U.S. patent application number 17/387350 was filed with the patent office on 2021-11-18 for functional surfaces.
The applicant listed for this patent is ORTHOBOND CORPORATION. Invention is credited to Randell Clevenger, Jordan Katz.
Application Number | 20210352903 17/387350 |
Document ID | / |
Family ID | 1000005742113 |
Filed Date | 2021-11-18 |
United States Patent
Application |
20210352903 |
Kind Code |
A1 |
Clevenger; Randell ; et
al. |
November 18, 2021 |
FUNCTIONAL SURFACES
Abstract
Articles having functional surfaces, for example antimicrobial
functional surfaces, are prepared by methods comprising
anodization. Organophosphorous compounds are deposited on a surface
by methods comprising anodization, followed by attaching functional
compounds, functional oligomers or functional polymers.
Alternatively, functional organophosphorous compounds, functional
oligomers or functional polymers are deposited on a surface by
methods comprising anodization.
Inventors: |
Clevenger; Randell; (North
Plainfield, NJ) ; Katz; Jordan; (Short Hills,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ORTHOBOND CORPORATION |
Princeton |
NJ |
US |
|
|
Family ID: |
1000005742113 |
Appl. No.: |
17/387350 |
Filed: |
July 28, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15785789 |
Oct 17, 2017 |
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17387350 |
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62408913 |
Oct 17, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C08F 220/36 20130101;
A01N 43/40 20130101; C25D 11/26 20130101; C25D 11/30 20130101; C09D
5/14 20130101; C08F 230/02 20130101; C25D 11/34 20130101; C08F
2438/01 20130101; A01N 57/16 20130101; C09D 143/02 20130101; C09D
133/14 20130101 |
International
Class: |
A01N 57/16 20060101
A01N057/16; C08F 220/36 20060101 C08F220/36; C09D 133/14 20060101
C09D133/14; C25D 11/26 20060101 C25D011/26; C09D 5/14 20060101
C09D005/14; A01N 43/40 20060101 A01N043/40; C09D 143/02 20060101
C09D143/02; C08F 230/02 20060101 C08F230/02 |
Claims
1.-28. (canceled)
29. A method for preparing an article having a functional surface,
the method comprising: preparing a solution including an
organophosphorous compound; placing the article having a metal
surface in the solution; and depositing the organophosphorous
compound on the metal surface via anodization, wherein the
organophosphorous compound comprises an organophosphonic acid, an
organophosphinic acid, or an organophosphoric acid, wherein the
organophosphorous compound is modified by attaching one or more
functional compounds, functional oligomers, or functional polymers
to the organophosphorous layer to form a functional layer, and
wherein the one or more functional compounds, functional oligomers,
or functional polymers comprise a quaternary ammonium salt, a
pyridinium salt, or a phosphonium salt.
30. The method of claim 29, wherein an organo group of the
organophosphorous compound is a C.sub.2-C.sub.12 hydrocarbyl
group.
31. The method of claim 29, wherein the metal surface comprises a
surface comprising titanium, a titanium alloy, stainless steel, a
cobalt chrome alloy, nickel, molybdenum, tantalum, zirconium,
magnesium, or an alloy containing one or more of nickel,
molybdenum, tantalum, zirconium, and magnesium.
32. The method of claim 29, wherein the metal surface comprises a
titanium surface.
33. The method of claim 29, wherein an organo group of the
organophosphorous compound is reacted with a diamine or an
aminoalcohol to provide a distal amine which is subsequently
quaternized to provide the functional layer comprising a quaternary
ammonium compound.
34. The method of claim 29, wherein the organophosphorous compound
is an unsaturated organophosphorous monomer, and wherein the
unsaturated organophosphorous monomer is reacted with an
unsaturated functional monomer to form the functional layer
comprising one or more of the functional oligomers or the
functional polymers.
35. The method of claim 34, wherein the unsaturated functional
monomer is an antimicrobial monomer optionally comprising an
ammonium salt, a pyridinium salt, or a phosphonium salt.
36. The method of claim 35, wherein the antimicrobial monomer
comprises a methacryloyloxydodecylpyridinium salt,
diallyldimethylammonium chloride, a
methacryloyloxyhexadecylpyridinium salt, a
methacryloyloxydecyltriethylammonium salt, a
4-hexadecylmethacryloyloxyethylpyridinium salt, a
methacryloyloxyethylhexadecylbipyridinium salt, a
methacryloyloxydodecyltrimethylphosphonium salt, a
methacryloyloxyoctadecyltriethylphosphonium salt, a
4-methacryloyloxyethyldodecylpyrldinium salt, a
di(4-vinylbenzyl)hexadecylmethylammonium salt, a
di(methacryloyloxyethyl)dodecylmethylammonium salt, or
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halide.
37. The method of claim 34, wherein the unsaturated functional
monomer comprises vinyl phosphonic acid, allyl phosphonic acid,
2-methyl allylphosphonic acid, 2-butenyl phosphonic acid, allyl
phosphate, or ethyleneglycol methacrylatephosphate.
38. The method of claim 29, wherein in the modifying step, atom
transfer radial polymerization of an unsaturated functional monomer
is utilized to attach one or more of the functional oligomers or
the functional polymers to the organophosphorous layer to form the
functional layer.
