DE102012210804A1 - Producing antibacterial layer on base body made of e.g. titanium-based alloy, comprises carrying out electrochemical process in first aqueous electrolyte having aqueous solution containing e.g. silver(I) phosphate and ammonium hydroxide - Google Patents

Abstract

Producing an antibacterial layer on a base body made of titanium or a titanium-based alloy, comprises carrying out an electrochemical process in a first aqueous electrolyte, preferably at least two first aqueous electrolytes. The first aqueous electrolyte comprises an aqueous solution containing: silver(I) phosphate and ammonium hydroxide; gallium(III) nitrate, L-(+)-ascorbic acid and phosphoric acid; zinc(II) acetate, ammonium dihydrogen phosphate and ammonium hydroxide; or bismuth oxide nitrate, bismuth salicylate, bismuth citrate, ammonium bismuth citrate and/or bismuth-triacetate. Producing an antibacterial layer on a base body made of titanium or a titanium-based alloy, comprises carrying out an electrochemical process in a first aqueous electrolyte, preferably at least two first aqueous electrolytes. The first aqueous electrolyte comprises an aqueous solution containing: silver(I) phosphate and ammonium hydroxide; gallium(III) nitrate, L-(+)-ascorbic acid and phosphoric acid; zinc(II) acetate, ammonium dihydrogen phosphate and ammonium hydroxide; or bismuth oxide nitrate, bismuth salicylate, bismuth citrate, ammonium bismuth citrate, bismuth-triacetate, ammonium dihydrogen phosphate and/or disodium ethylenediaminetetraacetic acid. An independent claim is also included for an implant, preferably osteo-synthetic implant or dental implant comprising the base body made of titanium or titanium-based alloy with an applied bactericidal layer.

Description

The invention relates to a method for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy and to the use of the base body coated in this way as an implant.

Bone defects are caused by bone fistulas, debris fractures and tumors. The treatment can be carried out by filling with suitable implants made of titanium and titanium-based alloys. Basic bodies made of titanium or titanium-based alloys for osteosynthesis implants and also dental implants can be provided with untreated, electrochemically coated and in mechanically aftertreated form or combinations thereof with biotolerant, bioinert, biocompatible, bioactive or osteoinductive properties. Thus, ingrowth of the surrounding bone tissue for permanent implants can both be favored and prevented for temporary implants. The treatment of bone defects becomes even more problematic, even with advanced implants or optimized implant coatings of the highest technological standard and low complication rate, whenever additional bacterial infections manifest themselves.

Infections of endoprostheses and biomaterials represent a central problem in the treatment of bone and joint diseases. For example, infection rates of approximately 5% are described in the osteosynthetic stabilization of fractures; in primary total joint replacement the infection rates are approximately 0.5% -2 %. For the endoprosthetic joint replacement after the resection of bone tumors infection rates of 5% -35% are given. The modern surgical procedures under consideration of aseptic conditions and an optimized perioperative antibiotic prophylaxis do not adequately protect against bacterial infections. The human body consists of about 10 ¹³ cells and is populated with about 10 ¹⁴ microorganisms from up to 500 different species ( Schumann, W. (2011), Biotope Man, We Are Colonized, Biology in Our Time, 41: 182-189 ) The microorganisms have been colonizing the earth for 2 · 10 ⁹ years, whereas humans have only been trying to adapt to the conditions on earth for about 40,000 years. Although this results in an evolutionary advantage of the microorganisms, mammals and microorganisms are in a steady state of defense and pathogenicity.

Dangerous germs that shift the steady state in their favor and thus cause increased pathogenicity, are usually coagulase positive cocci such as Staphylococcus aureus. Cocci (S. epidermidis), which do not secrete coagulation factors and thus can not cause coagulation of the blood to mask themselves from the cleavage products with endogenous proteins, are usually non-pathogenic or can be pushed back into steady state by the defense of the body if no immunosuppression due to old age, chronic diseases, drug abuse, unbalanced diet, environmental toxins, ionizing radiation, stress, sleep deficit, lack of exercise, cold, etc. is present. Another problem is the biofilm, which does not require as previously suspected only for mechanical reasons, a much higher MIC value (maximum inhibitory concentration) of antibiotics (approximately by a factor of 10 ³ higher), but so-called quorum sensing signals for the increased resistance to antibiotics are responsible. The presence of many bacteria leads to a tremendous increase in the communication molecules (quorum sensing signals) above a certain threshold. The communication organizes the behavior of the bacteria, leads to bacterial competence, activates or deactivates different gene segments, reduces the effectiveness of the antibiotics and converts from a non-pathogenic behavior into a pathogenic behavior with biofilm formation and secretion of toxins. Hygiene, killing by antibiotic prophylaxis, prevention of attachment and high levels of effect at the site of the infection are the most effective weapons against bacterial colonization and the risk of biofilm formation. A useful property profile of implants now ranges from adjustable complication-free removability via adjustable stimulation of bone growth to accelerate fracture healing to microcidal or antibacterial features under adhesion-reducing conditions for pathogenic microorganisms. Titanium and titanium-based alloys are suitable and long-established implant base materials. Targeted design of the surface coatings and post-treatments can further increase biocompatibility as a generic term for the property profile mentioned above.

