EP1434607A1

EP1434607A1 - Osteophilic implants

Info

Publication number: EP1434607A1
Application number: EP02764480A
Authority: EP
Inventors: Alain J. Denzer; James P. Simpson
Original assignee: Straumann Holding AG
Current assignee: Straumann Holding AG
Priority date: 2001-10-11
Filing date: 2002-10-11
Publication date: 2004-07-07
Also published as: AU2002328762B2; HK1071526A1; JP2005505352A; WO2003030957A1; US20040210309A1; CN1568200A; CN100366300C

Abstract

Osteophilic implant with a roughened hydroxilated and hydrophilic surface, made from titanium or a titanium alloy and suitable for implantation in bones, whereby the implant is characterised in that said implant is treated in the hydroxilated state with high-energy ultra-violet radiation.

Description

Osteophilic implants

The present invention relates to osteophilic implants which are used for insertion into bones and which have significantly improved osteointegration properties, and to methods for their production.

Implants which are used for insertion into bones, such as, for example, hip or knee prostheses or pins to be screwed into the jaw for the construction of artificial teeth, are known per se. Such implants are preferably made of titanium or titanium-based alloys, e.g. Titanium / zirconium alloys, which may additionally contain niobium, tantalum or other tissue-compatible metallic additives. A key property of such implants is their osteointegration time, that is, the time it takes for the bone substance to have sufficient strength and to be permanently bonded to the implant surface, that is, integrated.

How firmly the implant is anchored in the bone can be determined with mechanical measurements, namely by measuring the force, be it as tension, pressure, shear or torque, which are necessary to pull the implant anchored in the bone out of its anchoring or unscrew it, ie to bring about an adhesion break between the surface of the implant and the bone substance connected to it. Such measurement methods are known per se and are described, for example, in Brunski, Clinical Materials, Vol. 10, 1992, pp. 153-201. Measurements have shown that titanium implants with a smooth surface structure anchor themselves insufficiently in the bone, while implants with a roughened surface result in a noticeably improved bone-implant bond in terms of tensile strength. Correspondingly, according to EP 0 388 576, a macroroughness is applied to the implant surface in a first step by means of sandblasting and this is then superimposed with a microroughness by means of treatment in an acid bath. The implant surface is roughened, for example, by means of sandblasting and then treated with an etching agent, for example with hydrofluoric acid or a hydrochloric acid / sulfuric acid mixture. The surface thus provided with a defined roughness is then washed with water and solvents and subjected to a sterilization treatment.

The chemical state of surfaces such as those made of titanium or titanium-based alloys is complex. It is assumed that the surface of titanium metal spontaneously oxidizes in air and water and that a reaction with water then takes place on the surface, that is to say in the outermost atomic layer, with hydroxyl groups being formed. This surface, which contains hydroxyl groups, is referred to in the literature as a "hydroxylated" surface. See HP Boeh, Acidic and Basic Properties of Hydroxylated Metal Oxide Surfaces, Discussions Faraday Society, Vol. 52, 1971, pp. 264-275. A hydroxylated surface can only develop its full effect if it is in the “hydrophilic” state, that is, if it is not covered with volatile hydrocarbons and other compounds, such as sulfur dioxide or nitrogen monoxide, which are present in the air Other impurities can also get onto the implant surface at any stage of the manufacturing process, for example in the cleaning process, if the implant is treated with organic solvents such as methanol or acetone A hydroxylated and hydrophilic surface, for example of titanium or a titanium Tan alloy has biologically active properties or can be described as biologically active. A hydroxylated and hydrophilic implant surface grows together with the bone substance to form a strong bond much faster than an identical hydroxylated but non-hydrophilic surface. The production of a hydroxylated and at the same time hydrophilic implant surface is described in WO 0044305 (PCT / EP00 / 00619).

