts for 92%-98.9% of the mass of the coating solution.

Further, the coating solution in the S2 includes at least two kinds, namely a first coating solution and a second coating solution, and the first coating solution is composed of a drug, a polymer and a solvent; the The second coating solution includes at least a polymer and a solvent; the S2 specifically includes: placing the mask plate 3 on the surface-treated metal part of the implantable medical device 2, and then respectively applying the first coating The coating solution and the second coating solution are sequentially sprayed on the surface of the implantable medical device.

Wherein, in the first coating solution, the mass of the drug accounts for 0.1%-3% of the mass of the first coating solution, and the mass of the polymer accounts for 1% of the mass of the first coating solution. %-5%, the mass of the solvent accounts for 92%-98.9% of the mass of the first coating solution.

In the second coating solution, the second coating solution may be composed of a polymer and a solvent, wherein the mass of the polymer accounts for 1%-5% of the mass of the second coating solution, so The mass of the solvent accounts for 95%-99% of the mass of the second coating solution.

The second coating solution may also include medicine, consisting of medicine, polymer and solvent, wherein the quality of the medicine accounts for 0.1%-3% of the mass of the second coating solution, and the mass of the polymer Accounting for 1%-5% of the mass of the second coating solution, the mass of the solvent accounts for 92%-98.9% of the mass of the second coating solution.

In the above scheme, the drug is selected from one or more combinations of analgesics, antibacterials, anti-inflammatory drugs and anesthetics.

The analgesic is selected from one or more combinations of aspirin, ibuprofen, bupivacaine and celecoxib.

Described antibacterial agent is selected from rifampicin, minocycline, gentamicin, macrolide, penicillin, tetracycline, chloramphenicol, vancomycin, fusidic acid, trimethoprim, chlorin Comycin, triclosan, chlorhexidine, cephalosporin, aztreonam, cefotetan, clocarbef, cefaclor, ceftizoxime, cefixime, cefazolin, cephalexin, penicillin, new One or more combinations of mycin and colistin, or one or more combinations selected from the salts of these compounds.

The anti-inflammatory drug is selected from naproxen, tyroprofen, ibuprofen, diclofenac, celecoxib, sulindac, diflunisal, piroxicam, indomethacin, meloxicam, fluridine One or more combinations of profen, mefenamic acid, nabumetone, toluoylpyridine acetic acid, ketorolac, magnesium choline, aspirin, salicylic acid, and acetylsalicylate, or selected from these compounds One or more combinations of salts.

The anesthetic is selected from lidocaine, bupivacaine, carbocaine, paracetamol, clonine, benzodiazepine, flumazenil, carbamazepine, meperidine, zaleplon, One or more combinations of trimhydramine maleate, buprenorphine, nalbuphine, methadone, hydromorphone, hydrocodone, and morphine.

The polymer is selected from one or more of polyglutamic acid, polylysine, polyaspartic acid, polyethylene glycol, polylactic acid, polycaprolactone, polyglycolide and polycarbonate combination, or one or more combinations selected from the copolymers of these compounds.

The solvent is selected from one of water, ethanol, methanol, tetrahydrofuran, hexafluoroisopropanol, trifluoroethanol, trifluoroacetic acid, methylene chloride, chloroform, dimethylformamide, ethyl acetate and acetone or multiple combinations.

Preferably, in this embodiment, by mass percentage, the composition of the coating solution is: 0.1% drug, 1% polymer and 98.9% solvent.

Among them, the drug is preferably clindamycin; the polymer is preferably poly-D-lactic acid; the solvent is preferably a mixed solution of dichloromethane and dimethylformamide, and the amount of the two substances is 3:1.

In the above step S2, the coating solution is sprayed on the surface of the implantable medical device by means of electrostatic spraying, ultrasonic spraying or air spraying. In this embodiment, electrostatic spraying is preferred.

In the prepared IMD containing the antibacterial coating, the area of the antibacterial coating accounts for 60%-90% of the surface area of the implantable medical device, and the mass of the antibacterial coating accounts for 60%-90% of the surface area of the implant containing the antibacterial coating. 0.1%-0.8% of the total mass of the intrusive medical device, preferably 0.1%, and the drug release time in the antibacterial coating is 3 days.

Example 2

The preparation method of the antibacterial coating of the implantable medical device provided in this example is basically the same as that of Example 1, and only the differences will be described below.

In this embodiment, the solution containing dopamine in the step S1 is a Tris-HCl solution of dopamine, the pH value of the solution is 8.5, and the concentration of dopamine in the solution is 0.03mol/L. Soak in Tris-HCl solution of dopamine for 6h.