The DE 10 2008 046 198 B3 discloses a process of plasma chemical oxidation to produce a biodegradation-stable surface layer on implants of titanium and titanium alloys.

The invention is based on the object to provide an improved method for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy.

The object is achieved by a method having the features of claim 1.

Advantageous embodiments of the invention are the subject of the dependent claims.

An inventive method for producing a bactericidal layer on a base body of titanium or a titanium-based alloy comprises an electrochemical process in a first aqueous electrolyte. As the first electrolyte, an aqueous solution containing the components silver (I) phosphate (Ag ₃ PO ₄ ), for example, 0.005 mol l ^-1 to 0.05 mol·l ^-1 and ammonium hydroxide (NH ₄ OH), for example, 1.34 mol L ^-1 to 13.4 mol·l ^-1 or an aqueous solution containing the constituents copper (II) acetate (Cu (C ₂ H ₃ O ₂ ) ₂ ), for example 0.005 mol l ^-1 to 0.05 mol · l ^-1 , ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), for example 0.01 mol l ^-1 to 0.1 mol l ^-1 and ammonium hydroxide (NH ₄ OH), for example 1.34 mol·l ^-1 to 13, 4 mol·l ^-1 or an aqueous solution with the constituents gallium (III) nitrate (Ga (NO ₃ ) ₃ ), for example 0.01 mol l ^-1 to 0.1 mol·l ^-1 , L - (+) -Ascorbic acid (C ₆ H ₈ O ₆ ), for example, 0.06 mol l ^-1 to 0.6 mol l ^-1 and phosphoric acid (H ₃ PO ₄ ), for example, 0.18 mol l ^-1 to 1.8 mol l ^-1 or an aqueous solution with the constituents zinc (II) acetate (Zn (C ₂ H ₃ O ₂ ) ₂ ), for example 0.05 mol l ^-1 to 0.5 mol·l ^-1 , ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), for example 0.01 mol l ^-1 to 0.1 mol l ^-1 and ammonium hydroxide (NH ₄ OH), for example, 1.34 mol l ^-1 to 13 , 4 mol l ^-1 or an aqueous solution of bismuth oxide (BiNO ₄ ), for example, 0.05 mol l ^-1 to 0.5 mol·l ^-1 , ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), for example, 0.01 mol L ^-1 to 0.1 mol l ^-1 and ethylene diamine (C ₂ H ₈ N ₂ ), for example, 0.2 mol l ^-1 to 0.9 mol l ^-1 are used. Alternatively or in addition to bismuth oxide nitrate, bismuth salicylate and / or bismuth citrate and / or ammonium bismuth citrate and / or bismuth triacetate may be used. It is also possible to use a combination of at least two of the abovementioned aqueous solutions as the first electrolyte.

Through each of the first electrolytes, a bactericidal coating containing Ag (I), Cu (II), Ga (III), Zn (II) or bismuth (III) ions is obtained so that the body is resistant to bacterial inflammation becomes.

Metals such as silver, but also zinc, copper, gallium and bismuth are known for their antibacterial effect. Even in antiquity, for example, Ointments mixed with scraped silver (Ag). Silver filaments embedded in the gauze cover of severe burns effectively prevent their bacterial inflammation. For all metallic ingredients, it depends on the right dosage: too much harms the human body and too little leaves a dose without effect. For the antibacterial effectiveness, the concentration of the metal ions is crucial. A consistently stable effect is achieved by the applied by the process according to the invention layers of silver, zinc, copper, gallium or bismuth. The release of the metal ions is continuously possible directly from the deposited layer, so that the bactericidal effect over a longer period of time, for example a few years in the course of very slow material loss by electrochemical corrosion (about 0.5 microns per year - 1 micron per year).

