WO2013044746A1

WO2013044746A1 - Preparation method of copper-containing composite coating on metal part of medical device and medical device

Info

Publication number: WO2013044746A1
Application number: PCT/CN2012/081637
Authority: WO
Inventors: 刘恒全; 张德元
Original assignee: 先健科技(深圳)有限公司
Priority date: 2011-09-30
Filing date: 2012-09-20
Publication date: 2013-04-04
Also published as: CN105343938B; CN103031523B; CN103031523A; CN105343938A

Abstract

The present invention relates to a copper-containing composite coating on the metal part of a medical device and a preparation method thereof. The preparation method comprises the following steps: step 1, cleaning the surface of the metal part of the medical device; step 2, putting the metal part of the medical device in a vacuum chamber and pre-processing same; step 3, producing copper ions in the vacuum chamber, and making the copper ions move toward the surface of the metal part of the medical device under the effect of a bias voltage, the copper ions and the ions of another element combine in the vacuum chamber and react on the surface of the metal part of the medical device to form the copper-containing composite coating. The copper-containing composite coating on the metal part of the medical device provided in the present invention not only has good compatibility with the blood, but can also prevent cell growth on the surface of the device so as to inhibit endothelialization of the surface of the material. The present invention also relates to a medical device.

Description

Method for preparing copper-containing composite coating on metal parts of medical device and medical device

Technical field

The invention relates to a medical device and a preparation method thereof, in particular to a composite coating on a metal implanted device in contact with blood and a preparation method thereof.

Background technique

Cardiovascular disease is one of the leading causes of threat to human health and life. Medical device interventional therapy is a convenient and effective treatment, which has the characteristics of small trauma, rapid recovery and small side effects. Cardiovascular implant devices that have been widely used include vascular stents, heart valve rings, venous thrombus filters, embolization devices, etc. Most of these medical devices are designed and manufactured using biomedical metal materials. At present, such biomedical metal materials include medical stainless steel, cobalt-based alloys, titanium and titanium alloys, absorbable metal materials, nickel-titanium shape memory alloys, precious metals and alloys such as bismuth, antimony, gold and silver.

At present, the main problems in the application of medical metal materials are: 1) the material biocompatibility (hemocompatility) is not good, it is easy to cause coagulation or cause inflammation of surrounding tissues; 2) the degree of endothelialization of materials is low; 3) due to physiological environment Corrosion can cause metal ions to diffuse to surrounding tissues and the nature of the implant material itself. The former may cause toxic side effects, while the latter often leads to material failure.

The above problems are generally achieved by surface modification methods, such as preparing a metal or ceramic coating on the surface of the material to increase the biocompatibility of the material, reducing the rejection of the material and the surrounding tissue, and promoting the endothelialization of the surface of the material. The coating is a diamond-like carbon film (DLC), a compound of titanium or titanium (TiN, Ti-O, Ti-C, etc.), a Si-N film, or the like. Allen M. Through research, DLC has good biocompatibility and wear resistance, and has been used in artificial mechanical heart valves. TiN and Ti-O film coatings have been used in cardiovascular implant devices such as coronary stents, occluders, and heart valves because of their good biocompatibility and blood compatibility.

In some implanted devices that come into contact with blood, only the coating is required to have good biocompatibility, no coagulation or thrombosis, but it is not expected to be endothelialized for a certain period of time, such as venous thrombus filter. In the capture of the embolus, the surface is not expected to be endothelialized in order to facilitate the removal of the device; during the use of the bioabsorbable metal device, it is not expected to degrade too fast in the early stage to ensure long-lasting mechanical properties, and later hope that the surface does not cling to the endothelium. In order to affect the degradation rate of the stent; the pivotal pomelo region of the mechanical heart annulus does not expect endothelialization to affect the flexibility of the leaflets. J. Botsoa found that SiC can cause cell apoptosis, but its research is limited to SiC quantum dots (5.4 nm) for detecting the imaging of living cells; Hauert R. found through experiments that a certain dose of silicon is implanted on the surface of the material, which is not conducive to cells. Growth and proliferation, but due to the physical properties of the silicon atom itself, can not effectively ensure the implantation dose of the material surface, Amstein CF research found that the deposition of a layer of silicon compounds such as SiN, SiC, SiO ₂ , the surface of the material is not easy to grow cells, but this type The silicide is brittle and the mechanical properties of the coating are not satisfactory. Danlel M discloses that depositing a titanium metal layer on the surface of silicon can inhibit cell growth to some extent, but in polymers (eg PE, US Patent Publication No. 2010020477A1). Titanium coating deposited on PTFE, UHMWPE) or metal surfaces promotes cell growth.

