Control of polymer surface molecular architecture via amphipathic endgroups

• US 20050282997A1
• Filed: 08/26/2005
• Published: 12/22/2005
• Est. Priority Date: 11/12/2002
• Status: Active Grant

• Current Assignee: Polymer Technology Group, Inc. (DSM-Firmenich AG)
• Original Assignee: Polymer Technology Group, Inc. (DSM-Firmenich AG)
• Inventors: Ward, Robert S., McCrea, Keith R., Parakka, James P., Tian, Yuan
• Granted Patent: US 7,671,162 B2
• Time in Patent Office: Days
• US Class Current: 528/403
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08G 18/0823 containing carboxylate salt groups or groups forming them
• CPC Class Codes: C08G 18/12 using two or more compounds having active hydrogen in the first polymerisation step
• CPC Class Codes: C08G 18/283 Compounds containing ether groups, e.g. oxyalkylated monohydroxy compounds
• CPC Class Codes: C08G 18/2865 Compounds having only one primary or secondary amino group; Ammonia
• CPC Class Codes: C08G 18/289 containing silicon
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/5024 containing primary and/or secondary amino groups
• CPC Class Codes: C08G 18/5039 containing amide groups
• CPC Class Codes: C08G 18/6283 Polymers of nitrogen containing compounds having carbon-to-carbon double bonds C08G18/6262, C08G18/6266 take precedence
• CPC Class Codes: C08G 18/6287 Polymers of sulfur containing compounds having carbon-to-carbon double bonds
• CPC Class Codes: C08G 18/6795 Unsaturated polyethers
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

Polymers whose surfaces are modified by endgroups that include amphipathic surface-modifying moieties. An amphipathic endgroup of a polymer molecule is an endgroup that contains at least two moieties of significantly differing composition, such that the amphipathic endgroup spontaneously rearranges its positioning in a polymer body to position the moiety on the surface of the body, depending upon the composition of the medium with which the body is in contact, when that re-positioning causes a reduction in interfacial energy. An example of an amphipathic surface-modifying endgroup is one that has both a hydrophobic moiety and a hydrophilic moiety in a single endgroup. For instance, a hydrophilic poly(ethylene oxide) terminated with a hydrophilic hydroxyl group is not surface active in air when the surface-modifying endgroup is bonded to a more hydrophobic base polymer. If the hydroxyl group on the oligomeric poly(ethylene oxide) is replaced by a hydrophobic methoxy ether terminus, the poly(ethylene oxide) becomes surface active in air, and allows the poly(ethylene oxide) groups to crystallize in the air-facing surface. In this example, immersion in water destroys the crystallinity as the poly(ethylene oxide) sorbs water and the hydrophobic methoxy group retreats below the surface of the polymer. Also disclosed are methods and articles of manufacture that make use of these polymers.

Claims

1. A medical device or prosthesis or packaging assembly comprising a polymer body, wherein the polymer body comprises a plurality of polymer molecules located internally within said body, at least some of which internal polymer molecules have endgroups that comprise a surface of the body, wherein the surface endgroups include at least one surface-modifying amphipathic moiety, provided that at least some of said covalently bonded surface-modifying amphipathic moieties are other than alkylene ether-terminated poly(alkylene oxides), wherein the polymer comprising the surface-modifying amphipathic moieties in the polymer body is a first polymer making up the entirety of a major portion of the body and having a weight average molecular weight in the range 5000-5,000,000 daltons, or is a second polymer, having a weight average molecular weight in the range 1000-500,000 daltons, which comprises an additive to the first polymer making up the entirety or a major portion of the body.

2. The medical device or prosthesis or packaging assembly of claim 1, wherein said first polymer has a weight average molecular weight in the range 50,000-5,000,000 daltons.

3. The device or prosthesis of claim 1, configured as an implantable medical device or prosthesis or as a non-implantable disposable or extracorporeal medical device or prosthesis or as an in vitro or in vivo diagnostic device, wherein said device or prostheses has a tissue, fluid, and/or blood-contacting surface.

4. The device or prosthesis of claim 1, wherein said polymer body comprises a dense or microporous membrane component in an implantable medical device or prosthesis or in a non-implantable disposable or extracorporeal medical device or prosthesis or as an in vitro or in vivo diagnostic device, and wherein, when said polymer body comprises a membrane component in a diagnostic device, said component contains immuno-reactants.

