Abstract:
Intravascular filters can include a filter membrane having a hydrophilic polymer coating on the filter membrane. The hydrophilic polymer coating can be on an inner surface, an outer surface or both an inner surface and an outer surface of the filter membrane. Intravascular filters including a hydrophilic polymer coating may be considered as providing increased hemocompatibility, decreased risk of filter-induced thrombosis and reduced sheathing forces.

Description:
TECHNICAL FIELD  
       [0001]     The invention relates generally to intravascular devices and more particularly to emboli-capturing devices. In particular, the invention relates to lubricious emboli-capturing devices such as filters.  
       BACKGROUND  
       [0002]     Heart and vascular disease are major problems in the United Sates and throughout the world. Conditions such as atherosclerosis result in blood vessels becoming blocked or narrowed. This blockage can result in lack of oxygenation of the heart, which has significant consequences since the heart muscle must be well oxygenated in order to maintain its blood pumping action.  
         [0003]     Occluded, stenotic or narrowed blood vessels may be treated with a number of relatively non-invasive medical procedures including percutaneous transluminal angioplasty (PTA), percutaneous transluminal coronary angioplasty (PTCA), and atherectomy. Angioplasty techniques such as PTA and PTCA typically involve the use of a balloon catheter. The balloon catheter is advanced over a guidewire such that the balloon is positioned adjacent a stenotic lesion. The balloon is then inflated, and the restriction in the vessel is opened. During an atherectomy procedure, the stenotic lesion may be mechanically or otherwise cut away from the blood vessel wall using an atherectomy catheter.  
         [0004]     During procedures such as angioplasty and atherectomy procedures, embolic debris can be separated from the wall of the blood vessel. If this debris enters the circulatory system, it can block other vascular regions including the neural and pulmonary vasculature. During angioplasty procedures, stenotic debris may also break loose due to manipulation of the blood vessel.  
         [0005]     Because of this debris, a number of devices such as intravascular filters have been developed. A need remains for improved intravascular filters and filter membranes. A need remains for improved method of manufacture of intravascular filters and filter membranes.  
       SUMMARY  
       [0006]     The present invention is directed to improved intravascular filters and methods of manufacture thereof. In particular, the present invention is directed to intravascular filters that include a filter membrane and a hydrophilic polymer coating disposed on the filter membrane. The hydrophilic polymer coating can be on an inner surface, an outer surface or both an inner surface and an outer surface of the filter membrane. The present invention is directed to intravascular filters that in some embodiments may be considered as possessing increased hemocompatibility and posing a reduced risk of filter-induced thrombosis. In some cases, the present invention is directed to intravascular filters that may be considered as providing reduced sheathing forces.  
         [0007]     Accordingly, an example embodiment of the invention can be found in a method of forming an intravascular filter that includes a polymeric base layer and a hydrophilic layer disposed on the base layer. A filter forming mandrel is provided, and the filter forming mandrel is sprayed with a hydrophilic polymer to form the hydrophilic layer. Subsequently, the hydrophilic layer is sprayed with a base polymer to form the base layer.  
         [0008]     Another example embodiment of the invention can be found in a method of forming an intravascular filter that includes a polymeric base layer and a hydrophilic layer disposed on the base layer. A filter forming mandrel is provided, and the filter forming mandrel is sprayed with a base polymer to form the base layer. Subsequently, the base layer is sprayed with a hydrophilic polymer to form the hydrophilic layer.  
         [0009]     Yet another example embodiment of the invention can be found in an intravascular filter that includes a filter membrane having an inner surface and an outer surface. A hydrophilic polyurethane coating can be disposed on the filter membrane on at least one of the inner surface of the filter membrane and the outer surface of the filter membrane.  
         [0010]     The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The Figures, Detailed Description and Examples which follow more particularly exemplify these embodiments. 