A contamination-free, hydroxylated surface has a high surface energy, which means that volatile hydrocarbons and other contaminants that occur in unpurified air are quickly adsorbed. Initially, for example, the adsorbed hydrocarbons form a monomolecular layer (monolayer) on the hydroxylated surface, whereby the hydrophilic character of the surface is lost. However, the longer the implant is exposed to the air, the thicker the contamination layer. A clean hydroxylated surface made of titanium is hydrophilic and has a contact angle of less than 50 ° when wetted with water, while a contaminated hydroxylated surface has a contact angle of over 70 ° and is referred to as hydrophobic. It is true that the hydroxylated and hydrophilic surface, and thus also its biological activity, can be maintained largely unchanged if this surface is sealed in a covering in such a way that contact of the surface with compounds which can impair the hydrophilic character of the implant surface is prevented becomes. However, if the covering is broken open, which is necessary shortly before the implantation, contact of the implant surface with the atmospheric outside air and thus a reduction in the hydrophilic character of the implant surface cannot be prevented. There is therefore a need to convert the hydroxylated and hydrophilic implant To produce or treat the surface in such a way that its hydrophilic character is largely retained over an extended period of time even in contact with the atmospheric outside air.

It has now been found that a hydroxylated but contaminated, ie contaminated, hydrophobic implant surface acquires a hydrophilic character when this surface is treated with high-energy ultraviolet radiation (UV rays). Surprisingly, the thus obtained _^ hydroxylated and hydrophilic surface against the occupancy by foreign substances atmosphärichen the outside air is significantly less sensitive than a hydroxylated and hydrophilic implant surface, which has been obtained for example by acid etching. It was also found that the stability of the hydrophilic character of a hydroxylated and hydrophilic implant surface obtained with acid etching increases significantly when treated in the hydrophilic state with high-energy ultraviolet radiation. Another advantage of this treatment is that there is no need for additional sterilization of the implants.

The present invention is defined in the claims. In particular, the present invention relates to an osteophilic implant with a particularly roughened, hydroxylated and hydrophilic surface, this implant preferably consisting of titanium or a titanium alloy and being suitable for implantation in bones, characterized in that the implant in the hydroxylated state with high-energy ultraviolet radiation was treated. However, other materials, for example other metals and ceramics, are also conceivable. The expression “implant in the hydroxylated state” denotes both an implant which has been produced with a hydroxylated surface but whose surface has a hydrophobic character, and also an implant with a hydroxylated and hydrophilic surface. The implant according to the invention shows a significantly increased stability against the loss of the hydrophilic character and thus improved osteointegration properties.

The present invention also relates to methods for producing an osteophilic implant with a roughened, hydroxylated and hydrophilic surface in particular, wherein this implant preferably consists of titanium or a titanium alloy and is suitable for implantation in bone, characterized in that the implant is in the hydroxylated state treated with high-energy ultraviolet radiation.

The implants according to the invention preferably consist of a titanium alloy, preferably of a titanium / zirconium alloy, which may additionally contain niobium, tantalum or other tissue-compatible metallic additives. Other suitable materials can also be used in the context of the invention. These implants are preferably used as hip or knee prostheses or as pins to be screwed into the jaw for building artificial teeth. Such implants, their nature and the metallic materials used for their production are known per se and are described, for example, in J. Black, G. Hastings, Handbook of Biomaterials Properties, pages 135-200, Chapman & Hall, London, 1998.

The structural and functional anchoring, for example a dental implant, in the bone is usually achieved by attaching a macro roughness, such as a screw thread or a recess. Formations in the surface and / or optionally an additional microroughness is achieved, the microroughness being applied to the surface either in an additive process by means of plasma technology or in a subtractive process by chemical etching. The application of a macro roughness, such as a screw thread or of depressions in the surface and, if appropriate, an additional micro roughness is known per se. For the implementation of the present invention, that is to say for the production of an implant which is provided with a macro roughness which is additionally superimposed on a micro roughness, the procedure is preferably as described in EP 0 388 576 or in WO 0044305 (PCT / EP00 / 00619). The implant obtained in this way can then be treated according to the invention with high-energy ultraviolet radiation.

