KR101652274B1 - Artificial biomaterial using copper based compound - Google Patents

Abstract

We present an artificial biomaterial containing a copper-based compound that is relatively inexpensive, easy to process, has no toxicity, and has excellent antibacterial properties. The material is formed by forming a coating film containing a copper compound on the surface of an artificial living body base material inserted into the human body, wherein the copper compound is formed by reacting copper sulfate (CuSO ₄ ) and a sulfur flame in an aqueous solution at a molar ratio of 1: 1 CuxSy (x / y = 0.8 to 1.5).

Description

TECHNICAL FIELD The present invention relates to an artificial biomaterial using a copper based compound,

TECHNICAL FIELD The present invention relates to a biomaterial using a copper-based compound, and more particularly, to an artificial biomaterial having an antimicrobial property enhanced by a copper-based compound having conductivity.

An artificial biomaterial refers to a material used in contact with a living tissue other than the normal skin of a human body. As people with disabilities and the aging population increase due to various accidents, artificial biomaterials that are inserted into the body to replace damaged parts or assist in the treatment of organs such as the heart are being widened. Currently, artificial biomaterials such as artificial bones, artificial joints, artificial teeth, and stents are widely used. In the future, much of the human body is likely to be replaced by artificial biomaterials. Base materials used in artificial biomaterials can be broadly classified into metal materials, polymer materials, ceramic materials, and composite materials. Artificial biomaterials are at risk of being infected with pathogens due to poor antimicrobial activity in the process of transplanting into the human body. Pathogens easily cluster on the surface of biomaterials, resulting in serious contamination problems.

Conventionally, in order to impart antimicrobial properties to an artificial biomaterial, silver (Ag) and silver salts which emit silver ions have been used. Silver (Ag) is highly toxic to bacteria at very low concentrations and has a low propensity to develop resistance to pathogens. US Patent No. 3800087, German Patent No. 4328999, and Korean Patent No. 10-0987728 disclose a method of coating silver (Ag) on the surface of a biological material. In addition, nanocrystalline silver (Ag) can be thermoplastically doped as described in WO 01/09229 A1, WO 2004/024205 A1 and EP 0 711 113 A and Muenstedt et al., Advanced Engineering Materials 2000, 2 (6), pages 380 to 386 Is incorporated into polyurethane.

However, when the silver is coated or incorporated into the biomaterial, the process for increasing the adhesion of silver (Ag) is very complicated, and only a small amount of silver (Ag) is antimicrobial compared to silver (Ag). Although it is known that silver (Ag) used in the past is excellent in antibacterial property, there are many limitations in practical use. Silver (Ag) has high antimicrobial properties and convenience, but it is overpriced. In order to solve this problem, a salt of Ag was included in the antibacterial coating. However, compared to silver (silver), there may be anions that can be toxic in certain circumstances. Some silver salts such as silver nitrate dissolve very well in water, so silver ions from the surface coating are delivered too quickly to the surroundings and other silver salts such as silver chloride may be too late to be delivered to the silver fluid due to insufficient solubility.

An object of the present invention is to provide an artificial biomaterial comprising a copper-based compound which is relatively inexpensive, easy to process, free from toxicity, and excellent in antibacterial activity.

An artificial biomaterial including a copper based compound for solving the problems of the present invention forms an artificial living body base material to be inserted into a human body and a coating film containing a copper based compound on the surface of the base material. At this time, the compound is a copper-based compound of CuxSy (x / y = 0.8-1.5) produced by reacting copper sulfate (CuSO ₄ ) with a sulfur flame at a molar ratio of 1: 1 in an aqueous solution.

In the preferred artificial biomaterial of the present invention, the coating film may be formed by any one of wet coating, vapor deposition, and plating. When the coating film is formed by wet coating, the coating solution for forming the coating film may contain more than 0 wt% and less than 50 wt%, more preferably 0.01 to 30 wt%, of the compound.

In the artificial biomaterial of the present invention, the artificial living body base material may be any one selected from a metal material, a ceramic material, a polymer material, and a composite material in which at least one of them is mixed. The artificial biomaterial may be one in which a compound is coated on the surface of any one of the metal material, the ceramic material and a part of the composite material. The artificial biomaterial may be coated with the compound on the surface of any one of the polymer material and a part of the composite material, or the compound may be dispersed in the base material.

In a preferred embodiment of the present invention, the artificial biomaterial in which the compound is dispersed is contained in an amount of 0.1 to 2 wt% with respect to the whole biomaterial, and is at least one selected from the group consisting of chromium, manganese, iron, cobalt, nickel, And may include fine particles. A coating liquid containing 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyesters, water-soluble urethane and water-soluble acrylic is applied before coating the compound on the artificial biomaterial can do.