The mask in the step S2 is made of polydimethylsiloxane (PDMS). The holes on the surface of the mask are square holes with a size of 2mm×2mm and a porosity of 70%.

The coating solution is composed of medicine, polymer and solvent, and the components of the coating solution are: 1% of medicine, 2% of polymer and 97% of solvent in terms of mass percentage.

Among them, the drug is preferably rifampicin; the polymer is preferably a copolymer of lactic acid and glycolide; the solvent is preferably tetrahydrofuran.

In the step S2, the coating solution is sprayed on the surface of the implantable medical device by means of ultrasonic spraying.

In the prepared IMD containing the antibacterial coating, the mass of the antibacterial coating accounts for 0.3% of the total mass of the implantable medical device containing the antibacterial coating, and the drug release time in the antibacterial coating is 7 days.

Example 3

The preparation method of the antibacterial coating of the implantable medical device provided in this example is basically the same as that of Example 1, and only the differences will be described below.

In this embodiment, the solution containing dopamine in the step S1 is a Tris-HCl solution of dopamine, the pH value of the solution is 8.5, and the concentration of dopamine in the solution is 0.04mol/L. Soak in Tris-HCl solution of dopamine for 8h.

The mask in the step S2 is made of polydimethylsiloxane (PDMS), and the holes on the surface of the mask are circular holes with a diameter of 3mm and a porosity of 80%.

The coating solution is composed of medicine, polymer and solvent. According to mass percentage, the composition of the coating solution is: 3% of medicine, 5% of polymer and 92% of solvent.

Among them, the drug is preferably cephalosporin; the polymer is preferably polyethylene glycol-polylactic acid-polyglutamic acid triblock copolymer; the solvent is preferably methylene chloride.

In the step S2, the coating solution is sprayed on the surface of the implantable medical device by means of air spraying.

In the prepared IMD containing the antibacterial coating, the mass of the antibacterial coating accounts for 0.5% of the total mass of the implantable medical device containing the antibacterial coating, and the drug release time in the antibacterial coating is 9 days.

Example 4

The preparation method of the antibacterial coating of the implantable medical device provided in this example is basically the same as that of Example 1, and only the differences will be described below.

In this embodiment, the solution containing dopamine in the step S1 is a Tris-HCl solution of dopamine, the pH value of the solution is 8.5, and the concentration of dopamine in the solution is 0.04mol/L. Soak in Tris-HCl solution of dopamine for 8h.

The mask in the step S2 is made of polydimethylsiloxane (PDMS), and the holes on the surface of the mask are circular holes with a diameter of 3mm and a porosity of 80%.

The coating solution in the step S2 includes a first coating solution and a second coating solution.

The first coating solution is composed of medicine, polymer and solvent, and the components of the first coating solution are: 3% of medicine, 5% of polymer and 92% of solvent in terms of mass percentage. Among them, the drug is preferably cephalosporin; the polymer is preferably polyethylene glycol-polylactic acid-polyglutamic acid triblock copolymer; the solvent is preferably methylene chloride.

The second coating solution is composed of a polymer and a solvent, and the composition of the second coating solution is: 5% polymer and 95% solvent by mass percentage. Among them, the polymer is preferably polyglutamic acid; the solvent is preferably water.

In the step S2, the first coating solution and the second coating solution are sequentially sprayed on the surface of the implantable medical device by air spraying.

In the prepared IMD containing the antibacterial coating, the mass of the antibacterial coating accounts for 0.5% of the total mass of the implantable medical device containing the antibacterial coating, and the drug release time is 14 days.

Example 5

The preparation method of the antibacterial coating of the implantable medical device provided in this example is basically the same as that of Example 1, and only the differences will be described below.

In this embodiment, the solution containing dopamine in the step S1 is a Tris-HCl solution of dopamine, the pH value of the solution is 8.5, and the concentration of dopamine in the solution is 0.03mol/L. Soak in Tris-HCl solution of dopamine for 6h.

The mask plate in the step S2 is made of polydimethylsiloxane (PDMS), the holes on the surface of the mask plate are square holes, the size of the holes is 2mm×2mm, and the porosity is 70%.

The coating solution is composed of medicine, polymer and solvent, and the components of the coating solution are: 1% of medicine, 2% of polymer and 97% of solvent in terms of mass percentage.

Wherein, the drug is preferably a combination of rifampicin and minocycline (the mass ratio of the two is 1:1); the polymer is preferably a copolymer of lactic acid and glycolide; the solvent is preferably a mixed solution of tetrahydrofuran and methanol ( The volume ratio of the two is 9:1).

In the step S2, the coating solution is sprayed on the surface of the implantable medical device by means of air spraying.

