Intravascular stent pump

A multi-layer vascular therapeutic-containing prosthesis designed and arranged to "pump" the therapeutics into the blood stream.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a multi-layer vascular therapeutic-containing 
prothesis designed and arranged to "pump" the therapeutics into the blood 
stream. 
2. Description of Related Art 
Japanese Patent Application J63-97158A published Apr. 27, 1988 discloses an 
artificial blood vessel having heparin in the pores of an inner wall 
sealed with a water-swelling polymer. Polyurethane is used as a continuous 
cell structure. The tubular structure is treated with heparin and a 
water-swelling polymer such as polyvinylpyrrolidone, polyethylene glycol, 
polyacrylic acid or the like. 
U.S. Pat. No. 5,085,629 issued to Goldberg et al on Feb. 4, 1992 discloses 
a resorbable stem comprising a terpolymer of: L(-)lactide, glycolide, and 
epsilon caprolactone. 
European Patent 382158A published on Aug. 16, 1990 describes an implantable 
prothesis comprising an absorbable layer 3, a permeable support layer 4 
and another permeable layer 2 (page 5, lines 8-20). Absorbable polyesters 
include polylactate, polyglycolate and poly-E-caprolactone ester, (page 6, 
lines 5-8). A tube of copolymer of polylactate and polyglycolate 
containing heparin (in sustained release form) can be cast from solution 
onto the surface of a silicone tube to serve as an anti-thrombotic 
artificial blood vessel (page 7, lines 20-27). 
U.S. Pat. No. 5,201,778 issued to Brotzu et al on Apr. 13, 1993 discloses a 
vascular prothesis comprising a spindle between a prothesis 1 and 
prosthesis 3 in which microcapsules are placed (Col. 2, lines 23-28). In 
such a vascular prosthesis, the hematic flow allows for the circulation of 
the hormones secreted by the cells (Col. 2, lines 36-40). 
The prior art discloses resorbable stents made of polymers, e.g. 
polylactides, polyglycolates and caprolactones. U.S. Pat. No. 5,085,629 is 
an example. A water swelling polymer e.g. polyvinylpyrrolidone, serving in 
an artificial blood vessel as a drug releasing wall of the vessel is shown 
in J63-97158A. The use of a collagen as a supportive wall in an implanted 
artificial blood vessel is disclosed in U.S. Pat. No. 5,028,597 for 
example. 
SUMMARY OF THE INVENTION 
The prior art does not disclose the stent-like construction and arrangement 
of the subject invention in which an inner porous support layer and an 
outer support layer trap and hold therebetween a swellable drug or 
therapeutic-containing layer.

DETAILED DESCRIPTION OF THE INVENTION 
The characteristics and advantages of the vascular prosthesis of the 
invention will be better understood from the following detailed 
description. 
In its most preferred form, the stent-like construction comprises an 
intravascular, resorbable, UV curable drug delivery stent-pump in the form 
of a multi-layer cylindrical device constructed and arranged for 
implantation in a blood vessel or other duct or body passage. An inner 
polymeric layer and an outer polymeric layer support therebetween a 
swellable drug or therapeutic layer. 
The stent-pump in this form is UV curable in situ to allow it to stay in 
the expanded state upon placement and expansion in a vessel. If the device 
was not cured upon deployment or implantation following expansion it would 
simply shrink back down to its pre-expanded size. The material, without 
curing, behaves much like a rubber band. The device can be cured or rather 
"rigidified" in situ by means other than UV light. These other means may 
be: 
1. Exposure to a chemical that can initiate polymerization. Micro spheres 
which can contain a peroxide or strong acid may be dispersed throughout 
the inner and outer layers. Upon expansion of the device, these spheres 
would rupture, thus releasing the materials which effect the cure. 
2. Heat may also be employed to effect the cure. Heat sensitive initiators 
are stable at room temperature, but when exposed to elevated temperatures 
they decompose into fragments which may spontaneously start a 
polymerization. 
The stent-pump is implanted via a modified balloon angioplasty catheter 
(not shown). The modification which needs to be made to a standard 
catheter is the fitting of the device with an optical fiber which is used 
to deliver the UV energy to the stent-pump, effecting the cure. An optical 
fiber (as well as the use of UV light) would not be necessary with the use 
of the "micro sphere technology". Optical fibers on catheters are known in 
the art. Inflation of the balloon expands the stent-pump cylindrical 
diameter which is then held in place until cured by the UV radiation or 
other curing means. The balloon is then deflated and the catheter is 
removed, leaving the expanded stent-pump in place. 
The stent-pump of this embodiment is shown in FIGS. 1 and 2. It is 
cylindrical in form, the OD being selected to correspond substantially to 
the ID of the implantation site. Obviously, the device can be made in 
various selected sizes. The cylindrical structure generally designated at 
10 is comprised of at least three layers, an inner layer 12, an 
intermediate layer 14, and an outer layer 16, and is arranged so that 
blood can flow through its inner diameter when implanted in a blood 
vessel. In this way blood being exposed to the permeable inner layer 12 
can diffuse through it and into layer 14. The intermediate layer 14 is 
made up of a blood-swellable material. As it swells between the binding 
layers 12 and 16 upon absorbing blood in layer 14, it is subjected to a 
squeezing action. This pump-like action tends to force any drug or other 
therapeutic contained in layer 14 through the porous layer 12 and into the 
blood stream. As already indicated, most preferably layers 12 and 14 are 
of polymeric material, although other materials may be used as is 
discussed hereinbelow. 
