Treatment of implants with phosphonic acid compounds

Abstract

The present invention relates to a process of treating an implant, comprising a step of treating the surface of the implant with at least one phosphonic acid compound or a pharmaceutically acceptable salt, ester or amide thereof under sonication at a temperature of about 50° C. to about 90° C. This process is highly advantageous in that it allows the formation of a monolayer of the phosphonic acid compound on the implant surface, having a particularly dense surface coverage which, in turn, results in an improved implant biocompatibility and improved osseointegration. The invention further relates to a surface-treated implant obtainable by this process and, in particular, it provides an implant having a surface made of a metal, a metal alloy or a ceramic, wherein a phosphonic acid compound or a pharmaceutically acceptable salt, ester or amide thereof is bound to the surface of the implant and forms a monolayer having an implant surface coverage, in terms of the ratio of the phosphorus content to the metal content as determined by X-ray photoelectron spectroscopy (XPS), of at least 70% of a reference maximum surface coverage.

Claims

1. A process of treating an implant, the process comprising the following step: treating the surface of the implant with at least one phosphonic acid compound or a pharmaceutically acceptable salt, ester or amide thereof under sonication at a temperature of about 50° C. to about 90° C.; wherein the process further comprises, before the step of treatment with the phosphonic acid compound, a step of pre-treating the surface of the implant with a cleaning agent, wherein the cleaning agent is a 0.5% (v/v) to 5% (v/v) aqueous solution of an alkaline phosphate-free liquid concentrate, wherein the liquid concentrate has a pH greater than 12 and comprises about 5% (w/w) to about 15% (w/w) of methylglycinediacetate and about 1% (w/w) to about 5% (w/w) of an inorganic base, and wherein said 0.5% (v/v) to 5% (v/v) aqueous solution has a pH equal to or greater than 11.

2. The process of claim 1, wherein the step of treatment with the phosphonic acid compound is conducted under sonication at a temperature of about 60° C. to about 70° C.

3. The process of claim 1, wherein the step of pre-treatment with the cleaning agent is conducted at a temperature of about 50° C. to about 90° C.

4. The process of claim 1, wherein the step of pre-treatment with the cleaning agent is conducted under sonication.

5. The process of claim 1, wherein the phosphonic acid compound is a C.sub.1-30 hydrocarbon which is substituted with 1 to 6 phosphonic acid groups, wherein said hydrocarbon is optionally substituted with one or more groups independently selected from the group consisting of hydroxy and halogen, and further wherein one or more carbon atoms comprised in said hydrocarbon are optionally each replaced by a heteroatom independently selected from the group consisting of nitrogen, oxygen and sulfur.

6. The process of claim 1, wherein the phosphonic acid compound is a C.sub.1-15 hydrocarbon which is substituted with 1 to 6 phosphonic acid groups.

7. The process of claim 6, wherein said hydrocarbon is substituted with 3 to 6 phosphonic acid groups.

8. The process of claim 1, wherein the phosphonic acid compound is a C.sub.1-10 alkane which is substituted with 3 to 6 phosphonic acid groups.

9. The process of claim 1, wherein the phosphonic acid compound is a linear C.sub.2-6 alkane which is substituted with 3 or 4 phosphonic acid groups.