39. The method of claim 38, wherein the unsaturated functional
monomer comprises a methacryloyloxydodecylpyridinium salt,
diallyldimethylammonium chloride, a
methacryloyloxyhexadecylpyridinium salt, a
methacryloyloxydecyltriethylammonium salt, a
4-hexadecylmethacryloyloxyethylpyridinium salt, a
methacryloyloxyethylhexadecylbipyridinium salt, a
methacryloyloxydodecyltrimethylphosphonium salt, a
methacryloyloxyoctadecyltriethylphosphonium salt, a
4-methacryloyloxyethyldodecylpyrldinium salt, a
di(4-vinylbenzyl)hexadecylmethylammonium salt, a
di(methacryloyloxyethyl)dodecylmethylammonium salt, or
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halide.
40. The method of claim 29, wherein the organophosphorous compound
is covalently bonded to an oxide layer through phosphinate,
phosphonate, or phosphate moieties.
41. The method of claim 29, wherein the depositing step comprises:
connecting the metal surface to a positive terminal of an electric
power supply; connecting a counter electrode placed in the solution
to a negative electrode of the power supply; and applying a voltage
for a predetermined period.
42. The method of claim 41, wherein the voltage ranges from about 1
to about 400 volts.
43. The method of claim 41, wherein the predetermined period ranges
from about 1 to about 60 seconds.
44. The method of claim 29, wherein the article is a medical
device.
45. The method of claim 29, wherein the solution is partially
aqueous.
46. The method of claim 45, wherein the solution comprises an
alcohol.
47. An article having a functional surface, the article prepared by
the method of claim 29.
48. An article, comprising: a metal surface having a functional
layer disposed thereon, wherein the functional layer comprises one
or more functional compounds, functional oligomers, or functional
polymers, wherein the one or more functional compounds, functional
oligomers, or functional polymers comprise a quaternary ammonium
salt, a pyridinium salt, or a phosphonium salt, and an
organophosphorous compound deposited on the metal surface, wherein
one or more functional compounds, functional oligomers, or
functional polymers are attached to the organophosphorous
compound.
49. The article of claim 48, wherein the organophosphorous compound
comprises an organophosphonic acid, an organophosphinic acid, or an
organophosphoric acid.
50. The article of claim 48, wherein an organo group of the
organophosphorous compound is a C.sub.2-C.sub.12 hydrocarbyl
group.
51. The article of claim 48, wherein the metal surface comprises a
surface comprising titanium, a titanium alloy, stainless steel, a
cobalt chrome alloy, nickel, molybdenum, tantalum, zirconium,
magnesium, or an alloy containing one or more of nickel,
molybdenum, tantalum, zirconium, and magnesium.
52. The article of claim 48, wherein the metal surface comprises a
titanium surface.
53. The article of claim 48, an organo group of the
organophosphorous compound is reacted with a diamine or an
aminoalcohol to provide a distal amine which is subsequently
quaternized to provide the functional layer comprising the
quaternary ammonium compound.
54. The article of claim 48, wherein the organophosphorous compound
is an unsaturated organophosphorous monomer, and wherein the
unsaturated organophosphorous monomer is reacted with an
unsaturated functional monomer to form the functional layer
comprising one or more of the functional oligomers or the
functional polymers.
55. The article of claim 54, wherein the unsaturated functional
monomer is an antimicrobial monomer optionally comprising an
ammonium salt, a pyridinium salt, or a phosphonium salt.
56. The article of claim 55, wherein the antimicrobial monomer
comprises a methacryloyloxydodecylpyridinium salt,
diallyldimethylammonium chloride, a
methacryloyloxyhexadecylpyridinium salt, a
methacryloyloxydecyltriethylammonium salt, a
4-hexadecylmethacryloyloxyethylpyridinium salt, a
methacryloyloxyethylhexadecylbipyridinium salt, a
methacryloyloxydodecyltrimethylphosphonium salt, a
methacryloyloxyoctadecyltriethylphosphonium salt, a
4-methacryloyloxyethyldodecylpyrldinium salt, a
di(4-vinylbenzyl)hexadecylmethylammonium salt, a
di(methacryloyloxyethyl)dodecylmethylammonium salt, or
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halide.
57. The article of claim 48, wherein the organophosphorous compound
is covalently bonded to an oxide layer through phosphinate,
phosphonate, or phosphate moieties.
58. The article of claim 48, wherein the organophosphorous compound
is deposited on the metal surface via anodization.
59. The article of claim 48, wherein the article is a medical
device.
Description
[0001] The invention relates to articles having functional surfaces
and methods of preparing the surfaces. In some embodiments, the
functional surfaces are antimicrobial functional surfaces.
BACKGROUND
[0002] The need for control of infection is a vital concern for
many, from public health officials, hospital and school
administrators and the like, to private citizens. Typically,
control of infection can be achieved by the topical application of
disinfectants, antiseptics, antibacterials and the like to surfaces
likely to be contacted by infectious agents. Common disinfectants
only have a short-term effect and need to be reapplied
constantly.
[0003] Antibiotics can be administered to stop infection in
individuals. However, such administration is not always effective.
Numerous medical applications, including orthopedic, trauma, spine
and general surgery applications, where the potential for infection
is a serious concern, are not amenable to simple application of an
antiseptic or treatment with antibiotics. For example, infection
can be a devastating complication of a total joint arthroplasty
(TJA). While some infections may be treated by antibiotic
suppression alone, more aggressive therapies, such as two-stage
re-implantation, are often required. TJA infections occur when
bacteria colonize the surface of the implant. These species then
form a resistant biofilm on the implant surface, which nullifies
the body's normal antibody response.