In a preferred embodiment of the present invention, the artificial living body material is applied to the artificial joint and may include the compound plating film plated on the surface of the artificial joint base material. The plating may be electroless plating or electrolytic plating. It is preferable that the plating is performed by electroless plating first, followed by electrolytic plating. The thickness of the plated film may be 0.01 to 5.0 mu m.

In the artificial joint which is an artificial biomaterial of the present invention, the surface of the artificial joint may be treated with a conductive polymer emulsion solution containing a transition metal before forming the plating film. 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyester, water-soluble urethane and water-soluble acrylic are applied to the surface of the artificial joint . At this time, the residual solid content of the water-dispersed coating liquid is preferably 0.001 to 0.1 g / m ² .

According to the artificial biomaterial containing the copper-based compound of the present invention, by coating the compound containing copper sulfide, the cost is relatively low, the processing is easy, and there is no toxicity. In addition, since the compound containing copper sulfide is excellent in antimicrobial activity, it can be applied to improve the antimicrobial activity of an artificial biomaterial. Further, the surface of the artificial joint, which is one of the artificial living materials, is plated with a compound containing copper sulfide to conform to the shape of the artificial joint and coated on a smooth surface, and has high antibacterial and film strength. Plating on artificial joints is a coating method suitable for artificial joints that are repeatedly rotated and have to withstand user's load, since the film strength is relatively high.

1 is an XRD graph showing the crystal structure of copper sulfide produced by the present invention.
2A and 2B are photographs of a plan view and a cross-sectional view, respectively, of an artificial biomaterial coated with copper sulfide produced by the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The embodiments described below can be modified into various other forms, and the scope of the present invention is not limited to the embodiments described below. The embodiments of the present invention are provided to enable those skilled in the art to more fully understand the present invention.

An embodiment of the present invention proposes an artificial biomaterial which is relatively inexpensive, easy to process, has no toxicity, and has excellent antimicrobial activity by using a compound containing copper sulfide. Artificial biomaterials are inserted into the human body to replace damaged parts or assist in the treatment of organs. Currently, there are artificial bones, artificial joints, artificial teeth, and stents. Methods for imparting antimicrobial properties to such artificial biomaterials include a dispersion method in which a compound containing copper sulfide is dispersed in an artificial biological material and a coating method in which the compound is coated on the surface of the material. The embodiment of the present invention will be described in detail by dividing it into the dispersion method and the coating method. The process of plating a copper-based compound on an artificial joint, which is an artificial biomaterial, will be described in detail.

An artificial living body base material can be roughly classified into a metal material, a polymer material, a ceramic material, and a composite material. Examples of the metallic material include stainless steel, a chromium-cobalt alloy, and a titanium-based alloy. Examples of the ceramic material include a calcium oxide-silica-based activated glass and a crystallized glass, and a calcium phosphate compound including apatite as an inorganic component of bone. The utilization of the thermoplastic resin, particularly the biodegradable polymer, is increasing in the polymer material, and the composite material is a mixture of at least one selected from metals, polymers and ceramics at a certain ratio.

A polymer resin, that is, a thermoplastic resin and a thermosetting resin are all possible, and a thermoplastic resin advantageous for molding is more preferable. The thermoplastic resin mainly includes polyethylene terephthalate, polylactic acid, polyethylene, polypropylene, polycarbonate, polymethylmethacrylate, polyvinyl chloride, polyurethane, silicone, and the like. The thermosetting resin is preferably an epoxy resin or the like. Polyurethane is more preferable because it is flexible, nontoxic and has good chemical resistance.

The copper-based compound applied to the embodiment of the present invention was synthesized by reacting copper sulfate (CuSO ₄ ) and a sulfur flame in an aqueous solution at a molar ratio of 1: 1 at a temperature of 10 to 80 ° C. At this time, the copper sulfide synthesized by using sodium sulfide and copper sulfate was the best. The chemical structure of the synthesized copper sulfide particles is in the form of Cu _x S _y , and the synthesis conditions are limited so that the ratio x / y is 0.8 to 1.5. Examples of the sulfur flame that can be used in the present invention include sodium sulfide, iron sulfide, potassium sulfide, and zinc sulfide.

When the reaction temperature is lower than 10 캜, the reactivity between the copper sulfate and the salt is poor when the copper nanoparticles are synthesized, but the antibacterial property is good. However, the yield for producing copper sulfide is low. When the reaction temperature is 80 ° C or higher, the reaction rate becomes excessively high, and the density of the crystals on the surface of the copper sulfide increases and the antibacterial property decreases as the copper concentration increases. Further, when the binding ratio of x / y of the copper-based nanoparticles is 0.8 or less, the concentration of sulfur (S) becomes excessively high and the antibacterial property is good. However, the chemical stability of copper sulfide drops. If it is more than 1.5, the copper concentration increases and the antibacterial property is lowered.