     
    
     BRIEF DESCRIPTION OF THE FIGURES  
       [0011]     The invention may be more completely understood in consideration of the following detailed description of various embodiments of the invention in connection with the accompanying drawings, in which:  
         [0012]      FIG. 1  is a schematic perspective view of an intravascular filter in accordance with an embodiment of the invention;  
         [0013]      FIG. 2  is a magnified view of a portion of the filter membrane included in the intravascular filter of  FIG. 1 ;  
         [0014]      FIG. 3  is a schematic illustration of a filter forming mandrel and spray apparatus in accordance with an embodiment of the invention;  
         [0015]      FIG. 4  is a schematic illustration of the apparatus of  FIG. 3 , including a first layer formed on the filter forming mandrel;  
         [0016]      FIG. 5  is a schematic illustration of the apparatus of  FIG. 3 , including a second layer formed on the filter forming mandrel;  
         [0017]      FIG. 6  is a schematic perspective view of a filter membrane made by the method illustrated in  FIGS. 3-6 ; and  
         [0018]      FIG. 7  is a cross-section taken along line  7 - 7  of  FIG. 6 . 
     
    
       [0019]     While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.  
       DETAILED DESCRIPTION  
       [0020]     For the following defined terms, these definitions shall be applied, unless a different definition is given in the claims or elsewhere in this specification.  
         [0021]     All numeric values are herein assumed to be modified by the term “about”, whether or not explicitly indicated. The term “about” generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value, i.e., having the same function or result. In many instances, the term “about” may include numbers that are rounded to the nearest significant figure.  
         [0022]     The recitation of numerical ranges by endpoints includes all numbers within that range. For example, a range of 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4 and 5.  
         [0023]     As used in this specification and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise. As used in this specification and in the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.  
         [0024]     The following description should be read with reference to the drawings, in which like elements in different drawings are numbered in like fashion. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. Although examples of construction, dimensions, and materials are illustrated for the various elements, those skilled in the art will recognize that many of the examples provided have suitable alternatives that may be utilized.  
         [0025]     A hydrophilic polymer is a polymer that attracts or binds water molecules when the polymer is placed in contact with an aqueous system. Examples of aqueous systems that can provide water molecules that can bind to a hydrophilic polymer include blood and other bodily fluids. When a hydrophilic polymer comes into contact with such a system, water molecules can bind to the polymer via mechanisms such as hydrogen bonding between the water molecules and substituents or functional groups present within or on the polymer. In some instances, a hydrophilic polymer can bind at least 2 times its own weight in water and in particular instances some hydrophilic polymers can bind up to about 20 times their own weight in water.  
         [0026]     One class of polymers that can be considered as hydrophilic includes certain nonionic polymers such as hydrophilic polyurethanes. Examples of suitable materials include nonionic polyether polyurethanes available commercially under the HYDROSLIP® name. Another suitable material includes nonionic aliphatic polyether polyurethanes available commercially under the TECOGEL® name. Examples of other suitable nonionic polymers include polymers such as poly (hydroxy methacrylate), poly (vinyl alcohol), poly (ethylene oxide), poly (n-vinyl-2-pyrolidone), poly (acrylamide) and other similar materials.  
         [0027]     Another class of polymers that can be considered as hydrophilic includes ionomer polymers. An ionomer polymer is a polymer that has includes charged functional groups. The charged functional groups can be positively charged, in which case the polymer can be referred to be a cationomer, or the functional groups can be negatively charged, in which case the polymer can be referred to as an anionomer.  
         [0028]     An ionomeric polymer can be formed using a variety of negatively charged functional groups. The negatively charged functional group can be added to a previously formed polymer, or the negatively charged functional groups can be part of one or more of the monomers used to form the ionomeric polymer.  
         [0029]     Examples of suitable negatively charged functional groups include sulfonates and carboxylates. The ionomeric polymer can, in particular, include sulfonate functional groups. These groups are negatively charged and can readily hydrogen bond sufficient amounts of water when brought into contact with a source of water such as an aqueous system. Additional examples of ionomeric polymers include poly (acrylic acid), poly (methacrylic acid), hydroluronic acid, collagen, and other similar materials.  