[0004] External fixation devices provide temporary and necessary
rigid constraints to facilitate bone healing. However, patients
risk pin-tract infection at the site extending from the skin-pin
interface to within the bone tissue. Such complications can result
in sepsis and osteomyelitis, which could require sequestrectomy for
correction. Even the most stringent pin-handling and post-procedure
protocols have only a limited effect. Studies have shown that such
protocols do not reduce the chance of infection.
[0005] In minimally-invasive spine fusions, pedicle screws are
first implanted in the bone of the vertebrae, and then rods are
fixed into the heads of the screws to immobilize and stabilize the
affected segments. Screws and rods pass through the patient's skin
into the spine space via a cannulated channel. As in external
fixation, screws and rods are also prone to pin-tract infections;
due to the implants' pathway through the skin, the chance of
contacting and/or passing harmful bacteria is greatly
increased.
[0006] Catheters and shunts are placed in any number of body
cavities and vessels to facilitate the injection, drainage or
exchange of fluids. Infections are common in catheter placements
and are largely dependent on how long the patient is
catheterized.
[0007] There is a need for anti-infective surfaces that may be
employed in locations particularly susceptible to hosting
infectious agents, such as public places, common areas of
buildings, fixtures and the like. Moreover, there is a need for
articles and materials with anti-infective surfaces, such as
medical devices including implants, screws, rods, pins, catheters,
stents, surgical tools and the like which could prevent infections
by proactively killing bacteria that attempt to colonize the device
surface both pre- and post-operatively.
SUMMARY
[0008] Disclosed in certain embodiments is a process for preparing
an article having a functional surface, the process comprising
depositing water soluble organophosphorous compounds on a surface
of an article (e.g., a medical device) to form an organophosphorous
layer and attaching one or more functional compounds or functional
oligomers or polymers to the organophosphorous layer to form a
functional layer, wherein the depositing of the organophosphorous
compounds on the article surface comprises anodization.
[0009] Also disclosed in certain embodiments is a process for
preparing an article having a functional surface, the process
comprising depositing functional organophosphorous compounds or
functional oligomers or polymers on a surface of an article (e.g.,
a medical device) to form a functional layer, wherein the
depositing of the functional organophosphorous compounds, oligomers
or polymers on the article surface comprises anodization.
[0010] Also disclosed in certain embodiments is an article (e.g., a
medical device) that is prepared according to any of the processes
disclosed herein.
[0011] Other embodiments of the disclosure are directed to methods
of treating patients using the medical devices disclosed
herein.
DETAILED DISCLOSURE
[0012] The functional layer comprises a water soluble
organophosphorous layer attached to an article surface and
functional compounds or functional oligomers or polymers attached
(e.g., covalently bonded) to the organophosphorous layer. In
certain embodiments, the functional layer comprises an oxide layer,
an organophosphorous layer attached to the oxide layer through,
e.g., phosphinate, phosphonate or phosphate moieties and functional
compounds, functional oligomers or functional polymers attached
(e.g., covalently bonded) to the organophosphorous layer through
the organo groups.
[0013] The anodization process utilized in the present disclosure
may form an oxide layer on a metal surface and/or may form an oxide
layer on a native oxide layer as the organophosphorous compounds
are deposited. The anodization process may also form an oxide layer
on a synthetic oxide layer. Synthetic oxide layers include oxide,
alkoxide and mixed oxide/alkoxide layers.
[0014] In some embodiments, the organo group may be a
C.sub.2-C.sub.12 hydrocarbyl group, a C.sub.2-C.sub.9 hydrocarbyl
group, or a C.sub.2-C.sub.6 hydrocarbyl group allowing the
requirement of water solubility of the organophosphorous compound.
Hydrocarbyl is any hydrocarbon containing group, for example
straight or branched chain alkyl or alkenyl which may be
interrupted by or substituted by one or more heteroatom-containing
groups or aryl groups, for instance interrupted by one or more
--O--, --NH-- or --C(O)O-- groups and/or substituted by one or more
hydroxyl, carboxylic, amino, thiol, phosphonate or aryl groups.
Aryl includes phenyl. Hydrocarbyl also includes aryl.
[0015] In certain embodiments, the present articles prepared by the
anodization process of the disclosure comprise metal surfaces.
Suitable metals include but are not limited to titanium, titanium
alloys, stainless steel, cobalt chrome alloys, nickel, molybdenum,
tantalum, zirconium, magnesium and alloys containing nickel,
molybdenum, tantalum, zirconium, magnesium, mixtures thereof and
alloys thereof.
[0016] Metals may have native oxide surfaces or may be imparted
with a synthetic oxide surface. Synthetic oxide surfaces are for
instance prepared by reacting a surface with a metal alkoxide as
described in U.S. Pat. No. 6,645,644 and U.S. Pub. No.
2010/0215643, optionally followed by full or partial hydrolysis.
Suitable metal oxides include tantalum ethoxide, titanium
tetra-t-butoxide and zirconium tetra-t-butoxide. Present synthetic
oxide surfaces include metal oxides, metal alkoxides and mixed
metal oxide/alkoxides. In certain embodiments, the metal surfaces
may be cleaned to remove or partially remove any oxide surface
prior to anodization or alternatively, may be subject to the
anodization process with a native or synthetic oxide surface.