The implant surface according to the invention preferably has a macro roughness in the range from 5 μm to 100 μm (in each case peak to valley), in particular in the range from 20 μm to 40 μm and a superimposed micro roughness in the range from 0.5 μm to 20 μm, in particular in the range from 0.5 μm to 10 μm, in particular approximately 2 .mu.m.

These two superimposed roughnesses can be produced in two successive stages. For example, the macro-roughness of the implant surface is generated by sandblasting with corundum grains with an average grain size in the range of 0.25-0.5 mm, after which the micro-roughness can be achieved by treatment with an aqueous hydrochloric acid / sulfuric acid mixture in the ratio of HC1: H ₂ S0: H ₂ 0 of 2 : 1: 1 at a temperature in the range of 80 ° C to about 110 ° C for about five minutes. After the acid bath, the surface-structured titanium parts, respectively. the implants, washed thoroughly with pure water until neutral, if necessary treated with alcohol, acetone or another organic solvent or disinfectant, and dried in hot air. The implants obtained in this way can finally be packaged and, if necessary, sterilized with gamma rays. In this method, a hydrophilic implant surface is obtained if, after the acid bath, the implant surface is washed thoroughly with neutral water and dried in an atmosphere which is inert to the hydrophilic surface and the implant is kept in an inert atmosphere. A hydrophobic implant surface is obtained when treated with alcohol, acetone or another organic solvent or a disinfectant and when dried in hot atmospheric air.

The "pure" water used for washing is preferably multiply distilled water or water produced by inverse osmosis, which is preferably in an inert atmosphere, i.e. e.g. was produced under reduced pressure, in a nitrogen or inert gas atmosphere. Furthermore, the pure water has an electrical resistance of at least 2 Moh cm (electrical resistance> 2 Mohm cm) and a total organic carbon (TOC) content of at most 10 ppb (<10 ppb).

According to the invention, the implant is treated in the hydroxylated state with high-energy ultraviolet radiation. The high-energy ultraviolet radiation (UV radiation) causes the implant surface to become hydrophilic and the impurities on the surface to be removed. According to the invention, the high-energy UV radiation used is UV radiation with a wavelength in the range from 150 nm to 300 nm, preferably in the range from 170 nm to 260 nm, and in particular UV radiation in the range of the absorption maximum of acid. Material, that is with a wavelength of about 184.9nm and in the range of the absorption maximum of ozone, that is with a wavelength of about 253.7nm. Wavelengths in this range promote the simultaneous formation or decay of ozone and are able to break high-energy chemical bonds, such as the ethylenic carbon-carbon double bond. Wavelengths in the ranges mentioned are generated by so-called xenon radiators, which are commercially available.

Since the intensity of the radiation decreases exponentially with the distance from the UV source, it is advantageous that the distance of the implant surface to be treated from the UV source is kept small, for example in the range of approximately 1 mm. The duration of the UV treatment depends on the type and thickness of the contamination layer and can easily be determined or optimized by a person skilled in the art. In general, the irradiation time is in the range from 1 minute to 15 minutes. As a rule, the treatment according to the invention of a hydrophilic (and thus already relatively clean) surface also results in a cleaner product compared to the treatment of a contaminated surface.

XPS (X-ray excited Photoelectron Specroscopy) or Auger Electron Spectroscopy (AES) are advantageously used to analyze the implant surfaces treated with UV rays. An implant surface, such as that which occurs immediately after acid etching and is hydroxylated and hydrophilic, has a wetting angle with water of less than 50 ° (<50 °) when the water drop penetrates the surface or less than 20 ° (<20 °) in the case of the regressing drop, and has a remarkable biological activity. The same applies to an implant surface treated with UV rays. Chen, whose hydrophilic character remains in contact with the atmospheric outside air according to the invention over a prolonged period of time.