In fact, the surface of biocompatible materials is generally easy to be endothelialized. To inhibit the adhesion of endothelial cells, it is only dependent on drugs or targeted toxic ions, and it is required that this cytotoxicity has a limited effect in a certain period of time, and is minimized. side effect. Felicia Suska tried to deposit copper film on the surface of titanium, which can significantly inhibit the growth of monocytes, but the surface of the copper film is easy to produce hemolysis, which affects the blood compatibility of the material. Paul KC uses plasma technology to inject copper into the metal surface. The purpose is to achieve a certain antibacterial effect by using copper atoms. Therefore, the number of copper atoms on the surface of the material is limited and no continuous and complete film is formed, which has less influence on the blood compatibility of the material surface. However, the surface of the material is also relatively easy to grow cells. Nosaka T has been used to prepare copper nitride films by magnetron sputtering, but such films are generally only used for optical energy storage and electronic materials, and have not been used to solve technical problems in biological materials.

Copper is one of the trace elements required by the human body. The normal content of copper in the adult body is 100-150 mg. Only when the amount of copper ingested exceeds 10 times of the normal value, obvious poisoning will occur. Therefore, the surface of the metal medical device material contains a certain amount of copper to help prevent early endothelialization of the surface of the material, and to improve the blood compatibility of the material by controlling the copper content of the surface, and has no obvious side effects on the human body.

The use of the above-mentioned prior art medical metal material coating changes the biocompatibility of the material and the degree of endothelialization of the surface of the cardiovascular implant device to some extent, but also has the following disadvantages:

1. The coatings commonly used in cardiovascular medical devices are mainly used to improve the blood compatibility of materials, and also promote endothelialization, but some metal implanted devices only expect good blood compatibility and do not promote in the short term. For endothelialization, the above coatings are difficult to meet the latter requirements.

2. Preparation of continuous elemental copper film on the surface of titanium material can inhibit cell growth, but the elemental copper film itself is easy to cause hemolysis, which reduces the blood compatibility of the device, and excessive copper ions dissolved in the blood may cause toxic side effects.

3. Plasma injection of copper on metal medical devices can achieve bacteriostatic effects. However, due to the limited implantation dose and the inability to form a complete cover film on the surface, the effect of effectively inhibiting cell growth cannot be achieved.

4. Copper nitrides have been extensively studied in electronics due to their good optical properties, but copper-containing nitride coatings have not been used to solve the technical problem of inhibiting endothelialization on the surface of biological materials.

5. Although the above coatings have good mechanical properties, they can not achieve good blood compatibility and control the degree of endothelialization at the same time. This technical problem has not been effectively solved so far.

technical problem

The technical problem to be solved by the present invention is to provide a copper-containing composite coating on a metal part of a medical device and a preparation method thereof, which not only has good blood compatibility, but also can prevent cells from growing on the surface of the device, thereby achieving suppression. The surface of the material is endothelialized.

Technical solution

The technical solution adopted to solve the technical problem of the present invention is:

A method of preparing a copper-containing composite coating on a metal component of a medical device, the method comprising the steps of:

Step 1: cleaning the surface of the metal component of the medical device;

In step two, the metal parts of the medical device are placed in a vacuum chamber and pretreated;

In step 3, copper ions are generated in the vacuum chamber, and under the action of the bias, the copper ions are moved to the surface of the metal part of the medical device, and the other element of the copper ion vacuum chamber is ion-coupled in the metal part of the medical device. The surface reacts to form a copper-containing composite coating.

As a further improvement of the present invention, in the third step, the other element is titanium. In the vacuum chamber, the titanium is evaporated and ionized by an electric current, and the titanium ion is irradiated to the metal part of the medical device under the action of the bias voltage. The surface moves to form a copper-titanium mixed coating on the surface of the metal part of the medical device.

As a further improvement of the present invention, in the third step, the other element is nitrogen, and a copper nitride coating is formed on the surface of the metal part of the medical device table by chemical reaction of copper ions with nitrogen ions in the vacuum chamber.

As a further improvement of the present invention, the pretreatment step in the second step is as follows: after the metal part of the medical device is placed in the vacuum chamber, the pressure of the vacuum chamber is less than 3.0×10 ^-3 Pa, and the flow rate of the argon gas is adjusted so that the pressure of the vacuum chamber reaches 0.5. Pa, and biased to discharge argon glow, at this time adjust the bias power to 400-500V, so that argon ions are sputtered to clean the surface of the metal parts of the medical device, the cleaning time is 5-10 minutes.

