Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
2000-12-12
2003-04-08
Nutter, Nathan M. (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C525S242000, C525S221000, C424S501000, C424S423000
Reexamination Certificate
active
06545097
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compositions for therapeutic agent delivery comprising a therapeutic-agent-loaded block copolymer. The present invention also relates to biocompatible block copolymer materials for use in connection with intravascular or intervascular medical devices.
BACKGROUND AND SUMMARY OF THE INVENTION
Polymers that release drug upon implantation or insertion into the body are known. However, a need remains in the art for a polymer that is effective for drug-release, while at the same time having good mechanical integrity and biocompatibility.
It is also known to use polymers in connection with implantable or insertable medical devices. However, such polymers frequently elicit a vigorous immune or foreign body response. This is particularly true of intravascular or intervascular medical devices, which commonly suffer from the consequences of inflammation and neointimal thickening after placement within the vasculature.
The above and other needs in the prior art have been met by the present invention. According to one aspect of the invention, a composition for delivery of a therapeutic agent is provided, which comprises: (a) a biocompatible block copolymer comprising one or more elastomeric blocks and one or more thermoplastic blocks and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent.
Numerous therapeutic agents are appropriate for use in connection with the present invention including anti-thrombotic agents, anti-proliferative agents, anti-inflammatory agents, anti-migratory agents, agents affecting extracellular matrix production and organization, antineoplastic agents, anti-mitotic agents, anesthetic agents, anti-coagulants, vascular cell growth promoters, vascular cell growth inhibitors, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vascoactive mechanisms, and combinations thereof. One specific example of a therapeutic agent is paclitaxel. The loaded block copolymer preferably comprises 0.1 to 70 wt % therapeutic agent.
Regarding the polymer configuration, the block copolymer is preferably of the formula X—(AB)
n
, where A is an elastomeric block, B is a thermoplastic block, n is a positive whole number and X is a seed molecule.
Regarding the blocks within the copolymer, the elastomeric blocks are preferably polyolefin blocks. More preferably, the polyolefin blocks are of the general formula —(CRR′—CH
2
)
n
—, where R and R′ are linear or branched aliphatic groups or cyclic aliphatic groups. Even more preferably, the polyolefin blocks are polyisobutylene blocks. The amount of polyolefin blocks preferably ranges from between 95 and 45 mol % of the block copolymer.
The thermoplastic blocks are preferably selected from vinyl aromatic blocks and methacrylate blocks. The methacrylate blocks are preferably selected from methylmethacrylate, ethylmethacrylate and hydroxyethyl methacrylate monomers, as well as blocks of mixtures of these monomers. The vinyl aromatic polymer blocks are preferably selected from blocks of styrene and &agr;-methylstyrene, as well as blocks of mixtures of these monomers.
The molecular weight of the block copolymer preferably ranges from 80,000 to 300,000 Daltons. In some embodiments, the molecular weight of the polyolefin blocks preferably ranges from 60,000 to 200,000 Daltons, and the molecular weight of the vinyl aromatic polymer blocks preferably ranges from 20,000 to 100,000 Daltons.
According to another aspect of the present invention, a medical device is provided, at least a portion of which is insertable or implantable into the body of a patient. The medical device comprises (a) the above block copolymer and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent.
In some embodiments, only a portion of the medical device comprises the block copolymer. As an example, the portion of the medical device can be in the form of a coating on the medical device. Preferred coating dimensions are 0.1 to 50 microns in thickness.
Preferably, the therapeutic agent is released over an extended period after implantation in a patient.
Preferred sites for implantation or insertion of the medical device are the coronary vasculature, peripheral vasculature, esophagus, trachea, colon, gastrointestinal tract, biliary tract, urinary tract, prostate and brain.
In some embodiments, the medical device is adapted such that at least a portion of the block copolymer is exposed to bodily fluid upon insertion or implantation in the body. In others, the medical device is adapted to expose at least a portion of the block copolymer to tissue such as solid tissue.
Preferred medical devices include catheters, guide wires, balloons, filters, stents, stent grafts, vascular grafts, vascular patches, shunts and intraluminal paving systems. In some embodiments, the medical device is provided with a sheath for covering the block copolymer during insertion into the body to prevent premature therapeutic agent release.
In certain embodiments, the medical device further comprises a polymer or copolymer of one or more of the following: a polycarboxylic acid, a cellulose acetate polymer, a cellulose nitrate polymer, a gelatin, a polyvinylpyrrolidone, a cross-linked polyvinylpyrrolidone, a polyanhydride, a polyamide, a polyvinyl alcohol, a polyvinyl ether, a polyvinyl aromatic, a polyethylene oxide, a glycosaminoglycan, a polysaccharide, a polyester, a polyacrylamide, a polyether, a polyether sulfone, a polycarbonate, a polyalkylene, a halogenated polyalkylene, a polyurethane, a polyorthoester, a polypeptide, a silicone, a siloxane polymer, a polylactic acid, a polyglycolic acid, a polycaprolactone, a polyhydroxybutyrate valerate, a fibrin, a collagen, a collagen derivative or a hyaluronic acid. Particularly preferred polymers and copolymers are polyacrylic acids, ethylene-vinyl acetate copolymers, and copolymers of polylactic acid and polycaprolactone.
Such polymers or copolymers can be blended with the biocompatible block copolymer, or they can be provided in a layer that does not contain the biocompatible block copolymer.
According to another aspect of the present invention, a method of treatment is provided in which the above device is implanted or inserted into a patient, resulting in the release of therapeutic agent in the patient over an extended period of time.
According to yet another aspect of the invention, a coated medical device is provided which comprises: (a) an intravascular or intervascular medical device; and (b) a coating over at least a portion of the intravascular or intervascular medical device, the coating comprising the above biocompatible block copolymer. Preferred intravascular or intervascular medical devices for this aspect of the invention include balloons, stents, stent grafts, vascular grafts, vascular patches, shunts, catheters and filters.
One advantage of the present invention is that it provides a polymer-based drug delivery composition with good mechanical integrity.
Another advantage is that a polymer-based drug delivery composition can be provided that has good biocompatibility.
Another advantage of the present invention is that medical devices can be provided that, upon placement in the vasculature, result in reduced inflammation and neointimal thickening relative to other traditionally used polymeric materials.
Still other embodiments and advantages will become readily apparent to those skilled in the art upon review of the Specification and claims to follow.
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Kamath Kalpana
Nott Sepideh
Pinchuk Leonard
Schwarz Marlene
Asinovsky Olga
Bonham, Esq. David B.
Mayer Fortkort & Williams PC
Nutter Nathan M.
Scimed Life Systems Inc.
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