Patent Application
20100266656
The technical field of this disclosure relates to vascular treatment devices. More specifically, the disclosure relates to a splittable elastomeric drug delivery device.
Heart disease, specifically coronary artery disease, is a major cause of death, disability, and healthcare expense in the United States and other industrialized countries. A number of methods and devices for treating coronary artery disease have been developed, some of which are specifically designed to treat the complications resulting from atherosclerosis and other forms of coronary arterial narrowing.
One method for treating such vascular conditions is percutaneous transluminal coronary angioplasty (PTCA). During PTCA, a balloon catheter device is inflated to dilate a stenotic blood vessel. The stenosis may be the result of a lesion such as a plaque or thrombus. When inflated, the pressurized balloon exerts a compressive force on the lesion, thereby increasing the inner diameter of the affected vessel. The increased interior vessel diameter improves blood flow.
However, soon after the procedure, a significant proportion of treated vessels restenose. Various methods have been developed to prevent or inhibit this restenosis. One method is to provide a drug or therapeutic agent to assist in preventing inflammation, infection, thrombosis, and proliferation of cell growth that can occlude the vessel lumen.
There are several drawbacks to current drug eluting technology. One of the drawbacks is that the drug can be exposed to the environment before deployment to the treatment site. Handling the drug before delivery can cause the drug to lose some of its efficacy. Another problem is that the drug is sometimes accidentally released before reaching the treatment site. Yet another problem is that many times the drug delivery device must be cured at high temperatures in order to achieve the desired properties of the drug delivery device. However, curing at high temperatures after the drug has been added to the drug delivery device can damage the drug and reduce its therapeutic effectiveness. Therefore, it would be desirable to have a system and method for treating a vascular condition that can overcome the aforementioned and other disadvantages.
One aspect of the present invention provides a system for treating a vascular condition. The system includes a catheter and a splittable elastomeric drug delivery device. The splittable elastomeric drug delivery device includes a balloon disposed on the catheter. The balloon includes a first elastic layer and a second elastic layer. A therapeutic agent layer is disposed on at least a portion of the first elastic layer, and the second elastic layer is disposed on the first elastic layer and the therapeutic agent layer. The first elastic layer has a first elongation-at-break percentage and the second elastic layer has a second elongation-at-break percentage.
Another aspect of the present invention provides a method of formation of a splittable elastomeric drug delivery device. The method includes forming a first coat on a balloon mandrel; curing the first coat to form a first elastic layer; forming a therapeutic agent layer disposed on at least a portion of the first elastic layer; forming a second coat disposed on the first elastic layer and the therapeutic agent layer; and curing the second coat to form a second elastic layer. The first elastic layer has a first elongation-at-break percentage and the second elastic layer has a second elongation-at-break percentage.
Another aspect of the present invention provides a method for treating a vascular condition. The method includes advancing a splittable elastomeric drug delivery device to a treatment site and inflating the balloon. The device includes a balloon having a first elastic layer, a therapeutic agent layer disposed over at least a portion of the first elastic layer, and a second elastic layer disposed over the first elastic layer and the therapeutic agent layer. The inflating splits the second elastic layer to expose the therapeutic agent layer to the treatment site.
The foregoing and other features and advantages of the invention will become further apparent from the following detailed description of the presently preferred embodiments, read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative of the invention, rather than limiting the scope of the invention being defined by the appended claims and equivalents thereof.
The catheter 110 includes an inflation lumen 112 for inflating the drug delivery balloon 120. The catheter 110 may be any catheter known in the art for delivering a drug delivery balloon to a treatment site within a vessel. The catheter 110 may be a percutaneous transluminal coronary angioplasty (PTCA) balloon catheter. Methods for the formation of the first elastic layer 130, the therapeutic agent layer 140, and the second elastic layer 150 are discussed in detail below.