As a further improvement of the present invention, in the third step, after the pressure of the vacuum chamber is lowered to 5×10 ^-5 Pa, the heating power is turned on to make the temperature of the metal parts of the medical device reach 200-300 ° C and keep warm, and argon is introduced. The gas ensures that the pressure in the vacuum chamber is maintained at 0.2-0.5 Pa, the bias voltage is adjusted to 200-600 V, and the power supply of the copper target and the titanium target is respectively turned on, so that titanium and copper are evaporated and ionized, and the titanium ions and copper ions are biased. The surface of the metal part of the medical device is moved downward, and a copper-titanium mixed coating is deposited on the surface of the metal part of the medical device.

As a further improvement of the present invention, in the third step, after the pressure of the vacuum chamber is lowered to 1×10 ^-5 Pa, then argon gas is introduced to ensure that the pressure of the vacuum chamber is maintained at 0.2-0.5 Pa, and the bias voltage is adjusted to 1000-2000V, respectively turn on the power supply of the copper target and the titanium target, so that the titanium and copper are evaporated and ionized, and the ionized ions are screened through the magnetic filter tube, and the titanium ions and the copper ions are biased to the metal parts of the medical device. The surface moves and is injected into the surface layer of the metal part of the medical device.

As a further improvement of the present invention, the deposition time is 10-20 minutes.

As a further improvement of the present invention, in step 3, after the pressure of the vacuum chamber is lowered to 5×10 ^-5 Pa, the heating power source is turned on to make the temperature of the metal parts of the medical device reach 175-225 ° C and the temperature is maintained, and the vacuum chamber is ensured by the nitrogen gas. The gas pressure was maintained at 0.5-0.7 Pa, the bias was adjusted to 280-320 V, and the deposition time was 5-10 minutes.

Another technical solution adopted to solve the technical problem of the present invention is to provide a medical device comprising a metal member and a copper-containing composite coating formed on the metal member, the copper-containing composite coating comprising copper element And at least another element, the copper element being present in an amount sufficient to inhibit cell growth on the surface of the metal part of the medical device, the other element being biocompatible.

As a further improvement of the invention, the other element is a titanium or nitrogen element.

As a further improvement of the present invention, the metal member is made of nickel titanium alloy or stainless steel or pure iron.

As a further improvement of the present invention, the copper-containing composite coating layer has a thickness of 50 nm to 320 nm.

As a further improvement of the present invention, the copper-containing composite coating has a copper mass fraction of between 10% and 45%.

Beneficial effect

Compared with the prior art, the present invention has the following advantages: the copper-containing composite coating on the metal medical device provided by the invention not only has good blood compatibility, but also prevents cells from growing on the surface of the device, thereby suppressing the surface of the material. Endothelialization. The composite coating is a copper-titanium mixed coating or a copper nitrided coating. In particular, it relates to a copper-containing composite coating which has a good mixing ratio with a common medical metal material by adjusting a preparation process, and the copper-containing composite coating not only has good toughness and ductility to adapt to metal. The deformation of the medical device, and the degree of inhibition of cell growth by the surface of the coating can be achieved by changing the mass fraction of copper in the coating.

DRAWINGS

The present invention will be further described below in conjunction with the accompanying drawings and embodiments, in which:

Figure 1 is a comparison of the platelet number density on the surface of different samples.

Figure 2 is a comparison of the hemolysis rates of different sample surfaces.

Figure 3 is a graph comparing the number density of cells grown on different sample surfaces.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It is understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The invention will be further described in detail below with reference to the drawings and specific embodiments.

In the present invention, the medical device is a metal medical device or a medical device containing a metal member. In the following embodiments, the medical device is a metal medical device.

Example 1

A copper-titanium mixed coating is deposited on the surface of the medical nickel-titanium alloy by plasma arc plating.

In the first step, the medical nickel-titanium alloy product is first cleaned. It is preferred to polish the article prior to cleaning to achieve a better cleaning effect. After cleaning, the article is preferably dried and then stored in a drying dish for use in order to facilitate rapid batch production.

In step two, the nickel-titanium alloy product after the first step is further pretreated. An easy-to-implement pretreatment process is as follows: a vacuum system is established to place a nickel-titanium alloy product into a vacuum chamber such that the pressure in the vacuum chamber is less than 3.0×10 ^-3 Pa, and the flow rate of the argon gas is 30-50 sccm (sccm: standard cc /min), so that the vacuum chamber pressure reaches 0.5Pa, and biased to argon glow discharge, at this time slowly adjust the bias power to 400-500V, so that argon ions are sputtered to clean the surface of NiTi alloy products, cleaning time It is 5-10 minutes.