         [0030]     Turning now to the Figures,  FIG. 1  is a perspective view of an example intravascular filter  10 , which includes a filter membrane  12 . The filter membrane  12  can be formed from any suitable material or combination of materials as will be discussed in greater detail hereinafter. The filter membrane  12  can be porous, having pores  14  that are configured to permit blood flow while retaining embolic material of a desired size. The filter membrane  12  can have a mouth  16  and a closed end  18  and is capable of moving between an open state and a closed state. The mouth  16  can be sized to occlude the lumen of the body vessel in which the filter may be installed, thereby directing all fluid and any emboli into the filter with emboli retained therein.  
         [0031]     A support hoop  20  can be attached to the filter membrane  12  at or proximate to the mouth  16 . The support hoop  20  can be attached to the filter membrane  12  through melt bonding or other suitable means. In some embodiments, as discussed in greater detail hereinafter, the support loop  20  can be integrally molded within the filter membrane  12 . The support hoop  20  has an expanded state and a compressed state. The expanded state of the support hoop  20  is configured to urge the mouth  16  to its full size, while the compressed state permits insertion into a small lumen.  
         [0032]     The support hoop  20  can be made from a flexible metal such as spring steel, from a super-elastic elastic material such as a suitable nickel-titanium alloy, or from other suitable material. The support hoop  20  can be a closed hoop made from a wire of uniform diameter, it can be a closed hoop made from a wire having a portion with a smaller diameter, it can be an open hoop having a gap, or it can have another suitable configuration.  
         [0033]     A strut  22  can be fixedly or slideably attached to and extend from the support hoop  20 . An elongate member  24  can be attached to and extend from the strut  22 . The elongate member  24  can be attached to the strut  22  at an angle or the strut  22  can have a small bend, either at a point or over a region. The strut  22  can be attached to the support hoop  20  at a slight angle such that when the elongate member  24 , the strut  22 , and the support hoop  20  are in an unconstrained position, the elongate member  24  can generally extend perpendicular to the support hoop  20 .  
         [0034]     In the unconstrained position, the elongate member  24  can also lie along an axis which passes through the center of the region created by the support hoop  20 . This may help position the support hoop  20  in contact with the wall of a vascular lumen or it may help in enhancing predictability or reliability during deployment. In some embodiments, the elongate member  24  can terminate at the strut  22 . In other embodiments, the elongate member  24  can extend through the filter membrane  12 , as shown. Whether or not the elongate member  24  extends through the filter membrane  12 , it may be fixedly or slideably/rotatably attached to the filter membrane  12 .  
         [0035]     The filter membrane  12  can include a waist  26  at a closed end  28 . In some embodiments, the waist  26  can be integrally formed with the filter membrane  12 . In other embodiments, the filter membrane  12  can be further processed to form the waist  26 . In some embodiments, integrally forming the waist  26  with the filter membrane  12  can reduce the outer diameter of the filter device when in a compressed state, increase the reliability and uniformity of the bond between the filter membrane and the elongate member, and reduce the number of steps or components needed to form the filter device.  
         [0036]     The waist  26  is a region largely incapable of moving between two states and having a lumen of substantially constant diameter therethrough. The elongate member  24  can extend through and be bonded to the waist  26 . This bonding can be heat bonding such as laser bonding, or may be an adhesive or other suitable means.  
         [0037]      FIGS. 3 through 5  illustrate exemplary methods of forming the filter membrane  12  in accordance with the invention.  FIG. 3  shows a filter forming mandrel  28  and a spray apparatus  30 . The filter forming mandrel  28  can be dimensioned as appropriate for any particular filter size and configuration and can be formed of any suitable metallic or polymeric material. In some instances, the filter forming mandrel  28  can have a release coating applied thereto in order to facilitate removal of a finished filter membrane  12 .  
         [0038]     The spray apparatus  30  can generically represent any suitable spraying apparatus that can be configured to provide appropriately sized particles of whichever polymeric material is being applied. In some instances, the spray apparatus  30  can provide particle sizes in the range of about 5 μm to about 100 μm and more particularly about 15 μm to about 60 μm when spraying suitable materials such as polyurethanes.  