Referring to
The therapeutic agent layer 140 is disposed on at least a portion of the first elastic layer 130 by, for example, dipping or spraying. The therapeutic agent layer 140 may include, for example, an antineoplastic agent, an antiproliferative agent, an antibiotic, an antithrombogenic agent, an anticoagulant, an antiplatelet agent, an anti-inflammatory agent, or combinations of the above. Various other therapeutic agents such as fibrinolytics, therapeutic proteins or peptides, recombinant DNA products, or other bioactive agents, diagnostic agents, radioactive isotopes, or radiopaque substances may be included in the therapeutic agent layer 140 depending on the anticipated needs of the patient. Those of skill in the art will appreciate that the therapeutic agent in the therapeutic agent layer 140 may be included in any form allowing the therapeutic agent to flow through the split formed in the second elastic layer, such as a liquid, a loose powder, a paste, a capsule, or the like. The therapeutic agent may exit the split in its original form, or may be mixed with or dissolved in fluid flowing in the lumen in which the balloon 120 is deployed. In one embodiment, the therapeutic agent layer 140 can be a powdered drug, which is defined herein as a ground, pulverized, or otherwise finely dispersed solid particles of a therapeutic agent, and can include encapsulated particles or nano-particles. In another embodiment, the therapeutic agent layer 140 can be a low temperature drug, which is defined herein as a therapeutic agent that is damaged by exposure to temperatures other than low temperatures, such as by exposure to curing at elevated temperatures. The formulation containing the therapeutic agent layer 140 may additionally contain excipients including solvents or other solubilizers, stabilizers, suspending agents, antioxidants, and preservatives, as needed to deliver an effective dose of the therapeutic agent to the treatment site.
The second elastic layer 150 is disposed on the first elastic layer 130 and the therapeutic agent layer 140. In one embodiment, the second elastic layer 150 is an oxime cured silicone dispersion. The resulting material is a lower elongation-at-break material than the first elastic layer, preferably with an elongation-at-break percentage in the range of 550% to 750%.
Those skilled in the art will appreciate that the first elastic layer 130 and the second elastic layer 150 may be formed from any biocompatible polymeric material having elastomeric characteristics such as those described above. The elastomeric material may be, for example, high temperature vulcanized or room temperature vulcanized silicones, or combinations thereof. In one embodiment, the elongation-at-break percentage differential between the first elastic layer and the second elastic layer is at least 250%.
Forming the first coat on the balloon mandrel 210 can be accomplished by any method known in the art such as dipping, spraying, painting, wiping, rolling, printing and combinations thereof. The mandrel is a mold having an outer surface which yields the desired dimensions and shape of the elastomeric drug delivery device. In one embodiment, the mandrel is a mold having the dimensions and shape required to form a spherical elastomeric drug delivery device.
The first coat is formed on the mandrel by dipping the mandrel in a liquid undercoat medium that contains an elastomeric polymer. The liquid undercoat medium may be latex or a solution of the polymer in an organic solvent. Organic solvents may be, for example, ethers, amines, esters or alcohols. In one embodiment, the liquid undercoat medium is a solution of silicone in xylene. In another embodiment, the undercoat medium is a solution of silicone in hexane. Dipping the mandrel into the liquid undercoat medium and then withdrawing the mandrel will leave a film of the liquid undercoat medium over an outer surface of the mandrel. The thickness of the first coat may be increased by dipping the mandrel multiple times in order to produce a first coat of a desired thickness.
The undercoat elastomeric film can be partially cured on the mandrel between each dipping to allow for the adhesion of the first intermediate layers to increase the thickness of the first coat. The length of time that the dipped mandrel is cured between dips to provide sufficient adhesion depends on such factors as type of polymer, type of solvent and the desired degree of viscosity. Once the desired thickness is achieved, the first coat may be cured 220, preferably at an elevated temperature, for example from about 250° F. to about 350° F. for about 120 minutes to about 150 minutes to form the first elastic layer. In one embodiment, the cure is a platinum cure carried out at about 170° F. for approximately 45 minutes, followed by an additional approximate 135 minutes at about 300° F. Those of skill in the art will appreciate that the cure may be carried out at different combinations of time and temperature for the same effect. For example, the cure may be carried out at lower temperatures for a longer period of time.
Next, forming the therapeutic agent layer 230 includes applying a therapeutic agent to the entire first elastic layer or any portion thereof. A portion of the first coat may be masked before dipping the mandrel into the overcoat solution in order to suit a particular application. The therapeutic agent layer may be applied by any method known in the art such as, for example, by dipping, spraying, painting, wiping, rolling, printing, and combinations thereof. The therapeutic agent layer can be preferentially applied to the apex of the balloon, i.e., to the portion of the balloon that becomes an apex portion of the balloon upon inflation where the circumference of the balloon changes dramatically. In one embodiment, the elastomeric drug delivery device is secured to a delivery catheter prior to adding the therapeutic agent layer.