10. The process of claim 1, wherein the phosphonic acid compound is selected from the group consisting of methanephosphonic acid, ethanephosphonic acid, propane-1-phosphonic acid, propane-2-phosphonic acid, methane-1,1-diphosphonic acid, ethane-1,1-diphosphonic acid, ethane-1,2-diphosphonic acid, propane-1,1-diphosphonic acid, propane-2,2-diphosphonic acid, propane-1,2-diphosphonic acid, propane-1,3-diphosphonic acid, ethane-1,1,1-triphosphonic acid, ethane-1,1,2-triphosphonic acid, propane-1,1,1-triphosphonic acid, propane-1,1,2-triphosphonic acid, propane-1,1,3-triphosphonic acid, propane-1,2,2-triphosphonic acid, propane-1,2,3-triphosphonic acid, butane-1,1,1-triphosphonic acid, butane-1,1,2-triphosphonic acid, butane-1,1,3-triphosphonic acid, butane-1,1,4-triphosphonic acid, butane-1,2,2-triphosphonic acid, butane-2,2,3-triphosphonic acid, butane-1,3,3-triphosphonic acid, butane-1,2,3-triphosphonic acid, butane-1,2,4-triphosphonic acid, pentane-1,1,5-triphosphonic acid, pentane-2,2,5-triphosphonic acid, hexane-1,1,6-triphosphonic acid, hexane-2,2,6-triphosphonic acid, propane-1,1,1,2-tetraphosphonic acid, propane-1,1,1,3-tetraphosphonic acid, propane-1,1,2,2-tetraphosphonic acid, propane-1,1,2,3-tetraphosphonic acid, propane-1,1,3,3-tetraphosphonic acid, propane-1,2,2,3-tetraphosphonic acid, butane-1,1,4,4-tetraphosphonic acid, pentane-1,1,5,5-tetraphosphonic acid, hexane-1,1,6,6-tetraphosphonic acid, heptane-1,4,4,7-tetraphosphonic acid, octane-1,4,4,8-tetraphosphonic acid, nonane-1,5,5,9-tetraphosphonic acid, pentane-1,1,3,5,5-pentaphosphonic acid, pentane-1,1,2,4,5,5-hexaphosphonic acid, tert-butyl phosphonic acid,2-methyl-propane-1,1,1-triphosphonic acid, 2-methyl-propane-1,1,3-triphosphonic acid, 2-(phosphono-methyl)-propane-1,3-diphosphonic acid, 2-methyl-propane-1,1,3,3-tetraphosphonic acid, 2-methyl-butane -1,1,1-triphosphonic acid, 3-methyl-butane-1,1,1-triphosphonic acid, 2-(phosphono -methyl)-propane-1,1-diphosphonic acid, 2-methyl-butane-1,1,3-triphosphonic acid, 2-methyl-butane-1,1,4-triphosphonic acid, 3-methyl-butane-2,2,4-triphosphonic acid, 3-methyl-butane-1,1,4-triphosphonic acid, 2-(phosphono-methyl)-butane-1,3-diphosphonic acid, 2-(phosphono-methyl)-butane-1,4-diphosphonic acid, 3-methyl-butane-1,1,2-triphosphonic acid, 2-methyl-butane-1,1,4,4-tetraphosphonic acid, 2-methyl-pentane -1,1,1-triphosphonic acid, 2-(phosphono-methyl)-pentane-1,1-diphosphonic acid, 2-methyl-pentane-1,1,3-triphosphonic acid, 2-methyl-pentane-1,1,4-triphosphonic acid, 2-methyl-pentane-1,1,5-triphosphonic acid, 2-methyl-pentane-1,3,3-triphosphonic acid, 4-methyl-pentane-2,2,5-triphosphonic acid, 4-methyl-pentane- 1,1,5-triphosphonic acid, 2-(phosphono-methyl)-pentane-1,3-diphosphonic acid, 2-methyl-pentane- 1,3,4-triphosphonic acid, 2-(phosphono-methyl)-pentane-1,4-diphosphonic acid, 2-(phosphono -methyl)-pentane-1,5-diphosphonic acid, 2-methyl-pentane-1,3,5-triphosphonic acid, 4-methyl-pentane-1,2,5-triphosphonic acid, 2-methyl-pentane-1,1,5,5-tetraphosphonic acid, 3-methyl-pentane-1,1,1-triphosphonic acid, 3-methyl-pentane-1,1,2-triphosphonic acid, 3-(phosphono-methyl)-pentane-1,1-diphosphonic acid, 3-methyl-pentane-1,1,5-triphosphonic acid, 3-(triphosphono-methyl)-pentane, 3-(phosphono-methyl)-pentane -1,5-diphosphonic acid, 3-methyl-pentane-2,2,5-triphosphonic acid, 2-methyl-hexane -1,1,1-triphosphonic acid, 2-(phosphono-methyl)-hexane-1,6-diphosphonic acid, 2-methyl-hexane-1,1,6,6-tetraphosphonic acid, 4-methyl-heptane-1,1,1-triphosphonic acid, 4-methyl-heptane-1,1,6,6-tetraphosphonic acid, 2-methyl-octane-1,1,1-triphosphonic acid, 2-methyl-octane-1,1,8,8-tetraphosphonic acid, 3-(bisphosphono -methyl)-butane-1,1,4,4-tetraphosphonic acid, 3-(bisphosphono-methyl)-pentane-1,1,5,5-tetraphosphonic acid, diethylenetriamine penta(methylene phosphonic acid), vinyl phosphonic acid, 1-propene-3-phosphonic acid, 2-propene-3-phosphonic acid, 1-propene -2-phosphonic acid, ethene-1,1-diphosphonic acid, ethene-1,2-diphosphonic acid, 1-propene-1,1-diphosphonic acid, 1-propene-3,3-diphosphonic acid, 1-propene-1,2-diphosphonic acid, 1-propene-2,3-diphosphonic acid, 1-propene-1,3-diphosphonic acid, 1-ethene-1,1,2-triphosphonic acid, 1-propene-3,3,3-triphosphonic acid, 1-propene-1,1,2-triphosphonic acid, 1-propene-2,3,3-triphosphonic acid, 1-propene-1,1,3-triphosphonic acid, 1-propene-1,3,3-triphosphonic acid, 1-propene-1,2,3-triphosphonic acid, 1-butene -4,4,4-triphosphonic acid, 2-butene-4,4,4-triphosphonic acid, 1-butene-1,1,2-triphosphonic acid, 2-butene-3,4,4-triphosphonic acid, 1-butene-3,4,4-triphosphonic acid, 1-butene -1,1,3-triphosphonic acid, 2-butene-1,1,3-triphosphonic acid, 1-butene-2,4,4-triphosphonic acid, 1-butene-1,1,4-triphosphonic acid, 2-butene-1,1,4-triphosphonic acid, 1-butene -1,4,4-triphosphonic acid, 1-butene-3,3,4-triphosphonic acid, 1-butene-2,3,3-triphosphonic acid, 1-butene-1,3,3-triphosphonic acid, 1-butene-1,2,3-triphosphonic acid, 2-butene -2,3,4-triphosphonic acid, 1-butene-2,3,4-triphosphonic acid, 1-butene-1,2,4-triphosphonic acid, 2-butene-1,2,4-triphosphonic acid, 1-butene-1,3,4-triphosphonic acid, 2-pentene -1,1,5-triphosphonic acid, 2-pentene-1,5,5-triphosphonic acid, 1-pentene-1,5,5-triphosphonic acid, 2-pentene-1,4,4-triphosphonic acid, 1-pentene-1,4,4-triphosphonic acid, 1-hexene-1,1,6-triphosphonic acid, 2-hexene-1,1,6-triphosphonic acid, 3-hexene -1,1,6-triphosphonic acid, 2-hexene-1,6,6-triphosphonic acid, 1-hexene-1,6,6-triphosphonic acid, 1-hexene-1,5,5-triphosphonic acid, 2-hexene-1,5,5-triphosphonic acid, 3-hexene-2,2,6-triphosphonic acid, 1-propene-2,3,3,3-tetraphosphonic acid, 1-propene-1,3,3,3-tetraphosphonic acid, 1-propene-1,2,3,3-tetraphosphonic acid, 1-propene-1,1,3,3-tetraphosphonic acid, 1-butene-1,1,4,4-tetraphosphonic acid, 2-butene -1,1,4,4-tetraphosphonic acid, 1-pentene-1,1,5,5-tetraphosphonic acid, 2-pentene-1,1,5,5-tetraphosphonic acid, 1-hexene-1,1,6,6-tetraphosphonic acid, 2-hexene-1,1,6,6-tetraphosphonic acid, 3-hexene-1,1,6,6-tetraphosphonic acid, 1-heptene-1,4,4,7-tetraphosphonic acid, 2-heptene-1,4,4,7-tetraphosphonic acid, 1-octene-1,4,4,8-tetraphosphonic acid, 2-octene-1,4,4,8-tetraphosphonic acid, 3-octene-1,5,5,8-tetraphosphonic acid, 1-nonene-1,5,5,9-tetraphosphonic acid, 2-nonene-1,5,5,9-tetraphosphonic acid, 3-nonene-1,5,5,9-tetraphosphonic acid, 1-cyclopentyl-phosphonic acid, 1,1-cyclopentyl-diphosphonic acid, 1,2-cyclopentyl-diphosphonic acid, 1,3-cyclopentyl-diphosphonic acid, 1-cyclohexyl-phosphonic acid, 1,1-cyclohexyl -diphosphonic acid, 1,2-cyclohexyl-diphosphonic acid, 1,3-cyclohexyl-diphosphonic acid, 1,4-cyclohexyl-diphosphonic acid, and phenyl-1-phosphonic acid.