Copper sulphide is decomposed at a temperature of 400 ° C or higher, and sulfur (S) is released from copper sulfide (CuS). Pores are formed in the copper sulfide (CuS) by the separated sulfur (S). A biomaterial such as a metal material or a ceramic material usually forms an artificial biomaterial by casting, sintering, or the like. Since the casting or sintering proceeds at a temperature of 400 ° C or higher at which sulfur (S) is separated from copper sulfide (CuS), the copper sulfide dispersion method is not useful. An artificial biomaterial made of a metal material or a ceramic material is preferably a coating method in which the surface of the biomaterial is coated. Dispersion of copper sulfide microparticles in a polymer material or a part of a composite material can be performed by a kneading method with a relatively low processing temperature, and therefore, both the dispersion method and the coating method can be utilized depending on the situation.

For convenience of explanation, the biomaterial is classified into a first material which is useful for the coating method, a second material which can be dispersed, and a third material which is both a dispersion method and a coating method. Embodiments of the present invention will be described mainly with respect to a third material which can be both a dispersion method and a coating method. The dispersion method of the third material can be applied to the first and second materials, and the coating method of the third material can be applied to the first and second materials. Hereinafter, among the above compounds, copper sulfide will be mainly described.

<Artificial Biomaterials in which copper sulfide microparticles are dispersed>

As the dispersion method, a mixing method and a compounding method can be applied, and a kneading method is particularly preferable. The shape of the biomaterial can be completed by extrusion, injection, cutting, and the like. The kneading method is used to increase the dispersibility between the polymer resin and the copper sulfide microparticles. The kneading was carried out at a barrel temperature 30 to 50 DEG C higher than the melting temperature of the resin. The kneading is carried out in a kneader equipped with a biaxially-oriented screw having excellent dispersibility rather than a uniaxial screw. The L / D ratio range of the kneader is preferably 30 to 40. The kneaded resin is stored in a bunker in the form of a chip. In case of extrusion, the extrusion temperature is 30 to 50 ° C higher than the melt temperature of the polymer resin used. Thereafter, it is produced in the form of artificial biomaterial required through molding, primary cooling, heat treatment, and secondary cooling. The content of the copper sulfide is preferably greater than 0 wt% and less than 50 wt%, more preferably from 0.01 to 30 wt%, based on the weight of the bulk material.

However, when the artificial biomaterial is produced by kneading the copper sulfide microparticles according to the embodiment of the present invention with the polymer resin, the dispersibility of the copper sulfide microparticles is deteriorated. As a result, a phenomenon in which the pressure (extrusion pressure) increases during extrusion may occur. In order to prevent the extrusion pressure from rising, at least one metal fine particle selected from the group consisting of chromium, manganese, iron, cobalt, nickel and zinc, which is a transition metal selected in four cycles of the periodic table, 0.1 to 2 wt% can be added. When the transition metal is mixed with a copper-based compound, the transition metal is excellent in dispersibility as well as antimicrobial activity compared with a typical metal such as Al.

In order to reduce the extrusion pressure, it is preferable that the average particle diameter of the metal fine particles is smaller than the particle diameter of the copper-based compound fine particles. When kneaded with the thermoplastic resin, the mixing pressure of the metal fine particles was increased when the mixing concentration was lower than 0.1 wt% or higher than 2 wt%. As described above, the metal microparticles are added to control the extrusion pressure, and the antimicrobial properties required in artificial biomaterials can be obtained by using only copper-based compounds. Accordingly, an artificial biomaterial can be produced without metal fine particles within the scope of the present invention. At this time, the added metal fine particles were selected so as not to impair the antimicrobial activity required in the artificial biomaterial of the present invention.

<Artificial biomaterials coated with copper sulfide microparticles>

The surface coating of copper sulfide on an artificial biomaterial according to an embodiment of the present invention can be performed by various methods such as wet coating, plating, and deposition. Wet application is advantageous in that the bonding strength is lower than that of plating or vapor deposition, but the method is simple and inexpensive. The coating solution is prepared by adding copper sulfide powder to a mixed solvent of IPA, toluene, benzene, and a binder and then sufficiently dispersing the coating solution. The coating solution is coated on the surface of the artificial biological material by dip coating, spray coating, This is possible. Concentration of copper sulfide is determined by considering the dispersibility and thickening phenomenon. When a dispersant is used, it is possible to prepare a coating solution at a high concentration. The content of the copper sulfide is preferably greater than 0 wt% and less than 50 wt%, more preferably from 0.01 to 30 wt%, based on the coating solution.

The thickness of the coating is suitably about 300 to 600 Å, and the thickness can be controlled by repeating the coating or adjusting the viscosity of the coating solution. The coated biomaterial is dried and it is advisable to distinguish between the first stage low temperature drying step and the second stage sintering step. Step 1 is a step of gradually removing the moisture and the solvent of the coating liquid, and is preferably sufficiently dried at 90 to 100 ° C for 1 to 2 hours. Step 2 is the step of increasing the bonding strength between copper sulfide. Since copper sulfide tends to be decomposed at 400 ° C or higher, sintering at 200 to 300 ° C for 1 to 2 hours is preferable. When the coating is dried at an excessively high temperature and for a long time, the coating film is split and the appearance of the coating film is deteriorated, and the sulfur component is released, resulting in a remarkably poor antibacterial property. Especially in the case of spray coating, it is better to use a supercritical fluid such as carbon dioxide to prepare a coating solution. Supercritical conditions can shorten drying times and resolve harmful effects of organic solvents.