Industrially manufactured surfaces of titanium and titanium alloys for processing in laboratories and clinics generally have contaminants that essentially consist of carbon compounds and traces of nitrogen, calcium, sulfur, phosphorus and silicon. These contaminants are concentrated in the outermost metal oxide layer. The hydroxylated and hydrophilic implant surface obtained according to the invention preferably contains at most 20 atomic% carbon, measured by spectroscopic methods such as XPS or AES or other spectroscopic methods known per se.

Following the UV radiation, the implant obtained is preferably stored in a casing filled with gases which are inert to the implant surface. Such inert gases, that is to say gases which do not influence the hydrophilic character of the surface or its biological activity, are for example nitrogen, oxygen or noble gas, such as e.g. Argon. The casing is preferably impermeable to gases and liquids. Compounds that can impair the biological activity of the implant surface include, as already mentioned, methanol, ethanol, acetone and related ketones, as well as numerous other organic compounds, or carbon dioxide.

The covering can, if appropriate, be partially or completely filled with pure water, which may optionally contain additives, at least such an amount of water being present that the roughened implant surface is kept moist or wetted. Suitable additives are, for example, monovalent alkali cations, such as Na ⁺ or K ⁺ , with corresponding anions in the form of inorganic salts, such as, for example, sodium chloride, potassium chloride, sodium or potassium chlorate, sodium or potassium nitrate, sodium or potassium phosphate or a mixture of such salts. Divalent cations in the form of water-soluble inorganic salts can also be added. Suitable cations are in particular Mg ⁺² , Ca ⁺² , Sr ⁺² and / or Mn ⁺² in the form of the chlorides or their mixtures. Suitable anions are also phosphate and phosphonate anions, which in each case also include monoorthophosphate anions and diorthophosphate anions or monoorthophosphonate anions and diorthophosphonate anions, in combination with the cations mentioned.

Cations and anions which are already present in the body fluid are preferred, in particular in the respective physiological concentration and at a physiological acid value (pH value) in the range from preferably 4 to 9 and preferably at an acid value in the range from 6 to 8. Preferred cations are Na ⁺ , K ⁺ , Mg ⁺² and Ca ⁺² . The preferred anion is Cl ^" . The total amount of the cations or anions mentioned is in each case in the range from about 50 mEq / 1 to 250 mEq / 1, preferably about 100 mEq / 1 to 200 mEq / 1 and preferably about 150 mEq / 1 1. Eq / 1 means (formula) equivalent weight or Eq / 1 corresponds to the atomic weight of the formula unit divided by the valency. MEq / 1 means milliequivalents per liter. Contains the coating divalent cations, especially Mg ⁺² , Ca ⁺² , Sr ⁺² and / or Mn ⁺² , alone or in combination with the monovalent cations mentioned, the total amount of divalent cations present is preferably in the range from 1 mEq / 1 to 20 mEq / 1.

The gas- and liquid-tight envelope is preferably a welded ampoule made of glass, metal, a synthetic polymer. lymeren or another gas- and liquid-tight material or consists of a combination of these materials. The metal is preferably in the form of a thin metal foil, it being possible for polymeric materials and metallic foils, but also glass, to be combined with one another in a manner known per se to form suitable packaging.

A particular advantage of the present invention, however, is that packaging of the implant in a gas- and liquid-tight envelope, as described above, can be dispensed with if the implant within a useful period following the treatment according to the invention with UV rays Time period, for example within an hour, is implanted. As mentioned at the beginning, the implant surface treated according to the invention surprisingly retains its hydrophilic character largely unchanged during this time even in contact with atmospheric air. Suitable comparatively compact UV devices are available today and can be easily installed in the doctor's office. It is therefore sufficient to pack an implant provided with a roughened but hydrophobic surface, the manufacture of which has been described above and is known per se, in a dust-free manner. The operating physician (dental surgeon) can treat the implant provided with a hydrophobic surface with the UV rays according to the invention immediately before the implantation in the UV device, a sterile (sterilized) implant with a hydroxylated and hydrophilic surface being obtained. This hydroxylated and hydrophilic state of the implant surface, and thus also its biological activity, is thus largely retained until the implantation.