11. The process of claim 1, wherein the phosphonic acid compound is propane-1,1,3,3-tetraphosphonic acid.

12. The process of claim 1, wherein the implant is a dental abutment, a coronary stent, a dental implant, a hip implant, a spinal implant, a small joints implant, a shoulder implant, or a knee implant.

13. The process of claim 1, wherein the surface of the implant is made of titanium, chromium, niobium, tantalum, vanadium, zirconium, aluminum, cobalt, nickel, stainless steel, or an alloy of any of the aforementioned metals.

14. The process of claim 1, wherein the surface of the implant is made of titanium or a titanium alloy.

15. The process of claim 1, wherein the surface of the implant is made of a cobalt-chromium alloy.

16. The process of claim 1, wherein the surface of the implant is made of a ceramic which is an oxide, a carbide, a nitride, an oxynitride, a carbonitride, or an oxycarbide of a metal or of a metal alloy, wherein said metal or metal alloy is selected from the group consisting of titanium, chromium, niobium, tantalum, vanadium, zirconium, aluminum, cobalt, nickel, stainless steel, and alloys thereof.

Description

(1) The invention is also described by the following illustrative figures. The appended figures show:

(2) FIG. 1: Phosphorus over metal ratio (“Phosphorus/Metal”) of titanium grade 4 cylinders, the surface of which was treated with a phosphonic acid compound using either the process according to the invention (Example 12) or a comparative process according to EP-A-1343545 (Example 13). See Example 14.

(3) FIG. 2: Phosphorus over metal ratio (“Phosphorus/Metal”) of titanium grade 4 cylinders, the surface of which was treated with a phosphonic acid compound at different temperatures in accordance with the present invention or at a lower temperature (reference). See Example 15.

(4) FIG. 3: Phosphorus over metal ratio (“Phosphorus/Metal”) of titanium grade 4 cylinders, the surface of which was treated with a phosphonic acid compound in accordance with the invention, carrying out a pre-treatment cleaning step for different time periods. See Example 16.

(5) FIG. 4: Phosphorus over metal ratio (“Phosphorus/Metal”) of titanium grade 4 cylinders, the surface of which was treated with a phosphonic acid compound for different time periods in accordance with the invention. See Example 17.

(6) FIG. 5: Phosphorus over metal ratio (“Phosphorus/Metal”) of cobalt chrome discs, the surface of which was treated with a phosphonic acid compound using either the process according to the invention (Example 18) or a comparative process according to EP-A-1343545 (Example 19). See Example 20.

(7) FIG. 6: Determination of the thickness of a layer of phosphonic acid compound on the surface of ceramic discs by depth profiling using XPS (see Example 27).

(8) The invention will now be described by reference to the following examples which are merely illustrative and are not to be construed as a limitation of the scope of the present invention.

EXAMPLES

Example 1

(9) A Titanium grade 23 dental implant (bulk composition atomic concentration Titanium 90%, Aluminum 6%, Vanadium 4%; length 11.0 mm, diameter 3.75 mm) was provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The dental implant was immersed in 40 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 30 min. The implant was removed from the cleaning agent solution and rinsed with water as follows: 2 times with 40 ml, swirling at room temperature; 4 times with 40 ml, sonicating for 2 min at 65° C.; 1 time with 40 ml, swirling at room temperature. The implant was then placed into 5 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 65° C. for 10 min. The implant was rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The dental implant was dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 2

(10) A ceramic disc (bulk composition atomic concentration Alumina 80%, Zirconia 20%; length 1.5 mm, diameter 10.0 mm) was provided with a smooth surface. The disc was immersed in 40 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 30 min. The disc was removed from the cleaning agent solution and rinsed with water as follows: 2 times with 50 ml, swirling at room temperature; 4 times with 50 ml, sonicating for 2 min at 65° C. The disc was then placed into 10 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 65° C. for 60 min. The disc was rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C. The disc was dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 3