For deposition, copper sulfide is first synthesized to produce a target for vacuum deposition. A water-dispersion coating liquid containing 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyester, water-soluble urethane and water-soluble acrylic is applied to the surface of the biomaterial. The water dispersion coating liquid can increase the vapor deposition strength. The residual solids in the water-dispersed coating liquid are adjusted to be 0.001 to 0.1 g / m ² . Deposition is carried out under a vacuum of 10 ^-5 to 10 ^-3 torr so that the vapor pressure of the metal is maintained at 10 ^-2 to 10 ^-1 , and copper sulfide is deposited on the surface of the bio-material at a thickness of 300 to 600 Å. The deposition strength of the deposition layer is preferably at least 60 g / 25 mm or more.

The plating is disadvantageous in that it is difficult and expensive compared to vapor deposition or wet application, but it is suitable for artificial biomaterial which is used repeatedly over a long period because of its excellent durability. In order to increase the plating strength, the surface of the biomaterial is preferably treated with a conductive polymer emulsion solution containing a transition metal before plating. A water-dispersed coating liquid containing 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyester, water-soluble urethane and water-soluble acrylic is applied to the surface of the biomaterial. The residual solids in the water-dispersed coating liquid are adjusted to be 0.001 to 0.1 g / m ² . Plating can be performed by electrolytic plating or electroless plating after ionizing the copper sulfide in a plating bath. For example, the plating can be carried out by placing a copper salt and a compound in a plating solution, depositing copper sulfide by using a reducing agent and adhering to the surface of the biomaterial. The plating thickness of the copper sulfide plated on the biomaterial is preferably 0.01 to 5.0 mu m.

In the examples of the present invention, dip coating was used. Specifically, a predetermined amount of copper sulfide is added to a solvent such as IPA (isopropyl alcohol) and stirred at room temperature for several hours to prepare a coating solution having excellent dispersibility. Thereafter, the artificial biomaterial was dip-coated using the coating solution. The coated biomaterial was first dried at several degrees Celsius for several hours and then subjected to secondary heat treatment at 400 degrees Celsius for several tens of minutes. For use as a biomaterial with excellent antimicrobial properties, the coating was repeated in the same manner so that the copper sulfide concentration could be sufficiently coated on the surface of the artificial biomaterial.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are intended to illustrate but not limit the invention. The performance of the artificial biomaterials prepared in Examples and Comparative Examples of the present invention was evaluated by the following methods.

(1) Antimicrobial activity

 Escherichia coli (ATCC 25922) was used as a strain to bring the test strain into contact with the specimen. The specimen was then incubated at 25 ° C for 24 hours, and the bacterial count was counted to evaluate the antibacterial activity of the specimen.

(2) Extrusion pressure

The dispersibility of the copper sulfide and metal fine particles added in the polymer resin was evaluated by the change value of the extrusion pressure applied to the filter. (Kg / (mm ² × h)] = ΔP / h} of the filter pressure applied to the 350 mesh filter per a fixed time when the resin was extruded at a rate of 30 kg per hour using a pilot extruder. The better the dispersibility of the copper sulfide and the metal fine particles was.

&Lt; Example 1 >

CuSO ₄ and Na ₂ S were added to distilled water, and the mixture was stirred for 30 minutes. Then, the mixture was reacted in an isothermal reactor at 50 ° C. for 30 minutes to synthesize copper sulfide microparticles. At this time, the sulfur content of the synthesized copper sulfide was 45 mol%. The crystal structure of the synthesized copper sulfide had a unique structure of copper sulfide as shown in Fig. According to Fig. 1, no peak was observed due to the absence of a crystal structure of sulfur, but peaks at 55 degrees, 65 degrees, 99 degrees, 125 degrees and 137 degrees of copper. X-ray powder diffraction (XRD, XD-3A, Shimadzu, Japan) was used for observation of the fine particles. A method of coating the surface of a living body base material made of a copper alloy with Ti as described above with a Ti alloy (Ti-6Al-4V) is as follows. First, 0.1wt% of copper sulfide is mixed with IPA (isopropyl alcohol) Lt; 0 &gt; C for a period of time to prepare a coating solution having excellent dispersibility.