         [0039]     In  FIG. 4 , a first layer  32  has been sprayed onto the filter forming mandrel  28 . In some instances, the first layer  32  can be a base layer while in other cases the first layer  32  can be a hydrophilic layer. A second layer  34  can subsequently be applied, as shown schematically in  FIG. 5 . If the first layer  32  is a base layer, the second layer  34  can be a hydrophilic layer. Conversely, if the first layer is a hydrophilic layer, then the second layer  34  can be a base layer. While not expressly illustrated, additional layers can also be applied. For example, in some cases it can be useful to have a hydrophilic layer on an inside surface of the base layer as well as on the outside surface of the base layer.  
         [0040]      FIG. 6  is a perspective view of the finished filter membrane  12 .  FIG. 7  is a cross-section illustrating the multi-layer construction of the filter membrane  12 .  FIG. 7  shows first layer  32  and second layer  34 , although additional layers are permissible as discussed above. Merely for illustrative purposes, the first layer  32  can be considered to represent a base layer while the second layer  34  can be considered as representing a hydrophilic layer. The first layer  32  has an inner surface  36  and an outer surface  38 . As illustrated, the second layer  34  (representing the hydrophilic layer) is disposed on the outer surface  38  of the first layer  32  (representing the base layer).  
         [0041]     In some embodiments, the base layer can be applied to have a thickness that is in the range of about 5 μm to about 50 μm. In particular embodiments, the base layer can have a thickness that is in the range of about 10 μm to about 50 μm. The hydrophilic layer can have a thickness that is in the range of about 0.5 μm to about 8 μm. In particular embodiments, the hydrophilic layer can have a thickness that is in the range of about 0.5 μm to about 5 μm.  
         [0042]     In other embodiments, the hydrophilic layer can be disposed on the inner surface  36  of the first layer  32 . In some instances, a first hydrophilic layer can be disposed on the inner surface  36  of the first layer  32  while a second hydrophilic layer can be disposed on the outer surface  38  of the first layer  32 , assuming of course that the first layer  32  represents a base layer.  
         [0043]     The base layer can be formed of any suitable polymeric materials, such as polyether block amide, polybutylene terephthalate/polybutylene oxide copolymers sold under the Hytrel® and Arnitel® trademarks, Nylon 11, Nylon 12, polyurethane, polyethylene terephthalate, polyvinyl chloride, polyethylene naphthalene dicarboxylate, olefin/ionomer copolymers, polybutylene terephthalate, polyethylene naphthalate, ethylene terephthalate, butylene terephthalate, ethylene naphthalate copolymers, polyamide/polyether/polyester, polyamides, aromatic polyamides, polyurethanes, aromatic polyisocyanates, polyamide/polyether, and polyester/polyether block copolymers, among others.  
         [0044]     In some embodiments, the base layer can be formed of a polyurethane that absorbs less than about 5 percent of its own weight in water. In some cases, the base layer can be formed from a polycarbonate urethane such as that available commercially under the BIONATE® name.  
         [0045]     The hydrophilic layer (or layers) can as discussed above be formed of hydrophilic materials that can absorb from about 2 to about 20 times their own weight in water. The hydrophilic material can be a nonionic material such as the HYDROSLIP® and TECOGEL® materials discussed above. In some embodiments, these materials can be particularly useful, as they are readily dissolvable in water/alcohol mixtures to form low viscosity solutions that are easily sprayable. These materials are compatible with materials used to form the base layer and exhibit good adhesion to the base layer.  
         [0046]     The hydrophilic material can be an anionic material such as a sulfonated polyurethane or a carboxylated polyurethane. A polyurethane can be formed from monomers, chain extenders or oligomers that include a desired functional group that can provide a polymer with desired anionomer character. In some embodiments, a diamine disulfonic acid can be used as a chain extender in synthesizing a sulfonated polyurethane. In particular, a sulfonated polyurethane can be produced using 4,4′-diamino-2,2′-biphenyl disulfonic acid as a chain extender. Alternatively, a polyurethane can be formed, and desired functional groups such as sulfonate groups can subsequently be added via a grafting reaction.  
