Low friction coatings for use in dental and medical devices

Abstract

The present invention provides an article, at least part of it being coated by inorganic fullerene-like (IF) nanoparticles or composite containing such nanoparticles. Preferably, the invention provides an article made of metal, for use in dentistry or medicine e.g. archwire, needle or catheter, having a friction-reducing film, and methods for coating such articles with a friction-reducing film.

Claims

1. An article, comprising: an exposed surface of the article, at least a portion of the exposed surface of the article being coated by a composite comprising inorganic fullerene-like (IF) nanoparticles in a matrix, the article being suitable for use in medicine or dentistry.

2. The article according to claim 1, wherein the article is in an elongated shape.

3. The article according to claim 2, wherein the article is in a form of wire or tube.

4. The article according to claim 1, wherein the article is circular or rectangular in cross-section.

5. The article according to claim 1, wherein the composite configured to reduce friction between a coated surface of the article and an adjacent object, surface or tissue, as compared to an uncoated surface of the article.

6. The article according to claim 1, wherein the composite is selected from the group consisting of a NiP-IF-nanoparticle composite, a CoPIF-nanoparticle composite, a CoB-IF-nanoparticle composite, a NiB-IF-nanoparticle composite, a metal film-IF composite, a polyurethane-IF composite, a polypropylene-IF composite, an epoxy-IF composite and a sol-gel glass-IF composite.

7. The article according to claim 1, wherein the IF nanoparticles comprise metal chalcogenide or metal dichalcogenide.

8. The article according to claim 1, wherein the IF nanoparticles comprise one or more compound selected from the group consisting of TiS.sub.2, TiSe.sub.2, TiTe.sub.2, WS.sub.2, WSe.sub.2, WTe.sub.2, MoS.sub.2, MoSe.sub.2, MoTe.sub.2, SnS.sub.2, SnSe.sub.2, SnTe.sub.7, RuS.sub.2, RuSe.sub.2, RuTe.sub.2, GaS, GaSe, GaTe, InS, InSe, HfS.sub.2, ZrS.sub.2, VS.sub.2, ReS.sub.2 and NbS.sub.2.

9. The article according to claim 6, wherein the composite comprises (i) NiP, CoP, CoB or NiB matrix, and (ii) IF-WS.sub.2 or IF-MoS.sub.2 nanoparticles.

10. The article according to claim 6, wherein the IF-nanoparticles are IF-WS.sub.2 or IF-MoS.sub.2 nanoparticles.

11. The article according to claim 1, wherein the composite is biocompatible.

12. The article according to claim 1, wherein the composite has a thickness of between 0.3 micron and 50 microns.

13. The article according to claim 12, wherein the composite has a thickness of between 1 micron and 10 microns.

14. The article according to claim 1, wherein the article is selected from the group consisting of a dental implant, a needle, a catheter, an orthodontic wire, an orthodontic bracket, a band, a bonded or banded orthodontic attachment, a palatal expander, a mobile functioning native or artificial human joint, a hip replacement, a tissue-penetrating device, an oral or nasal feeding tube and a tube used for laparoscopic surgery.

15. The article according to claim 14, wherein the article is an orthodontic archwire.

16. The article according to claim 14, wherein the article is a needle or catheter.

17. The article according to claim 14, wherein the article is a screw-type dental implant.

18. The article according to claim 1, wherein the article further comprises a material selected from the group consisting of metal, rubber, glass and plastic.

19. Method for coating an article of claim 1 for use in medicine or dentistry with a friction reducing film comprising: (i) dispersing IF nanoparticles within a matrix to obtain IF nanoparticles homogeneously dispersed in said matrix; (ii) contacting the article with said matrix and depositing said nanoparticles on one or more surfaces of said article through electroless or electrochemical deposition, thereby obtaining said article.

20. Method according to claim 19, comprising, prior to said contacting, exposing said article to a surface pre-treatment procedure.

21. Method according to claim 20, wherein the surface pre-treatment procedure is carried out with an etching acidic solution.

22. Method according to claim 21, wherein said acidic solution is HF.

23. Method according to claim 19, comprising one or more additional deposition steps prior to said contacting to form intermediate layers between the article and the outer, function-reducing film.

24. Method according to claim 19, further comprising annealing the coated article at high temperature.

25. Method according to claim 19, wherein said article is made of metal and said coating comprises a friction reducing film comprising composite of NiP, CoB, NiB or CoP and IF nanoparticles.

26. Method according to claim 19, wherein said friction reducing film has a thickness of between 0.3 micron and 50 microns.

27. An article, comprising: at least one material selected from the group consisting of metal, rubber, glass and plastic, the at least one material having an exposed surface, at least a portion of the exposed surface of the article being coated by a composite comprising inorganic fullerene-like (IF) nanoparticles in a matrix.