[0017] Functional compounds, functional oligomers and functional
polymers include but are not limited to one or more of
anti-infective agents, antileukotrienes or leukotriene receptor
antagonists, antihistamines, antiseptics, anti-inflammatory agents
including steroidal anti-inflammatory agents and non-steroidal
anti-inflammatory agents, decongestants, mucolytics,
anticholinergics, mast cell stabilizers, anti-thrombotic agents,
genetic active agents, proteins, amino acids, anabolics,
analgesics, drugs and the like.
[0018] Of particular interest are functional anti-infective agents.
Anti-infective agents include antimicrobial compounds,
anti-fungals, antibiotics, non-antibiotic antimicrobials,
anti-virals and antiseptics.
[0019] Antimicrobial agents that can be utilized in the present
disclosure include but are not limited to antiamebics, arsthinol,
bialamicol, carbarsone, cephaeline, chlorbetamide, chloroquine,
chlorphenoxamide, chlortetracycline, dehydroemetine,
dibromopropamidine, diloxanide, diphetarsone, emetine, fumagillin,
glaucarubin, glycobiarsol, 8-hydroxy-7-iodo-5-quinoline-sulfonic
acid, iodochlorhydroxyquin, iodoquinol, paromomycin, phanquinone,
polybenzarsol, propamidine, quinfamide, scenidazole, sulfarside,
teclozan, tetracycline, thiocarbamizine, thiocarbarsone,
tinidazole; antibiotics, e.g. amino-glycosides (such as amikacin,
apramycin, arbekacin, bambermycins, butirosin, dibekacin,
dihydrostreptomycin, fortimicin(s), gentamicin, isepamicin,
kaniamycin, micronomicin, neomycin, neomycin undecylenate,
netilmicin, paromomycin, ribostamycin, sisomicin, spectinomycin,
streptomycin, tobramycin, trospectomycin, and the like),
amphenicols (such as azidamfenicol, chloramphenicol, florfenicol,
thiamphenicol, and the like), ansamycins (such as rifamide,
rifampin, rifamycin, rifapentine, rifaximin, and the like),
.beta.-lactams (e.g., carbacephems, loracarbef, carbapenems (such
as biapenem, imipenem, meropenem, panipenem, and the like),
cephalosporins (such as cefaclor, cefadroxil, cefamandole,
cefatrizine, cefazedone, cefazolin, cefcapene povoxil, cefclidin,
cefdinir, cefditoren, cefepime, cefetamet, cefixime, cefinenoxine,
cefodizime, cefonicid, cefoperazone, ceforanide, cefotaxime,
cefotiam, cefozopran, cefpimizole, cefpiramide, cefpirome,
cefpodoxime proxetil, cefprozil, cefroxadine, cefsulodin,
ceftazidime, cefteram, ceftezole, ceftibuten, ceftizoxime,
ceftriaxone, cefuroxime, cefuzonam, cephacetrile sodium,
cephalexin, cephaloglycin, cephaloridine, cephalosporin,
cephalothin, cephapirin sodium, cephradine, pivcefalexin, and the
like), cephamycins (such as cefbuperazone, cefmetazole, cefminox,
cefotetan, cefoxitin, and the like), monobactams (such as
aztreonam, carumonam, tigemonam, and the like), oxacephens (such as
flomoxef, moxalactam, and the like), penicillins (such as
amdinocillin, amdinocillin pivoxil, amoxicillin, ampicillin,
apalcillin, aspoxicillin, azidocillin, azlocillin, bacampicillin,
benzylpenicillic acid, benzylpenicillin sodium, carbenicillin,
carindacillin, clometocillin, cloxacillin, cyclacillin,
dicloxacillin, epicillin, fenbenicillin, floxacillin, hetacillin,
lenampicillin, metampicillin, methicillin sodium, mezlocillin,
naacillin sodium, oxacillin, penamecillin, penethamate hydriodide,
penicillin G benethamine, penicillin G benzathine, penicillin G
benzhydrylamine, penicillin G calcium, penicillin G hydrabamine,
penicillin G potassium, penicillin G procaine, penicillin N,
penicillin 0, penicillin V, penicllin V benzathine, penicillin V
hydrabamine, penimepicycline, phenethicillin potassium,
piperacillin, pivampicillin, propicillin, quinacillin,
sulbenicillin, sultamicillin, talampicillin, temocillin,
ticarcillin, and the like), ritipenem, lincosamides (such as
clindamycin, lincomycin, and the like), macrolides (such as
azithromycin, capbomycin, clarithromycin, dirithromycin,
erythromycin, erythromycin acistrate, erythromycin estolate,
erythromycin glucoheptonate, erythromycin lactobionate,
erythromycin propionate, erythromycin stearate, Josamycin,
leucomycins, midecamycins, miokamycin, oleandomycin, primycin,
rokitamycin, rosaramicin, roxithromycin, spiramycin,
troleandomycin, and the like), polypeptides (such as amphomycin,
bacitracin, capreomycin, colistin, enduracidin, enviomycin,
fusafungine, gramicidin s, gramicidin(s), mikamycin, polymyxin,
pristinamycin, ristocetin, teicoplanin, thiostrepton,
tuberactinomycin, tyrocidine, tyrothricin, vancomycin, viomycin,
virginiamycin, zinc bacitracin, and the like), tetracyclines (such
as apicycline, chlortetracycline, clomocycline, demeclocycline,
doxycycline, guamecycline, lymecycline, meclocycline, methacycline,