5. The device or prosthesis of claim 1, wherein said device or prosthesis comprises a blood gas sensor, a compositional sensor, a substrate for combinatorial chemistry, a customizable active biochip, a semiconductor-based device for identifying and determining the function of genes, genetic mutations, and proteins, a drug discovery device, an immunochemical detection device, a glucose sensor, a pH sensor, a blood pressure sensor, a vascular catheter, a cardiac assist device, a prosthetic heart valve, an artificial heart, a vascular stent, a prosthetic spinal disc, a prosthetic spinal nucleus, a spine fixation device, a prosthetic joint, a cartilage repair device, a prosthetic tendon, a prosthetic ligament, a drug delivery device from which drug molecules are released over time, a drug delivery coating in which drugs are fixed permanently to polymer endgroups, a catheter balloon, a glove, a wound dressing, a blood collection device, a blood storage container, a blood processing device, a plasma filter, a plasma filtration catheter, a device for bone or tissue fixation, a urinary stent, a urinary catheter, a contact lens, an intraocular lens, an ophthalmic drug delivery device, a male condom, a female condom, devices and collection equipment for treating human infertility, a pacemaker lead, an implantable defibrillator lead, a neural stimulation lead, a scaffold for cell growth or tissue engineering, a prosthetic or cosmetic breast implant, a prosthetic or cosmetic pectoral implant, a prosthetic or cosmetic gluteus implant, a penile implant, an incontinence device, a laparoscope, a vessel or organ occlusion device, a bone plug, a hybrid artificial organ containing transplanted tissue, an in vitro or in vivo cell culture device, a blood filter, blood tubing, roller pump tubing, a cardiotomy reservoir, an oxygenator membrane, a dialysis membrane, an artificial lung, an artificial liver, or a column packing adsorbent or chelation agent for purifying or separating blood, plasma, or other fluids.

6. A drug delivery device in accordance with claim 5, wherein the drug is complexed to amphipathic surface-modifying endgroups and is released through diffusion or wherein the drug is complexed or covalently bound to amphipathic surface-modifying endgroups that degrade and release the drug over time.

7. A packaging assembly in accordance with claim 1 comprising a polymer body, wherein the polymer body comprises a plurality of polymer molecules located internally within said body, at least some of which internal polymer molecules have endgroups that comprise a surface of the body, wherein the surface endgroups include at least one surface-modifying amphipathic moiety,

wherein the polymer comprising the surface-modifying amphipathic moieties in the polymer body is a first polymer making up the entirety of a major portion of the body and having a weight average molecular weight in the range 5000-5,000,000 daltons, or is a second polymer, having a weight average molecular weight in the range 1000-500,000 daltons, which comprises an additive to the first polymer making up the entirety or a major portion of the body, or

wherein said packaging assembly comprises a plastic bottle and eyedropper assembly containing a sterile solution, wherein said surface-modifying amphipathic moieties bind an antimicrobial agent and wherein said bound antimicrobial agents maintain the sterility of said solution.

8. A method of immobilizing biologically-active entities, including proteins, peptides, and heparins, at a surface of a polymer body, which polymer body surface comprises a surface of an interface, which method comprises the sequential steps of

contacting the polymer body surface with a medium that delivers amphipathic molecular moieties containing chemically-reactive groups, capable of binding biologically-active entities to the surface, to the polymer body surface by interaction of chemical groups, chains, or oligomers, said amphipathic molecular moieties being covalently or ionically bonded to a polymer in the body and comprising one or more chemical groups, chains, or oligomers that spontaneously assemble in the outermost monolayer of the surface of the polymer body or one or more chemical groups, chains, or oligomers that spontaneously assemble within that portion of the polymer body that is at least one monolayer away form the outermost monolayer of the polymer body surface, and

binding said biologically-active entities to said reactive groups,

wherein the polymer comprising the surface-modifying amphipathic moieties in the polymer body is a first polymer making up the entirety of a major portion of the body and having a weight average molecular weight in the range 5000-5,000,000 daltons, or is a second polymer, having a weight average molecular weight in the range 1000-500,000 daltons, which comprises an additive to the first polymer making up the entirety or a major portion of the body, or

wherein said amphipathic molecular moieties containing binding groups comprise methoxy ether-terminated polyethyleneoxide oligomers having one or more amino, hydroxyl, or carboxyl groups along the polyethyleneoxide chain.