In this sense, the present invention also relates to a method for implanting an osteophilic implant with a roughened hydroxylated and hydrophilic surface, whereby this implant consists of titanium or a titanium alloy and is suitable for implantation in bones, characterized in that the implant is treated in the hydroxylated state with high-energy ultraviolet radiation and immediately after this treatment implanted in the bone. The following examples illustrate the invention.

example 1

A common form of a dental implant in the form of a screw 4 mm in diameter and 10 mm in length was produced. The raw form was obtained by machining and turning the cylindrical blank in a manner known per se. According to EP 0 388 576, the surface to be used in the bones was provided with a macroroughness by sandblasting with a grain of the average grain size 0.25-0.5 mm. The roughened surface, that is to say the macroroughness, was then treated with an aqueous hydrochloric acid / sulfuric acid mixture with a ratio of HC1: H ₂ S0 ₄ : H ₂ 0 of 2: 1: 1 at a temperature of 95 ° C. for five minutes, so that a ratio of the roughened implant surface to the comparable polished surface of 3.6, measured by means of voltammetry in aqueous electrolyte with 0.15M NaCl, (corresponding to a ratio of 3.9, measured with impedance spectrometry in 0.1 molar Na ₂ S0 ₄ electrolyte) was obtained. The shaped implant was carefully washed neutral with pure water, then dried in atmospheric air at 110 ° C and packed dust-free in a glass ampoule. Several identical implants were made in this way. The ampoules were opened after 4 weeks.

a) Some of the implants were implanted unchanged (comparison test). b) The other part of the implants was treated for five minutes in a xenon radiator from Radium (Lampenwerk Wipperfürth, Germany) with UV radiation with an emission maximum at 172 nm at a distance of 0.1 mm in atmospheric air.

The samples according to experiment a) [without UV treatment] had a wetting angle of over 70 ° (> 70 °) and a content of 20-40 atom% carbon on the surface. The samples from experiment b) [after UV treatment] were completely wettable, i.e. they had a wetting angle of 0 ° (zero degrees) and contained 8-13 atomic% carbon on the surface. The low-carbon state of the surfaces of the samples according to test b) remained practically unchanged over a period of at least one day.

The implants according to experiments a) and b) were implanted in the upper jaw of a mini pig. The anchorage in the bone was measured as the loosening torque of the screw implanted in the upper jaw of the mini-pig. The results obtained are shown in Table 1.

Table 1

* The anchoring is given as the loosening torque in Ncm (average values).

Claims

claims

1. Osteophilic implant with a hydroxylated surface consisting of titanium or a titanium alloy, preferably with a rough surface suitable for implantation in bones, characterized in that the implant is hydrophilic, that is to say essentially free of impurities on the surface.

2. Osteophilic implant with a rough surface consisting of titanium or a titanium alloy, produced by a manufacturing and preparation method, which comprises a surface treatment method that is effective until implantation, comprising the steps:

(a) hydroxylation of the surface of the implant and

(b) treatment of the surface of the implant by ultraviolet radiation to provide a hydrophilic surface, in particular to destroy and / or remove organic contaminants.

3. Implant according to claim 1 or 2, characterized in that the treated implant surface has a content of less than 20 atom% carbon, in particular less than 13 atom%.

4. Implant according to one of claims 1 or 3, characterized in that the surface is treated with UV radiation in order to achieve hydrophilicity and to free the surface of impurities.

5. Implants according to one of claims 1-4, characterized in that it consists of a titanium alloy, preferably of a titanium / zirconium alloy, which, if appropriate additionally contains niobium, tantalum or other tissue-compatible, in particular metallic additives.

6. Implant according to one of claims 1-5, characterized in that it represents a hip or knee prosthesis or a pin to be inserted into the jaw for the build-up of artificial teeth.