minocycline, oxytetracycline, penimepicycline, pipacycline,
rolitetracycline, sancycline, tetracycline, and the like),
cycloserine, mupirocin, tuberin; synthetic antibacterial agents,
e.g. 2,4-diaminopyrimidines (such as brodimoprim, textroxoprim,
trimethoprim, and the like), nitrofurans (such as furaltadone,
furazolium chloride, nifuradene, nifuratel, nifurfoline,
nifurpirinol, nifurprazine, nifurtoinol, nitrofirantoin, and the
like), quinolones and analogs (such as cinoxacin, ciprofloxacin,
clinafloxacin, difloxacin, enoxacin, fleroxacin, flumequine,
grepafloxacin, lomefloxacin, miloxacin, nadifloxacin, nadilixic
acid, norflaxacin, ofloxacin, oxolinic acid, pazufloxacin,
pefloxacin, pipemidic acid, piromidic acid, rosoxacin, rufloxacin,
sparfloxacin, temafloxacin, tosufloxacin, trovafloxacin, and the
like), sulfonamides (such as acetyl sulfamethoxpyrazine,
benzylsulfamide, chloramine-B, chloramine-T, dichloramine T,
N2-formylsulfisomidine, N4- -d-glucosylsulfanilamide, mafenide,
4'-(methylsulfamoyl)sulfanilanilide, noprylsulfainide,
phthalylsulfacetamide, phthalylsulfathiazole, salazosulfadimidine,
succinylsulfathiazole, sulfabenzamide, sulfacetamide,
sulfachlorpyridazine, sulfachrysoidine, sulfacytine, sulfadiazine,
sulfadicramide, sulfadimethoxine, sulfadoxine, sulfaethidole,
sulfaguanidine, sulfaguanol, sulfalene, sulfaloxic, sulfamerazine,
sulfameter, sulfamethazine, sulfamethizole, sulfamethomidine,
sulfamethoxazole, sulfamethoxypyridazine, sulfametrole,
sulfamidochrysoidine, sulfamoxole, sulfanilamide,
4-sulfanilamidosalicylic acid, n4-sulfanilylsulfanilamide,
sulfanilylurea, n-sulfanilyl-3,4-xylamide, sulfanitran,
sulfaperine, sulfaphenazole, sulfaproxyline, sulfapyrazine,
sulfapyridine, sulfasomizole, sulfasymazine, sulfathiazole,
sulfathiourea, sulfatolamide, sulfisomidine, sulfisoxazole, and the
like), sulfones (such as acedapsone, acediasulfone, acetosulfone
sodium, dapsone, diathymosulfone, glucosulfone sodium, solasulfone,
succisulfone, sulfanilic acid, p-sulfanilylbenzylamine, sulfoxone
sodium, thiazolsulfone, and the like), clofoctol, hexedine,
methenamine, methenamine anhydromethylenecitrate, methenamine
hippurate, methenamine mandelate, methenamine sulfosalicylate,
nitroxoline, taurolidine, xibomol, and the like; leprostatic
antibacterial agents, such as acedapsone, acetosulfone sodium,
clofazimine, dapsone, diathymosulfone, glucosulfone sodium,
hydnocarpic acid, solasulfone, succisulfone, sulfoxone sodium, and
the like, antifungal agents such as allylamines butenafine,
naftifine, terbinafine, imidazoles (e.g., bifonazole, butoconazole,
cholordantoin, chlormidazole, cloconazole, clotrimazole, econazole,
enilconazole, fenticonazole, flutrimazole, isoconazole,
Ketoconazole, lanoconazole, miconazole, omoconazole, oxiconazole
nitrate, sertaconazole, sulconazole, tioconazole, and the like),
thiocarbamates (e.g., tolcilate, tolindate, tolnaftate, and the
like), triazoles (e.g., fluconazole, itraconazole, saperconazole,
terconazole, and the like), acrisorcin, amorolfine, biphenamine,
bromosalicylchloranilide, buclosamide, calcium propionate,
chlorphenesin, ciclopirox, cloxyquin, coparaffinate, diamthazole
dihydrochloride, exalamide, flucytosine, halethazole, hexetidine,
loflucarban, nifuratel, potassium iodide, propionic acid,
pyrithione, salicylanilide, sodium propionate, sulbentine,
tenonitrozole, triacetin, ujothion, undecylenic acid, zinc
propionate, etc.; or the like; analogs/derivatives thereof; salts
thereof; or combinations thereof.
[0020] Other antimicrobial agents useful in the present invention
include, but are not limited to, Q-lactamase inhibitors (e.g.
clavulanic acid, sulbactam, tazobactam, and the like);
chldramphenicols (e.g. azidamphenicol, chloramphenicol,
thiaphenicol, and the like); fusidic acid; synthetic agents such as
trimethoprim, (optionally in combination with sulfonamides)
nitroimidazoles (e.g., metronidazole, tinidazole, nimorazole, and
the like), and the like; antimycobacterial agents (e.g.,
capreomycin, clofazimine, dapsone, ethambutol, isoniazid,
pyrazinamide, rifabutin, rifampicin, streptomycin, and the like);
antiviral agents (e.g., acryclovir, amantadine, azidothymidine,
ganciclovir, idoxuridine, tribavirin, trifluridine, vidarabine, and
the like); interferons; antiseptic agents (e.g., chlorhexidine,
gentian violet, octenidine, povidone iodine, quaternary ammonium
compounds, silver sulfadiazine, triclosan, and the like); or the
like; analogs/derivatives thereof; salts thereof; or combinations
thereof.
[0021] Antimicrobial functional groups are also taught for instance
in U.S. Pub. No. 2006/0194008.