In one embodiment of the method, prior to the electrochemical process, a biodegradation-stable calcium phosphate layer can be deposited on the base body by plasma chemical oxidation, in particular by precipitating the calcium phosphate layer in a second electrodeposition electrochemical plating process using an aqueous solution as the second electrolyte Components calcium di-sodium ethylenediaminetetraacetic acid (C ₁₀ H ₁₂ N ₂ O ₈ CaNa ₂ ), for example, 0.05 mol / l to 0.5 mol / l, ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), for example, 0.05 mol / l to 0.5 mol / l, phosphoric acid (H ₃ PO ₄ ), for example 0.05 mol / l to 0.5 mol / l, gallium nitrate monohydrate (Ga ₂ (NO ₃ ) ₃ × H ₂ O) , For example, 0.02 mol / l to 0.06 mol / l and ethylenediamine (C ₂ H ₈ N ₂ ), for example, 0.5 mol / l to 1.5 mol / l is used.

In this way, first a biocompatible coating on the base body of titanium or titanium alloys, by means of plasma chemical oxidation applied, the near-surface layer region is then equipped by the electrochemical process according to the invention antibacterial, so that there is an improved osteosynthesis material with adjustable properties and additional antibacterial properties.

Adjustable properties of the surface layer are, for example: bioinert, bioactive, chemically inert, chemically active, diffusion-inhibiting, resistant to degradation, porous, low in pores, adherent, sterilizable, heat-resistant, low roughness, reduced tendency to cold sweat, ductile, bone-like, brittle, etc.

An important combination of properties of this surface coating relates to the facultative removability of an implant after complication-free fracture healing when the osteosynthesis material has fulfilled its function and can be removed.

By means of a suitable elemental ratio in the second electrolyte and thus also in the correspondingly formed layer, it is furthermore possible to make the surface coating bioactive and thus to accelerate a colonization progress by osteoblasts when using the main body as an osteosynthesis implant. Of the Population progress through osteoblasts could now only be adversely affected by the competing colonization of pathogenic bacteria and subsequent degradation of the implant site. Increased complication rates may result especially in bacterial inflammations of open fractures. However, the bactericidal coating according to the invention containing Ag (I), Cu (II), Ga (III), Zn (II) or Bi (III) ions makes the basic body resistant to bacterial inflammation.

After the production process of the main body, a reproducible and optimized starting surface can be created by means of a suitable pretreatment. Subsequently, an equally porous and plastically deformable surface coating using plasma-chemical oxidation in a e.g. Ca and P ion-containing electrolyte and its characteristic layer formation potential range applied.

In one embodiment of the method, a temperature of the first and / or second electrolyte under normal pressure between 15 ° C and 50 ° C is set. The colder the electrolyte, the higher the efficiency of the active ingredient storage. The process heat can be dissipated better and the formation of the spark discharge thus runs more efficiently.

In one embodiment of the method, the base body to be coated consists of technically pure titanium or a titanium alloy with at least 60% by mass of titanium. Pure titanium is more elastic, thus more resistant to breakage and less firm than the titanium alloy Ti6Al4V. Pure titanium does not have any potentially toxic alloying elements, e.g. Vanadium (V). Both types of alloys as well as newer alloys (higher strength alloys) are used as implant material.

In one embodiment of the method, a surface roughness of the titanium basic body is generated before the electrolytic treatment R _{a of} less than 2.5 μm and R _t less than 15 μm. For bioinert or temporary implants, the starting surface should be smooth, as the process does not change the roughness of the surface but only reflects the initial state on the surface. Therefore, a corresponding pre-treatment, which produces smooth surfaces and thus improves the removability of the implant after fracture healing. In fractures in traumatology (sports injuries, motorcycle accident, dirty open fractures) in particular bioinert or temporary implants are used. In particular, these implants are additionally exposed to the risk of peri-implantitis with a high level of microbial contamination, which frequently occurs in open fractures in traumatology. This danger has so far been counteracted only with the systemic administration of antibiotics in the form of prophylaxis.

In one embodiment of the method, the main body is partially or completely immersed in the first and / or second electrolyte, anodically poled and subjected to a DC voltage less than or equal to 500 V electrochemical reactions on the surface. By an optional coating with antibacterial and / or osteoinductive (bone growth promoting) function can be different areas on one and the same implant depending on the requirements profile fluent within the limits of the functions. Older patients, for example, require osteoporotic bone-growth-promoting coatings and, due to the age-related poor immune response, at the same time mostly also provide antibacterial equipment for the implant.

