Surgery – Radioactive substance applied to body for therapy – Radioactive substance placed within body
Reexamination Certificate
2001-05-02
2004-03-23
Bennett, Henry (Department: 3743)
Surgery
Radioactive substance applied to body for therapy
Radioactive substance placed within body
C600S007000, C604S891100, C623S001390, C623S001420, C623S001450
Reexamination Certificate
active
06709379
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an implant and to a method for producing an implant and, more particularly, to implants having cavities for absorbing therapeutic agents.
BACKGROUND OF THE INVENTION
Here, the term “implant” is first of all, to be understood in a narrow sense, as referring to an element, at least temporarily insertable into the body of an animal or human, which may perform, e.g., therapeutic, support and/or joint functions, like temporary implants, for example the so-called “seeds”, or stents for tumor treatment or therapy, tracheal stents and the like. However, in a broader sense, this term is also be understood as referring to elements or the like being able to be brought, preferably temporarily, into contact with the body on the outside.
Implants in the form of stents are applied, e.g., for supporting widened vessels. After having widened constricted vessels, these tube-shaped inserts are inserted and then radially widened so that the stents support the vessel walls from the inside.
The stents grow into the vessel walls within about one to three months. A local radioactive irradiation of the vessel walls has proved to be effective in preventing an overgrowth of the vessel walls towards the inside which may lead to a re-stenosis, i.e. a re-constriction. The following possibilities present themselves in this respect.
Firstly, a balloon catheter filled with a radioactive liquid is applied. Since the balloon catheter at least partly closes the vessel in its expanded condition, contact with the vessel wall and thus application of the balloon catheter is very strongly limited in time. In order to locally obtain an effective dose, very large activity amounts must thus be applied which leads to technical problems in protection against radiation. In addition, there is a very high risk for the patient in the event of a mechanical failure of the balloon.
Secondly, a sealed radiation source may be inserted via a catheter. Here, because of the limited dwell time of the catheter in the vessel, great amounts of activity must also be applied which demands a great technological effort with regard to protection against radiation. Furthermore, there is the problem of centering the radiation sources.
Thirdly, radioactive stents may be applied. As a result, the aforementioned problems and risks are avoided and the desired or effective dose may be achieved with low amounts of radioactivity over an extended exposure time.
In the last case, i.e. the radioactive embodiment of the stents, it is already known to provide ion implantation. Here, radioactive phosphorus (
32
P) is implanted in existing stent surfaces by means of an ion beam. Further, it is known that a nickel-titanium stent may be bombarded with protons in a cyclotron or the like, in order to activate the titanium contained in ordinary nickel/titanium alloys into radioactive vanadium (
48
V).
Both ion implantation and proton activation are marked by a great technological effort, i.e. the stents can only be produced on a “custom-made basis”. Moreover, both methods are hitherto limited to a few manufacturing sites and a few radionuclides.
A further method for producing radioactive stents is provided by electrochemically precipitating radioactive rhenium on stent surfaces and then by covering them with a gold a layer as a protective layer. Here, as in all multi-layer structures, there is the risk of segmentation, i.e. detachment, which is very high for stents because of the deformation during the radial widening on the inside of the vessels. Even if only the protection layer is dissolved or in the event that it was applied incompletely, there is the risk that radioactive rhenium lying freely on a large surface area may then be partly dissolved in the blood and may be transported to other locations in the body with undesirable consequences.
Moreover, having drugs act as locally as possible may be meaningful in order to prevent, e.g., an expulsion of the implant or to perform local tumor treatment, for example.
A stent is already known from CA-A-2,235,031 corresponding to EP-A-0 875 218 which forms the starting point of the present invention; a stent which comprises a non-porous support with a porous covering layer in one embodiment. The porous covering layer is formed of sintered metal particles. A drug or a therapeutic agent is absorbed in the pores of the porous covering layer and it may be re-released from the stent in the implanted state if the porous covering layer is covered with a dissolvable or permeable covering layer for example. A radioactive material may also possibly be applied as a drug.
In the known stent, it is detrimental that the sintered metal particles of the porous covering layer form very irregular, indefinite pores. Accordingly, in the case of a drug to be released, only a relatively indefinite release behavior is achieved.
When a radioactive material is absorbed in the pores of the covering layer, there is the risk that the radioactive material uncontrollably and undesirably escapes because of irregular pores with indefinite openings. The optionally provided coating of the covering layer does not provide sufficient protection in this respect.
The mechanical strength and rigidity of the covering layer formed from the combined sintered metal particles is not very good, especially when deforming the stent. In particular, there is the risk that at least some individual metal particles break away from the covering layer. In addition, there is the risk of segmentation of the covering layer, especially in the radial widening of the stent. Here, there is the risk that, for example, blood circulation will transport portions of the covering layer to other locations in the body with undesirable consequences. This risk is particularly high in the application of radioactive material which, as a drug or a therapeutic agent, should remain fixed in the porous covering layer.
In addition, nickel, in particular, is suspected in metal implants of at least favouring excess cell growth, in particular in the area around an inserted implant. Moreover, other metals from metal surfaces—even when only in small amounts—which may also be dissolved by body fluids, such as blood, are increasingly made responsible for undesirable consequences or at least unpredictable reactions in the body. In this respect, the large surface area of the metal particles from the known stent's porous covering layer which may come into contact with body fluids or with the body tissue growing into the porous covering layer, is particularly detrimental. However, e.g., the application of ceramic covering layers or the coating of metal surfaces for use with implants is already known, for example from DE-A-43 11 772, DE-A 40 40 850, DE-A-32 41 589 or EP-A-0 520 721.
SUMMARY OF THE INVENTION
The object of the present invention is to provide an implant and a method for producing an implant so that an implant, in particular formed as a stent, may be produced relatively simply, wherein in particular the aforementioned drawbacks of the prior art may be avoided or at least minimized and wherein a therapeutic agent may be absorbed by the implant and—if desired—is locally re-releasable in the implanted condition, and in particular so that the implant, in particular a stent, enables radionuclides to be fixed securely on or in the surface.
In particular, the covering layer comprises a plurality of defined cavities with separate openings to the surface of the covering layer for absorbing at least one therapeutic agent. The term “cavities” should also be understood here as defined vacancies in crystal structures or the like which are suitable for absorbing a therapeutic agent.
Unlike the prior art, the structure of defined and preferably separate cavities in the covering layer allows very precise amounts of a therapeutic agent to be stored in the cavities, to be fixed in the cavities if necessary and to be re-released—if desired—in the implanted condition under definite conditions, such as with a desired release rate.
The term “therapeutic
Brandau Wolfgang
Fischer Alfons
Sawitowski Thomas
Schmid Güenter
Alcove Surfaces GmbH
Bennett Henry
Flynn Amanda
Friedman Stuart J.
Nixon & Peabody LLP
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