Implantable Device Having an Outer Surface Comprising Gold and Its Use as an Anti-Migration Device

Abstract

An implantable device comprising a core portion and a capsule encapsulating the core portion, said capsule having an outer surface, wherein at least a portion of the outer surface comprises gold.

Claims

1. An implantable device comprising a core portion and a capsule encapsulating the core portion, said capsule having an outer surface, wherein at least a portion of the outer surface comprises gold having a purity greater than 99.00% w/w, preferably 99.99% w/w.

2. The implantable device according to claim 1, wherein the gold is provided as a coating substantially covering the whole outer surface of the capsule.

3. The implantable device according claim 1, wherein the coating is provided as a patchy layer, continuous layer, wire and/or dots of predetermined sizes of pure gold.

4. The implantable device according to claim 1, wherein the capsule is a solid shell.

5. The implantable device according to claim 5, wherein the implantable device is an encapsulated microchip and the core portion comprises electrical components.

6. The implantable device according to claim 1, wherein the thickness of the coating can be uniformly or heterogeneously distributed across the outer surface of the capsule in the range from 10 0 nm to 4 μm, preferably from 50 nm to 3 μm, from 60 nm to 2 μm, from 70 nm to 1 μm, from 100 nm to 1 μm, from 200 nm to 800 nm, or from 300 nm to 500 nm.

7. The implantable device according to claim 1 for use as an anti-migrating device.

8. The implantable device according to claim 7, wherein the device is for use in the prevention of adverse effects associated with migrating implanted foreign bodies.

9. A method for producing an implantable device, comprising the steps of: a) providing an implantable device comprising a core portion, and a capsule encapsulating the core portion b) applying gold having a purity greater than 99.00% w/w, preferably 99.99% w/w on at least a part of the outer surface of the device provided in step a), thereby providing an outer surface portion, preventing migration of the device when implanted in a subject.

10. A method according to claim 9, wherein at least a part of the outer surface portion is provided as a gold coating, said gold coating being provided by spraying or otherwise applying gold onto the surface of the device.

11. A method for preventing the migration of an implantable device, the method comprising the steps of: a) providing an implantable device comprising a core portion, and a capsule encapsulating the core portion, said capsule having an outer surface, b) applying gold on the outer surface of the microchip provided in step a), thereby providing an outer surface portion preventing migration of the microchip when implanted in a subject, preferably the application is achieved by coating, and c) implanting the device into said subject at a predetermined location in the subject.

12. The method according to claim 11, wherein the predetermined location is in connective tissue under the skin.

13. The method according to claim 11, wherein the subject is a human, wild, or domestic animal or a pet.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The skilled artisan will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.

[0045] The drawings described in the following are to support the detailed description. The invention will be described with reference to the drawings in which:

[0046] FIGS. 1 A-C shows x-ray photographs of a dog with implanted gold, around the knee. A just after implantation B was taken about one year after implantation. FIG. 1C is another x-ray photograph of a dog with implanted gold

[0047] FIG. 2 shows x-ray photographs of a 45-year old man implanted gold in the lower lumbar region when 12 years old.

[0048] FIGS. 3 A and B show X-ray photographs of a patient with an implant just after implantation A and after 8 months B

DETAILED DESCRIPTION OF THE INVENTION

[0049] Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.

[0050] All patents and publications, including all sequences disclosed within such patents and publications, referred to herein are expressly incorporated by reference.

[0051] Numeric ranges are inclusive of the numbers defining the range.

[0052] The headings provided herein are not limitations of the various aspects or embodiments of the invention. Accordingly, the terms defined immediately below are more fully defined by reference to the specification as a whole.

[0053] The device according to the present invention may be any device for implantation into an animal, such as a mammal. In particular the device may be a microchip, microimplants, gold threads and needles used e.g. for stability after injuries.

[0054] In a particular embodiment the device is a microchip which may be produced from any commercially available microchip/transponder which is coatable, e.g. “ID-100A Microtransponder” from Trovan®.

[0055] The microchip according to an embodiment of the present invention can be implanted by use of a properly sized syringe with a plunger (e.g. the “IM-200 Syringe Implanter” from Trovan®), or by any commercially available implanter of a size suitable for the respective microchip.

[0056] Migration of a device according to the invention is to be understood as a device which has moved away from its initial or intended implant site. The specific distance regarded as migration may vary dependent on the position in the body into which the microchip is implanted. However, it is contemplated that any movement of a microchip, which is further than 5 cm from implant position, should be regarded as an inadvertent migration in the present context.

