Medical device with porous surface for controlled drug...

Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Arterial prosthesis – Having pores

Reexamination Certificate

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C623S001420, C623S001450, C427S458000, C427S472000

Reexamination Certificate

active

06652581

ABSTRACT:

FIELD OF THE INVENTION
This invention relates generally to medical devices for delivering a biologically active agent or drug to a desired location within the body of a patient. More particularly, the invention is directed to medical devices having a porous surface comprising a plurality of voids therein. The porous surface is capable of being loaded with a drug, e.g., by infusing or placing the drug into the voids, for release into the body, particularly upon expansion of the portion of the medical device with the porous surface. In one method of loading the porous surface, the drug is concentrated into the voids by electrophoresis.
BACKGROUND OF THE INVENTION
For certain diseases which are localized to a particular part of the body, the systemic administration of drugs for the treatment of these diseases is not preferred because of the inefficiencies associated with the indirect delivery of the drugs to the afflicted area. Also, if a drug causes significant side effects, it is generally inappropriate for systemic delivery.
Instead, it is preferred that the drug be directly applied to the diseased tissue. Because such localized delivery to the afflicted area usually requires a relatively small amount of drug, side effects of the drug are reduced. Also, since localized delivery requires smaller amounts of drugs, such delivery is desirable for expensive drugs.
However, such localized delivery of drugs to the walls of lumens, such as blood vessels and ducts, can be problematic since body lumens are generally involved in the transport of body fluids, which tend to carry the drug away from the afflicted area. Thus, there is a need for devices and methods for the localized delivery of drugs to afflicted tissue, especially body lumens.
Also, if a drug or biologically active agent is biologically derived (e.g., a gene, a protein or a lipid), it usually cannot withstand standard sterilization of the device (e.g., ETO, gamma, or e-beam sterilization, autoclaving). Thus, the number of drugs that can be incorporated into the implantable device is limited. Hence, there is a need for a method for including such drugs into a drug-releasing device.
A number of methods for delivering drugs to body lumens or vessels involve the use of catheters having expandable portions, such as a balloon, disposed on the catheter. For instance, U.S. Pat. No. 5,304,121 to Sahatjian, PCT application WO 95/03083 to Sahatjian et al. and U.S. Pat. No. 5,120,322 to Davis et al. describe medical devices in which the exterior surface of the device is coated with a swellable hydrogel polymer. A solution of a drug to be delivered to the afflicted tissue is incorporated into the hydrogel. The drug is usually pre-sterilized by such methods as filtration. The drug is held within the matrix of the hydrogel. In the case where the medical device is a balloon catheter, the drug is delivered by inserting the catheter into the body lumen and expanding the coated balloon against the afflicted tissue of the lumen to force the drug from the hydrogel into the tissue.
However, these hydrogel coated devices have certain disadvantages. In particular, because the loading of the drug into the hydrogel is based on diffusion, the amount of drug that can be loaded onto the devices is limited. Thus, there remains a need for a way to load more drug onto implantable devices.
Other methods for making a drug coated implantable device include ones in which a composition of a drug, a polymeric material and a solvent is applied to at least a surface of the device. Such a method is described in co-pending application Ser. No. 08/633,490, filed Jun. 13, 1996 and published as EP 0 822 788A2 on Feb. 11, 1998. Also, U.S. Pat. No. 5,464,650 to Berg et al. describes drug containing coatings for medical devices.
SUMMARY OF THE INVENTION
These and other objectives are accomplished by the present invention. To achieve the aforementioned objectives, a medical device and a method for making such device for the localized delivery of biologically active agents to a patient has been invented.
The medical devices of the invention comprise a portion which has a porous surface. The porous surface includes the pores and the material between the pores which make up the porous surface. The porous surface is made of a material, such as polymer or a polymer blend, having a plurality of voids therein. The void space of the coating is preferably greater than about 60% of the volume of the porous surface. The porous surface can be a porous coating covering the surface of the device. The thickness of such a coating can be tailored to meet individual needs for release of at least one biologically active agent. Alternatively, the porous surface can be a structural part of the device. For example, a stent graft formed of a porous membrane would have a porous surface. A biologically active agent is loaded into the voids for release when the device is implanted.
In another embodiment of the invention, the medical device is a stent endoprosthesis having at least a portion which is covered with a polymeric porous surface such as a polymeric coating or material with a plurality of voids therein. A biologically active agent or a drug is placed into the voids for controlled release when the stent is implanted or inserted into a body lumen.
In yet another embodiment, the medical device is a stent graft comprising at least one portion which is made of porous graft material, which can, but need not be further covered with a porous or “sponge” coating. A drug is loaded into the voids to form a drug-coated stent graft.
The devices of the present invention can be prepared by applying a porous coating composition to a surface of the device, e.g., stent or stent graft. The porous coating composition comprises a polymer dissolved in a solvent and an elutable particulate material. After the coating is cured, it is exposed to a solvent, e.g., water, which causes the particulate material to elute from the polymer to form a porous or sponge coating having a plurality of voids therein.
The porous surface or coating can be loaded with a drug in an electrophoresis method. In such a method, the drug is dissolved or suspended in a solvent to form a drug solution or suspension. The device and an electrode are placed into the solution or suspension. An electric current source, e.g., battery, is connected to the device and the electrode. When the current source is switched on, the drug (which has a positive or negative charge) in the solution or suspension will be loaded into the voids of the device's porous surface.
Furthermore, prior to placing the device into the drug solution or suspension, the porous surface of the device can already contain materials which do not dissolve in the solution or suspension. Such materials include drugs or radiopaque materials, which permit the device to be visible during implantation under fluoroscopy.
With certain devices which are formed of porous materials, such as a porous stent graft, such devices can be loaded without first applying a porous coating to the graft. However, a porous coating can be used in conjunction with this type of device. A device with such a porous surface can be directly loaded in an electrophoresis method as described above.


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patent: WO 95/03083 (1995-02-01), None
patent: WO 96/32907 (1996-10-01), None
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