Using this coating solution, a Ti alloy base material having a diameter of 1 cm and a length of 10 cm was dip-coated. The coated Ti alloy was first dried at 50 캜 for one hour and then subjected to secondary annealing at 350 캜 for 30 minutes. For use as a biomaterial excellent in antibacterial property, the coating was repeatedly formed to have a thickness of 2 탆 by the same method so that the copper sulfide concentration could be sufficiently coated on the surface of the Ti alloy biomaterial. The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 2 &gt;

The coating solution containing 10wt% of copper sulfide synthesized as in Example 1 was dip-coated on an artificial living body base material composed of apatite hydroxide 1cm in diameter and 10cm in length. The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 3 &gt;

The coating solution containing 30wt% of copper sulfide synthesized as in Example 1 was dip-coated on an artificial living body base material made of low density polyethylene (LDPE, specific gravity 0.92) having a diameter of 1 cm and a length of 10 cm. The antimicrobial activity of the biomaterial thus prepared was measured as described above. 2A and 2B are photographs showing planar and cross-sectional views of a coated state of an artificial living body base material made of LDPE.

<Example 4>

0.1 wt% of copper sulfide synthesized as in Example 1 was placed in a low density polyethylene (LDPE, specific gravity 0.92) and 1.5 wt% of zinc (Zn) fine particles were mixed to improve the extrusion pressure. . The manufactured chip was injected at an extrusion pressure of 0.07 kg / (mm ² × h) at a temperature of 130 ° C. using an injection machine to produce an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the mechanical properties of the biomaterial were improved through two cooling steps and a heat treatment step. The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 5 &gt;

10wt% of copper sulfide synthesized as in Example 1 and 1wt% of nickel (Ni) fine particles were put into low density polyethylene to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 0.1 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 6 >

5% by weight of copper sulfide and 0.2% by weight of manganese (Mn) were added to low density polyethylene in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 0.05 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 7 &gt;

Copper sulphide having a content of 20 wt% and iron (Fe) having a concentration of 0.6 wt% were put into high density polyethylene (HDPE) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 0.2 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 8 &gt;

Copper sulphide having a content of 30 wt% and cobalt (Co) having a concentration of 0.7 wt% were put into polypropylene (PP) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 0.3 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Example 9 &gt;

Copper sulphide having a content of 40 wt% and chromium (Cr) having a concentration of 2 wt% were put into polyethylene terephthalate (PET) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 0.5 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Comparative Example 1 &

 An artificial biomaterial having a diameter of 1 cm and a length of 10 cm was made of a Ti alloy (Ti-6Al-4V), and the antimicrobial activity was measured as described above.

&Lt; Comparative Example 2 &

 An artificial biomaterial having a diameter of 1 cm and a length of 10 cm was prepared from hydroxyapatite and the antimicrobial activity was measured as described above.

&Lt; Comparative Example 3 &

 An artificial biomaterial with a diameter of 1 cm and a length of 10 cm was prepared with low density polyethylene (LDPE) and the antimicrobial activity was measured as previously described.

&Lt; Comparative Example 4 &

Copper sulphide having a content of 20 wt% and iron (Fe) having a concentration of 0.01 wt% were put into high density polyethylene (HDPE) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 5 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Comparative Example 5 &

Copper sulphide having a content of 30 wt% and cobalt (Co) having a concentration of 40 wt% were put into polypropylene (PP) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 15 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

&Lt; Comparative Example 6 &gt;

Copper sulphide having a content of 40 wt% and aluminum (Al) having a concentration of 2 wt% were put into polyethylene terephthalate (PET) in the same manner as in Example 4 to prepare an artificial biomaterial having a diameter of 1 cm and a length of 10 cm. At this time, the extrusion pressure was 12 kg / (mm ² × h). The antimicrobial activity of the biomaterial thus prepared was measured as described above.

Table 1 compares the antibacterial properties (dogs / mL) of the artificial biomaterials of Examples 1 to 9 and Comparative Examples 1 to 6 of the present invention. At this time, it means that the number of bacteria of Escherichia coli (ATCC 25922) per mL is 10 ¹⁰ or more, which means that measurement is impossible.

division

Living body
material Conductor particle Container sheet Copper sulfide
Particulate metal
Particulate Extrusion pressure
(? P / h)
Antimicrobial activity
(Dogs / mL)
Particle size
(nm) content
(wt%) metal
Kinds Particle size
(nm) content
(wt%)

room
city
Yes

One Ti alloy 55 0.1 / / / / 3.2 x 10 ⁴ 2 Apatite 55 10 / / / / 3.4 × 10 ⁴ 3 LDPE 55 30 / / / / 3.2 x 10 ⁴ 4 LDPE 50 0.1 Zn 10 1.5 0.07 4.0 × 10 ⁷ 5 LDPE 55 10 Ni 15 One 0.1 3.2 × 10 ⁶ 6 LDPE 20 5 Mn 10 0.2 0.05 6.5 × 10 ⁶ 7 HDPE 45 20 Fe 25 0.6 0.2 2.2 x 10 ⁵ 8 PP 85 30 Co 30 0.7 0.3 1.2 × 10 ⁵ 9 PET 100 40 Cr 30 2 0.5 1.3 x 10 ⁵
ratio
School
Yes