Step 3, preparing to activate the cathode target in the vacuum chamber, the cathode target is a titanium target (Ti 99.99%) and a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, so that the vacuum chamber pressure is reduced to 5 After ×10 ^-5 Pa, turn on the heating power to make the nickel-titanium alloy temperature reach 250-300 °C and keep warm. Then, argon gas is introduced to ensure that the vacuum chamber pressure is maintained at 0.2 Pa, the bias voltage is adjusted to 400 V, and then the copper target is turned on. The power source of the titanium target, titanium and copper are evaporated and ionized, and a certain proportion of titanium copper ions are moved to the surface of the nickel-titanium alloy product under the action of a bias voltage, and a mixed coating of copper and titanium uniformly mixed on the surface of the nickel-titanium alloy product is deposited. . According to the characteristics of copper target and titanium target ionization, the copper target current is controlled to 60 amps (A), the titanium target current is 10 amps (A), and the deposition time is 20 minutes, and the copper-titanium mixed coating with a thickness of 280-300 nm can be obtained. Floor.

Step 4: After the heating power source and the target power source are turned off, the argon gas is continuously introduced to gradually increase the pressure of the vacuum chamber, and the nickel-titanium alloy product in the vacuum chamber is sufficiently cooled to room temperature, until the pressure in the vacuum chamber is consistent with the external atmospheric pressure, and finally the removal has A nickel-titanium alloy product of a copper-titanium mixed coating.

X-ray photoelectron spectroscopy (XPS) detection, the copper-titanium mixed coating obtained by the above conditions mainly contains two elements of copper and titanium, the copper mass fraction is about 75%, and the titanium mass fraction is about 25%.

Example 2

In the first step, the medical nickel-titanium alloy product is first polished, washed, dried and stored in a drying dish for use.

In the second step, the nickel-titanium alloy product in the drying dish is taken out and pretreated, and the pretreatment process is as follows: a vacuum system is established, and the nickel-titanium alloy product is placed in a vacuum chamber, so that the vacuum chamber pressure is less than 3.0×10 ^-3 Pa. , the flow rate of argon gas is 30-50sccm (sccm: standard cc / min), so that the pressure of the vacuum chamber reaches 0.5Pa, and the argon glow discharge is applied by biasing, and the bias power supply is slowly adjusted to 400-500V. The surface of the Nitinol article was sputter cleaned with argon ions for a cleaning time of 5-10 minutes.

Step 3, preparing to activate the cathode target in the vacuum chamber, the cathode target is a titanium target (Ti 99.99%) and a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, so that the vacuum chamber pressure is reduced to 5 ×10 ^-5 Pa; then argon gas is introduced into the vacuum chamber, so that the pressure in the vacuum chamber is maintained at 0.2 Pa, the heating power is turned on, the temperature of the nickel-titanium alloy reaches 250-300 ° C and the temperature is maintained, the bias voltage is adjusted to 300 V, and then turned on separately. The power source of copper target and titanium target, titanium and copper are evaporated and ionized, and a certain proportion of titanium copper ions are moved to the surface of the nickel-titanium alloy product under the action of bias voltage, and copper-titanium is uniformly mixed on the surface of the nickel-titanium alloy product. Mixed coating. According to the characteristics of copper target and titanium target ionization, the copper target current is controlled to 10 amps (A), the titanium target current is 60 amps (A), and the deposition time is 15 minutes, and the copper-titanium mixed coating with a thickness of 270-320 nm can be obtained. Floor.

The mixed coating was determined to contain a copper mass fraction of 5% and a titanium mass fraction of about 95%.

Example 3

Step 3, preparing to activate the cathode target in the vacuum chamber, the cathode target is a titanium target (Ti 99.99%) and a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, so that the vacuum chamber pressure is reduced to 5 After ×10 ^-5 Pa, turn on the heating power to make the nickel-titanium alloy temperature reach 250-300 °C and keep it warm. Then, argon gas is introduced to ensure that the vacuum chamber pressure is kept at 0.5 Pa, the bias voltage is adjusted to 500 V, and then the copper target is turned on. The power source of the titanium target, titanium and copper are evaporated and ionized, and a certain proportion of titanium copper ions are moved to the surface of the nickel-titanium alloy product under the action of a bias voltage, and a mixed coating of copper and titanium uniformly mixed on the surface of the nickel-titanium alloy product is deposited. . According to the characteristics of copper target and titanium target ionization, the copper target current is controlled to 40 amps (A), the titanium target current is 20 amps (A), and the deposition time is 15 minutes, and the copper-titanium mixed coating with a thickness of 280-310 nm can be obtained. Floor.

The mixed coating copper was tested to have a mass fraction of 45% and a titanium mass fraction of 55%.

Using the plasma arc plating method described above, during the preparation of the coating, substantially the same argon flow rate, vacuum chamber pressure, and metal medical device products (such as nickel-titanium alloy products) are set to adjust the bias voltage and the copper target, respectively. The current and/or the titanium target current can result in a copper-titanium mixed coating having a copper mass fraction between 5% and 75%.