After forming the therapeutic agent layer 230, the second coat is formed disposed on the first layer and the therapeutic agent layer 240. The mandrel with the therapeutic coat is dipped into an overcoat polymeric solution to form the second coat. The forming of the second coat 240 is similar to the forming of the first coat. The second coat can also be formed by any method known in the art such as dipping, spraying, painting, wiping, rolling, printing and combinations thereof. Application of the second coat traps the therapeutic agent coat between the first coat and the second coat. The thickness of the second coat may be increased by performing additional dipping and drying cycles to form second intermediate layers. The second intermediate layers can be added until the desired thickness of the second coat is achieved. The thickness of the second coat may vary in order to make certain portions of the second coat more elastic than other portions. Once the desired thickness is achieved, the second coat may be cured 250, for example at room temperatures ranging from about 70° F. to 77° F., preferably for at least 24 hours, to form the second elastic layer.
The elastomeric drug delivery device of this embodiment is formed on a mandrel using a dipping process similar to the process described with respect to
When the coated mandrel is dipped into fluidized salt, salt particles adhere to the surface. The amount of granular salt that adheres to the first coat depends on such factors as, for example, the dipping technique, the time of immersion, the amount of air flow through the salt, the size of the granular particles, and the like. The fluidized granular salt particles will adhere to those portions having a first coat. The particles may be disposed on the first coat by other methods, such as, for example, by spraying the particles onto the first coat.
In one embodiment, the mandrel with the first coat including adhered particles is dipped into the undercoat polymeric solution containing the first coat to add first intermediate layers to the first coat. In another embodiment, a different polymeric solution having a higher viscosity than the first coat may be used to add intermediate layers to the first coat. The application of the first intermediate layers traps the granular particles within the first coat. The thickness of the first elastic layer may be increased by performing additional dipping and drying cycles to add more intermediate layers. The coated mandrel is dipped and partially cured until the desired thickness of the first coat is achieved. In one embodiment, the first coat is applied in a series of dips so that the adhered salt particles are substantially covered by the undercoat polymeric solution. Once the desired thickness is achieved, the first coat may be cured 615 to form the first elastic layer. The first coat may be cured at about 250° F. to about 350° F. for about 120 minutes to about 150 minutes. In one embodiment, the first coat is cured at 170° F. for approximately 45 minutes followed by an additional approximate 135 minutes at about 200° F. Those skilled in the art will appreciate that the cure may be carried out at different combinations of time and temperature for the same effect as desired for a particular application.
To form the expandable pores, the first coat can be scrubbed or otherwise brushed to remove a thin layer of the first coat in order to break the surface and to expose the embedded soluble particles 620. Once exposed, the mandrel is placed in a bath containing a liquid such as water to dissolve the particles 625, leaving expandable pores within the first coat. Any loose or poorly adhered particles may be removed after the mandrel is removed from the fluidized particle bath.
The first coat of the elastomeric drug delivery device is then removed from the mandrel. To deposit the therapeutic agent in the expandable pores 640, the elastomeric drug delivery device is inflated 630 to open and expand the pores. Once expanded, the therapeutic agent is deposited in a least a portion of the expanded pores 635. The therapeutic agent may be applied by any method known in the art such as, for example, by dipping, spraying, painting, wiping, rolling, printing, and combinations thereof. In one embodiment, the elastomeric drug delivery device is secured to a delivery catheter prior to loading the therapeutic agent. In another embodiment, the elastomeric drug delivery device is secured to an inflation mandrel, loaded with the therapeutic agent, removed from the inflation mandrel and secured to the delivery catheter. A portion of the first coat can be masked before dipping the mandrel into the second coat solution 645 or prior to applying the therapeutic agent 635. The mask, if present, may be removed after application of the additional layers to the first coat as described above or after exposure of the granular particles 620. Once the therapeutic agent is applied, the elastomeric drug delivery device is deflated 640, thereby collapsing the pore openings to trap the therapeutic agent within the expandable pores. In this embodiment, the embedded therapeutic agent in the pores is the therapeutic agent layer.
Next, the drug delivery device is placed back on the mandrel in order to form the second coat disposed on the first coat and the therapeutic agent layer 645. The mandrel with the first coat and therapeutic agent is then dipped into an overcoat polymeric solution to form the second coat adjacent to the therapeutic agent layer 645. The second coat is applied in a similar manner to the second coat as described for FIG. 2. Referring to
It is important to note that
While the embodiments of the invention disclosed herein are presently considered to be preferred, various changes and modifications can be made without departing from the spirit and scope of the invention. The scope of the invention is indicated in the appended claims, and all changes that come within the meaning and range of equivalents are intended to be embraced therein.
