Patent Application
20080039924
Bioactive Materials: As used herein the phrase, “bioactive materials” refers to any organic, inorganic, or living agent that is biologically active or relevant. For example, a bioactive material can be a protein, a polypeptide, a polysaccharide (e.g. heparin), an oligosaccharide, a mono- or disaccharide, an organic compound, an organometallic compound, or an inorganic compound. It can include a living or senescent cell, bacterium, virus, or part thereof. It can include a biologically active molecule such as a hormone, a growth factor, a growth factor producing virus, a growth factor inhibitor, a growth factor receptor, an anti-inflammatory agent, an antimetabolite, an integrin blocker, or a complete or partial functional insense or antisense gene. It can also include a man-made particle or material, which carries a biologically relevant or active material. An example is a nanoparticle comprising a core with a drug and a coating on the core.
Bioactive materials also can include drugs such as chemical or biological compounds that can have a therapeutic effect on a biological organism. Bioactive materials include those that are especially useful for long-term therapy such as hormonal treatment. Examples include drugs for contraception and hormone replacement therapy, and for the treatment of diseases such as osteoporosis, cancer, epilepsy, Parkinson's disease and pain. Suitable biological materials can include, e.g., anti-inflammatory agents, anti-infective agents (e.g., antibiotics and antiviral agents), analgesics and analgesic combinations, antiasthmatic agents, anticonvulsants, antidepressants, antidiabetic agents, antineoplastics, anticancer agents, antipsychotics, and agents used for cardiovascular diseases such as anti-restenosis and anti-coagulant compounds. Exemplary drugs include, but are not limited to, antiproliferatives such as paclitaxel and rampamycin, everolimus, tacrolimus, des-aspartate angiotensin I, exochelins, nitric oxide, apocynin, gamma-tocopheryl, pleiotrophin, estradiol, heparin, aspirin and 5-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) reductase inhibitors such as atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, etc.
Bioactive materials also can include precursor materials that exhibit the relevant biological activity after being metabolized, broken-down (e.g. cleaving molecular components), or otherwise processed and modified within the body. These can include such precursor materials that might otherwise be considered relatively biologically inert or otherwise not effective for a particular result related to the medical condition to be treated prior to such modification.
Combinations, blends, or other preparations of any of the foregoing examples can be made and still be considered bioactive materials within the intended meaning herein. Aspects of the present invention directed toward bioactive materials can include any or all of the foregoing examples.
Stents: As used herein, the term “stents” refers to devices that are used to maintain patency of a body lumen or interstitial tract. There are two categories of stents; those which are balloon expandable (e.g., stainless steel) and those which are self-expanding (e.g., nitinol). Stents are currently used in peripheral, coronary, and cerebrovascular vessels, the alimentary, hepatobiliary, and urologic systems, the liver parenchyma (e.g., porto-systemic shunts), and the spine (e.g., fusion cages). In the future, stents will be used in smaller vessels (currently minimum stent diameters are limited to about 2 millimeters). For example, they will be used in the interstitium to create conduits between the ventricles of the heart and coronary arteries, or between coronary arteries and coronary veins. In the eye, stents are being developed for the Canal of Schlem to treat glaucoma.
Substantially Simultaneously: As used herein, the term “substantially simultaneously” means that all sections of a self-expanding stent can expand closer together in time than would otherwise be allowed by the withdrawal of a retractable sheath.
Once a stent body configuration is chosen, a device with an appropriately-sized and spaced slotted design can be manufactured (note that “slots” can include openings with or without pockets or flaps thereunder).
As will be understood by one of ordinary skill in the art, the slotted devices of the present invention can be part of a delivery catheter system wherein the slotted device is attached to the distal end of a control mechanism of the delivery catheter. Once a self-expanding stent is confined in a compressed form by a slotted device of the present invention and is positioned at an intended treatment site, the controlling mechanism attached to the slotted device can move the slotted device proximally in relation to the distal end of the delivery catheter (longitudinal slot design) or can rotate the slotted device (circumferential slotted design). The controlling mechanism could also expand the slotted device (longitudinal or circumferential slotted design). Movement or expansion of the slotted device in these manners can release all sections of a self-expanding stent substantially simultaneously, thus avoiding many of the described problems associated with retractable sheaths. In contrast to a retractable sheath that must be moved proximally along the entire length of a self-expanding stent to fully deploy the stent, the slotted device of the present invention must only be moved or expanded a sufficient amount to release, for example, portions 10, 11, 111, 12, 122, 13 and 133 as depicted in
In addition to the described slotted devices, the present invention also includes tethering systems that can be used to maintain a self-expanding stent in a compressed form during delivery to an intended treatment site. The tethering systems, which will be hereinafter described in more detail, also reduce the occurrence of problems associated with release of self-expanding stents through withdrawal of an outer retractable sheath.
While a preferred embodiment of tethering according to the present invention includes all tethers loosening or breaking substantially simultaneously, other embodiments allow for independent loosening or breaking of tethers or sections of tethers. When a balloon (or sleeve thereover) is adopted as a substrate, this can be achieved by, without limitation, using tethers of different strengths or a balloon with non-uniform (in one embodiment sequential) expansion properties. Control wires can also be used to independently control tethers or sections of tethers through a variety of means well known to those of skill in the art, including, without limitation, the previously mentioned pull wire activation, other mechanical means, heat, current, electrical charge and combinations thereof.
Turning to circumferential tethering and referring to
During deployment of the stent 16 at an intended treatment site, the balloon 14 is expanded as part of a routine angioplasty procedure. As shown in
The tethers depicted in
As stated previously, in certain embodiments, tethers can loosen rather than break. In these embodiments, controls that can re-tighten loosened tethers can be employed so that expanded stents can be retracted and repositioned when necessary. For example, individual tethers or sections of tethers can be formed with an elastic material that is held taut through one or more control wires within a delivery catheter. The control wires can allow the tethers to expand and then require the tethers to re-tighten (retracting the since expanded stent) as desired.
Tethers of the present invention can be constructed from a variety of materials. Non-limiting examples of such materials include polyamides (nylons, Pebax, etc.), polyolefins (HDPE, LLDPE, etc.), polyesters (PET, Dacron, Teflon, etc.), polyimides, polyurethanes, metals, wires, and/or ribbons. In one embodiment, when breaking tether systems are employed with stronger tethering materials, the tethering material can be perforated to help to ensure that it breaks when appropriate.
Stents used in accordance with the present invention can comprise bioactive materials that can be released at the treatment site once the stent is deployed. Various methods of coating stents with bioactive materials are well-known to those of skill in the art and will not be described in detail herein. Appropriate methods for depositing bioactive materials onto the self-expanding stents of the present invention can include spray coating, dip coating, roll coating, polymer coatings, electroplated coatings, electrolessly deposited coatings, etc. Electroplating and electroless deposition are described in detail in co-pending United States Patent Application Publication Nos. 2006-0051397A1, 2006-0062820A1 and 2006-0115512A1, which are fully incorporated by reference herein.
It is to be understood that the present invention is not limited to the particular embodiments, materials, and examples described herein, as these can vary. Further, the tabs of the present invention can be made of material that is dissimilar to the material or materials that make up the other portions of the stent. It also is to be understood that the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a stent” or “a tab” is a reference to one or more stents or tabs and includes equivalents thereof known to those skilled in the art and so forth.
Unless defined otherwise, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Specific methods, devices, and materials are described, although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention.
Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on those preferred embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
Furthermore, numerous references have been made to patents and printed publications throughout this specification. Each of the above cited references and printed publications are herein individually incorporated by reference in their entirety.
In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described.