28. An article selected from the group consisting of a dental implant, a needle, a catheter, an orthodontic wire, an orthodontic bracket, a hand, a bonded or handed orthodontic attachment, a palatal expander, a mobile functioning native or artificial human joint, a hip replacement, a tissue-penetrating device, an oral or nasal feeding tube and a tube used for laparoscopic surgery, the article comprising: an exposed surface of the article, at least a portion of the exposed surface being coated by a composite comprising inorganic fullerene-like (IF).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) In order to understand the invention and to see how it may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting examples only, with reference to the accompanying drawings, in which:

(2) FIG. 1 is a photograph illustrating the orthodontic setup of a fixed orthodontic appliance.

(3) FIG. 2 is a SEM magnification 12000 of NiP coating on SS wire.

(4) FIGS. 3A and 3B show TEM images of single IF-WS.sub.2 nanoparticles after ultrasonic dispersion within a NiP matrix after 2 minutes of sonification and one hour of plating activity, respectively. FIGS. 3C and 3D show an enlarged TEM image of the IF where the layers are observed with no apparent damage.

(5) FIG. 4 is an optical micrograph of the surface of a NiP-IF-WS.sub.2 film, after 100 cycles of dry friction.

(6) FIG. 5 shows optical micrographs of the surface of Si.sub.3N.sub.4 ball after the friction with NiP-IF coating using Mouth Kote fluid (A)Before cleaning, (B)After cleaning.

(7) FIG. 6 is a graph showing the friction coefficient of the orthodontic wire vs. number of cycles, compared to a wire coated with NiPWS.sub.2 composite.

(8) FIG. 7A is a graph of force (N) vs. displacement (mm) in non coated SS wire, taken at 0 angle of contact between the bracket and the wire; average force is 1.32N (STANDARD DEVIATION (SD))=0.12).

(9) FIG. 7B is a graph of force (N) vs. displacement (mm) in coated wire, taken at 0 angle of contact between the bracket and the wire, tested on the same bracket; average force is 1.10N (SD=0.06).

(10) FIG. 8A is a graph of force (N) vs. displacement (mm) in non coated SS wire, taken at 5 angle of contact between the bracket and the wire; average force is 2.95N (SD=0.09).

(11) FIG. 8B is a graph of force (N) vs. displacement (mm) in coated wire, taken at 5 angle of contact between the bracket and the wire, tested on the same bracket; average force is 1.58N (SD=0.25).

(12) FIG. 9A is a graph of force (N) vs. displacement (mm) in non coated SS wire, tested in dry mode at 10 angle of contact between the bracket and the wire; average force is 4N (SD=0.19).

(13) FIG. 9B is a graph of force (N) vs. displacement (mm) in non coated SS wire, tested in wet mode at 10 angle of contact between the bracket and the wire; average force is 3.35N (SD=0.21).

(14) FIG. 9C is a graph of force (N) vs. displacement (mm) in coated wire, tested in wet mode at 10 angle of contact between the bracket and the wire, tested on the same wet bracket; average force is 1.57N (SD=0.23).

(15) FIG. 10 is a photograph of the bracket-mounting apparatus.

(16) FIG. 11 is a photograph of an angulation device with an aluminum plate screwed in the 10 angle slot.

(17) FIG. 12 is a photograph showing an orthodontic wire inserted into the bracket slot and ligated by an elastic module. The wire is connected on the top to the load cell and on the bottom to the 150 g weight.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

(18) The present invention provides an article for use in medicine or dentistry, preferably made of metal, at least part of its surface being coated by friction reducing film comprising inorganic fullerene-like (IF) nanoparticles or composite containing such IF nanoparticles.

(19) The article may be, for example, an elongated article such as a metallic wire e.g. orthodontic archwire or elongated medical article e.g. needle, catheter, etc.

(20) The present invention further provides methods for coating the articles with a friction-reducing film which comprises IF nanoparticles or composite containing such nanoparticles.

(21) When the article is a dental article, it may comprise a metallic article which is placed temporarily or permanently in the mouth of an individual. Such articles include, for example, orthodontic appliances such as archwires or screw-type dental implants. The orthodontic wires or dental implants may be comprised of any metals suitable for use in dental devices, for example stainless steel, titanium, titanium-molybdenum alloy (TMA), beta-titanium, nitinol, alumina, zirconia, nickel-titanium, and alloys and blends of these materials. Beta-titanium, stainless steel and nickel-titanium alloys are currently preferred archwire materials.

(22) Materials useful for the friction-reducing film include hard, relatively inert metals which do not tend to form oxides in the environment of the mouth, biocompatible IF nanoparticles and composites with such nanoparticles. The coated wire of the invention also may include one or more additional intermediate layers between the wire and the outer, function-reducing film. The intermediate layer(s) preferably comprise a metallic material selected from the group consisting of Ni and NiCr.