7. Implant according to one of claims 1-6, characterized in that the implant surface is provided with a macro roughness, preferably a screw thread or with recesses in the surface, and optionally additionally with a micro roughness superimposed on the macro roughness.

8. The implant according to claim 7, characterized in that the macro roughness in the range from 5 μm to 100 μm (in each case peak to valley), in particular in the range from 20 μm to 40 μm, and the superimposed micro roughness in the range from 0.5 μm to 20 μm, in particular in the range from 0.5 μm to 10 μm, in particular of approximately 2 μm.

9. Implant according to one of claims 1-8, characterized in that the UV rays are those with a wavelength in the range from 150 nm to 300 nm, preferably in the range from 170 nm to 260 nm, and in particular UV rays with a wavelength of about 184.9 nm and about 253.7nm.

10. Implant according to one of claims 1-9, characterized in that the irradiation lasted from 1 minute to 15 minutes.

11. Implant according to one of claims 1-10, characterized in that it is packed in an envelope filled with gases which are inert to the implant surface, preferably with nitrogen, oxygen or inert gas, and which is impermeable to gases and liquids.

12. The implant according to claim 11, characterized in that the covering is partially or completely filled with pure water, which may contain additives.

13. Implant according to claim 12, characterized in that the water alkali cations, preferably Na ⁺ or K ⁺ , with corresponding anions in the form of inorganic salts, preferably sodium chloride, potassium chloride, sodium or potassium chlorate, sodium or potassium nitrate, sodium or potassium phosphate or a mixture of such salts, or divalent cations in the form of water-soluble inorganic salts, preferably Mg ²⁺ , Ca ²⁺ , Sr ²⁺ and / or Mn ²⁺ , preferably in the form of the chlorides, or water-soluble phosphates and / or phosphonates, contains.

14. Implant according to claim 12 or 13, characterized in that the total amount of cations or anions in each case in the range from 50 mEq / 1 to 250 mEq / 1, preferably in the range from 100 mEq / 1 to 200 mEq / 1 and preferably at about 150 mEq / 1.

15. Implant according to one of claims 11-14, characterized in that the gas- and liquid-tight envelope represents an ampoule made of glass, metal, a synthetic polymer or another gas- and liquid-tight material or consists of a combination of these materials.

16. Osteophilic implant according to one of claims 1-15 with a roughened hydroxylated and hydrophilic surface, wherein this implant consists of titanium or a titanium alloy, characterized in that the implant was treated in the hydroxylated state with high-energy ultraviolet radiation.

17. A method for implanting an osteophilic implant with a hydroxylated and hydrophilic, preferably with a rough, surface suitable for implantation in bone, this implant consisting of titanium or a titanium alloy, characterized in that the implant in the hydroxylated state with ultraviolet radiation treated, UV rays with a wavelength in the range from 150 nm to 300 nm, preferably in the range from 170 nm to 260 nm, and in particular UV rays with a wavelength of about 184.9 nm and about 253.7 nm, and the implant is used immediately implanted in the bone after this treatment.

18. A method for implanting an osteophilic implant with a hydroxylated and hydrophilic, preferably with a rough, surface suitable for implantation in bone, this implant consisting of titanium or a titanium alloy, characterized in that the implant in the hydroxylated state with ultraviolet radiation treated as UV rays with a wavelength in the range of 150nm to 300nm, preferably in the range of 170nm to 260nm, and in particular UV rays with a wavelength of about 184.9nm and about 253.7nm, and those obtained in this way , hydrophilic state of the surface is preserved by suitable storage, the implantation in the bone being carried out at a later time.

9. Use of an osteophilic implant consisting of titanium or a titanium alloy, preferably with a rough surface suitable for the implantation, the surface being hydroxylated and exposed to such UV radiation, in particular high-energy radiation, in such a way that organic substances present on the surface Impurities are destroyed or rendered ineffective for the implantation of a dental implant.