(11) A ceramic dental implant (alumina toughened zirconia, yttria stabilized; length 11.0 mm, diameter 3.8 mm) was provided with a smooth surface. The dental implant was immersed in 50 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 70° C. for 15 min. This step was repeated a second time. The implant was removed from the cleaning agent solution and rinsed with water as follows: 2 times with 50 ml, swirling at room temperature; 3 times with 50 ml, sonicating for 2 min at 70° C. The implant was then placed into 15 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 70° C. for 60 min. The implant was rinsed with water as follows: 1 time with 10 ml, swirling at room temperature; 2 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The dental implant was dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 4

(12) Ten Titanium grade 23 dental implants (bulk composition atomic concentration Titanium 90%, Aluminum 6%, Vanadium 4%; length 11.0 mm, diameter 3.75 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The dental implants were immersed in 400 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 30 min. The implants were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 400 ml, swirling at room temperature; 4 times with 400 ml, sonicating for 2 min at 65° C.; 1 time with 400 ml, swirling at room temperature. The implants were then placed one after the other into 5 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 65° C. for 10 min. After the treatment with the phosphonic acid, each implant was rinsed with water as follows: 1 time with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The dental implants were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 30 mbar) for at least 3 hours.

Example 5 (Comparative Example)

(13) A Titanium grade 23 dental implant (bulk composition atomic concentration Titanium 90%, Aluminum 6%, Vanadium 4%; length 13.0 mm, diameter 3.75 mm) was provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The implant was immersed in 13 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in an ultrasonic bath and sonicated at room temperature for 10 min. The implant was rinsed with water as follows: 1 time with 10 ml, swirling at room temperature; 2 times with 10 ml, sonicating for 1 min at room temperature. The dental implant was dried in a heating oven (ca 70° C.) for at least 1 hour. This surface treatment is in accordance with the surface treatment described in EP-A-1343545.

Example 6 (Comparative Example)

(14) A ceramic disc (bulk composition atomic concentration Alumina 80%, Zirconia 20%; length 5.0 mm, diameter 15.0 mm) was provided with a smooth surface on one side and a roughened surface on the other side. The sample was immersed in 30 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at room temperature for 5 min. The solution was then removed and replaced by fresh 2% (v/v) aqueous solution of deconex 15 PF-x. Sonication was repeated at room temperature for 5 min. This cleaning step was repeated 4 times in total. The disc was removed from the cleaning agent solution and rinsed with water as follows: 6 times with 30 ml, sonicating for 5 min at room temperature. The water from the second to last rinse was tested and a pH greater than 6.2 was found. The disc was then placed into 20 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was swirled thoroughly and left to stand at room temperature for 30 min. It was briefly swirled again and left to stand for an additional 5 min. The disc was rinsed with water as follows: 3 times with 20 ml, swirling at room temperature. The ceramic disc was dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. This surface treatment is in accordance with the surface treatment described in EP-A-1343545.

Example 7 (Comparative Example)

(15) A ceramic disc (EZY95Bio-TZP, bulk composition atomic concentration Zirconia+Yttria+HfO.sub.2=99.9%; length 5.0 mm, diameter 1.25 mm) was provided with a smooth surface. The sample was immersed in 30 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at room temperature for 5 min. The solution was then removed and replaced by fresh 2% (v/v) aqueous solution of deconex 15 PF-x. Sonication was repeated at room temperature for 5 min. This cleaning step was repeated 4 times in total. The sample was removed from the cleaning agent solution and rinsed with water as follows: 6 times with 65 ml, sonicating for 5 min at room temperature. The water from the second to last rinse was tested and a pH of 5.8 was found. The disc was rinsed again with water as follows: 4 times with 30 ml, sonicating for 5 min at room temperature. The water from the last rinse was tested and a pH of 5.9 was found. This was considered acceptable. The disc was then placed into 1.5 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was swirled thoroughly and left to stand at room temperature for 30 min. It was briefly swirled again and left to stand for an additional 5 min. The disc was rinsed with water as follows: 3 times with 20 ml, swirling at room temperature. The ceramic disc was dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. This surface treatment is in accordance with the surface treatment described in EP-A-1343545.

Example 8

(16) Following the surface treatment with one phosphonic acid compound as described in Examples 1 to 7 the samples were analyzed by X-ray photoelectron spectroscopy (XPS). XPS analyses were performed on an Axis Ultra spectrometer from Kratos (Kratos, Manchester, U.K.) equipped with a concentric hemispherical analyzer and using a monochromatized aluminum anode X-ray source (Al Kα.sub.1,2 1486.6 eV, full width at half maximum, fwhm=0.85 eV, 15 kV, 150 W). The samples were investigated under ultrahigh vacuum conditions: 10.sup.−8-10.sup.−7 Pa. Spectra were taken at a 90° takeoff angle with respect to the surface. A sample area of 300×700 μm.sup.2 or 700×700 μm.sup.2 was analyzed with a pass energy of 80.0 eV for survey scans. The spectrometer was calibrated by using Cu 2p3/2 (932.7 eV) and Au 4f7/2 (84.0 eV) signals. Surface sensitivity factors used to determine the atomic concentrations were those of the instrument. Spectra were peak fitted after background subtraction by assuming a Gaussian/Lorentzian (90-70/10-30) peak shape. All peaks between 0 eV to 1200 eV were inspected. The % atomic concentration of each element is shown in the table below.