(23) One method of applying the friction reducing film is by incorporating the IF nanoparticles into a coating by composite electroless deposition. Electroless plating has gained popularity since the beginning of the last century when it was first introduced, due to the production of coatings with excellent corrosion, wear and abrasion resistance. Electroless plating is a chemical process of oxidation and reduction by which a metallic ion is reduced from an aqueous solution containing a reducing agent onto a surface having a catalytic site with no need to transfer a current. Of the variety of metal ions that are in use, nickel and cobalt have proven supremacy in corrosion and wear resistance when deposited as nickel phosphorus (NiP), cobalt phosphorus (CoP), or mixtures of CoP or NiP with other transition metals such as for example CoNiP, CoRhP, CoWP or CoFeP. The incorporation of IF-WS.sub.2 nanoparticles into NiP matrix was carried out by a method similar to that reported by Chen et al [Chen et al, Adv. Eng. Mat. 4(9):686-690 (2002)].

(24) Another way of coating an article with a friction reducing film is by electrochemical deposition. In this way the article is first exposed to a surface pre-treatment procedure. In the next step, the article is immersed in a metal solution and a current is applied. A similar solution containing IF nanoparticles is then prepared by sonication and the article is immersed in this solution and a current is applied. Alternatively, the article is first immersed in a metal solution, such as Cr or Ti and then in the next step is immersed in another solution of NiP or Cr containing the IF nanoparticles.

(25) The metal solution for the electrochemical deposition may be any metal solution. For example, the metal may be Ni, Pt, Co, Cr, Fe, or alloys thereof.

(26) In a preferred embodiment of the invention the article is coated with a polymer (e.g. polyurethane or polypropylene) or epoxy coating. In this embodiment, the polymer is heated until a non-viscous polymer is obtained and then IF-nanoparticles are added. In the next step, the article is painted with the polymer or immersed in the polymeric solution. Then the polymer is treated by curing (radiation) or by cross-linking (e.g. with UV light).

(27) In a further preferred embodiment, a sol-gel glass coating is applied on the article.

(28) Another way of coating an article with a friction reducing film is implemented by burnishing nanoparticles powder with cloth for a few minutes and then burnishing the article with the cloth until a coating of the nanoparticles is applied on the article, which serves as a self-lubricating coating.

(29) Electroless NiP Coatings on Stainless Steel (SS) Orthodontic Wires

(30) FIG. 2 shows a smooth, homogenous film of electroless NiP on a stainless steel wire. The scotch bond test caused peeling of the coating, as opposed to a same test carried on a stainless steel plate coated with similar NiP film by electroless deposition, indicating poor adhesion to the wire substrate. The SEM images of the two substrates showed different microscopic morphology in spite of having the same SS composition. This difference in the surface morphology is suggested to be the cause to the poor adhesion of NiP film exhibited by the wires as opposed to plates.

(31) Electroless Plating Composite of NiP with IF-WS.sub.2 Particles

(32) Preparation of electroless bath: enabling a mixture of IF-WS.sub.2 particles (or other desired IF particles) into the electroless Ni plating solution required the nanoparticles dispersion within the electroless plating bath. This was achieved by agitating a dispersion of the WS.sub.2 nanoparticles in the electroless bath (commercially available solution sold under the name Enplate Ni-425, Enthone Inc.) by ultrasonic stirrer and also by the use of suitable surfactants. Among the series of surfactants used, i.e. anionic (SDS-sodium dodecyl sulfate), cationic (CTAB-cetyl trimethyl ammonium bromide) and non-ionic (Triton-x), CTAB seemed to show the best results.

(33) FIGS. 3A and 3B show TEM images of single IF-WS.sub.2 nanoparticles after ultrasonic dispersion within a NiP matrix after 2 minutes of sonification and one hour of plating activity, respectively. FIGS. 3C and 3D show an enlarged TEM image of the IF where the layers are observed with no apparent damage.

(34) The electroless reaction was carried out first by treating the wire with an HF solution, in order to cause pitting of the substrate and consequently mechanically enhance the adhesiveness of the coating to the wire substrate. In a second step the wire was subjected to electroless coating in a commercially available plating bath containing essentially IF particles, Ni and phosphate, to obtain a wire coated with composite NiP-IF-WS.sub.2 film that had adequate adhesive strength to the w/e surface (adequate adhesive strength as measured by the scotch-bond test). The thickness of the NiP-IF-particles film obtained by the method of the present invention is between about 0.3 microns to about 50 microns, more preferably between about 1 to about 10 microns.

(35) Electroless Plating Composite of CoP with IF-WS.sub.2 Particles

(36) In a similar manner the inventors obtained a composite film of CoP with IF-WS.sub.2 particles, by electroless plating. The plating solution (pH 6.85) consisted of 0.3 M sodium citrate (Na.sub.3C.sub.6H.sub.5O.sub.7), 0.1M sodium hypophosphate and 0.1 M ammonium chloride (NH.sub.4Cl). The concentration of cobalt (II) chloride (CoCl.sub.2) was increased up to 0.1 M. The hydrazine (N.sub.2H.sub.4) concentration was increased up to 0.3 M. The pH was controlled by increasing the sodium hydroxide (NaOH) concentration up to 1.25 M.

