1. Field of the Invention
The present invention relates to a process for coating medical devices, and more particularly, to a process for dip coating medical devices having complex configurations or geometries utilizing aqueous latex polymeric emulsions. The present invention also relates to a method for coating medical devices on site in a surgeon room just prior to use on a patient and conducting a therapeutic intervention on the patient with the recently coated medical device. The present invention further relates to a method for dip coating medical devices having complex configurations or geometries utilizing aqueous latex polymeric emulsions on site in a surgeon room just prior to use on a patient and conducting an intervention on the patient with the recently dip coated medical device.
2. Discussion of the Related Art
Stents, which are generally open tubular structures, have become increasingly important in medical procedures to restore the function of body lumens. Stents are now commonly used in translumenial procedures such as angioplasty to restore an adequate blood flow to the heart. However, stents may stimulate foreign body reactions that result in thrombosis or restenosis. To avoid these complications, a variety of polymeric stent coatings and compositions have been proposed in the literature, both to reduce the incidence of these or other complications or by delivering therapeutic compounds such as thrombolytics to the lumen to prevent thrombosis or restenosis. For example, stents coated with polymers containing thrombolytics such as heparin have been proposed in the literature.
Stents are typically coated by a simple dip or spray coating of the stent with polymer or polymer and a pharmaceutical/therapeutic agent or drug. These methods were acceptable for early stent designs that were of open construction fabricated from wires or from ribbons. Dip coating with relatively low coating weights (about four percent polymer) could successfully coat such stents without any problems such as excess coating bridging, i.e. forming a film across the open space between structural members of the device. This bridging is of particular concern when coating more modern stents that are of less open construction. Bridging of the open space (slots) is undesirable because it can interfere with the mechanical performance of the stent, such as expansion during deployment in a vessel lumen. Bridges may rupture upon expansion and provide sites that activate platelet deposition by creating flow disturbances in the adjacent hemodynamic environment, or pieces of the bridging film may break off and cause further complications. Bridging of the open slots may also prevent endothelial cell migration, thereby complicating the endothelial cell encapsulation of the stent. The bridging problem is of particular concern in medical devices having complex configurations or designs, such as stents, which comprise a multiplicity of curved surfaces.
Similarly, spray coating can be problematic in that there is a significant amount of spray lost during the spray process and many of the pharmaceutical agents that one would like to incorporate in the device are quite costly. In addition, in some cases it would be desirable to provide coated stents with high levels of coating and drug. High concentration coatings (approximately fifteen percent polymer with additional drug) are the preferred means to achieve high drug loading. Multiple dip coating has been described in the literature as a means to build thicker coatings on the stent. However, composition and phase dispersion of the pharmaceutical agents affect sustained release profile of the pharmaceutical agent. In addition, the application of multiple dip coats from low concentration solutions often has the effect of reaching a limiting loading level as an equilibrium state is reached between the solution concentration and the amount of coating, with or without pharmaceutical agent, deposited on the stent. Thus there is a continuing need for new and improved stent coating techniques.
Another potential problem associated with coating stents and other implantable medical devices having complex designs or configurations is the use of organic based solvents. Presently, polymeric coatings are applied from solutions of one or more polymers in one or more organic solvents. These solvents do not permit repeated dipping to build up the desired amount of coating as the solvent will re-dissolve the coating applied during the previous dipping. Accordingly, spin or spray coating techniques are utilized. However, as described above, this type of coating process may result in a significant amount of material lost.
Spray coating utilizing organic solvents generally involves dissolving a polymer or polymers and a therapeutic agent or agents in an organic solvent or solvents. The polymer(s) and therapeutic agent(s) may be dissolved at the same time or at different times, for example, it may be beneficial to add the therapeutic agent(s) just prior to coating because of the short shelf-life of the agent(s). Certain therapeutic agents may be dissolved in organic solvents while others may not. For example, rapamycin may be mixed with poly- (vinylidenefluoride) -co-hexafluoropropylene and dissolved in a mixture of methyl ethyl ketone (MEK) and dimethylacetamide (DMAC) for use as a coating on a stent to prevent or substantially minimize restenosis. Water based therapeutic agents may not be dissolvable in organic solvents, although it may be possible to disperse very fine powder form therapeutic agents in an organic solvent polymer emulsion. Therefore, whole classes of therapeutic agents may not be available for use in local delivery applications on implantable medical devices.
In addition, organic solvents may be difficult to work with due to their potentially flammable or combustible nature.
Accordingly, there exists a need for a coating process that allows for the safe, efficient, cost effective coating of medical devices for a wide range of polymers and therapeutic drugs, agents and/or compounds.
Furthermore, as is well known in the field, the process for manufacturing, handling and using of medical devices coated with polymers and therapeutic drugs, agents and/or compounds is extremely time consuming, labor intensive and costly.
One example of a known process for manufacturing, handling and using a medical device coated with polymers and therapeutic drugs, agents and/or compounds can be found with those processes relating to stents and the stent delivery systems (SDS) such as a catheter. FIG. 3 best depicts the current known process, generally designated 50, for manufacturing, handling and using a drug coated stent and the related SDS. As shown, the known process 50 comprises a number of elaborate and separate steps, which in totality are labor intensive, time consuming and costly.
Stent manufacturing 52 is conducting along with separate delivery device (catheter) manufacturing 53. A subsequent step after stent manufacture 52 is stent coating step 54. The stent coating 54 usually consists of coating the stent with polymers and therapeutic drugs, agents and/or compounds. It is also well known that stent coating 54 is an important step in the overall process 50. After the stents are coated, both catheters and stents are brought together at a single location for mounting the stent on the catheter 56 to create the SDS. After mounting 56, the SDS is packaged 58 and the packaged SDS is undergoes sterilization 60. After sterilization 60, the SDS is transported to the customer 62. Transportation 60 to the customer or end user, i.e. hospital, catheterization laboratory, clinic, etc. can usually take several days to several weeks depending on circumstances especially when factoring in waiting and storage times prior to the SDS actually being used on a patient. In this case, the actual use on a patient is a catheterization procedure 64 whereby the SDS is used on the patient and the stent is delivered intravascularly to the site in the patient's body where drug coated stent treatment is required.
Accordingly, to date, there are no methods that address the known drawbacks associated with current process 50.