A large number of studies have proved that the biocompatibility of titanium is very good. The biological properties of the above-mentioned copper-titanium mixed coating are mainly affected by the copper content in the coating. When the copper mass fraction in the above copper-titanium mixed coating is more than 10%, the mixed coating can inhibit cell growth on the surface thereof. When the copper mass fraction is low, the copper atoms in the coating are "diluted" by the titanium atoms, so that the mixed coating has better blood compatibility. Therefore, a coating having a different copper to titanium mass ratio can be selected according to the actual requirements for inhibiting cell growth.

The coating thickness was controlled by changing the bias voltage and deposition time under the same vacuum chamber conditions and the same target current conditions. The copper target current was controlled to 40 A, the titanium target current was 20 A, the bias voltage was 200 V, and the deposition time was 10 minutes, and a copper-titanium mixed coating having a thickness of about 50 nm was obtained. Increasing the bias voltage increases the deposition rate while maintaining the target current. The bias voltage is selected to be 600 V and the deposition time is 12 minutes. A copper-titanium mixed coating having a thickness of about 300 nm can be obtained. In the coatings of the above 50 nm and 300 nm thicknesses, the copper to titanium mass ratio was approximately 1:1. The coating on the surface of the metal device should have continuity, flatness and good adhesion, with a preferred thickness of the coating being between 50 and 300 nm. According to the actual requirements, in the preparation process of copper-titanium mixed coating, select the appropriate copper target and titanium target current, the bias voltage is adjusted within the range of 200-600V, the deposition time is 10-15 minutes, and the thickness can be prepared at 50-300nm. A copper-titanium mixed coating. The copper-titanium mixed coating has metal characteristics, good toughness and ductility, and can adapt to large deformation of medical nickel-titanium alloy instruments.

The contrast experiments were carried out using fresh rabbit blood under the same experimental conditions. The adhesion density of platelets on the surface of different samples is shown in Fig. 1. The samples were all prepared by the method in the above examples, and the samples having the same characteristics have the same reference numerals: 0# samples are uncoated nickel-titanium alloy, 1# samples are conventional copper coatings, and 2# samples are copper-containing. The copper-titanium mixed coating with a mass fraction of 75%, the copper-titanium mixed coating with a copper content of 45% for the 3# sample, and the copper-titanium mixed coating with a copper content of 25% for the 4# sample, 5# The sample is a copper-titanium mixed coating containing 10% copper by mass, the 6# sample is a copper-titanium mixed coating containing 5% by mass of copper, and the 7# sample is a conventional titanium coating. It can be seen that under the same experimental conditions, the amount of platelet adhesion per unit area of nickel-titanium alloy is much higher than that of the copper-titanium mixed coating, so the copper-titanium mixed coating has obvious advantages. As the content of copper in the copper-titanium mixed coating decreases and the amount of titanium increases, the number of platelets adhered to the surface of the copper-titanium coating decreases.

Figure 2 is the hemolysis rate of the different sample surfaces. It can be seen from Fig. 2 that as the content of copper in the coating increases, the hemolysis rate gradually increases. The copper-titanium mixed coating with a copper mass fraction of 45% has a hemolysis rate very close to 5%, while materials with a hemolysis rate above 5% do not meet the biomedical safety requirements.

The above platelet adhesion and hemolysis rate experiments show that a copper-titanium mixed coating with a copper mass fraction of less than 45% can meet the requirements of blood compatibility.

Figure 3 is a comparison of the growth of endothelial cells after three days of culture on different samples. It can be seen that the surface of the 1#, 2#, 3#, and 4# samples did not have any cell growth, that is, completely inhibited the growth of the cells on the surface of the coating, but the growth cells on the surface of the 5# sample were only weakly inhibited. That is to say, a copper-titanium mixed coating having a copper mass fraction of more than 10% can effectively inhibit cell growth on the surface of the coating.

Combining the data in Fig. 1, Fig. 2 and Fig. 3, in order to achieve good blood compatibility at the same time and effectively inhibit the growth of cells on the surface of the coating, the copper mass fraction in the copper-titanium mixed coating preferably ranges from 10% to Between 45%.

Example 4

A copper-titanium mixed coating was prepared on the surface of a pure iron vascular stent by ion implantation deposition.

In the first step, the pure iron blood vessel stent is first polished, washed, dried, and stored in a drying dish for use.

In the second step, the pure iron blood vessel stent in the drying dish is taken out and pretreated, and the pretreatment process is as follows: a vacuum system is established, and the pure iron blood vessel stent is placed in the vacuum chamber, so that the pressure in the vacuum chamber is less than 3.0×10 ^-3 Pa. , the flow rate of argon gas is 30-50sccm (sccm: standard cc / min), so that the pressure of the vacuum chamber reaches 0.5Pa, and the argon glow discharge is applied by biasing, and the bias power supply is slowly adjusted to 400-500V. The surface of the Nitinol article was sputter cleaned with argon ions for a cleaning time of 5-10 minutes. In addition, the same pretreatment effect can be achieved by guiding the argon ion source with a magnetron.