(17) TABLE-US-00001 % atomic concentration from survey spectra Titanium Titanium Titanium Titanium Grade 23 Grade 23 Grade 23 Ceramic Grade 23 dental dental dental Ceramic Ceramic dental dental implant implant implant Ceramic disc dental implant Element implant #8 #10 (Comp. disc (Comp. implant (Comp. from survey.sup.a (Ex. 1) (Ex. 4) (Ex. 4) Ex. 5) (Ex. 2) Ex. 6) Ex. 3) Ex. 7) Ti2p 18.5 17.7 18.3 16.9 0.0 0.0 0.0 0.0 Al2s 2.3 1.8 3.1 2.4 19.0.sup.b 27.0.sup.b 8.8 0.0 Zr3d 0.0 0.0 0.0 0.0 6.5 4.6 14.1 20.4 V2p 0.4 0.4 0.5 0.5 0.0 0.0 0.0 0.0 Y3d 0.0 0.0 0.0 0.0 0.2 0.2 1.8 2.6 Hf4d 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.5 O1s 54.4 55.3 55.6 50.5 58.9 54.5 59.0 57.6 C1s 19.5 19.3 18.0 23.7 11.4 10.9 13.0 14.4 P2p 4.0 3.7 3.3 2.2 3.6 2.0 3.0 2.1 Phosphorus/ 0.18.sup.c 0.18.sup.c 0.15.sup.c 0.11.sup.c 0.14.sup.d 0.06.sup.d 0.12.sup.e 0.08.sup.f Metal .sup.aS2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤1%. .sup.bAl2p was measured. .sup.cMetal = sum % atomic concentrations (Ti2p + Al2s + V2p) .sup.dMetal = sum % atomic concentrations (Al2p + Zr3d) .sup.eMetal = sum % atomic concentrations (Al2s + Zr3d + Y3d) .sup.fMetal = sum % atomic concentrations (Zr3d + Y3d + Hf4d)

(18) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated dividing the % atomic concentration of phosphorus by the sum of the % atomic concentrations of all metals expected in the analyzed sample. When the phosphorus over metal ratios obtained with the surface treatment process according to the present invention (Examples 1 to 4) were compared to those obtained in Comparative Examples 5 to 7 (obtained in accordance with the surface treatment described in EP-A-1343545), it was found that the ratios obtained with the process according to the invention were significantly higher than those obtained in Comparative Examples 5 to 7, which indicates that a better surface coverage was obtained with the surface treatment process of the invention. The XPS results of the implants treated as per Example 4 furthermore showed that 5 ml of a 0.7 mM solution of 1,1,3,3-propane tetraphosphonic acid can be used to treat up to 8 dental implants.

Example 9

(19) Ten Titanium grade 23 dental implants (bulk composition atomic concentration Titanium 90%, Aluminum 6%, Vanadium 4%; length 11.0 mm, diameter 3.75 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The dental implants were immersed in 400 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 30 min. The implants were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 400 ml, swirling at room temperature; 4 times with 400 ml, sonicating for 2 min at 65° C.; 1 time with 400 ml, swirling at room temperature. The implants were then placed by group of 2 into 5 ml of the following concentrations of 1,1,3,3-propane tetraphosphonic acid: 0.7 mM, 2 mM, 3.5 mM, 5 mM, 7 mM. The solutions were placed in the ultrasonic bath and sonicated at 65° C. for 10 min. After the treatment with the phosphonic acid, each implant was rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The implants were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 30 mbar) for at least 3 hours. The samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(20) TABLE-US-00002 % atomic concentration from survey spectra Titanium Titanium Titanium Titanium Titanium Grade 23 Grade 23 Grade 23 Grade 23 Grade 23 Element from dental implant dental implant dental implant dental implant dental implant survey.sup.a (0.7 mM) (2 mM) (3.5 mM) (5 mM) (7 mM) Ti2p 18.5 18.6 19.0 19.2 19.2 Al2s 2.3 2.5 2.8 2.5 2.5 V2p 0.4 0.5 0.5 0.5 0.5 O1s 54.4 54.1 56.7 56.7 56.2 C1s 19.5 19.9 16.7 16.2 16.6 P2p 4.0 3.8 3.7 4.0 4.0 Phosphorus/Metal.sup.b 0.19 0.18 0.17 0.18 0.18 .sup.aZr3d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration < 1%. .sup.bMetal = sum % atomic concentrations (Ti2p + Al2s + V2p)

(21) The phosphorus over metal ratio was calculated and was the same at each concentration tested. This indicated the formation of a full monolayer of phosphonic acid molecules at all concentrations.

Example 10

(22) Four ceramic dental implants (alumina toughened zirconia, yttria stabilized; length 11.0 mm, diameter 3.8 mm) were provided with a smooth surface. The dental implants were immersed in 300 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 70° C. for 15 min. This step was repeated a second time. The implants were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 300 ml, swirling at room temperature; 3 times with 300 ml, sonicating for 2 min at 70° C. The implants were then placed into 15 ml of the following concentrations of 1,1,3,3-propane tetraphosphonic acid: 0.7 mM, 2.5 mM, 5 mM, 10 mM. The solutions were placed in the ultrasonic bath and sonicated at 70° C. for 60 min. After treatment, the implants were rinsed with water as follows: 1 time with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 70° C.; 1 time with 10 ml, swirling at room temperature. The implants were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. The samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(23) TABLE-US-00003 % atomic concentration from survey spectra Ceramic Ceramic Ceramic dental dental dental Ceramic dental Element from implant implant implant implant survey.sup.a (0.7 mM) (2.5 mM) (5 mM) (10 mM) Al2s 8.8 9.6 9.5 9.0 Zr3d 14.1 14.8 14.9 15.5 Y3d 1.8 1.8 1.7 1.7 O1s 59.0 56.5 57.8 58.8 C1s 13.0 13.4 12.4 11.6 P2p 3.0 3.1 2.9 3.2 Phosphorus/Metal.sup.b 0.12 0.12 0.11 0.12 .sup.aTi2p, V2p, N1s, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. Si2p was detected at % atomic concentration < 1%. .sup.bMetal = sum % atomic concentrations (Al2s + Zr3d + Y3d)

(24) The phosphorus over metal ratio was calculated and was the same at each concentration tested. This indicated the formation of a full monolayer of phosphonic acid molecules at all concentrations.