(37) IF-WS.sub.2 particles were dispersed in the Co electroless bath by using an anionic surfactant, for example SDS (sodium dodecyl sulfate). A uniform film of CoP or Co (depending on the existence or absence of sodium hypophosphate in the plating solution) with the IF particles was obtained.

(38) Electrochemical Plating Film of Co with IF-WS.sub.2 Particles

(39) A film of Co with IF-WS.sub.2 particles was obtained by electrochemical plating. A stainless-steel plate (55 mm.sup.2) was cleaned first by immersion in HF (20%) solution for 2 min. The plate was subsequently rinsed carefully in water and dried under N.sub.2 gas stream. In the next step, the plate was immersed in a solution containing 40 ml CoCl.sub.2 1M (and optionally 40 ml NiCl.sub.2 1M) and 0.2 ml acetic acid was added to the solution to bring the pH to 3.5. A current of 1 mA was applied on the plate which served as cathode with Pt gauge as an anode. The stainless steel plate was rinsed and immersed in a similar solution but now containing 3 wt % of IF-WS.sub.2, which was prepared by sonication. A current of 1 mA was applied for 20 second. A black film was obtained. The overall thickness of the film was about 6 micron.

(40) Sol Gel Glass Coating with IF-WS.sub.2 Particles

(41) A mother solution of Zirconia is prepared. Glacial acetic acid (3 ml) is slowly added to 10 ml of zirconia tetrapropoxide (Zr(OC.sub.3H.sub.7).sub.4, TPOZ) and stirred for 30 minutes. Then 20 ml of n-propanol (C.sub.3H.sub.7OH) is added to the solution, which is further stirred for 15 minutes at room temperature. The solution is hydrolyzed with 4 ml of 50% diluted solution of acetic acid in deionized (DI) water. Following this step, the solution is stirred for another 30 minutes at room temperature, filtered, and stored in a refrigerator for up to 4 days. The solution is transparent and its color pale yellow.

(42) In the next step, alcoholic suspension of the IF-WS.sub.2 nanoparticles is prepared by sonication of 10 mg of the nanoparticles and is added dropwise to the stirred mother solution. After that the articles are immersed in the suspension and after withdrawing (dip coating) and drying are annealed in 40 C. for an hour. The final step is annealing of the articles at 300 C. in inert gas atmosphere.

(43) Friction and Wear Testing

(44) The tests were performed using a ball-on-flat device with a sliding velocity of 0.2 mm/s and a load of 50 gr. A bearing ball with a diameter of 2 mm was used as a counter body. Dry and wet friction with paraffin oil lubricant were carried out during 50-200 cycles. Optical magnification of micrographs is 240.

(45) The surface of NiP-IF-WS.sub.2 coating with a wear track after 100 cycles of dry friction is shown in FIG. 4.

(46) In order to simulate the friction behavior of the coatings in the mouth at definite fluid medium, some drops of Mouth Kote (oral moisturizer) have been fed into the interface between the steel ball and the coating. In this experiment the ball used was made of silicone nitride. Corrosion tracks on the surface of the ball were not observed, as can be seen in FIG. 5A. The IF particles are observed on the surface of the silicon nitride ball before cleaning with hexane. No wear track and particles on the surface of the ball were observed after the cleaning, as can be seen in the photograph in FIG. 5B.

(47) In another test the inventors compared the friction coefficient of an uncoated orthodontic wire substrate to that of a wire coated with a composite of NiPWS.sub.2. The graph in FIG. 6 shows the results of 30 cycles of this test, from which it is evident that after the first cycle the friction coefficient of the uncoated wire was 0.1 and that of the coated wire was 0.08, while after 30 cycles the uncoated-wire friction coefficient was 0.25 and that of the coated wire was 0.05.

(48) Instron Testing

(49) The coated wires were compared to uncoated wires at conditions simulating the movement of the tooth and bracket on the wire in the mouth, by using the Instron assembly. The tests were set at 3 different angles of contact between the bracket and the wire. From the results presented in FIG. 6 it was obvious that a run-in period was needed before testing the wires on the Instron. The run-in period of the wire was done by repeated back and forth movements of the wire in a bracket slot before connecting the wire to the Instron. A different bracket was used for the Instron testing. Data is presented in Table I below and comparative graphs in FIGS. 7-9 showing the relation between force and displacement of brackets where the peak indicates the maximum force needed to begin movement of the bracket on the wire (static friction).

(50) TABLE-US-00001 TABLE I Summary of Instron testing. Results or Force are in N SD. ANGLE 5 5 10 10 Uncoated wire Coated wire Uncoated wire Coated wire COATING 0 tested first tested first tested first tested first Non 1.32 0.12 2.95 0.09 2.64 0.16 4.00 0.19 2.76 0.26 coated Dry wet wire 3.35 0.21 wet NiP + IF 1.10 0.06 1.58 0.25 1.61 0.18 1.57 0.23 1.85 0.21 coated wet dry wire 1.85 0.31 wet

(51) The highest angle of 10 was tested in the dry and wet mode. DI water was used instead of the Mouth Kote lubrication fluid due to the possible damage to the Instron equipment. Angles 5 and 10 were repeated in a reverse order for the purpose of investigating the effect of residual nanoparticles remaining in the bracket slot.