Step 3, preparing to activate the cathode target in the vacuum chamber, the cathode target is a titanium target (Ti 99.99%) and a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, so that the vacuum chamber pressure is reduced to 1 After ×10 ^-5 Pa, then, argon gas is introduced to ensure that the pressure in the vacuum chamber is maintained at 0.2 Pa, the bias voltage is appropriately adjusted, and the power supply of the copper target and the titanium target is respectively turned on, and titanium and copper are evaporated and ionized, and magnetically filtered. The tube screens the ionized ions, and under a higher bias voltage, a certain proportion of titanium copper ions are moved to the surface of the pure iron blood vessel stent and injected into the surface layer of the pure iron blood vessel stent, and ion implantation is performed on the surface of the pure iron blood vessel stent. Deposition to obtain a copper-titanium mixed coating. According to the characteristics of copper target and titanium target ionization, the copper target current is controlled to 30 amps (A), the titanium target current is 10 amps (A), the bias voltage is adjusted to 1500V, and the ion implantation time is 15 minutes. The surface of the stent was obtained as a copper-titanium mixed coating having a thickness of about 100 nm.

Step 4: After the target power is turned off, the argon gas is continuously introduced to gradually increase the pressure of the vacuum chamber, so that the pure iron blood vessel stent in the vacuum chamber is sufficiently cooled to room temperature, and the pressure in the vacuum chamber is consistent with the external atmospheric pressure, and finally the copper-titanium mixture is taken out. Coated pure iron vascular stent.

It was determined that the copper mass fraction in the copper-titanium mixed coating was 45%, and the titanium mass fraction was 55%.

The copper-titanium mass ratio in the coating can be adjusted by changing the current of the copper target and the titanium target under the conditions of the above vacuum chamber. Other conditions are the same, the copper target current is changed to 10A, the titanium target current is 30A, the bias voltage is 2000V, and the injection time is 20 minutes. A copper-titanium mixed coating with a thickness of about 300 nm can be obtained on the surface of the pure iron blood vessel stent. . After the target power was turned off, argon gas was continuously supplied, the vacuum chamber was sufficiently cooled to room temperature, and the pure iron blood vessel stent was taken out, and the mass fraction of copper in the coating was determined to be 10%, and the mass fraction of titanium was 90%.

The coating thickness was controlled by changing the bias voltage and deposition time under the same vacuum chamber conditions and the same target current conditions. Other conditions are the same, the copper target current is changed to 10A, the titanium target current is 30A, the injection deposition bias is 1000V, and the injection time is 10 minutes, and a copper-titanium mixture with a thickness of about 50 nm can be obtained on the surface of the pure iron blood vessel stent. coating. Based on the technical principle of the present embodiment, a copper-titanium mixed coating having a thickness of 50-300 nm and a copper mass fraction of 10% to 45% can be obtained by changing the coating preparation process. Further, the basic characteristics of the copper-titanium mixed coating layer are the same as those of the first to third embodiments, and therefore have a good blood compatibility and a technical effect of inhibiting cell growth.

Based on the plasma arc plating equipment used in Example 1, a slight modification is made into a plasma immersion injection deposition apparatus: the cathode uses 99.99% of copper and titanium, generates ions at a certain voltage, and screens ionization through a magnetic filter tube. The ions are then applied with a higher bias voltage to achieve ion implantation deposition on the surface of the pure iron vascular stent. The copper-titanium mixed coating obtained by ion implantation deposition is advantageous for improving the adhesion of the coating due to the presence of an injection layer below the interface between the coating and the metal substrate, and is suitable for a heterogeneous metal matrix material. Due to the heating effect of continuous ion bombardment, the sample heating power supply is no longer needed.

Example 5

A copper-titanium mixed coating is prepared on the surface of the medical stainless steel.

In the first step, the medical stainless steel product is first polished, washed, dried and stored in a drying dish for use.

Step 2, take out the stainless steel product in the drying dish and pretreat it. The pretreatment process is as follows: establish a vacuum system, put the stainless steel product into the vacuum chamber, so that the pressure of the vacuum chamber is less than 3.0×10 ^-3 Pa, and argon is introduced. The gas flow rate is 30-50sccm (sccm: standard cc/min), so that the pressure in the vacuum chamber reaches 0.5Pa, and the argon glow discharge is applied by biasing. At this time, the bias power supply is slowly adjusted to 400-500V to make argon ions. Sputter the surface of the stainless steel product for 5-10 minutes.