Example 11

(25) A Titanium grade 5 dental implant (bulk composition atomic concentration Titanium 90%, Aluminum 6%, Vanadium 4%; length 11.0 mm, diameter 3.75 mm) is provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The dental implant is immersed in 30 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution is placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The implant is removed from the cleaning agent solution and rinsed with water as follows: 2 times with 30 ml, swirling at room temperature; 4 times with 30 ml, sonicating for 2 min at 65° C.; 1 time with 30 ml, swirling at room temperature. The implant is then placed into 5 ml of a 0.5 mM aqueous solution of one of the following phosphonic acids: propane-1-phosphonic acid (PA-1), propane-1,3-diphosphonic acid (PA-2), tert-butyl phosphonic acid (PA-3), 1-propene-3-phosphonic acid (PA-4), 1-cyclohexyl phosphonic acid (PA-5), phenyl-1-phosphonic acid (PA-6), diethylenetriamine penta(methylene phosphonic acid) (PA-7), 2-amino-3-phosphonopropionic acid (PA-8), 2-(2-phosphonoacetoxy)benzoic acid (PA-9), etidronic acid (PA-10). The solution is placed in the ultrasonic bath and sonicated at 65° C. for 10 min. The implant is rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The dental implant is dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. The samples are analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 are used. The prospective % atomic concentration of each element is shown in the table below.

(26) TABLE-US-00004 % atomic concentration from survey spectra (prospective data) From survey.sup.a PA-1 PA-2 PA-3 PA-4 PA-5 PA-6 PA-7 PA-8 PA-9 PA-10 Phosphorus/ 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 0.16-0.20 Metal.sup.b (surface treatment as described herein above) Phosphorus/Metal 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 0.05-0.11 (surface treatment as described in Comp. Example 6) .sup.aThe XPS survey shows the expected elements (Ti2p, Al2s, V2p, O1s, C1s, P2p, N1s) for all compounds tested. Other elements Zr3d, Y3d, Si2p, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s. .sup.bMetal = sum % atomic concentrations (Ti2p + Al2s + V2p)

Example 12

(27) Two Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed into 6 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 13 (Comparative Example)

(28) Two Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at room temperature for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at room temperature; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed into 6 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was swirled thoroughly and left to stand at room temperature for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at room temperature; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. This surface treatment is in accordance with the surface treatment described in EP-A-1343545.

Example 14

(29) Following the surface treatment with one phosphonic acid compound as described in Examples 12 and 13, the samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(30) TABLE-US-00005 % atomic concentration from survey spectra (average of 2 analysis points) Titanium Titanium Grade 4 cylinder Grade 4 cylinder Element from survey.sup.a (Example 12) (Example 13) Ti2p 16.4 17.7 O1s 53.5 48.2 C1s 24.0 30.7 P2p 4.0 2.6 Phosphorus/Metal 0.25.sup.b 0.15.sup.b .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤ 2.2%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(31) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that the ratio obtained with the process according to the present invention (Example 12) was significantly higher than that obtained with the comparative process described in Example 13, as also illustrated in FIG. 1. This indicates that a better surface coverage was obtained with the surface treatment process of the invention.

Example 15

(32) Twelve Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed by 2 into 6 glass bottles and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The 6 solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 40° C., 50° C., 60° C., 70° C., 80° C. and 90° C., respectively, for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 40° C., 50° C., 60° C., 70° C., 80° C. and 90° C., respectively; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed by 2 into 6 glass bottles and immersed in 6 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The 6 solutions were placed in the ultrasonic bath and sonicated at 40° C., 50° C., 60° C., 70° C., 80° C. and 90° C., respectively, for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 40° C., 50° C., 60° C., 70° C., 80° C. and 90° C., respectively; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

(33) The samples were then analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(34) TABLE-US-00006 % atomic concentration from survey spectra (average of 2 analysis points) Element from survey.sup.a 40° C. 50° C. 60° C. 70° C. 80° C. 90° C. Ti2p 17.9 17.3 17.0 16.6 16.6 15.7 O1s 50.9 51.1 51.9 52.6 51.2 50.7 C1s 27.0 26.4 26.0 25.7 27.1 28.2 P2p 3.9 4.5 4.2 4.1 4.5 4.3 Phosphorus/ 0.22.sup.b 0.26.sup.b 0.25.sup.b 0.25.sup.b 0.27.sup.b 0.27.sup.b Metal .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤1.0%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(35) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that a better surface coverage was obtained at a temperature ≥50° C. This is also illustrated in FIG. 2.

Example 16

(36) Six Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed by 2 into 3 glass bottles and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The 3 solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 5, 15 and 30 min, respectively. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed by 2 into 3 glass bottles and immersed in 6 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The 3 solutions were placed in the ultrasonic bath and sonicated at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

(37) The samples were then analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(38) TABLE-US-00007 % atomic concentration from survey spectra (average of 2 analysis points) Deconex Deconex Deconex 15PF-x 15PF-x 15PF-x Element from survey.sup.a 5 min 15 min 30 min Ti2p 14.6 15.8 15.7 O1s 51.0 51.7 51.6 C1s 27.9 26.4 27.0 P2p 5.3 5.1 4.9 Phosphorus/Metal 0.36.sup.b 0.32.sup.b 0.32.sup.b .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤ 1.2%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(39) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that a better surface coverage was obtained when the pre-treatment with deconex 15 PF-x is carried out for 5 min with sonication. This is also shown in FIG. 3.

