Surgery – Controlled release therapeutic device or system
Reexamination Certificate
2001-06-06
2002-09-03
Beck, Shrive P. (Department: 1762)
Surgery
Controlled release therapeutic device or system
C604S891100, C604S892100, C604S067000, C604S070000, C604S131000, C604S151000, C623S001210, C623S002220, C623S006120, C427S002100, C427S002240, C427S002250, C427S002280, C427S002300, C427S508000, C427S407100, C427S409000
Reexamination Certificate
active
06443942
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to reusable and disposable medical devices that are used to store, contain or deliver protein-based medications. More particularly, this invention relates to improved medical devices that have one or more protein-contacting surfaces treated to reduce the protein adsorption and denaturation that can occur on an untreated surface.
BACKGROUND OF THE INVENTION
Medication infusion pumps are generally known in the art for use in delivering a selected medication to a patient in a preprogrammed or patient-programmed manner. In recent years, infusion pumps have been developed in compact form and adapted to deliver a specific medication, such as insulin, to the patient in patient-programmed continuous doses over an extended time period. Medication infusion pumps have also been used to deliver a wide variety of other drugs to a patient. Such medications or drugs include, for example, baclofen, morphine and other pain medications, various antibiotics, and a number of chemotherapeutic agents.
As protein-based medications become more prevalent, problems arise in reliable long-term administration of these medications to a patient. More specifically, bolus drug injections are not optimal to achieve relatively constant blood concentration levels. Many of the newer protein-based medications are relatively complex, having a high molecular weight, such that bolus therapy subcutaneous drug delivery can be problematic due to relatively fast clearance by the renal and hepatic systems.
One problem encountered with medical devices is that medication contacting surfaces are typically constructed from materials, such as metals, polymers or other materials, that have low free surface energies, typically on the order of about 40 dyne/cm2. At this low free surface energy, protein-based medications can be adsorbed quite readily and can subsequently denature on the medication contacting surfaces. Once denaturation occurs, the protein-based substances can aggregate to a form that is generally not bio-available to the patient and may in some cases lead to undesired immunological response.
While practitioners in the art have employed a variety of methods to address problems associated with the denaturation of proteins at surfaces in medical devices, protein adsorbtion continues to be a problem in the field. For example, over time coating materials may disadhere from a matrix, thereby exposing proteins to the destabilizing surfaces. In addition, because proteins are heterogeneous in both their structural and chemical properties, it is difficult to identify a single coating material that works to inhibit the denaturation of the spectrum of different protein-based medications used in medical devices. Consequently there is a need in the art to identify additional coatings and methods for attaching them to a surface of a medical device, in particular those tailored to inhibit the denaturation of specific protein-based medications.
The present invention meets this need in the art by providing methods for generating improved medical devices having a hydrophilic internal surface coatings that are highly stable in the presence of complex protein-based medications, in particular, insulin based medications.
SUMMARY OF THE PREFERRED EMBODIMENTS
The present invention provides methods for inhibiting the denaturation of proteins such as insulin at surfaces in medical devices. In particular, the invention provided herein identifies specific polymers that retain the ability to inhibit the destabilization and/or degradation of insulin even after undergoing the chemical modification required to permanently attach the polymers to a surface in a medical device. In accordance with one aspect of the present invention, there is provided a medical device having a surface contacted by a selected protein-based medication. Typically the surface has a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees, and also exhibits a protein adsorption profile of less than about 1.0 microgram per square centimeter when measured with insulin.
In more specific embodiments, the medical device is a medication infusion pump. The medication infusion pump can be reusable or disposable, and can be externally worn or implantable. The medical device according to the invention is not limited to a medication infusion pump, however, but can also be a device such as a prefilled medication cartridge, a syringe, a catheter, an IV bag, and the like.
In one preferred embodiment the surface is a metallic surface such as titanium. In another preferred embodiment, the surface is a non-metallic polymeric surface, such as a rubber, a polyurethane, a polyethylene, a polypropylene or a polyvinylchloride. In a particular preferred embodiment, the polymeric surface is comprised of a bromobutyl rubber or a chlorobutyl rubber.
Preferably, the surface treatment is a coating comprised of polymeric materials such as hydrophilic polyurethanes, polyureas, acrylics, polycarbonates or other hydrophilic materials, in particular materials such as polyethylene glycols, polyethylene/polypropylene glycol copolymers or other poloxamers which are chemically (covalently) attached to the treated surface.
A preferred illustrative embodiment of the invention consists of a medical device having a surface comprising a polypropylene glycol/polyethylene glycol polymer covalently attached thereto, wherein the polypropylene glycol/polyethylene glycol polymer has a molecular weight of about 1800 Daltons and comprises a compound of the following general formula:
Typically, the surface having the polypropylene glycol/polyethylene glycol polymer covalently attached thereto defines a surface contact angle less than about 45 degrees and exhibits an insulin adsorption profile of less than about 1.0 microgram per square centimeter. In preferred embodiments, the surface contact angle is less than about 35 degrees and the surface exhibits an insulin adsorption profile of less than about 0.5 microgram per square centimeter. In highly preferred embodiments, the surface exhibits an insulin adsorption profile of less than about 0.1 microgram per square centimeter.
In accordance with a further aspect of the present invention, there is provided a medication infusion device for contacting a selected protein-based medication, the device having a surface for contacting the medication. The surface has a coating to reduce the surface contact angle and protein adsorption profile. Preferably, the surface is a polymeric surface as set forth above, and the coating is a polymeric material as set forth above.
In accordance with still another aspect of the present invention, a component for use in a medication infusion device as described herein is provided. The component has a surface having a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees and exhibits a protein adsorption profile of less than about 1.0 microgram per square centimeter when measured with insulin.
In accordance with yet another aspect of the present invention, there is provided a method of treating a surface for use in a medical device for contacting a selected protein-based medication. The method includes the step of treating the surface to produce a covalently attached surface treatment that defines a surface contact angle less than about 45 degrees and exhibits a protein adsorption profile of less than about 1.0 microgram per centimeter when measured with insulin.
Preferably the surface is a polymeric surface as set forth above, and the treating step includes the application of a coating of a polymeric material as set forth above to the polymeric surface.
In a more specific embodiment, the polymeric material is applied to the surface by dipping, spraying, pre-polymerization followed by polymeric attachment, RF-plasma attachment, grafting, or silane-based primer attachment, and subsequently cured, preferably by exposure to actinic radiation (e.g., UV radiation), free radicals, elevated temperature, RF
Adomian Gerald E.
Gulati Poonam S.
Van Antwerp William Peter
Beck Shrive P.
Gates & Cooper LLP
Kolb Michener Jennifer
MiniMed Inc.
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