In one embodiment of the method, the DC voltage is changed periodically. By pulsing the DC voltage gives a finer pore distribution on the surface and possibly also a higher active ingredient storage. When pulsing at higher frequencies than 1 kHz, for example in the MHz range, novel layer properties can be achieved by the increasingly non-thermal nature of the plasma.

In one embodiment of the method, the frequency of the periodic voltage change may be set equal to or less than 2000 s ^-1 .

In one embodiment of the method, a pore volume in the surface layer produced is reduced by mechanical compression from originally 30% by volume to 70% by volume to 0% by volume to 30% by volume.

In one embodiment of the method, the compression may be effected by the impact of pneumatically accelerated blasting bodies comprising glass beads or ceramic beads with a diameter of 5 μm to 200 μm. In this way, an adjustable surface topography with specific roughness is provided. In this way, the pores are reduced or closed and thus produce a homogeneous surface with homogeneous, lowest possible roughness.

The base body of titanium or a titanium alloy coated by means of the method according to the invention can be used as an osteosynthesis implant.

Embodiments of the invention will be explained in more detail below.

Embodiment 1

A base body of titanium or titanium-based alloys is in an aqueous first electrolyte with 0.005 mol l ^-1 to 0.05 mol·l ^-1 silver (I) phosphate (Ag ₃ PO ₄ ) and 1.34 mol·l ^-1 to 13, 4 mol·l ^-1 ammonium hydroxide (NH ₄ OH) electrochemically treated. The basic body of pure titanium or a titanium alloy (≥ 60 M .-% titanium) with a roughness of R _a ≤ 2.5 microns or R _t ≤ 15 microns is partially or completely submerged and anodically poled in the aqueous first electrolyte. The electrochemical process is carried out at DC voltage or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 ° C to 50 ° C under atmospheric pressure. After reaching a final tension of ≦ 500 V, the coated base body is freed in a multi-stage flushing with water from adhering electrolyte and dried with air. Subsequently, the coated base body can be subjected to a blasting treatment in which the pore volume of the surface layer produced is reduced by mechanical compression from originally 30% by volume to 70% by volume to 0 to 30% by volume. For this purpose, pneumatically accelerated jet bodies made of glass or ceramic with a diameter of 5 .mu.m to 200 .mu.m are used.

Embodiment 2

A base body made of titanium or titanium-based alloys in an aqueous first electrolyte with 0.005 mol l ^-1 to 0.05 mol.l ^-1 of copper (II) acetate (Cu (C ₂ H ₃ O _{2) 2),} 0.01 mol l ^-1 to 0.1 mol ^{-1 of} ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ) and 1.34 mol·l ^-1 to 13.4 mol·l ^{-1 of} ammonium hydroxide (NH ₄ OH) are electrochemically treated. The basic body of pure titanium or a titanium alloy (≥60 M .-% titanium) with a roughness of R _a ≤ 2.5 microns or R _t ≤ 15 microns is partially or completely submerged and anodically poled in the aqueous first electrolyte. The electrochemical process is carried out at DC voltage or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 ° C to 50 ° C under atmospheric pressure. After reaching a final tension of ≦ 500 V, the coated base body is freed in a multi-stage flushing with water from adhering electrolyte and dried with air. Subsequently, the coated base body can be subjected to a blasting treatment in which the pore volume of the surface layer produced is reduced by mechanical compression from originally 30% by volume to 70% by volume to 0 to 30% by volume. For this purpose, pneumatically accelerated jet bodies made of glass or ceramic with a diameter of 5 .mu.m to 200 .mu.m are used.