One Ti alloy / / / / / / Side charge 2 Apatite / / / / / / Side charge 3 LDPE / / / / / / Side charge 4 LDPE 45 20 Fe 25 0.01 5 7.2 x 10 ⁵ 5 PP 85 30 Co 85 40 15 5.2 × 10 ¹⁰ 6 PET 100 40 Al 30 2 12 6.2 × 10 ¹⁰

According to Table 1, the coating solution was 0.1 to 30 wt% of copper sulfide and had a diameter of 55 nm. The antimicrobial activity in Examples 1 to 3 was about 3.2 x 10 ⁴ (number / ml). In contrast, in Comparative Examples 1 to 3 in which copper sulfide was not coated, antimicrobial activity was significantly deteriorated to such an extent that measurement was impossible. It was found that antibacterial activity was higher than that of Examples 4 to 9 dispersed by kneading when copper sulfide was coated. However, the coating may be less stable over time than the dispersion. In practical application of some artificial biomaterials, it is necessary to consider the stability of the coating film.

Next, regarding the artificial biomaterials produced by kneading, the bio-materials of Examples 4 to 9 of the present invention contained 0.1 to 40 wt% of copper sulfide. The added fine metal particles are at least one selected from chromium, manganese, iron, cobalt, nickel and zinc, and the concentration is 0.1 to 2 wt% with respect to the whole biomaterial. At this time, the antibacterial activity was 1.2 × 10 ⁵ to 6.5 × 10 ⁶ (number / ml). Also, the extruded pressure showed a value within the range of 0.05 to 0.5 kg / (mm ² × h). On the other hand, Comparative Examples 1 to 3, in which copper sulfide was not dispersed, were greatly deteriorated to such an extent that antibacterial activity could not be measured.

Comparative Example 4 is a case where the concentration of iron (Fe) as the metal fine particle, and Comparative Example 5 is a case where the concentration of cobalt (Co) as the metal fine particle does not satisfy 10 to 30 nm and 0.1 to 2 wt% as an embodiment of the present invention. At this time, the antimicrobial activity was 7.2 × 10 ⁵ (cells / mL) and 5.2 × 10 ¹⁰ (cells / mL), respectively. Specifically, in Comparative Example 4 in which the concentration of the metal fine particles deviates from the examples of the present invention, the antimicrobial activity did not deteriorate significantly, but was unsuitable for extrusion pressure of 5 kg / (mm ² × h). In Comparative Example 5 in which the concentration was out of the range, the extrusion pressure was not able to be extruded to 15 kg / (mm ² × h), and the antibacterial property tended to be greatly deteriorated.

Comparative Example 6 is a case where aluminum (Al) other than chromium, manganese, iron, cobalt, nickel and zinc, which are metal fine particles proposed by the present invention, is added. At this time, the antimicrobial activity was 6.2 × 10 ¹⁰ (dog / mL) and the extrusion pressure was 12 kg / (mm ² × h). Aluminum is a typical metal in three cycles of the periodic table. This is different from transition metals in the four cycles of the periodic table of the present invention. When aluminum is added, antimicrobial activity deteriorates, and the extrusion pressure is high, resulting in poor production efficiency. Accordingly, the metal fine particles of the present invention are preferably chromium, manganese, iron, cobalt, nickel and zinc, which are transition metals in four cycles of the periodic table.

<Copper-plated artificial joints>

Artificial joints are made of metal or ceramics, such as a pair of articulation and matching articulation, to replace the function of the joints of the human body. The artificial joint can rotate according to the user's movement or bear the load of the user. The materials used for the artificial joints are various, but hard metal or ceramic material such as Ti alloy steel which is resistant to wear and abrasion is often used. These artificial joints are manufactured in a sophisticated form including various bends. Artificial joints are smooth and precisely machined to minimize traction caused by movement.

Plating has a disadvantage that it is difficult and expensive compared with deposition or wet application, but it is suitable for artificial joints which are used repeatedly over a long period because of its excellent durability. In order to increase the film strength, it is preferable to treat the surface of the artificial joint with a conductive polymer emulsion solution containing a transition metal before plating. 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyester, water-soluble urethane and water-soluble acrylic are applied to the surface of the artificial joint. The residual solids in the water-dispersed coating liquid are adjusted to be 0.001 to 0.1 g / m ² . Plating is a method in which copper sulfide is placed in a plating bath and then plated on the plated body. However, there is a method in which a copper salt and a compound are put into a plating bath and plating is carried out on the surface of the biomaterial using a reducing agent It is more reasonable. The plating thickness of the copper sulfide plated on the biomaterial is preferably 0.01 to 5.0 mu m.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are intended to illustrate but not limit the invention. The performance evaluation of the artificial joint manufactured in the examples and the comparative examples of the present invention was carried out as follows. Hereinafter, among the above compounds, copper sulfide will be mainly described.