Step 3, preparing to activate the cathode target in the vacuum chamber, the cathode target is a titanium target (Ti 99.99%) and a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, so that the vacuum chamber pressure is reduced to 5 After ×10 ^-5 Pa, the heating power is turned on to make the temperature of the stainless steel product reach 300 ° C and keep warm. Then, argon gas is introduced to ensure that the pressure of the vacuum chamber is maintained at 0.4 Pa, the bias voltage is adjusted to 200 V, and the copper target and the titanium target are respectively turned on. The power source, titanium and copper are evaporated and ionized, and a certain proportion of titanium copper ions are moved to the surface of the stainless steel product under the action of a bias voltage, and a mixed coating of copper and titanium uniformly mixed is deposited on the surface of the stainless steel product. According to the characteristics of copper target and titanium target ionization, the copper target current is controlled by 30-60 amps (A), the titanium target current is 10-30 amps (A), and the deposition time is 10-15 minutes, and the thickness is 50- 200nm copper-titanium mixed coating.

Step 4: After the heating power source and the target power source are turned off, the argon gas is continuously introduced to gradually increase the pressure of the vacuum chamber, and the stainless steel product in the vacuum chamber is sufficiently cooled to room temperature, until the pressure in the vacuum chamber is consistent with the external atmospheric pressure, and finally the copper and titanium are taken out. Mixed coated stainless steel products.

X-ray photoelectron spectroscopy (XPS) detection, the copper-titanium mixed coating obtained by the above conditions mainly contains two elements of copper and titanium, and the copper mass fraction is about 10%-45%.

Because the bonding force between the copper-titanium mixed coating and the medical nickel-titanium alloy is better than the combination of the copper-titanium mixed coating and the medical stainless steel, the preferred thickness range of the copper-titanium mixed coating on the medical stainless steel product is reduced, but coated The layer composition was similar to that described in Example 1 to Example 3, so that the copper-titanium mixed coating of the medical stainless steel surface was similar in blood compatibility and cell growth inhibition effect to Examples 1 to 3.

Example 6

A copper nitride coating is deposited on the surface of the medical nickel-titanium alloy by plasma arc plating.

Step 3, preparing a cathode target, the cathode target is a copper target (Cu 99.99%); stopping the introduction of argon into the vacuum chamber, causing the vacuum chamber pressure to drop to 5×10 ^-5 Pa, and then turning on the heating power source to make the nickel-titanium The alloy temperature reaches 175 ° C ~ 225 ° C (preferably 200 ° C) and is kept warm, then, nitrogen gas is introduced (the nitrogen flow rate can be selected within the range of 40-60 sccm) to ensure that the vacuum chamber pressure is maintained at 0.5-0.7 Pa, and the bias voltage is adjusted to 280. ~320V (preferably 300V), and then turn on the power of the copper target, copper evaporates and ionizes, under the action of bias, a certain proportion of copper ions move to the surface of the Nitinol product and chemicalize with the nitrogen gas that is passed in. The reaction (under the action of a bias, a nitrogen discharge produces ions), and a copper nitride coating is deposited on the surface of the Nitinol article. In order to promote the ionization of nitrogen, argon gas may also be introduced while the nitrogen gas is introduced (the flow rate of argon gas is selected in the range of 10-30 sccm). According to the characteristics of copper target ionization, the copper target current is controlled to be 20-60 amps (A), and the deposition time is 5-10 minutes, and a copper nitride coating layer having a thickness of 50-100 nm can be obtained.

Step 4: After the heating power source and the target power source are turned off, the argon gas is continuously introduced to gradually increase the pressure of the vacuum chamber, and the nickel-titanium alloy product in the vacuum chamber is sufficiently cooled to room temperature, until the pressure in the vacuum chamber is consistent with the external atmospheric pressure, and finally the removal has Nickel-titanium alloy product of copper nitride coating.

The copper nitride coating obtained by the above conditions has a copper content of about 25-45% by X-ray photoelectron spectroscopy (XPS).

The copper nitride coating having a thickness in the range of 50-100 nm has a good bonding force and can conform to the deformation and bending of the surface of the metal instrument. The results of cytological experiments show that the copper nitride coating can effectively inhibit the growth of endothelial cells and has good blood compatibility.

In a nitrogen atmosphere in a vacuum chamber, copper is evaporated and ionized by a certain current, and a certain amount of copper ions is moved to the surface of the nitinol product under the action of a bias voltage, and chemistry is performed with nitrogen gas discharged under a bias voltage. The reaction forms a copper nitride coating on the surface of the nickel-titanium alloy.