Embodiment 3

A base body of titanium or titanium-based alloys is in an aqueous first electrolyte with 0.01 mol l ^-1 to 0.1 mol·l ^-1 gallium (III) nitrate (Ga (NO ₃ ) ₃ ), 0.06 mol l ^-1 to 0.6 mol l ^-1 L - (+) - ascorbic acid (C ₆ H ₈ O ₆ ) and 0.18 mol l ^-1 to 1.8 mol l ^-1 phosphoric acid (H ₃ PO ₄ ) electrochemically treated. The basic body of pure titanium or a titanium alloy (≥ 60 M .-% titanium) with a roughness of R _a ≤ 2.5 microns or R _t ≤ 15 microns is partially or completely submerged and anodically poled in the aqueous first electrolyte. The electrochemical process is carried out at DC voltage or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 ° C to 50 ° C under atmospheric pressure. After reaching a final tension of ≦ 500 V, the coated base body is freed in a multi-stage flushing with water from adhering electrolyte and dried with air. Subsequently, the coated base body can be subjected to a blasting treatment in which the pore volume of the surface layer produced is reduced by mechanical compression from originally 30% by volume to 70% by volume to 0 to 30% by volume. For this purpose, pneumatically accelerated jet bodies made of glass or ceramic with a diameter of 5 .mu.m to 200 .mu.m are used.

Embodiment 4

A base body made of titanium or titanium-based alloys in an aqueous first electrolyte containing 0.05 mol l ^-1 to 0.5 mol·l ^-1 zinc (II) acetate (Zn (C ₂ H ₃ O _{2) 2),} 0.01 mol 1 ^-1 to 0.1 mol 1 ^-1 ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ) and 1.34 mol 1 ^-1 to 13.4 mol 1 ^-1 ammonium hydroxide (NH ₄ OH) electrochemically treated. The basic body of pure titanium or a titanium alloy (≥ 60 M .-% titanium) with a roughness of R _a ≤ 2.5 microns or R _t ≤ 15 microns is partially or completely submerged and anodically poled in the aqueous first electrolyte. The electrochemical process is carried out at DC voltage or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 ° C to 50 ° C under atmospheric pressure. After reaching a final tension of ≦ 500 V, the coated base body is freed in a multi-stage flushing with water from adhering electrolyte and dried with air. Subsequently, the coated base body can be subjected to a blasting treatment in which the pore volume of the surface layer produced is reduced by mechanical compression from originally 30% by volume to 70% by volume to 0 to 30% by volume. For this purpose, pneumatically accelerated jet bodies made of glass or ceramic with a diameter of 5 .mu.m to 200 .mu.m are used.

Embodiment 5

An aqueous electrolyte containing from 0.05 mol·l ^-1 to 0.5 mol·l ^-1 disodium ethylenediaminetetraacetic acid (C ₁₀ H ₁₄ N ₂ O ₈ Na ₂ ), 0.05 mol·l ^-1 to 0.5 mol·l ^-1 ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), 0.5 mol·l ^-1 to 5 mol·l ^-1 hydrogen peroxide (H ₂ O ₂ ) and 0.01 mol·l ^-1 to 0.1 mol·l ^-1 bismuth salicylate (C ₇ H ₅ BiO ₄ ) or alternatively 0.01 mol·l ^-1 to 0.1 mol·l ^-1 bismuth citrate (C ₆ H ₅ BiO ₇ ) or alternatively 0.01 mol·l ¹ to 0.1 mol·l ^-1 bismuth triacetate ((CH ₃ CO ₂ ) ₃ Bi) or alternatively 0.01 mol·l ^-1 to 0.1 mol·l ^-1 ammonium bismuth citrate (C ₆ H ₇ O ₇ . xBi.xH ₃ N) is adjusted to a pH of 5 to 7. The basic body of pure titanium or a titanium alloy (≥ 60 M .-% titanium) with a starting roughness of Ra ≤ 2.5 microns or Rt ≤ 15 microns is cleaned in an ultrasonic bath and partially or completely submerged in the aqueous electrolyte and poled anodically. The electrochemical immersion process is carried out at DC or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 C to 50 ° C under atmospheric pressure. After reaching the final tension of ≤ 400 V, the coated body is freed of adhering electrolyte in a multistage rinse with water and dried with air. Subsequently, the coated body is subjected to a blast treatment, in which the pore volume of the surface layer produced is reduced by mechanical compression of originally 30 vol .-% to 70 vol .-% to 0 to 30 vol .-%. For this purpose, pneumatically accelerated glass jet bodies with a diameter of 5 μm to 200 μm are used.