Example 17

(40) Eight Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed by 2 into 4 glass bottles and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The 4 solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed by 2 into 4 glass bottles and immersed in 6 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The 4 solutions were placed in the ultrasonic bath and sonicated at 65° C. for 5, 10, 30 and 60 min, respectively. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

(41) The samples were then analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(42) TABLE-US-00008 % atomic concentration from survey spectra (average of 2 analysis points) Phosphonic Phosphonic Phosphonic Phosphonic Element from acid acid acid acid survey.sup.a 5 min 10 min 30 min 60 min Ti2p 17.0 16.4 16.3 16.8 O1s 50.9 51.4 52.4 52.3 C1s 27.0 26.7 25.7 25.3 P2p 4.1 4.5 4.8 4.8 Phosphorus/ 0.24.sup.b 0.28.sup.b 0.30.sup.b 0.28.sup.b Metal .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤ 1.0%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(43) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that a better surface coverage was obtained when the treatment with the phosphonic acid is carried out from 10 to 60 min with sonication. This is also shown in FIG. 4.

Example 18

(44) Two Cobalt Chrome discs (bulk composition atomic concentration Cobalt 64%, Chrome 28%, Molybdenum 6%, other elements 2%; length 1.5 mm, diameter 5.0 mm) were provided with a machined surface. The 2 discs were placed into a glass bottle and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The discs were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The discs were then placed into a glass bottle and immersed in 4 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was placed in the ultrasonic bath and sonicated at 65° C. for 15 min. The discs were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The discs were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 19 (Comparative Example)

(45) Two Cobalt Chrome discs (bulk composition atomic concentration Cobalt 64%, Chrome 28%, Molybdenum 6%, other elements 2%; length 1.5 mm, diameter 5.0 mm) were provided with a machined surface. The 2 discs were placed into a glass bottle and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at room temperature for 15 min. The discs were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at room temperature; 1 time with 10 ml, swirling at room temperature. The discs were then placed into a glass bottle and immersed in 4 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solution was swirled thoroughly and left to stand at room temperature for 15 min. The discs were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at room temperature; 1 time with 10 ml, swirling at room temperature. The discs were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours. This surface treatment is in accordance with the surface treatment described in EP-A-1343545.

Example 20

(46) Following the surface treatment with one phosphonic acid compound as described in Examples 18 and 19, the samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(47) TABLE-US-00009 % atomic concentration from survey spectra (average of 2 analysis points) Element Cobalt Chrome disc Cobalt Chrome disc from survey.sup.a (Example 18) (Example 19) Cr2p 12.2 11.0 Co2p 8.6 8.6 Mo3d 1.5 1.5 O1s 29.5 24.8 C1s 39.6 47.3 P2p 1.7 0.0 Phosphorus/Metal 0.08.sup.b 0.00.sup.b .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, Si2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Fe2p, Ti2p, Mg2p and F1s were not detected. N1s and S2p were detected at % atomic concentration ≤ 7.0%. .sup.bMetal = sum % atomic concentrations (Cr2p + Co2p + Mo3d)

(48) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that the ratio obtained with the process according to the present invention (Example 18) was significantly higher than that obtained with the comparative process described in Example 19, which indicates that a better surface coverage was obtained with the surface treatment process of the invention. This is also illustrated in FIG. 5.

Example 21

(49) Twelve Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed by 2 into 6 glass bottles and immersed in 6 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The 6 solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed by 2 into 6 glass bottles and immersed in 6 ml of the phosphonic acid compound described in the table below at the reported concentrations. The 6 solutions were placed in the ultrasonic bath and sonicated at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

(50) The samples were then analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(51) TABLE-US-00010 % atomic concentration from survey spectra (average of 2 analysis points) Methylene- Propane-1- t-Butyl Phenyl-1- Diethylenetriamine 1,1-di phosphonic phosphonic phosphonic penta(methylene Etidronic phosphonic Element from acid acid acid phosphonic acid) acid acid survey.sup.a (A) (B) (C) (D) (E) (F) Concentration 2 2 2 0.4 1 1 (mM) Ti2p 21.9 21.8 21.9 19.3 21.4 20.5 O1s 50.8 50.0 50.3 51.9 52.2 52.4 C1s 26.5 27.5 26.9 22.8 24.4 24.7 P2p 0.5 0.4 0.7 3.0 2.0 2.2 Phosphorus/Metal 0.02.sup.b 0.02.sup.b 0.03.sup.b 0.16.sup.b 0.09.sup.b 0.10.sup.b .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤0.3%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(52) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that using the process according to the present invention, titanium cylinders could be successfully treated with a variety of phosphonic acid compounds.

Example 22

(53) Three Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed in 3 glass bottles and immersed in 5 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed into 3 glass bottles and immersed into 3 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solutions were placed in the ultrasonic bath and sonicated at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 23

(54) Three Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed in 3 glass bottles and immersed in 5 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 4 times with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were then placed into 3 glass bottles and immersed into 3 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solutions were swirled thoroughly and left to stand at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 24

(55) Following the surface treatment with one phosphonic acid compound as described in Examples 22 and 23, the samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(56) TABLE-US-00011 % atomic concentration from survey spectra (average of 6 analysis points) Element Titanium Grade 4 cylinder Titanium Grade 4 cylinder from survey.sup.a (Example 22) (Example 23) Ti2p 17.7 18.1 O1s 53.0 53.0 C1s 23.1 23.1 P2p 4.9 4.0 Phosphorus/ 0.28.sup.b 0.22.sup.b Metal .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤ 1.7%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(57) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that using sonication during the surface treatment with the phosphonic acid compound (Example 22) led to a better surface coverage when compared to the surface treatment with the phosphonic acid compound whereby sonication was not carried out (Example 23).