         [0047]     An illustrative but non-limiting method of forming a sulfonated polyurethane is described herein. A polyurethane can be formed by first reacting a diisocyanate with an active hydrogen source to create a polyurethane backbone, and subsequently substituting a desired functional group. For example, a desirable functional group includes a sulfonate functional group. A sulfonate functional group can be added to a polyurethane backbone by reacting the polyurethane with a molecule bearing the desired substituent. An example of a desired substituent is a pendent propyl sulfonate group.  
         [0048]     One way of adding this functional group is to react the polyurethane backbone with propane sulftone, which is also known as 1,2-oxathiolane-2,2-dione and has the following structure:  
                         
 
         [0049]     Polyurethanes suitable for use in the present invention can also include copolymers formed by reacting a diisocyanate, a diol and an ether. In particular, a suitable polyurethane can be formed by reacting methylene bis-(p-phenyl isocyanate) (MDI), N-methyldiethanolamine (MDEA) and poly(tetra-methylene oxide) (PTMO). Alternatively, 1,4-butanediol can be used as a chain extender in place of the MDEA.  
         [0050]     A carboxylated polyurethane can be formed in a variety of ways. An illustrative but non-limiting method is described herein. A polyurethane bearing pendent carboxyl groups can be formed by reacting an aliphatic diisocyanate, a diol component and a carboxylic acid. In particular, a carboxylated polyurethane polymer can be produced as a reaction product of a diol component, an aliphatic diisocyanate, water and a 2,2-di-(hydroxymethyl) alkanoic acid. Alternatively, an amount of amine, such as diglycolamine can be used for at least a portion of the water in the reaction to form the reaction product.  
         [0051]     The diol component can include a polyoxyalkylene diol, such as polyoxyethylene diol having a molecular weight of from about 400 to about 20,000, polyoxypropylene diol having a number average molecular weight of about 200 to about 2,500, block copolymers of ethylene oxide and propylene oxide having a molecular weight of about 1,000 to about 9,000 and polyoxytetramethylene diol having a number average molecular weight of about 200 to about 4,000.  
         [0052]     The polyurethane can include a low molecular weight alkylene glycol such as ethylene glycol, propylene glycol, 2-ethyl-1-1,3-hexanediol, tripropylene glycol, triethylene glycol, 2,-4-pentane diol, 2-methyl-1,3-propanediol, 2,-methyl-1,3-pentanediol, cyclohexanediol, cyclohexanedimethanol, dipropylene glycol, diethylene glycol, and mixtures thereof.  
         [0053]     An amine can be used in the reaction for at least a portion of the water in the reaction mixture. The amine can be diglycolamine, although other amines such as ethylene diamine, propylene diamine, monoethanolamine, diglycolamine, and propylene diamine can also be used.  
         [0054]     The diisocyanate used can include both aliphatic and aromatic types and mixtures thereof. An example of a suitable isocyanate is methylene bis(cyclohexyl-4-isocyanate). Other examples of diisocyanates are trimethyl hexamethylene diisocyanate and isophorone diisocyanate. Representative examples of aliphatic diisocyanates include tetramethylene diisocyanate, hexamethylene diisocyanate, trimethylene diisocyanate, trimethylene hexamethylene diisocyanate, cyclohexyl 1,2-diisocyanate, cyclohexylene 1,4-diisocyanate, and aromatic diisocyanates such as 2,4-toluene diisocyanates and 2,6-toluene diisocyanates.  
         [0055]     The invention should not be considered limited to the particular examples described above, but rather should be understood to cover all aspects of the invention as set out in the attached claims. Various modifications, equivalent processes, as well as numerous structures to which the invention can be applicable will be readily apparent to those of skill in the art upon review of the instant specification.