Functionalizing implantable devices with a poly (diol co-citrate) polymer

Abstract

The present invention is directed to a novel poly(diol citrates)-based coating for implantable devices. More specifically, the specification describes methods and compositions for making and using implantable devices coated with citric acid copolymers or citric acid copolymers impregnated with therapeutic compositions and / or cells.

Description

[0001] The present application claims benefit of U.S. Provisional Application No. 60 / 771,348 filed Feb. 8, 2006. The entire text of the aforementioned application is incorporated herein by referenceFIELD OF THE INVENTION [0002] The present invention describes methods and compositions for coating implantable devices with a polymer to improve the long-term biocompatibility and / or patency of the device. BACKGROUND [0003] Implantable medical devices are used in the treatment and assessment of a variety of medical conditions. Such devices may be introduced into the body for a short period of time or may be placed therein permanently and have been used for the treatment of diseased, injured, or deformed body vessels. In cases where malfunctioning body vessels have reduced inner diameters, there is usually reduced flow of vital fluid or gas through the vessels and in extreme cases, the vessels often are occluded. Implantable medical devices have proven useful to open and / or expand, or to o...

AI Technical Summary

Benefits of technology

[0021] The invention provides methods of decreasing the thrombogenicity of a graft comprising coating said graft with a coating comprising a citric acid polyester having the generic formula (A-B-C)n, wherein A is a linear aliphatic dihydroxy monomer; B is citric acid, C is a linear aliphatic dihydroxy monomer, and n is an integer greater than 1 wherein said graft is less thrombogenic than a similar graft that does not comprise said coating.

Problems solved by technology

In addition, balloons such as angioplasty or dilation balloons are expanded to open a body passage or vessel lumen, thereby causing potential trauma or injury to the expanded passage or vessel.

While implantable medical devices have gained widespread use, they do have attendant drawback.

For example, introduction of a stent into the vascular system of a patient may cause the blood vessel walls into which the stent is being placed to become disrupted or injured.

Moreover, if the medical device is left within the patient for an extended period of time, thrombus often forms on the device itself, again causing stenosis.

As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, and stroke.

Thus, the use of such a medical device can entail the risk of precisely the problems that its use was intended to ameliorate.

Another site of injury during implantation of medical devices is the tissue at and beyond the ends of the implanted stent.

Regardless of the cause of the trauma or injury to the vessel wall, the tissue will react such as with smooth muscle cell proliferation and the like thereby creating an adverse reaction and subsequent closure or stenosis of the vessel.

Indeed, atherosclerotic vascular disease, in the form of coronary artery and peripheral vascular disease remains the leading cause of mortality in the United States.

However, for many patients suitable vein grafts are not available.

[2] Allografts are in short supply and carry the risk of poor healing characterized by slow wall lysis, compaction and loss of elastic tissue, ulceration, mural thrombosis, and calcification.

Unfortunately, Dacron and ePTFE are not applicable to small-diameter (≦6 mm inner diameter) blood vessels (SDBV), especially in locations below the knee.

Poor patency is problematic due in part to incomplete endothelialization, thrombosis, and intimal hyperplasia particularly at the distal anastomosis.

Significant progress has been made for in vitro regeneration of SDBV, [4-6] however, there is still a long way to go before tissue engineered blood vessel substitutes are approved by Food and Drug Adminstration (FDA).

In addition, the highly hydrophobic surfaces of ePTFE grafts limit endothelial cell adhesion.

[13-17] However, issues of stability of the coating, transmission of pathogens, and high costs remain.

However, without the inclusion of a polymerizable agent, the plasma-induced effects are temporary and difficult to control.

[24] Nevertheless, the resulting film is normally non-degradable, and long-term biocompatibility and the increased compliance mismatch of the modified grafts are a concern.

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