As well as pumping, them is a diffusion process which occurs to liberate 
drug from the device. The actual dynamics of drug release can be described 
by two mechanisms. First of all, the intermediate layer would swell, then 
the drug/polymer mixture would be forced out. After the pressures 
equalize, the remainder of the drug/polymer would elute out of the device 
via a diffusion mechanism. The terms "stent-pump" and "pump" or "pumping" 
are used herein in this sense. 
The inner layer 12 is porous or perforated or otherwise permeable to allow 
contact between the blood or other fluid flowing through the device and 
the intermediate layer 14 as well as to allow diffusion therethrough and 
into the blood stream or the like of the therapeutic and fluid squeezed 
from layer 14 as a result of its swelling between layers 12 and 16. The 
inner layer, when polymeric, can be made porous by one of several methods. 
One method involves scoring, or nicking the inner material. Upon 
expansion, the scored or nicked areas will stretch to the point of 
rupture, thus causing an open space. Another method involves the 
incorporation of a microcrystalline, water soluble material into the inner 
layer. Upon expansion, the material will be exposed to the flow of blood, 
and the water soluble portion will dissolve. The ensuing voids provide the 
pore structure which is necessary for blood to contact and swell the 
middle layer of the device. 
Layers 12 and 16 for the most preferred embodiment may be comprised of, for 
example, polylactics, polyacetates, polyacrylates, polyglycol and/or 
polycaprolactones. Layer 16 may also be comprised of collagen, for 
example. The polymers that comprise a portion of layers 12 and 16 are 
preferably polyester, polyether, polyamide, or a mixture thereof. The 
specific polymer which was used in the initial prototypes was 
poly-D,L-Lactic acid. In addition to the foregoing, layer 16 will 
preferably include photocure or heat curable additives to render layer 16 
hardenable such as by heat or UV. A list of materials which can be used to 
render layer 16 hardened or rigid is provided in the Table below. The 
reason why this is necessary is because the actual support of the device 
is provided by layer 16. The rigid layer 16 not only provides structural 
integrity to the device but can also act as a stent, keeping a narrowed 
artery wall open. For example, layer 16 might be comprised of 
poly-D,L-lactic acid, ethylene glycol dimethacrylate and the 
photoinitiator 2-hydroxy-2-methyl-1-propanone. 
TABLE 1 
______________________________________ 
Ethylene glycol dimethacrylate 
Cyclohexylmethacrylate 
Ethylene glycol diacrylate 
Neopentyl glycol diacrylate 
Polyethylene glycol (GOO) dimethacrylate 
Tripropylene glycol diacrylate 
Lauryl methacrylate 
Stearyl methacrylate 
Ethoxylated bisphenol A dimethacrylate 
Ethoxylated bisphenol A diacrylate 
Di-Trimethylol propane tetra acrylate (LTx) 
Iso decyl acrylate 
Dipurt acrythritol penta acrylate 
Isobornyl methacrylate 
Ethoxylated trionethylol propane triacrylate (LTx) 
Highly ethoxylated bisphenol A dimethacrylate 
Propoxylated trimethylol propane triacrylate 
Tridecyl methacrylate 
Ethoxylated pentaerythritol tetra acrylate 
caprolactone acrylate 
Highly ethoxylated TMPTA 
Highly propoxylated TMPTA 
Highly ethoxylated TMPTA 
Isobornyl acrylate 
Propoxylated Neopentyl glycol diacrylate 
Glyceryl propoxy triacrylate 
Highly propoxylated glyceryl triacrylate 
______________________________________ 
Intermediate layer 14, the blood or water swelling material, is the drug or 
therapeutic containing and dispensing matrix and may be comprised of, for 
example, polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide or 
polyvinyl alcohol made up in an aqueous solution containing dissolved drug 
or the like. Any intravenous type drug may be included such as heparin, 
himdin, and dextran to name a few. There are a plethora of pharmaceutical 
agents which may be incorporated into the device (layer 14). These should 
not be limited to the drugs used for heart/angioplasty purposes. One use 
of this device may be the treatment of local infection, another may be the 
delivery of antineoplastic agents to a tumor via its main blood supply. 
Also, the intermediate layer may contain therapeutic agents used to remedy 
an abnormal condition or disease state. There are many general classes of 
drugs that can be employed, from analgesics to urinary tract agents, it is 
difficult to list them all. An original focus was to incorporate 
thrombolytics such as urokinase or streptokinase, as well as the 
anticoagulants heparin, dextran or hirudin although this invention is 
clearly not limited to them. 
Since the device provides support to a blood vessel as well as providing 
controlled release and/or pumping of therapeutics into the blood stream or 
the like, it is referred to herein as a stent-pump. 