[0057] In the context of the present invention dissolucytosis is intended to mean liberation of gold ions, from gold of the outer surface portion.

[0058] The invention will now be explained in greater details with reference to a microchip embodying the device. The invention should however not be limited to a microchip and devices according to the invention may be prepared in a similar manner. An implantable microchip according to the invention may be prepared by coating a commercially available implantable microchip with a 10-80 nm thin layer of pure gold using the nonreactive physical vapor deposition (PVD) process named magnetron sputtering. Magnetron sputtering is a magnet field superimposed on a sputtering configuration. The superimposed magnetic field induces an additional force on the charged particles. The force is perpendicular to the speed direction, whereby the charged particles are forced to circulate in a spiral instead of moving in straight lines to the gold target, where the gold for the coating process is placed. The longer pathway increases the number of collisions between mainly electrons and ions and enables the plasma to be self-sustaining at a lower working pressure. The higher collision energy between the target and charged gas ions will apply a higher energy to the sputtered gold atoms and improve the adhesion to the porous surface on the implants.

[0059] Another contemplated preparation of the microchips embodying a non-limiting example of a device according to the invention, is as follows: Commercially available implantable microchips may be electrolytically cleaned by cathodic polarization of the implants for a heavy formation of hydrogen gas at the surface. The treatment is carried out in a strong alkaline solution containing e.g. NaOH. Each microchip is afterward immersed in a weak acid solution (e.g. 5% H.sub.2SO.sub.4), neutralizing the alkaline film at the surface. Initial electrolytic strike plating with gold (˜0.5 μm) is carried out in an acid gold electrolyte based upon a gold tetrachloride complex AuCl.sub.4—to improve the adhesion of the following gold layer. After assuring that the initial strike plating is made properly upon the surface, a pure gold coating with low mechanical stress is applied by deposition of a 3- to 4-μm-thick gold layer from a weak acid gold bath based upon AuCN. Between each of the process steps, careful rinse in pure water is carried out to avoid contamination.

[0060] It is contemplated that different thicknesses and patterns may be optimal in different cases, e.g. based on the type and size of subject, the implant position in the subject, etc. The anti-migration effects of gold ions are dependent on the amount of gold surface available for attack by macrophages. Thus, it is an advantage to provide a gold device with a surface as large as possible and further when the surface is large the layer of gold may be provided as thin as possible from an economical perspective.

[0061] The outer surface portion may be produced as a capsule or housing for the device thus being detachable from the inner core of the device such as a cover, lid or one or more separate pieces of noble metal which is kept on or around the microchip. In an embodiment it is contemplated that a thin gold wire is spun around the device, thus being a separate piece not directly attached to the device but rather associated with the device, and thus still prevented from leaving the microchip due to its geometry.

[0062] In a further embodiment of the invention a capsule made from a polymeric material completely encapsulating a microchip so as body liquids cannot come into contact with the electrical components of the microchip. The capsule is covered by a coating layer of high purity gold. The coating is provided as dots having a thickness between 10 nm to 4 μm and the distance between each dot is small enough (aprox. 100 my) to prevent the device from migrating independent on the direction of the device in the body.

[0063] In an embodiment similar to the above described, the coating may preferably be provided as a continuous coating layer covering the whole outer surface of the capsule and having a thickness of between 10 nm to 4.

[0064] In an embodiment of the invention, the coating of gold is applied and/or adhered to the surface of the device by dipping or submerging the implant into a physiological acceptable solution e.g. comprising hyaluronic acid and at least 0.1 g/L of gold particles according to the invention, which corresponds to approximately 7,200,000 gold particles. Preferably the concentration of gold particles is 5 g/L gold. The gold particles are of a purity above 99.00% w/w, preferably 99.99% w/w and are sized from 20 to 100 microns. The 0.1 g/L concentration of gold particles results in approximately 36 gold particles per cubic millimetre of coating solution. After dipping in the coating solution comprising gold particles according to the invention, the gold coated-implant is thus retrieved from the solution and allowed to dry. The implant may be placed in sterile wrapping until use or directly used implanted into the human body.

[0065] In order to further illustrate the present invention, the following specific examples are given with the understanding that they are being offered to illustrate the present invention and should not be construed in any way as limiting its scope.

Example 1

[0066] A study supporting the invention has been conducted with 10 dogs aged between 5.5 months and 7 years and 6 months, and weighing between 8 and 54 kg, attending the veterinary hospital because of limping walk were diagnosed with osteoarthritis in one or more joints. Two of the dogs were females, 5 males and 3 neutered. Prior to diagnosis a detailed anamnesis was taken from the owner and the animals were inspected and palpated before X-ray photographs were taken of the involved joints.