(52) The Instron results show a substantial reduction in the friction resistance to sliding at the different angles that were tested. At an angle of 0 the reduction of friction was 17%. As the angle grew to 5, the reduction rate grew to 46% and the 10 angle showed a 54% reduction of friction compared to the uncoated wire. Without being bound to theory, the mechanism by which this reduction is achieved may be explained by the theories suggested by Rapoport et al [Rapoport et al., Wear 255, 785-793 (2003)]. At the first stage when there is no angle between the slot and wire, the IF nanoparticles act as spacers and reduce the number of asperities that come in contact resulting in a lower coefficient of function. As the angle grows the load at the edges of the slot increases causing the higher friction levels on the uncoated wire. It is probably at this point on the coated wire that the exfoliation of the nanoparticles occurs, resulting in the dry lubrication of the sliding. The higher load at this point brings the asperities in close contact causing the saliva to be squeezed out of the gap between the wire and slot, relying on the dry lubrication properties of the materials in contact to allow the sliding. When the two materials are stainless steel, as is with the uncoated wire, the friction coefficient is higher. When IF particles are in the interface under high loads, the sliding occurs within these sheets reducing the coefficient of friction.

(53) Conclusions

(54) The tests, carried out on SS plates, resulted in a composite coating of an electroless NiP matrix and IF-WS.sub.2 nanoparticles dispersed within this matrix. The dynamic coefficient of friction was reduced from 0.6 on the stainless-steel substrate to 0.06 on the coated substrate, Comparing the tribological testing results of the plate substrate to the orthodontic wire shows that the orthodontic wire has an initial low dynamic coefficient of friction (0.1) even though they are composed of the same stainless steel substrate. This perhaps is attributed to the finishing process done by the manufacturer and is evident by the different surface morphologies seen in the SEM images. In spite of the low coefficient of friction, the orthodontic force that is needed in order to move a tooth along an archwire is still much higher than the biological requirement due to the friction force that develops during this movement. The friction coefficient of the wire increases dramatically when the load increases, which was indeed the case when the orthodontic wires were used in realistic conditions (by tilting the bracket). For this reason it is desirable to achieve a reduction in the friction coefficient of the wire. The coating of the wire with the composite NiP-IF-WS.sub.2 reduced the function coefficient to 0.05 after a run-in period. When the uncoated wire was tested in cycles, the friction coefficient was elevated to 0.25. This could mean that the force needed for orthodontic movement grows with time on the uncoated wire and is reduced with time on the coated one.

(55) Instron tests were carried out in order to simulate the actual type of forces that develop during the orthodontic tooth movement. The Instron simulates the tilt in the wire with respect to the bracket and consequently the entire load is exerted on a small area of the bracket (on the corners), resulting in much higher function. These tests resulted in the reduction of friction on the coated wire, a reduction that is pronounced with the elevation of the angle between the wire and the slot. At an angle of 10, the force needed to move the bracket along the archwire was 54% lower on the coated wire. Due to the tipping and uprighting type of movement that is encountered during orthodontic treatment, this type of lubrication is most desirable because the main problem of resistance to sliding is found at the angels higher than the critical contact angle.

(56) Tribological tests in the wet mode using a saliva substitute resulted in increased friction coefficients for both coated and uncoated SS plates tested with a tempered steel ball. When the wires were tested on the Instron in the wet mode, using DI water and SS brackets, a reduction in the force (friction) was recorded. This difference is attributed to the corrosion that developed on the tempered steel ball tester and to the fact that a different type of fluid was in use. The reduction observed with the wire and bracket in the Instron was attributed to the lubrication potential of the DI water and the short duration of the test:

(57) The method developed here for coating the orthodontic archwire substrate was aimed at overcoming the poor adhesive strength of the coating to the wire, compared to the SS plates. Use of Ni or NiCr+Ni by e-beam evaporation as an initiator of the electroless process was not sufficient. A conditioning step of etching the substrate by HF was needed for increasing the retention of the coating to the wire. The reason for the difference between the SS plate and the orthodontic wire is probably due to the finishing process and the flexibility of the wire, which can affect the bonding force between the coating and the wire.

(58) The coatings of the invention may be applied to other orthodontic materials as well. A self-ligating bracket, for example, should show even lower friction levels when the coating is in use. Moreover, this coating may be utilized in other biological systems where friction is a problem as in temporomandibular disorders or in hip replacements.

EXPERIMENTAL WORK

(59) Experiments were carried out on orthodontic archwire made of stainless steel (304). To begin the electroless plating process there is a need for preparation of the substrate surface. The first step is degreasing by acetone followed by propanol, water rinse and drying under nitrogen flow. The wire is then treated in a plasma asher (March) for 5 min and a pure nickel film (100 nm) is deposited by e-beam evaporation (Edwards Auto 306).

