AnB block copolymers containing poly (vinyl pyrrolidone)...

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

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C525S326700, C525S123000, C424S078360, C424S078240, C424S070150

Reexamination Certificate

active

06756449

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to polymers containing poly(vinyl pyrrolidone) copolymerized with other polymers such as polyurethanes, etc. Such materials are particularly useful as biomaterials in medical devices.
BACKGROUND OF THE INVENTION
The chemistry of block copolymers is extensive and well developed. They can be used to combine the properties of different polymers in one material. For example, a polymer having hydrophilic properties can form one block and a polymer having hydrophobic properties can form another block. Thus, one material can have combinations of properties that neither constituent polymer possesses alone. This can be of significant utility in the medical device arena.
Polymers used to create medical devices are typically chosen for their bulk properties; however, it is often desirable for the surfaces of such medical devices to possess different properties than that of the bulk polymer. For example, it may be desirable for a polymer surface to have a different level of compatibility with other polymers or tissues, surface energy, etc., than that of the bulk polymer. Thus, block copolymers are desirable materials to investigate for their utility in modifying polymer surfaces for medical device applications.
Block copolymers have been used to modify polyurethane surfaces, which are important biomedical polymers used in implantable devices such as artificial hearts, cardiovascular catheters, pacemaker lead insulation, etc. Such block copolymers have been used to enhance antimicrobial properties, lubricity, barrier properties, anticoagulant properties, and the like. For example, U.S. Pat. No. 4,675,361 (Ward, Jr.) discloses a block copolymer for improved biocompatibility. Also, U.S. Pat. No. 5,302,385 (Khan et al.) discloses a polyurethane-poly(vinyl pyrrolidone) copolymer foam having antimicrobial properties coated on a catheter. The resultant polymer is highly branched or a network polymer without a well-defined or controllable block architecture.
Other block copolymers are needed for modifying the surface properties of medical devices.
SUMMARY OF THE INVENTION
The present invention relates to block copolymers, particularly A
n
B block copolymers, wherein n is at least two, and more particularly A-B-A block (triblock) copolymers, that include poly(vinyl pyrrolidone) in the A blocks, and urethane groups, urea groups, amide groups, imide groups, ester groups, ether groups, or combinations thereof (e.g., polyurethanes, polyureas, or polyurethane-ureas) in the B block. This includes methods for making such polymers.
The block copolymers of the present invention are particularly useful as biomaterials in medical devices. Certain preferred embodiments of the block copolymers can also provide a lubricious surface (e.g., a slip coating on a polymeric surface). Lubricous surfaces are desirable for many medical devices, particularly the inner surfaces of lead delivery catheters. Coating conventional materials on the inner surfaces of such catheters can be difficult and expensive, however. The block copolymers of the present invention provide an opportunity to more easily manufacture such devices. Methods involving dip coating followed by solvent removal techniques can be used to apply the block copolymers of the present invention to a substrate. Alternatively, the block copolymers can be coextruded with another thermoplastic polymer to form a layered construction. Extrusion methods can also involve reactive coextrusion.
In one embodiment, the present invention provides a thermoplastic A
n
B block copolymer, wherein the A blocks include poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ether groups, or combinations thereof, wherein n is at least two.
The present invention provides medical devices. One such device includes a surface that includes a thermoplastic A
n
B block copolymer, wherein the A block includes poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ester groups, ether groups, or combinations thereof, wherein n is at least two. The “surface” can be the surface of a coating, for example, of a thermoplastic A
n
B block copolymer on another substrate, such as a polymeric material. Alternatively, the “surface” can be the surface of an extruded layer, for example, of a thermoplastic A
n
B block copolymer, which can be coextruded with another polymeric material, or formed using reactive coextrusion.
The present invention also provides methods of modifying a surface of a medical device. One method includes: preparing a thermoplastic A
n
B block copolymer, wherein the A block includes poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ether groups, ester groups, or combinations thereof, wherein n is at least two; and applying the A
n
B copolymer to the surface of the medical device.
The present invention also provides methods of preparing a thermoplastic A
n
B block copolymer. One method includes reacting a substantially monofunctional poly(vinyl pyrrolidone) with a functionalized B-block precursor that includes functional groups reactive with the functional groups of the poly(vinyl pyrrolidone) to form the thermoplastic A
n
B block copolymer. In an alternative method, the block copolymer is made in one step using a substantially monofunctional poly(vinyl pyrrolidone) with reactants for the functionalized B-block precursor.
As used herein, the term “organic group” refers to a hydrocarbyl group (aliphatic and/or aromatic) optionally including other atoms (e.g., heteroatoms) or groups (e.g., functional groups) replacing the carbon and/or hydrogen atoms. The term “aliphatic group” means a saturated or unsaturated linear (i.e., straight chain), cyclic, or branched hydrocarbon group. This term is used to encompass alkyl (e.g., —CH
3
) (or alkylene if within a chain such as —CH
2
—), alkenyl (or alkenylene if within a chain), and alkynyl (or alkynylene if within a chain) groups, for example. The term “alkyl group” means a saturated linear or branched hydrocarbon group including, for example, methyl, ethyl, isopropyl, t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like. The term “alkenyl group” means an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon double bonds, such as a vinyl group. The term “alkynyl group” means an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon triple bonds. The term “aromatic group” or “aryl group” means a mono- or polynuclear aromatic hydrocarbon group. These hydrocarbon groups may be substituted with heteroatoms, which can be in the form of functional groups. The term “heteroatom” means an element other than carbon (e.g., nitrogen, oxygen, sulfur, chlorine, etc.).
As used herein, the terms “a,” “an,” “one or more,” and “at least one” are used interchangeably.
As used herein, a “thermoplastic” polymer is one that will melt and flow when heated and reform substantially the same material upon cooling.
As used herein, a “biomaterial” or “biocompatible material” may be defined as a material that is substantially insoluble in body fluids and tissues and that is designed and constructed to be placed in or onto the body or to contact fluid or tissue of the body. Ideally, a biocompatible material will not induce undesirable reactions in the body such as blood clotting, tissue death, tumor formation, allergic reaction, foreign body reaction (rejection) or inflammatory reaction; will have the physical properties such as strength, elasticity, permeability, and flexibility required to function for the intended purpose; can be purified, fabricated, and sterilized easily; and will substantially maintain its physical properties and function during the time that it remains implanted in or in contact with the body.
As used herein, a “medical devi

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