[0022] Functional compounds, functional oligomers and functional
polymers contain functional moieties, for instance antimicrobial
compounds contain antimicrobial moieties. Antimicrobial moieties
include for example chlorhexidine, ammonium salts, pyridinium salts
and phosphonium salts.
[0023] Ammonium, pyridinium and phosphonium salts are
hydrocarbyl-substituted at nitrogen or phosphorous. For example
ammonium salts are quaternary alkyl ammonium salts where the alkyl
groups are the same or different and are for example methyl, ethyl,
propyl, butyl, hexyl, heptyl or octyl.
[0024] Anions paired with the ammonium, pyridinium and phosphonium
cations include, for example, halides, F.sup.-, Cl.sup.-, Br.sup.-
or I.sup.-; anions of inorganic acids such as PO.sub.4.sup.3-,
HPO.sub.3.sup.2-, H.sub.2PO.sub.4.sup.-, Na.sub.2PO.sub.4.sup.-,
HSO.sub.4.sup.-, KSO.sub.4.sup.-, NO.sub.3.sup.-, etc.; anions of
organic acids such as methanesulfonic acid, acetic acid, propionic
acid, benzoic acid, phenol, p-toluenesulfonic acid, maleic acid,
oxalic acid, citric acid, etc. Anions also include
AlF.sub.6.sup.3-, AsFe.sup.-, BF.sub.4.sup.-, BiCl.sub.4.sup.2-,
BiCl.sub.3.sup.2-, SbCl.sub.6.sup.-, SbF.sub.6.sup.-,
PF.sub.6.sup.-, GaCl.sub.4.sup.-, InF.sub.4.sup.-,
TiF.sub.6.sup.2-, ZrF.sub.6.sup.-, FeI.sub.4.sup.-,
SnCl.sub.6.sup.-, etc.
[0025] Depositing organophosphorous compounds on a surface may
comprise reacting phosphinic acid, phosphonic acid or phosphoric
acid groups with an oxide layer on the surface. Such reaction
results in the attachment (e.g., by covalent bonding) of
phosphinate, phosphonate or phosphate moieties to the surface.
[0026] An article surface may be coated with a continuous oxide
layer, i.e., a layer that is formed by a matrix of individual
molecules that are chemically bonded and linked to each other, as
opposed to individual molecules covering the surface. For example,
metal alkoxide molecules may be bonded together on at least a
portion of a surface to form a continuous layer.
[0027] An article surface may be coated with an oxide layer in a
pattern or micropattern, for example via employing photoresist
techniques. Thus, the functional layer may be applied in a pattern
or micropattern.
[0028] The present functional layers are prepared via a process
comprising anodization or electrochemical deposition of water
soluble organophosphinic, organophosphonic or organophosphoric
acids with an article. This results in the formation of an
organophosphorous layer where the phosphinic, phosphonic or
phosphoric acid moieties are attached to an oxide surface (via
phosphinate, phosphonate or phosphate groups).
[0029] Anodization techniques that can be modified in view of the
present disclosure are described for example in U.S. Pat. No.
5,126,210. For example, a metal article or metal surfaced article
may optionally be cleaned with for example a mineral acid or a base
to remove any surface oxides. The cleaned article may be placed in
an aqueous solution or partially aqueous solution containing a
suitable organophosphinic, organophosphonic or organophosphoric
acid at a temperature e.g., of from about 5.degree. C. to about
60.degree. C. The metal surface is connected to the positive
terminal of an electric power supply. A counter electrode is
connected to the negative electrode of the power supply. The metal
surface is then anodized at a voltage, e.g., of from about 1 to
about 400 volts, for instance from about 30 to about 90 volts,
depending on the desired thickness of the formed organophosphorous
layer. Time periods may vary for example from about 1 second to
about 60 seconds or more or from about 1 second to about 30 seconds
or more.
[0030] Suitable water soluble organophosphorous compounds include
organophosphinic, organophosphonic or organophosphoric acids
containing as an organo group a C.sub.2-C.sub.12 hydrocarbyl group,
a C.sub.2-C.sub.9 hydrocarbyl group, for example a C.sub.2-C.sub.6
hydrocarbyl group. Hydrocarbyl is any hydrocarbon containing group,
for example straight or branched chain alkyl or alkenyl which may
be interrupted by or substituted by one or more
heteroatom-containing groups or aryl groups, for instance
interrupted by one or more --O--, --NH-- or --C(O)O-- groups and/or
substituted by one or more hydroxyl, carboxylic, amino, thiol,
phosphonate or aryl groups. Aryl includes phenyl. C.sub.2-C.sub.6
includes C.sub.2, C.sub.3, C.sub.4, C.sub.5 and C.sub.6.
[0031] Suitable organophosphorous compounds include for example
hydroxyalkylphosphonic acid and mercaptoalkylphosphonic acid. Such
suitable compounds provide a distal reactive group, in this case
hydroxy or thiol. The reactive group may be used in a further
reaction to incorporate a functional moiety, for instance an
antimicrobial moiety. Such suitable compounds may be "ethoxylated"
or "propoxylated", that is for example, reacting an
organophosphorous compound where the organo group contains an
amino, hydroxy or thiol substituent with ethylene oxide and/or
propylene oxide may provide an organophosphorous compound
containing repeating ethoxy or propoxy units and a distal reactive
hydroxy group.