(60) A commercial (ENPLATE Ni-425, Enthone Inc.) electroless plating NiP solution was used for the present experiments for coating the orthodontic wires (sds Ormco, Calif. 0.0190.025 inch rectangular stainless steel arch wires) and the coating seemed to have poor adhesion as tested by a simple scotch bond test. To overcome this problem a thin film of 80-20% nickel-chromium (NiCr) was deposited by e-beam evaporation instead of a pure Ni film. However the electroless reaction could not be initiated on this film. To overcome this difficulty and initiate the electroless plating, a layer of pure Ni was e-beam evaporated on the NiCr film and plating was achieved. The triple layer coating seemed to have adequate adhesion strength tested by scotch-bond and by bending the wire.

(61) The next step was to add the inorganic fullerene-like nanoparticles of WS.sub.2 (IF-WS.sub.2) to the electroless plating solution in order to incorporate it into the NiP layer. For that purpose, 200 mg of WS.sub.2 were added to 100 ml solution and dispersed by a magnetic stirrer. However this process did not result in a stable suspension. The LF-nanoparticles quickly agglomerated and precipitated. To suspend the IF-nanoparticles in the plating bath, a series of surfactants were tested including Triton-x, sodium dodecylsulfate (SDS) and cetyltrimethylammoniumbromide (CTAB). The CTAB cationic surfactant gave the best results but the amount of the agglomerated nanoparticles was still very high. In order to achieve a more stable suspension, an ultrasonic probe (sonifaier 150, Branson-30 watts output) was inserted into the solution for one minute. This resulted in an evenly dispersed solution that was stable for long periods of time. Transmission electron microscopy (model CM120, FED)(TEM) analysis indicated that under these conditions the agglomerates of the IF nanoparticles could be suspended without damaging the nanoparticles.

(62) With this resulting solution, SS wires were coated. First, the wires were treated with 20% HF and were inserted in the electroless bath. In this case a coating of NiP-IF-WS.sub.2 was accomplished. Having a layer of NiCr and/or Ni underneath the NiP-IF-WS.sub.2 further improved the continuous properties of the coating. The wires were then annealed at 400 C. in N.sub.2 atmosphere for one hour and then tested with a ball on flat tester as described above and compared to the uncoated wires.

(63) To simulate the type of movement, which occurs during orthodontic treatment when the sliding of a tooth across an archwire is preformed, a system described by Redlich et al was utilized [Redlich et al., Am. J. Orthod. Dentofacial Orthop. 124, 69-73 (2003)]. Upper right incisor (0.0220.028) SS straight wire brackets (GAC, NY) were bonded with cyanoacrylate glue to aluminum plates by a bracket-mounting apparatus (FIG. 10)). This apparatus insures the accurate and similar positioning of the brackets on the plates. These plates were then connected to the base of an INSTRON 4502 testing machine through a device with 3 different notches angulated at 0, 5 and 10 to the long axis of the device (FIG. 11). Angulations represent the contact angle between the wire and bracket during the movement of the tooth. 12-cm segments of the orthodontic wires (coated & uncoated) were attached, on their upper part, to a 10 Newton load cell and the lower end was connected to a 150 g weight. The wires were then inserted into the slots in the brackets and ligated with an elastomeric module (Sani-Ties Silvar, GAC) to all 4 wings of the brackets (FIG. 12).

(64) In this setup the Instron was set to move the bracket down along the wire at a constant speed of 10 nm/min to a distance of 5 mm. The test begins with a steady increase in the force and reaches a maximum when movement begins on the wire. This maximum represents the static friction and is the force that is of interest in this case.

(65) Uncoated and coated wires were tested at the 3 different angles. The first tests on the coated wires resulted in high friction levels that were overcome by a run-in period of repeated back and forth movements of the wire in the bracket. At the highest angle (10) the tests were further conducted in a wet mode with DI water dripping on the bracket and wire during the test simulating the saliva in the interface when the movement occurs in the mouth. The tests were repeated 5 times for each group and all the data was recorded onto the operating system of the INSTRON and then analyzed and plotted.

(66) Biocompatibility Tests and Results

(67) Toxicology tests of the IF-WS.sub.2 reported the material as being non-toxic in an oral administration in rats. The presence of Ni in orthodontic appliances is known and they are approved for use (except in people with an allergic sensitivity to Ni).

(68) Experimental Design Conditions:

(69) Replace Tablenot Clear

(70) 1. Constitution of Test Groups and Dose Levels:

(71) TABLE-US-00002 TREATMENT Volume Group No. & Group Individual Dose Dosage General.sup.(d) Size.sup.(d) Animal No.'s Test Compound Route (mg/kg) (ml/kg) 1F n = 6 1, 2, 3, 4, 5, 6 Inorganic PO 300 5 ml/kg 2F n = 6 7, 8, 9, 10, 11, 12 fullerene-like WS.sub.2 2000 nanospheres (IF-WS.sub.2)
2. Principles of the Test:

(72) Due to the lack of information regarding potential toxicity, and in accordance with the Guideline recommendation, the sequential method applied in this study represents a stepwise procedure, using a minimum amount of animals. Dosing was sequential and the time interval between the test groups dosing was determined by the lack of adverse effects following dosing.