In the prepared IMD containing the antibacterial coating, the mass of the antibacterial coating accounts for 0.6% of the total mass of the implantable medical device containing the antibacterial coating, and the drug release time is 12 days.

Example 6

The preparation method of the antibacterial coating of the implantable medical device provided in this example is basically the same as that of Example 1, and only the differences will be described below.

In this embodiment, the solution containing dopamine in the step S1 is a Tris-HCl solution of dopamine, the pH value of the solution is 8.5, and the concentration of dopamine in the solution is 0.05mol/L. Soak in Tris-HCl solution of dopamine for 24h.

The mask in the step S2 is made of polydimethylsiloxane (PDMS). The holes on the surface of the mask are pentagonal holes with a side length of 3mm and a porosity of 90%.

The coating solution in the step S2 includes a first coating solution and a second coating solution.

The first coating solution is composed of medicine, polymer and solvent, and the components of the first coating solution are: 1% of medicine, 1% of polymer and 98% of solvent in terms of mass percentage. Among them, the drug is preferably cephalosporin; the polymer is preferably polyethylene glycol-polylactic acid-polyglutamic acid triblock copolymer; the solvent is preferably methylene chloride.

The second coating solution is composed of medicine, polymer and solvent, and the components of the second coating solution are: 1% of medicine, 1% of polymer and 98% of solvent in terms of mass percentage. Among them, the drug is preferably carbamazepine; the polymer is preferably a copolymer of lactic acid and glycolide; the solvent is preferably chloroform.

In the step S2, the first coating solution and the second coating solution are sequentially sprayed on the surface of the implantable medical device by means of ultrasonic spraying.

In the prepared IMD containing the antibacterial coating, the mass of the antibacterial coating accounts for 0.8% of the total mass of the implantable medical device containing the antibacterial coating, and the drug release time is 14 days.

The advantage of the preparation method of the antibacterial coating of implantable medical device provided by the present invention is:

1. The antibacterial coating has good coating adhesion to metal parts on the surface of implantable medical devices, silicone connectors or other plastic parts;

2. There are uncoated hole areas on the surface of the metal parts of implantable medical devices. On the one hand, it is conducive to the direct contact between the pacemaker and the interstitial fluid, which is conducive to its normal work in the unipolar state; on the other hand, it increases The contact area between the drug and the tissue fluid can promote the degradation of the coating material and the release of the drug;

3. The preparation process provided by the present invention is simple, and the antibacterial coating on the surface of implantable medical devices can be realized with only simple operations, which is easy for large-scale production.

Each embodiment in this specification is described in a progressive manner, each embodiment focuses on the difference from other embodiments, and the same and similar parts of each embodiment can be referred to each other.

The above description is only a description of the preferred embodiments of the present invention, and does not limit the scope of the present invention. Any changes and modifications made by those of ordinary skill in the field of the present invention based on the above disclosures shall fall within the protection scope of the claims.

Claims (18)