[0032] For example, an organophosphorous compound where the organo
group contains an amino, hydroxy or thiol substituent may be
reacted with a cross-coupling reagent such as (p-nitrophenyl)
chloroformate, followed by reaction with a diamine or
amino-alcohol. The free remaining distal amino group then may be
quaternized to provide a quaternary ammonium moiety.
[0033] Diamines include 1,12-diaminododecane, 1,11-diaminoundecane,
1,10-diaminodecane, 1,8-diaminooctane, 1,9-diaminononane,
4,9-dioxa-1,12-dodecanediamine, hexamethylenediamine and the like.
Aminoalcohols include ethanolamine and the like.
[0034] Therefore, "attaching" one or more functional compounds
includes attaching a compound and further modifying the attached
compound to provide the functional attached compound; and providing
the functional layer.
[0035] The hydrocarbyl group containing one or more, for instance 1
to 3 nucleophilic substituents is also suitable for reacting with
an atom transfer radical polymerization (ATRP) initiator, for
example substituents selected from hydroxyl, amino and thiol.
[0036] In this case, an organophosphinic, organophosphonic or
organophosphoric acid where the organo group contains a substituent
suitable for reacting with an ATRP initiator is attached to an
article surface. Suitable substituents of the organo group of
organophosphorous compounds are in particular nucleophilic
substituents.
[0037] In present ATRP processes, the organophosphinic,
organophosphonic or organophosphoric acid compounds containing
suitable substituents are attached to a surface via anodization
processes as described above. The organophosphorous layer is then
reacted with an ATRP initiator such as alpha-bromoisobutyryl
bromide. This provides an initiator organophosphorous layer. In the
case of a hydroxyl substituent, this results in formation of a
--O(CO)C(CH.sub.3).sub.2Br substituent on the organo group.
Following this, ATRP is performed with unsaturated functional
monomers in the presence of an ATRP catalyst.
[0038] In certain embodiments, the ATRP process provides articles
having a surface having a functional layer disposed thereon, the
functional layer comprising an organophosphorous layer and
functional oligomers or polymers bonded to the organophosphorous
layer.
[0039] In certain embodiments, the initiator layer may contain
--(CO)C(CH.sub.3).sub.2Br initiator substituents on a plurality of
the organo groups, that is, on at least some of the organo groups.
Examples of initiator substituents in the initiator layer include
--O(CO)C(CH.sub.3).sub.2Br, --NH(CO)C(CH.sub.3).sub.2Br and
--S(CO)C(CH.sub.3).sub.2Br.
[0040] ATRP catalyst systems include for example CuBr and a
polyamine ligand, such as pentamethyldiethylenetriamine,
tris(2-pyridylmethyl)amine or
tris[2-(dimethylamino)ethyl]amine.
[0041] Present functional layers prepared via ATRP may be
characterized as containing functional oligomers or polymers
containing a residual ATRP initiator moiety such as
--O(CO)C(CH.sub.3).sub.2--, --NH(CO)C(CH.sub.3).sub.2-- or
--S(CO)C(CH.sub.3).sub.2--.
[0042] Accordingly, disclosed in certain embodiments is an article
having a functional surface, the article comprising a surface
having a functional layer disposed thereon, the functional layer
comprising an organophosphorous layer and functional oligomers or
polymers bonded to the organophosphorous layer, where the
functional oligomers or polymers contain a
--O(CO)C(CH.sub.3).sub.2--, --NH(CO)C(CH.sub.3).sub.2-- or a
--S(CO)C(CH.sub.3).sub.2-- moiety.
[0043] In another embodiment, the anodization process may comprise
depositing unsaturated organophosphorous compounds on an article
surface to provide an unsaturated organophosphorous layer. The
unsaturated organophosphorous layer may be reacted with one or more
functional unsaturated monomers by methods comprising free-radical
polymerization, anionic polymerization or cationic
polymerization.
[0044] This process provides articles having a surface having a
functional layer disposed thereon, the functional layer comprising
an organophosphorous layer and functional oligomers or polymers
bonded to the organophosphorous layer.
[0045] As used herein, the term unsaturated means ethylenically or
propargylly unsaturated.
[0046] Functional oligomers and polymers contain functional monomer
units. Monomer units are reacted or "polymerized" monomers.
Antimicrobial functional monomers are described for instance in
U.S. Pat. No. 6,355,704. Antimicrobial oligomers, polymers,
monomers and monomer units contain antimicrobial moieties.
Antimicrobial moieties include for example ammonium salts,
pyridinium salts and phosphonium salts.
[0047] Present functional monomers contain for example ethylenic
unsaturation. For instance, suitable antimicrobial monomers include
but are not limited to (meth)acryloyloxydodecylpyridinium salts,
(meth)acryloyloxyhexadecylpyridinium salts,
(meth)acryloyloxydecyltriethylammonium salts,
4-hexadecyl(meth)acryloyloxyethylpyridinium salts,
(meth)acryloyloxyethyl-hexadecylbipyridinium salts,
(meth)acryloyloxydodecyltrimethylphosphonium salts,
(meth)acryloyloxyoctadecyltriethylphosphonium salts,
4-(meth)acryloyloxy-ethyldodecylpyrldinium salts,
di(4-vinylbenzyl)hexadecylmethylammonium salts,
di((meth)acryloyloxyethyl)dodecylmethylammonium salts and
(meth)acryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halides. The term "(meth)acryl" means acryl or methacryl.