(73) 3. Administration:

(74) 3.1 Route of Administration: All animals were subjected to a single oral gavage (PO) administration.

(75) 3.2 Dose Levels: The Test Item as supplied by the Sponsor was administered at two dose levels of 300 and 2000 mg/kg.

(76) 3.3 Volume Dosage: In all instances the volume dosage was 5 ml/kg.
4. Justification for Route of Administration and Dose Levels:

(77) The oral route was chosen as the route of administration since in order to assess the toxic characteristics of substances the determination of acute oral toxicity is usually an initial step. The initial dose level selected was based on the Sponsor's specific request and according to the respective guideline.

(78) 5. Observations and Examinations:

(79) 5.1 Clinical Signs: Animals were observed continuously during the first 7-8 hours following dosing and then periodically during the first 24 hours. Clinical signs were recorded. Animals were observed for a total during of 14 days. Observations included that of the skin, fur, eyes, mucous membranes, occurrence of secretions and excretions (e.g. diarrhea) and autonomic activity (e.g. lacrimation, salivation, piloerection, pupil size, unusual respiratory pattern). Additional items that were observed were the gait, posture and response to handling, as well monitoring for any presence of bizarre behavior, tremors, convulsions, sleep and coma.

(80) 5.2 Body Weight: Determination of individual body weights of animals was made shortly before Test Item administration, 2 and 7 days following dosing and at the end of the study prior to the scheduled necropsy.
6. Necropsy Procedures and Macroscopic Examination:

(81) All test animals were subjected to full detailed macroscopic necropsy. All gross pathological changes were recorded for each animal.

(82) Data Evaluation:

(83) Evaluation included monitoring the relationship, if any, between the animals' exposure to the Test Item and the incidence and severity of all abnormalities including: effects on mortality, behavioral and clinical abnormalities, body weight changes, gross lesions, and any other toxic effects.

(84) Animal Care and Use Statement:

(85) Results:

(86) 1. Mortality (Table 1):

(87) No mortality occurred in any of the animals throughout the entire 14-day observation period.

(88) 2. Clinical Signs (Table 2):

(89) No noticeable clinical signs in reaction to dosing were evident in any of the animals administered with Inorganic fullerene-like WS.sub.2 nanospheres (IF=WS.sub.2) at the immediate post-dosing period or during the entire 14-day observation period.

(90) 3. Body Weight (Table 3-5):

(91) Body weight gain of all animals was found to be within range of normally expected values.

(92) 4. Macroscopic Examination: (Table 6):

(93) No pathological changes were observed in any of the animals during necropsy procedure.

CONCLUSION

(94) In consideration of the lack of mortality at dose levels of 300 and 2000 mg/kg PO (oral administration), the Test Item Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) is allocated to Category 5 or Unclassified in accordance with the classification by GHS (Globally Harmonized System) (e)

(95) TABLE-US-00003 TABLE 1 Mortality Incidence Observed throughout the Entire 14-day Observation Period, in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No.: HP6): MORTALITY Group (Number affected/ No. & Group Total number Gender Size Test Material of animals) 1F n = 6 Inorganic fullerene-like WS.sub.2 0/6 nanospheres (IF-WS.sub.2) (300 mg/kg) 2F n = 6 Inorganic fullerene-like WS.sub.2 0/6 nanospheres (IF-WS.sub.2) (2000 mg/kg)

(96) TABLE-US-00004 TABLE 2 Individual Clinical Signs Observed throughout the Entire 14-day Observation Period, in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2): OBSERVATION (Number affected/ Total number of animals Group Day of No. & Individual Dosing Gender Animal No. Test Material (Day 0) Day 1-13 1F 1 Inorganic fullerene- NAD NAD 2 like WS.sub.2 nanospheres NAD NAD 3 (IF-WS.sub.2) (300 mg/kg) NAD NAD 4 NAD NAD 5 NAD NAD 6 NAD NAD 2F 7 Inorganic fullerene- NAD NAD 8 like WS.sub.2 nanospheres NAD NAD 9 (IF-WS.sub.2) (2000 mg/kg) NAD NAD 10 NAD NAD 11 NAD NAD 12 NAD NAD NAD = No Abnormality Detected