1. A preparation method for an antibacterial coating of an implantable medical device, comprising the steps of: S1: soak the implantable medical device in a solution containing dopamine for treatment to obtain a surface-treated implantable medical device; S2: Put a mask on the surface-treated metal part of the implantable medical device, and then spray the coating solution on the surface of the implantable medical device; S3: removing the mask to obtain an implantable medical device containing an antibacterial coating; Wherein, the shape of the mask plate matches the shape of the metal part of the implantable medical device, and holes are opened on the surface of the mask plate. 2. The preparation method of the antibacterial coating of implantable medical device according to claim 1, is characterized in that, described solution that contains dopamine is the Tris-HCl solution of dopamine, in described S1, described implantation Sexual medical devices are soaked in the Tris-HCl solution of dopamine for 4-24 hours, and then dried with nitrogen gas for later use. 3. the preparation method of the antibacterial coating of implantable medical device according to claim 2 is characterized in that, in the Tris-HCl solution of described dopamine, the concentration of dopamine is 0.02-0.05mol/L, the pH of solution The value is 8.5. 4. the preparation method of the antibacterial coating of implantable medical device according to claim 1, is characterized in that, described mask plate adopts polydimethylsiloxane to make, and its thickness is 0.1-2mm, and pore The rate is 60%-90%, and the holes are evenly distributed. 5. the preparation method of the antibacterial coating of implantable medical device according to claim 1 is characterized in that, described coating solution is made up of medicine, polymkeric substance and solvent; The quality of described medicine accounts for described coating 0.1%-3% of the mass of the solution, the mass of the polymer accounts for 1%-5% of the mass of the coating solution, and the mass of the solvent accounts for 92%-98.9% of the mass of the coating solution. 6. The preparation method of the antibacterial coating of implantable medical device according to claim 1, is characterized in that, described coating solution in the described S2 comprises at least two kinds, is respectively the first coating solution and the second a coating solution, the first coating solution is composed of a drug, a polymer and a solvent, and the second coating solution includes at least a polymer and a solvent; The S2 includes: putting a mask on the surface-treated metal part of the implantable medical device, and then respectively spraying the first coating solution and the second coating solution on the Surfaces of implantable medical devices. 7. The preparation method of the antibacterial coating of implantable medical device according to claim 6, is characterized in that, in the first coating solution: the quality of the medicine accounts for 2% of the first coating solution quality 0.1%-3%, the mass of the polymer accounts for 1%-5% of the mass of the first coating solution, and the mass of the solvent accounts for 92%-98.9% of the mass of the first coating solution. 8. The preparation method of the antibacterial coating of implantable medical device according to claim 6, is characterized in that, described second coating solution is made up of polymer and solvent, and wherein, the quality of described polymer accounts for all 1%-5% of the mass of the second coating solution, and the mass of the solvent accounts for 95%-99% of the mass of the second coating solution. 9. the preparation method of the antibacterial coating of implantable medical device according to claim 6 is characterized in that, described second coating solution is made up of medicine, polymkeric substance and solvent, and wherein, the quality of described medicine accounts for 0.1%-3% of the mass of the second coating solution, the mass of the polymer accounts for 1%-5% of the mass of the second coating solution, and the mass of the solvent accounts for 92%-98.9% of the quality. 10. according to the preparation method of the antibacterial coating of implantable medical device described in any one in claim 5-9, it is characterized in that, described medicine is selected from the group consisting of analgesics, antibacterial agents, anti-inflammatory drugs and anesthetics One or more combinations. 11. the preparation method of the antimicrobial coating of implantable medical device according to claim 10, is characterized in that, described analgesic is selected from one in aspirin, ibuprofen, bupivacaine and celecoxib one or more combinations. 12. the preparation method of the antibacterial coating of implantable medical device according to claim 10, is characterized in that, described antibacterial agent is selected from rifampicin, minocycline, gentamicin, macrolide , penicillin, tetracycline, chloramphenicol, vancomycin, fusidic acid, trimethoprim, clindamycin, triclosan, chlorhexidine, cephalosporins, aztreonam, cefotetan, One or more combinations of clocarbef, cefaclor, ceftizoxime, cefixime, cefazolin, cephalexin, penicillin, neomycin and colistin, or selected from the salts of these compounds one or more combinations of . 13. The preparation method of the antibacterial coating of implantable medical device according to claim 10, is characterized in that, described anti-inflammatory drug is selected from naproxen, tyroprofen, ibuprofen, diclofenac, celecoxib Cloth, sulindac, diflunisal, piroxicam, indomethacin, meloxicam, flurbiprofen, mefenamic acid, nabumetone, toluoyl pyridine acetic acid, ketorolac, choline magnesium , one or more combinations of aspirin, salicylic acid and acetylsalicylate, or one or more combinations selected from the salts of these compounds. 14. the preparation method of the antibacterial coating of implantable medical device according to claim 10, is characterized in that, described anesthetic is selected from lidocaine, bupivacaine, carbocaine, paracetamol , Clonidine, Benzodiazepine, Flumazenil, Carbamazepine, Pethidine, Zaleplon, Trimethazine Maleate, Buprenorphine, Nalbuphine, Methadone, Dihydromorphone, One or more of hydrocodone and morphine. 15. according to the preparation method of the antibacterial coating of implantable medical device described in any one of claim 5-9, it is characterized in that, described polymer is selected from polyglutamic acid, polylysine, polyaspartic acid One or more combinations of amino acid, polyethylene glycol, polylactic acid, polycaprolactone, polyglycolide and polycarbonate, or one or more combinations selected from the copolymers of these compounds. 16. according to the preparation method of the antibacterial coating of implantable medical device described in any one in claim 5-9, it is characterized in that, described solvent is selected from water, ethanol, methyl alcohol, tetrahydrofuran, hexafluoroisopropanol, One or more combinations of trifluoroethanol, trifluoroacetic acid, dichloromethane, chloroform, dimethylformamide, ethyl acetate and acetone. 17. The preparation method of the antibacterial coating of implantable medical device according to claim 1, is characterized in that, in described S2, adopts the mode of electrostatic spraying, ultrasonic spraying or air spraying that described coating solution is sprayed on The surface of the implantable medical device. 18. The preparation method of the antibacterial coating of the implantable medical device according to claim 1, wherein the area of the antibacterial coating accounts for 60%-90% of the surface area of the implantable medical device, so The mass of the antibacterial coating accounts for 0.1%-0.8% of the total mass of the implantable medical device containing the antibacterial coating.