Prior to the electrochemical treatment according to any one of the preceding embodiments, a dip treatment of the body in a second aqueous electrolyte with 0.05 mol / l to 0.5 mol / l calcium di-sodium ethylenediaminetetraacetic acid (C ₁₀ H ₁₂ N ₂ O ₈ CaNa ₂ ), 0.05 mol / l to 0.5 mol / l ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), 0.05 mol / l to 0.5 mol / l phosphoric acid (H ₃ PO ₄ ), 0.02 mol / l to 0.06 mol / l gallium nitrate monohydrate (Ga ₂ (NO ₃ ) ₃ × H ₂ O) and from 0.5 mol / l to 1.5 mol / l of ethylenediamine (C ₂ H ₈ N ₂ ) , The second aqueous electrolyte is adjusted to a pH of 5 to 7. The basic body of pure titanium or titanium alloy (≥ 60 M .-% titanium) with a starting roughness of R _a ≤ 2.5 microns or R _t ≤ 15 microns is cleaned in an ultrasonic bath and partially or completely submerged in the aqueous second electrolyte and poled anodically. The electrochemical process is carried out at DC voltage or pulsed DC voltage (ƒ ≤ 1500 s ^-1 ) and a current density of ≤ 15 A · dm ^-2 at an electrolyte temperature of 15 ° C to 50 ° C under atmospheric pressure. After reaching the final tension of <400 V, the coated body is freed in a multi-stage rinse with water from adhering electrolyte and dried with air.

QUOTES INCLUDE IN THE DESCRIPTION

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Cited patent literature

• DE 102008046198 B3 [0005]

Cited non-patent literature

• Schumann, W. (2011), Biotope Man, We Are Colonized, Biology in Our Time, 41: 182-189 [0003]

Claims (12)

A process for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein the first electrolyte is an aqueous solution comprising the constituents silver (I) phosphate (Ag ₃ PO ₄ ) and ammonium hydroxide (NH ₄ OH) is used. Process for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein the first electrolyte is an aqueous solution containing the constituents copper (II) acetate (Cu (C ₂ H ₃ O ₂ ) ₂ ), ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ) and ammonium hydroxide (NH ₄ OH) is used. A method for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein the first electrolyte is an aqueous solution with the constituents gallium (III) nitrate (Ga (NO ₃ ) ₃ ), L - (+) - ascorbic acid (C ₆ H ₈ O ₆ ) and phosphoric acid (H ₃ PO ₄ ) is used. A process for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein the first electrolyte is an aqueous solution containing the constituents zinc (II) acetate (Zn (C ₂ H ₃ O ₂ ) ₂ ), ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ) and ammonium hydroxide (NH ₄ OH) is used. A process for producing a bactericidal layer on a base body made of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein the first electrolyte is an aqueous solution comprising the constituents bismuth oxide nitrate (BiNO ₄ ) and / or bismuth salicylate (C ₇ H ₅ BiO ₄ ) and / or bismuth citrate (C ₆ H ₅ BiO ₇ ) and / or ammonium bismuth citrate (C ₆ H ₇ O ₇ .xBi.xH ₃ N) and / or bismuth triacetate ((CH ₃ CO ₂ ) ₃ Bi) and ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), and disodium ethylenediaminetetraacetic acid (C ₁₀ H ₁₄ N ₂ O ₈ Na ₂ ) is used.  A method for producing a bactericidal layer on a base body of titanium or a titanium-based alloy, comprising an electrochemical process in a first aqueous electrolyte, wherein a combination of at least two of the first electrolytes according to two of claims 1 to 5 is used as the first electrolyte. Method according to one of the preceding claims, characterized in that before the electrochemical process, a biodegradation-stable calcium phosphate layer is deposited on the base body, in particular by means of plasma chemical oxidation. A method according to claim 7, characterized in that the calcium phosphate layer is deposited in an electrochemical immersion process with a second aqueous electrolyte, wherein as the second electrolyte, an aqueous solution with the components calcium di-sodium ethylenediaminetetraacetic acid (C ₁₀ H ₁₂ N ₂ O ₈ CaNa ₂ ), ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), phosphoric acid (H ₃ PO ₄ ), gallium nitrate monohydrate (Ga ₂ (NO ₃ ) ₃ × H ₂ O) and ethylenediamine (C ₂ H ₈ N ₂ ). Method according to one of claims 1 to 8, characterized in that the main body partially or completely immersed in the first and / or second electrolyte, anodically poled and subjected to a DC voltage less than or equal to 500 V electrochemical reactions on the surface. A method according to claim 9, characterized in that the DC voltage is changed periodically. A method according to claim 10, characterized in that the frequency of the periodic voltage change is set equal to or less than 2000 s ^-1 . Implant, in particular osteosynthesis implant or dental implant, comprising a base body made of titanium or a titanium-based alloy with a bactericidal layer applied by the method according to one of claims 1 to 11.