(97) TABLE-US-00005 TABLE 3 Individual and Mean (SD) Group Values of body Weights in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2): Group No. & Individual Body Weight (g) Gender Test Material Animal No. Day 0 Day 2 Day 7 Day 14 1F Inorganic-fullerene-like 1 177 194 209 228 WS.sub.2 nanospheres 2 183 203 225 233 (IF-WS.sub.2) 3 173 192 205 222 (300 mg/kg) 4 185 202 213 231 5 182 196 207 225 6 186 209 213 228 Mean 181 199 212 228 (n = 6) (n = 6) (n = 6) (n = 6) SD 5.0 6.4 7.1 4.0 2F Inorganic-fullerene-like 7 190 207 212 223 WS.sub.2 nanospheres 8 194 206 211 223 (IF-WS.sub.2) 9 209 217 228 238 (2000 mg/kg) 10 195 208 222 235 11 195 213 222 233 12 199 214 228 231 Mean 197 211 221 231 (n = 6) (n = 6) (n = 6) (n = 6) SD 6.5 4.4 7.5 5.3

(98) TABLE-US-00006 TABLE 4 Individual and Mean (SD) Group Values of Body Weight Gain (g) in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No.: HP6): Group No. & Individual Body Weight (g) Gender Test Material Animal No. Day 0-2 Day 2-7 Day 7-14 Day 0-14 1F Inorganic-fullerene-like 1 17 15 19 51 WS.sub.2 nanospheres 2 20 22 8 50 (IF-WS.sub.2) 3 19 13 17 49 (300 mg/kg) 4 17 11 18 46 5 14 11 18 43 6 23 4 15 42 Mean 18 13 16 47 (n = 6) (n = 6) (n = 6) (n = 6) SD 3.1 5.9 4.1 3.8 Inorganic-fullerene-like 7 17 5 11 33 WS.sub.2 nanospheres 8 12 5 12 29 (IF-WS.sub.2) 9 8 11 10 29 (2000 mg/kg) 10 13 14 13 40 11 18 9 11 38 12 13 14 3 32 Mean 14 10 10 34 (n = 6) (n = 6) (n = 6) (n = 6) SD 3.7 4.1 3.6 4.6

(99) TABLE-US-00007 TABLE 5 Individual and Mean (SD) Group Values of Percentage (%) Body Weight Gain in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No.: HP6): Group No. & Individual Body Weight (g) Gender Test Material Animal No. Day 0-2 Day 2-7 Day 7-14 Day 0-14 1F Inorganic-fullerene-like 1 9.6 7.7 9.1 28.8 WS.sub.2 nanospheres 2 10.9 10.8 3.6 27.3 (IF-WS.sub.2) 3 11.0 6.8 8.3 28.3 (300 mg/kg) 4 9.2 5.4 8.5 24.9 5 7.7 5.6 8.7 23.6 6 12.4 1.9 7.0 22.6 Mean 10 6 8 26 (n = 6) (n = 6) (n = 6) (n = 6) SD 1.6 2.9 2.1 2.6 2F Inorganic-fullerene-like 7 8.9 2.4 5.2 17.4 WS.sub.2 nanospheres 8 6.2 2.4 5.7 14.9 (IF-WS.sub.2) 9 3.8 5.1 4.4 13.9 (2000 mg/kg) 10 6.7 6.7 5.9 20.5 11 9.2 4.2 5.0 19.5 12 7.5 6.5 1.3 16.1 Mean 7 5 5 17 (n = 6) (n = 6) (n = 6) (n = 6) SD 2.0 1.9 1.7 2.6

(100) TABLE-US-00008 TABLE 6 Individual Gross Necropsy Findings in Female Sprague-Dawley Rats, Following a Single Oral Administration of Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No.: HP6): Group Animal No. TREATMENT No. OBSERVATION Inorganic-fullerene-like 1 NAD WS.sub.2 nanospheres 2 NAD (IF-WS.sub.2) 3 NAD (300 mg/kg) 4 NAD 5 NAD 6 NAD Inorganic-fullerene-like 7 NAD WS.sub.2 nanospheres 8 NAD (IF-WS.sub.2) 9 NAD (2000 mg/kg) 10 NAD 11 NAD 12 NAD

SUMMARY

(101) 1. The potential acute toxicity of the Test Item Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No. HP6) was assessed on the basis of the testing procedure recommended by OECD Guideline for the Testing of Chemicals, Section 4, No. 423, Acute Oral ToxicityAcute Toxic Class Method, adopted December 17.sup.th, 2001.
2. Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No. HP6) was administered successively to two groups of n=6 female Sprague-Dawley (SD) rats per each dose levels of 300 and 2000 mg/kg.
3. Animals were observed for a total duration of 14 days following dosing.
4. Body weight gain of all animals was found to be within range of normally expected values.sup.(b).
5. No mortality occurred in any of the animals throughout the entire 14-day study period.
6. No adverse signs in reaction to treatment were evident in any of the animals during the immediate post-dosing times or throughout the entire 14-day observation period.
7. No gross pathological findings were noted in any of the animals by necropsy inspection.
8. In consideration of the lack of mortality at dose levels of 300 and 2000 mg/kg PO (oral administration), the Test Item Inorganic fullerene-like WS.sub.2 nanospheres (IF-WS.sub.2) (Batch No. HP6) is allocated to Category 5 or Unclassified in accordance with the classification by GHS (Globally Harmonized System).sup.(c).