(1) Surface state of coating film

The surface state of the coating film was observed with a microscope to evaluate the presence or absence of protrusion on the surface of the coating film and the state of uncoated state, and the number of protrusions and unplated water observed per 10 cm ㅧ 10 cm was observed and evaluated.

○: 1 or less

?: 2 to 4

×: 5 or more

(2) Coating film thickness

The thickness of the coated film was measured using SEM (sanning electron microscopy, JSM-6390A, JEOL, USA).

(3) Coating film strength

 The coating strength of the coating film was controlled by the adhesion of the coating film, and the adhesion strength of the coating film measured when pulling with a load of 90 kg / sec was measured using a pull-down break point tester (Phto Teohnioa, USA).

○: 700 kg / cm ² or more

?: 100 to 700 kg / cm ²

X: 100 kg / cm ² or less

(4) Antimicrobial activity

Escherichia coli (ATCC 25922) was used as a strain to bring the test bacteria into contact with the specimens. The specimens were incubated at 25 ° C for 24 hours, and the bacterial counts of the specimens were evaluated. The antimicrobial activity was excellent when the number of bacteria was less than 10 &lt; ⁷ &gt; Escherichia coli (ATCC 25922) was labeled ^{10 if the} number of bacteria was more than 10 ¹⁰ per mL and measurement was impossible.

&Lt; Example 10 >

A water-dispersion coating liquid containing 0.5 wt% of colloidal transition metal fine particles and 1.0 wt% of emulsion of water-soluble polyester was applied to the surface of a Ti alloy (Ti-6Al-4V). The residual solids in the water-dispersed coating liquid were adjusted to 0.05 g / m ² . Then CuSO ₄ and Na ₂ S were added to the plating bath at a molar ratio of 1: 1 and copper sulfide was formed by using a reducing agent (composed of 70% formalin and 30% surfactant) as a Ti alloy having a diameter of 1 cm and a length of 10 cm (Ti-6Al -4V). The thickness of the plated copper sulfide was 2 mu m.

The crystal structure of the precipitated copper sulfide had a unique structure of copper sulfide as shown in Fig. According to Fig. 1, no peak was observed due to the absence of a crystal structure of sulfur, but peaks at 55 degrees, 65 degrees, 99 degrees, 125 degrees and 137 degrees of copper. X-ray powder diffraction (XRD, XD-3A, Shimadzu, Japan) was used for observation of the fine particles. The antimicrobial activity, surface condition and film strength of the artificial joints thus prepared were measured as described above.

&Lt; Example 11 >

Copper sulfide was deposited on the surface of Cr-Co-Mo alloy (SCM440H) having a diameter of 1 cm and a length of 10 cm as in Example 10 to form a coating film. The antimicrobial activity, surface condition and film strength of the artificial joints thus prepared were measured as described above.

&Lt; Example 12 >

Copper sulphide was deposited on the surface of zirconia-alumina composite ceramics having a diameter of 1 cm and a length of 10 cm as in Example 10 to form a coating film. The antimicrobial activity, surface condition and film strength of the artificial joints thus prepared were measured as described above.

&Lt; Comparative Example 7 &

0.1wt% of copper sulfide was mixed with IPA (isopropyl alcohol) and stirred at room temperature for 1 hour to prepare a coating solution. Using this coating solution, a Ti alloy (Ti-6Al-4V) having a diameter of 1 cm and a length of 10 cm was dip-coated. The coated Ti alloy (Ti-6Al-4V) was first dried at 50 ° C for 1 hour and then subjected to secondary annealing at 400 ° C for 30 minutes. For artificial joints with excellent antibacterial properties, the coating was repeatedly formed to have a thickness of 2 탆 by the same method so that the copper sulfide concentration could be sufficiently coated on the surface of the Ti alloy (Ti-6Al-4V). The antimicrobial activity, surface condition and film strength of the artificial joints thus prepared were measured as described above.

&Lt; Comparative Example 8 >

Copper sulphide was synthesized to prepare a target for vampirism. A water-dispersion coating liquid containing 0.5 wt% of colloidal transition metal fine particles and 1.0 wt% of emulsion of water-soluble polyester was applied to the surface of a Ti alloy (Ti-6Al-4V) having a diameter of 1 cm and a length of 10 cm. The residual solids in the water-dispersed coating liquid were adjusted to 0.05 g / m ² . The deposition was carried out under a vacuum of 10 ^-5 to 10 ^-3 torr so that the vapor pressure of the metal was maintained at 10 ^-2 to 10 ^-1 to deposit copper sulfide with a thickness of 400 Å on the surface of the Ti alloy (Ti-6Al-4V) . The antimicrobial activity, surface condition and film strength of the artificial joints thus prepared were measured as described above.