9. The method of immobilizing biologically-active entities according to claim 8, wherein the polymer comprising the surface-modifying amphipathic moieties in the polymer body is a first polymer making up the entirety of a major portion of the body and having a weight average molecular weight in the range 5000-5,000,000 daltons, or is a second polymer, having a weight average molecular weight in the range 1000-500,000 daltons, which comprises an additive to the first polymer making up the entirety or a major portion of the body.

10. The method of immobilizing biologically-active entities of claim 8, wherein said first polymer has a weight average molecular weight in the range 50,000-5,000,000 daltons.

11. The method of immobilizing biologically-active entities according to claim 8, wherein said amphipathic molecular moieties containing binding groups comprise methoxy ether-terminated polyethyleneoxide oligomers having one or more amino, hydroxyl, carboxyl, or phosphoryl choline groups along the polyethyleneoxide chain or at the terminal position.

12. A polymeric composition of matter having the formula

A_pA′

_1-p[BCD]_nZ_qZ′

_1-q

wherein B is a polymer block, C is a polymer block that may be the same as or different from B, and D is a polymer block that may be the same as one of or different from both of B and C, n is a number from 5 through 10⁵, A is a surface active endgroup, A′

is a surface-modifying amphipathic moiety different from A, Z is a surface-modifying amphipathic moiety that may be the same as one of or different from both of A and A′

, and Z′

is a surface active endgroup that is different from Z but may be the same as one of or different from both of A and A′

, with the proviso that at least one of A′ and

Z is other than an alkylene ether-terminated poly(alkylene oxide), and p and q may be the same or different and each is a number from 0 through 1, wherein said polymeric composition of matter has a weight average molecular weight in the range 5000-5,000,000 daltons.

13. The polymeric composition of claim 12, having a weight average molecular weight in the range 50,000-5,000,000 daltons.

14. The polymeric composition of matter of claim 12, wherein A′

and Z are methoxy ether-terminated polyethylene oxides having one or more crosslinkable reactive groups or groups capable of binding biologically-active molecules along the polyethyleneoxide chain.

15. The polymeric composition of matter of claim 12, wherein D is the same as C, p is 0, q is 0, B is a polymeric block selected from the group consisting of polyurethanes, polyureas, polyamides, aromatic polyesters, aromatic polycarbonates, polystyrenes, and polyacrylates, C is a polymeric block selected from the group consisting of polyethers, aliphatic polyesters, polyisoprenes, optionally-hydrogenated polyisoprenes, polyisobutylenes, optionally-hydrogenated polybutadienes, polyethylenebutylenes, and aliphatic polycarbonates, A is an endgroup selected from the group consisting of a polydimethylsiloxanes and poly(ethylene oxides), and Z is a methoxy ether-terminated polyethylene oxide which has one or more crosslinkable reactive groups or groups capable of binding biologically-active molecules along the polyethyleneoxide chain.

16. The polymeric composition of matter of claim 12, wherein D is the same as C which in turn is the same as B, or wherein D is the same as B and wherein C is different from B, or wherein p and q are both 1 and wherein A, B, C, D, and Z are all different from one another.

17. A block copolymer molecule in accordance with claim 12, having a polyurethane hard block, a polyoxyalkylene soft block, and at least two surface-modifying amphipathic moieties, wherein at least one of said moieties is a surface active endgroup having a chain that bears multiple pendant groups of different polarity or composition than the main chain of the surface active endgroup.

18. A polymer molecule in accordance with claim 12, comprising a polyoxyalkylene chain having at least one surface-modifying amphipathic moiety, wherein said moiety is a surface active hydrophilic endgroup having a chain bearing multiple pendant hydrophobic groups, wherein the polyoxyalkylene polymer comprising the at least one surface-modifying amphipathic moiety has a molecular weight in the range 5000-5,000,000 daltons.

19. A methoxy ether-terminated polyethyleneoxide polymer of claim 18, which has a plurality of acryloxy, methacryloxy, or other crosslinkable reactive groups along a polyethyleneoxide chain.

20. A methoxy ether-terminated polyethyleneoxide polymer of claim 18, which has a plurality of amino, hydroxyl, carboxyl, or other groups capable of binding biologically-active molecules along a polyethyleneoxide chain.