Example 25

(58) Three Titanium grade 4 cylinders (bulk composition atomic concentration Titanium 100%; length 6.0 mm, diameter 2.4 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The cylinders were placed in 3 glass bottles and immersed in 3 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solutions were placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 65° C. for 15 min. The cylinders were rinsed with water as follows: 2 times with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The cylinders were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

Example 26

(59) Following the surface treatment with one phosphonic acid compound as described in Examples 22 and 25, the samples were analyzed by X-ray photoelectron spectroscopy (XPS). Same analysis conditions as described in Example 8 were used. The % atomic concentration of each element is shown in the table below.

(60) TABLE-US-00012 % atomic concentration from survey spectra (average of 6 analysis points) Element from Titanium Grade 4 cylinder Titanium Grade 4 cylinder survey.sup.a (Example 22) (Example 25) Ti2p 17.7 17.3 O1s 53.0 51.6 C1s 23.1 25.4 P2p 4.9 4.2 Phosphorus/ 0.28.sup.b 0.24.sup.b Metal .sup.aAl2p, Zr3d, V2p, Y3d, Hf4d, S2p, Ca2p, Cl2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d, Mg2p and F1s were not detected. N1s and Si2p were detected at % atomic concentration ≤ 1.4%. .sup.bMetal = sum % atomic concentrations (Ti2p)

(61) The phosphorus over metal ratio (“Phosphorus/Metal”) was calculated and it was found that pre-treatment with deconex 15 PF-x enhances surface coverage (Example 22) when compared to the surface treatment whereby deconex 15 PF-x was not used (Example 25).

Example 27

(62) Two ceramic discs (yttria stabilized zirconia; length 5.0 mm, diameter 1.0 mm) were provided with a roughened surface, produced by sand blasting and acid etching according to industry standards. The discs were immersed in 80 ml of a 2% (v/v) aqueous solution of deconex 15 PF-x (which is a phosphate free, potassium hydroxide based standard cleaning agent). The solution was placed in an ultrasonic bath (output frequency 30 kHz) and sonicated at 70° C. for 15 min. This step was repeated a second time. The discs were removed from the cleaning agent solution and rinsed with water as follows: 2 times with 90 ml, swirling at room temperature; 3 times with 90 ml, sonicating for 2 min at 70° C. The discs were then placed into 2 glass bottles and immersed into 2.5 ml of a 0.7 mM aqueous solution of 1,1,3,3-propane tetraphosphonic acid. The solutions were placed in the ultrasonic bath and sonicated at 70° C. for 60 min. The discs were rinsed with water as follows: 1 time with 10 ml, swirling at room temperature; 1 time with 10 ml, sonicating for 2 min at 65° C.; 1 time with 10 ml, swirling at room temperature. The discs were dried in a desiccator over P.sub.2O.sub.5 and under vacuum (ca 20 mbar) for at least 3 hours.

(63) Following the surface treatment, the thickness of the phosphonic acid layer was determined by depth profiling using XPS. Ion gun sputtering cycles were alternated with XPS measurements. An ion gun was used to etch the material for a defined period of time. Once turned off, XPS spectra were acquired. The depth profiles were performed using a Kratos AXIS Nova high resolution spectrometer. An Al-standard source was used for the measurement. Depth profile sputtering was performed by scanning a 3.8 keV Ar+ beam at 100 μA extractor current over an area of 4 mm×4 mm. The sputter rate of Ta.sub.2O.sub.5 standards measured under these conditions (6 nm/min) was used to convert sputter time in approximate sputter depth. Spectra were measured after the following sputtering times: 0, 5, 10, 15, 20, 30, 40, 60 sec. Spectra were peak fitted after background subtraction by assuming a Gaussian/Lorentzian (90-70/10-30) peak shape. All peaks between 0 eV to 1200 eV were inspected. The % atomic concentration of each element is shown in the table below.

(64) TABLE-US-00013 % atomic concentration from survey spectra (average of 2 analysis points) Element from survey.sup.a 0 sec 5 sec 10 sec 15 sec 20 sec 30 sec 40 sec 60 sec Depth (nm) 0 0.5 1 1.5 2 3 4 6 Zr3d 18.0 29.4 29.9 30.6 31.4 26.8 27.4 32.7 Y3d 0.7 0.9 1.0 1.2 1.1 1.2 1.2 1.3 O1s 56.4 65.7 67.2 66.2 66.4 71.4 71.1 66.0 C1s 20.9 3.0 1.2 1.3 0.5 0.0 0.0 0.0 P2p 3.4 1.0 0.8 0.7 0.5 0.6 0.3 0.1 Phosphorus/Metal 0.18.sup.b 0.03.sup.b 0.02.sup.b 0.02.sup.b 0.01.sup.b 0.02.sup.b 0.01.sup.b 0.00.sup.b .sup.aAl2p, V2p, Hf4d, S2p, Ca2p, Cl2p, Si2p, Na1s, K2p, Zn2p, Cu2p, Pb4f, Ni2p, Co2p, Cr2p, Fe2p, Mo3d and Mg2p were not detected. N1s and F1s were detected at % atomic concentration ≤0.5%. .sup.bMetal = sum % atomic concentrations (Zr3d + Y3d)

(65) These results show that the phosphonic acid compound binds to the outermost surface of the discs. The phosphorus peak was measured at % atomic concentrations close to the detection limit (0.5%) after 10 seconds of sputtering. This indicated that the phosphonic acid compound formed a monolayer with a thickness of about 1 nm (which is the size of the molecule). This is also shown in FIG. 6.