&Lt; Comparative Example 9 &

The antimicrobial activity and the film strength of a Ti alloy (Ti-6Al-4V) having a diameter of 1 cm and a length of 10 cm without a copper sulfide coating film were measured as described above.

Table 2 compares the antibacterial properties (dogs / mL), the surface state (pieces / 100 cm 2) and the film strength (kg / cm 2) of the artificial joints of Examples 10 to 12 and Comparative Examples 6 to 8 of the present invention.

division

Artificial joint
Copper sulfide
Presence
coating
Way Properties Antimicrobial activity Surface condition Film strength room
city
Yes 10 Ti alloy ○ Plated ○ ○ ○ 11 Co alloy ○ Plated ○ ○ ○ 12 Zirconia series
ceramic ○ Plated ○ ○ ○ ratio
School
Yes 7 Ti alloy ○ Wet application ○ × × 8 Ti alloy ○ deposition ○ △ △ 9 Ti alloy × / Side charge / /

According to Table 2, Examples 10 to 12 and Comparative Examples 7 and 9 in which a copper sulfide coating film was formed by a plating method, a wet coating method and a vapor deposition method were excellent in antimicrobial activity. The copper sulfide coating showed high antimicrobial activity irrespective of the coating method. On the contrary, in Comparative Example 9 in which the copper sulfide coating film was not provided, the antibacterial property was extremely deteriorated to such an extent that measurement was impossible. However, when the coating is applied to the wet non-plating process, the film strength and showed a value of 100kg / cm ² or less, the coating film strength of the deposition was larger than the small and 100kg / cm ² than 700kg / cm ^2. When the film strength is less than 700 kg / cm ² , it is difficult to apply the present invention to the artificial joint according to the embodiment of the present invention. In addition, the surface state of the plated film by the plating method was superior to the wet coating method or the vapor deposition method. Therefore, it was found that the coating method suitable for artificial joints is a plating method.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but many variations and modifications may be made without departing from the scope of the present invention. It is possible.

Claims (17)

An artificial living body base material inserted into a human body; And
A coating film containing a copper compound is formed on the surface of the base material,
The copper-based compound is CuxSy (x / y = 0.8-1.5) produced by reacting copper sulfate (CuSO ₄ ) and a sulfur flame at a molar ratio of 1: 1 in an aqueous solution,
Wherein the Cu x S y (x / y = 0.8 to 1.5) contains a copper compound as a crystal form having a peak corresponding to the crystal structure of copper in an XRD graph. The artificial biomaterial according to claim 1, wherein the compound is copper sulfide. The artificial biomaterial according to claim 1, wherein the coating layer is formed by any one of wet coating, vapor deposition, and plating. 4. The method of claim 3, wherein the coating film is formed by wet coating, and the coating liquid for forming the coating film contains greater than 0 wt% and less than 50 wt% of the copper-based compound. Biomaterials. The artificial living body material according to claim 3, wherein the coating film is formed by wet coating, and the coating liquid for forming the coating film contains 0.01 to 30 wt% of the compound. The artificial biomaterial according to claim 1, wherein the artificial living body base material is any one selected from a metal material, a ceramic material, a polymer material, and a composite material in which at least one of them is mixed. 7. The artificial biomaterial according to claim 6, wherein the artificial biomaterial is formed by coating a compound on the surface of any one of the metal material, the ceramic material and a part of the composite material, Biomaterials. The artificial biomaterial according to claim 6, wherein the artificial biomaterial is coated with the compound on the surface of any one of the polymer material and a part of the composite material. [2] The method of claim 1, wherein the artificial biomaterial coated with the compound comprises 0.1 to 2 wt% of the metal microparticles and at least one metal microparticle selected from the group consisting of chromium, manganese, iron, cobalt, nickel, Wherein the copper-based compound is added to the copper-based compound. The artificial biomaterial according to claim 1, wherein the artificial biomaterial is applied to an artificial joint and comprises the compound plating film plated on the surface of the artificial joint base material. The artificial biomaterial according to claim 10, wherein the plating is electroless plating or electrolytic plating. 11. The artificial biomaterial according to claim 10, wherein the plating is performed by electroless plating first, followed by electrolytic plating. 11. The artificial biomaterial according to claim 10, wherein the thickness of the plating film is 0.01 to 5.0 mu m. The artificial biomaterial according to claim 10, wherein the surface of the artificial joint is treated with a conductive polymer emulsion solution containing a transition metal before forming the plating film. 15. The method according to claim 14, wherein 0.01 to 1.0 wt% of colloidal transition metal fine particles and 0.01 to 2.0 wt% of at least one emulsion selected from water-soluble polyester, water-soluble urethane and water- Wherein the copper-based compound is applied to the surface of the living body. The artificial biomaterial according to claim 15, wherein the residual solids of the water-dispersed coating liquid is 0.001 to 0.1 g / m ² . The artificial biomaterial according to claim 1, wherein the artificial living body base material comprises a polyurethane resin or a silicone resin.

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