[0067] The animals were fully anaesthetized after premedication with Atropin®, Plegicil® and Metadon®. Propofol® was injected followed by intubation and inhalation anesthetization with Isofluran®.

[0068] Gold implants, tiny oval balls consisting of a 300 mm long and 30 micron thick thread of 99.99% pure gold, were placed adjacent to the diseased joint i.e. in the capsule and surrounding looser connective tissue, but never in the joint cavity.

[0069] The area around the joint to be treated was prepared as for surgery and the needles placed as close as possible to the joint. For treatment of hip joints facet joints of big dogs (20-25 kg body weight) needles of 14 G with a length of 60 mm were used. In all cases X-ray photographs were taken when the needles have been placed, in order to ensure correct positioning before the gold implants were placed in the needle and pushed through the needle with a stiletto.

[0070] For treatment of smaller dogs and joints close to the surface of bigger dogs, 14G with a length of 38 mm were used.

[0071] In contrast to hip and spine implantations, X-ray photographs were not taken when injecting gold implants in elbow and knee joints, where a direct palpation of the needles could take place.

[0072] Immediately after the ‘auromedication’ X-ray photographs were taken of the implant-receiving joints, in order to determine the exact location of the gold implants. In a time span varying from 12 to 35 months after the ‘auromedication’, the dogs were X-ray-photographed again using the exact same projections as used at the first X-ray, FIGS. 1A-C show such photographs of the same dog.

[0073] By comparing the X-ray photographs, any migration of the gold implants would be visible as a difference between the photographs.

[0074] Referring again to FIGS. 1A-C showing the X-ray photographs of the dog implanted with a number of gold beads after approximately 1 year, each picture visualizes the position of the implanted gold beads from a different angle. The implanted gold beads are visible as small white dots on each of the pictures. From the pictures it is apparent that the gold beads are still located around the hip joints where they were implanted about a year earlier.

[0075] The results of this study, although the implants were tiny oval balls consisting of a 300 mm long and 30 micron thick thread of 99.99% pure gold, is thought to be representative of any gold coated object, such as a gilded or gold coated microchip, since the activity is provided by the pure gold accessible on the surface.

Example 2

[0076] In a study on humans, patients that have been subjected to gold implantation were analyzed for migration of the implants. The study supported the findings in the abovementioned study on dogs. In one example a 45 year old man had small gold threads implanted in his back at the age of 12 years. At the age of 12 year he had a serious back injury in the lumbar region and got acupuncture where small threads were placed as seen in the X-ray radiographs in FIG. 2. The radiographs of the 45 year old man show that the gold treads are still located in the region where they were injected (FIG. 2).

Example 3

[0077] In another example according to the invention a patient having a dental implant was treated for paradentosis by the insertion of gold implants, made up of a ball of a 50 micron thick wire of 99.99% pure gold, having a cross-section of 1000 μm. The gold implants/particles were injected into the periodontium in proximity to the gold implant as shown in FIG. 3A. FIG. 3B shows the position of the gold particles after 8 months. Neither the gold implants nor the dental implants had moved position in the period of time. A visible regrowth of bone had taken place. Thus, it has been shown that gold implants according to the invention strongly fixates to the surrounding tissue.

[0078] Further embodiments of the invention are

Embodiment 1

[0079] A method for preventing the migration of an implantable device, the method comprising the steps of:

[0080] a) providing an implantable device comprising a core portion, and a capsule encapsulating the core portion, said capsule having an outer surface,

[0081] b) applying gold on the outer surface of the microchip provided in step a), thereby providing an outer surface portion preventing migration of the microchip when implanted in a subject, preferably the application is achieved by coating, and

[0082] c) implanting the device into said subject at a predetermined location in the subject.

Embodiment 2

[0083] A method according to embodiment 1, wherein the predetermined location is in connective tissue under the skin.

Embodiment 3

[0084] A method according to embodiments 1 or 2, wherein the subject is a human, wild, or domestic animal or a pet.

Embodiment 4

[0085] Use of an implantable device comprising a core portion and a capsule encapsulating the core portion, said capsule having an outer surface, for the prevention of migration of the implanted device in a subject, wherein at least a portion of the outer surface comprises gold.

Embodiment 5

[0086] Use of an implantable microchip comprising a core portion with electrical components, and a capsule encapsulating the core portion, said capsule having an outer surface, for the prevention of migration of the implanted microchip in a subject, wherein at least a portion of the outer surface comprises gold.