The copper-containing composite coating on the metal medical device provided by the invention not only has good blood compatibility, but also prevents cells from growing on the surface of the device, thereby inhibiting the surface of the material from being endothelialized. The copper-containing composite coating is a copper-titanium mixed coating or a copper nitrided coating. In particular, it relates to a copper-containing composite coating which has a good mixing ratio with a common medical metal material by adjusting a preparation process, and the copper-containing composite coating not only has good toughness and ductility to adapt to metal. The deformation of the medical device, and the degree of inhibition of cell growth by the surface of the coating can be achieved by changing the mass fraction of copper in the coating.

The above is only the preferred embodiment of the present invention, and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection of the present invention. Within the scope.

Claims

A method for preparing a copper-containing composite coating on a metal component of a medical device, characterized in that the preparation method comprises the following steps:

Step 1: cleaning the surface of the metal component of the medical device;

In step two, the metal parts of the medical device are placed in a vacuum chamber and pretreated;

In step 3, copper ions are generated in the vacuum chamber, and under the action of the bias, the copper ions are moved to the surface of the metal part of the medical device, and the other element of the copper ion vacuum chamber is ion-coupled in the metal part of the medical device. The surface reacts to form a copper-containing composite coating.
The preparation method according to claim 1, wherein in the third step, the other element is titanium, and in the vacuum chamber, the titanium is evaporated and ionized by an electric current, and the titanium is applied under the action of a bias voltage. The ions move toward the surface of the metal part of the medical device, and a copper-titanium mixed coating is formed on the surface of the metal part of the medical device.
The preparation method according to claim 1, wherein in the third step, the other element is nitrogen, which is chemically reacted with nitrogen ions in the vacuum chamber by copper ions to form on the surface of the metal part of the medical device table. Copper nitride coating.
The preparation method according to claim 1, wherein the pretreatment step in the second step is as follows: after the metal component of the medical device is placed in the vacuum chamber, the pressure of the vacuum chamber is less than 3.0×10 -3 Pa, and the argon gas is adjusted. The flow rate makes the pressure of the vacuum chamber reach 0.5Pa, and the argon glow discharge is applied by biasing. At this time, the bias power supply is adjusted to 400-500V, and the argon ion is sputtered to clean the surface of the metal part of the medical device, and the cleaning time is 5- 10 minutes.
The preparation method according to claim 2, wherein in the third step, the pressure of the vacuum chamber is lowered to 5 × 10 -5 Pa, and then the heating power is turned on to bring the temperature of the metal parts of the medical device to 200-300. °C and keep warm, argon gas is passed to ensure that the pressure in the vacuum chamber is maintained at 0.2-0.5Pa, the bias voltage is adjusted to 200-600V, and the power supply of the copper target and the titanium target is respectively turned on, so that titanium and copper are evaporated and ionized, titanium ions and The copper ions move to the surface of the metal part of the medical device under the bias voltage, and a copper-titanium mixed coating is deposited on the surface of the metal part of the medical device.
The preparation method according to claim 2, wherein in the third step, the pressure of the vacuum chamber is lowered to 1 × 10 -5 Pa, and then argon gas is introduced to ensure that the pressure of the vacuum chamber is maintained at 0.2 - 0.5Pa, adjust the bias voltage to 1000-2000V, and then turn on the power supply of the copper target and the titanium target respectively, so that the titanium and copper are evaporated and ionized, and the ionized ions are screened through the magnetic filter tube, and the titanium ions and copper ions are biased. The surface of the metal component of the lower medical device is moved and injected into the surface layer of the metal component of the medical device.
The preparation method according to claim 5 or 6, wherein the deposition time is 10 to 20 minutes.
The preparation method according to claim 3, wherein in step 3, after the pressure of the vacuum chamber is lowered to 5 × 10 -5 Pa, the heating power source is turned on to make the temperature of the metal parts of the medical device reach 175-225 ° C and keep warm. Nitrogen gas is supplied to ensure that the pressure in the vacuum chamber is maintained at 0.5-0.7 Pa, the bias voltage is adjusted to 280-320 V, and the deposition time is 5-10 minutes.
A medical device comprising a metal component and a copper-containing composite coating formed on the metal component, wherein the copper-containing composite coating comprises a copper element and at least another element, the copper element The content is so large as to inhibit the growth of cells on the surface of the metal part of the medical device, the other element being biocompatible.
The medical device according to claim 9, wherein said another element is titanium or a nitrogen element.
The medical device according to claim 9, wherein the metal member is made of nickel titanium alloy or stainless steel or pure iron.
The medical device according to claim 9, wherein said copper-containing composite coating has a thickness of from 50 nm to 320 nm.
The medical device according to claim 9, wherein the copper-containing composite coating has a copper mass fraction of between 10% and 45%.