The device, in its most preferred form, may be made by preparing separate 
solutions of the three polymeric compositions selected to form the three 
layers 12, 14, and 16. A mandrel such as PTFE shrink tubing over a stiff 
rod is then dip coated by dipping the tubing into the solution of inner 
layer 12 material, then into the solution for intermediate layer 14 
material, then into the solution for outer layer 16 material. Typically, 
about 14 dips into each solution provides an adequate dip coating of each 
layer. This will, of course, vary depending on the size of the device 
desired, the concentration of the solutions, thickness of layers, etc. The 
dimensions of the finished device may vary from an outside diameter of a 
fraction of a millimeter up to ca. 1 cm. The teflon mandrel is smaller 
than the finished device, and would typically be in the range of 0.1-3 mm 
in outside diameter. The stiff rod would fit easily within the teflon 
mandrel, being slightly smaller than the teflon heat-shrink tube. In one 
method of the dip coating technique a long tube of stent-pump is prepared 
and then individual stents are cut off. These individual stents are then 
mounted on a separate mandrel and then the ends are dip coated a number of 
times to seal the intermediate layer. 
After hardening or curing of the dip coated laminate structure, it is 
removed from the mandrel by pulling out the core rod and by pulling on 
both exposed ends of the shrink tubing simultaneously to break it loose 
from the inner layer 12. 
Another technique for making the device is to cast sheets of each layer 
onto a smooth surface such as glass. Each sheet may be rolled or wrapped 
onto the mandrel or tubing successively, each wrapping being accompanied 
by rolling of the mandrel on a flat surface. The mandrel or tubing is then 
removed as already described. 
In summary, the various components of the most preferred embodiment of the 
device may be described as follows: 
Layer 16--The outer layer may be comprised of a polymer (polyester, 
polyether, polyamine, etc.) a reactive monomer (see the line 13 list) and 
a polymerization initiator. The initiator need not be limited to 
photoreactive materials, but rather materials which can produce radicals 
or acids upon the delivery of energy to the device. 
Layer 14--The intermediate drug bearing layer comprises a mixture of a 
therapeutic agent in any water (or blood) swelling/dissolving natural or 
synthetic material. Natural materials may include polysaccharides, or 
blood serum components. Polyvinyl pyrrolidone, polyethylene glycol, and 
polyvinyl alcohol (etc.) can be used as synthetic materials. 
Layer 12--The inner, bodily fluid contacting layer may be prepared from the 
same materials as the outer layer except in one case a microcrystalline 
salt or otherwise water/blood soluble material is added for porosity. 
These materials can be simple inorganic salts, sugars or polysaccharides. 
The preferred materials are as follows: 
Layer 16--poly-D,L-lactic acid, ethylene glycol dimethacrylate, and 
2-hydroxy-2-methyl-1-phenyl-1-propanone; 
Layer 14--polyvinylpyrrolidone, water and sodium heparin; and 
Layer 12--identical to layer 16 with the addition of micro crystalline (sub 
micron to micron particle size) sodium heparin. 
As already indicated, the preferred form of the invention is an expandable 
stent-like structure which may be expanded in situ to fit the vessel in 
which it is being placed. However, a stent-like structure of fixed 
diameter may also make use of the invention. In such an instance, stent 
pumps of various diameter would be available so that a vessel of 
particular diameter could be accommodated by selecting the nearest and 
best fit. 
Also, as already indicated, layers 12 and 16 are preferably of expandable 
polymeric materials. However, they may be made of other materials such as 
rigid plastics of which polylactide, polytetrafluoroethylene, polyurethane 
and acrylic based polymers are but a few examples. Inner layer 12 may be 
rendered permeable by including openings therein of a size selected to 
provide any desired flow through rate and diffusion rate. Metals such as 
stainless steel and nitinol may be used for these layers as well in either 
a fixed diameter or expandable configuration as is known in the art. 
Furthermore, the metal and plastic for layers 12 and/or 16 may be in a 
mesh form, a screen form or a filamentary form as shown for layer 12 in 
FIG. 3 and may further include collagen or other biological material 13 
supported thereon. Examples of such biological materials are shown in the 
following U.S. Pat. Nos. 4,956,178; 4,902,508; 5,275,826; 5,281,422; 
4,950,483; 5,110,064 and 5,024,841. Thickness of such support layers may 
range over 0.001 inch to 0.010 inch, for example. Such structures in their 
preferred cylindrical configuration may or may not be sealed at the ends, 
as described hereinabove. 
While this invention may be embodied in many different forms, there are 
described in detail herein specific preferred embodiments of the 
invention. This description is an exemplification of the principles of the 
invention and is not intended to limit the invention to the particular 
embodiments illustrated. These examples and the description will suggest 
many variations and alternatives to one of ordinary skill in this art. All 
these alternatives and variations are intended to be included within the 
scope of the attached claims. Those familiar with the art may recognize 
other equivalents to the specific embodiments described herein which 
equivalents are also intended to be encompassed by the claims attached 
hereto.