[0048] For example, suitable antimicrobial monomers include but are
not limited to methacryloyloxydodecylpyridinium bromide (MDPB),
diallyldimethylammonium chloride (DADMAC),
methacryloyloxyhexedecylpyridinium chloride (MHPC),
4-hexadecyhnethacryloyloxyethylpyridinium chloride (HMPC),
methacryloyloxyethylhexadecylbipyridinium dichloride (MHBP),
methacryloyloxyoctadecyltrimethylphosphonium chloride (DMPC),
methacryloyloxyoctadecyltriethylphosphonium acetate (OEPA),
4-methacryloyloxyethyldodecylpyridinium chloride (MEDP),
di(4-vinylbenzyl)hexadecylmethylammonium methylsulfate (VHMS),
di(methacryloyloxyethyl)dodecylmethylammonium chloride (DDMC) and
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
bromide (BMPS).
[0049] In certain embodiments, suitable organophosphinic,
organophosphonic and organophosphoric acids contain organo groups
having ethylenic or propargic unsaturation and may be referred to
as organophosphorous unsaturated monomers.
[0050] Monomers having ethylenic unsaturation contain for example a
vinyl group, allyl group, acrylic group or methacrylic group.
[0051] Suitable unsaturated organophosphorous monomers include
organophosphinic, organophosphonic and organophosphoric acids such
as vinyl phosphonic acid, allyl phosphonic acid, 2-methyl
allylphosphonic acid, 2-butenyl phosphonic acid, allyl phosphate,
ethyleneglycol methacrylatephosphate, dimethyl vinylphosphonate,
diethyl allylphosphonate, bis(2-chloroethyl) vinylphosphonate,
diethyl 3-butenylphosphonate, allyl phosphonic dichloride and
allylphosphinic acid.
[0052] In certain embodiments, attachment of unsaturated
organophosphinic, organophosphonic or organophosphoric acid monomer
compounds to the article surface provides an organophosphorous
layer having ethylenic or propargic unsaturation (an unsaturated
organophosphorous layer).
[0053] In certain embodiments, the surface containing the
unsaturated organophosphorous layer, where the organo group
contains unsaturation, is reacted with unsaturated functional
monomers for instance via a process comprising free-radical,
anionic or cationic polymerization. Conditions and reagent levels
are chosen to provide a desired level of oligomerization or
polymerization.
[0054] Free-radical polymerization includes thermal techniques with
the use of a free-radical initiator. Present polymerization methods
also include photopolymerization. For example present methods
comprise exposing a surface containing an unsaturated
organophosphorous layer to a polymerizable functional monomer and
ultraviolet (UV) and/or visible light. An article surface
containing an unsaturated organophosphorous layer may be coated
with a suitable polymerizable functional monomer followed by
exposure to UV and/or visible light. A photoinitiator may be
employed. Photoinitiators include acylphosphine oxides and
alpha-hydroxyketones as described for instance in U.S. Pat. No.
6,284,813.
[0055] Non-functional monomers may also be employed in the present
processes and articles, resulting in oligomers/polymers containing
functional and non-functional monomers. Non-functional monomers
include but are not limited to hydroxyalkyl acrylates or
methacrylates, for example, methyl, ethyl, butyl, 2-ethylhexyl- or
2-hydroxyethyl acrylate, isobornyl acrylate or methyl or ethyl
methacrylate. Silicone acrylates may also be included. Further
examples are acrylonitrile, acrylamide, methacrylamide,
N-substituted (meth)acrylamides, vinyl esters such as vinyl
acetate, vinyl ethers such as isobutyl vinyl ether, styrene, alkyl-
and halostyrenes, N-vinylpyrrolidone, vinyl chloride or vinylidene
chloride. Also optionally included are monomers containing two or
more double bonds such as diacrylates of ethylene glycol, propylene
glycol, neopentyl glycol, hexamethylene glycol and of bisphenol-A,
such as 4,4'-bis(2-acryloyloxyethoxy)diphenylpropane,
trimethylolpropane triacrylate, pentaerythritol triacrylate or
tetraacrylate, vinyl acrylate, divinyl benzene, divinyl succinate,
diallyl phthalate, triallyl phosphate, triallyl isocyanurate and
tris(2-acryloylethyl) isocyanurate.
[0056] In certain embodiments, the functional oligomers or polymers
of the invention contain for example from 2 to about 50,000 or more
functional monomer units, for instance from about 3, about 4, about
5, about 7, about 10, about 20, about 30, about 40, about 50 or
about 60 to about 70, about 80, about 90, about 100, about 125,
about 150, about 175, about 200, about 300, about 400, about 500,
about 600, about 700, about 800, about 900, about 1000, about 2000,
about 3000, about 5000 or about 10000 functional monomer units.
[0057] In other embodiments, the functional oligomers or polymers
of the invention contain for example from any one of about 2, about
3, about 4, about 5, about 7, about 10, about 20, about 30, about
40, about 50 or about 60 to about 70, about 80, about 90, about
100, about 125, about 150, about 175, about 200, about 300, about
400, about 500, about 600, about 700, about 800, about 900, about
1,000 monomer units to any one of about 1,500, about 2,000, about
3,000, about 5,000, bout 10,000, about 25,000, about 40,000 or
about 50,000 functional monomer units.
[0058] Organophosphorous layers of the invention may comprise a
complete or partial mono-layer of organophosphorous monomers or
compounds. Alternatively, they may comprise complete or partial
multi-layers of the organophosphorous monomers or compounds, for
instance from 1 to about 2, about 3, about 4, about 5, about 6,
about 7, about 8, about 9 or about 10 complete or partial
layers.
[0059] Alternatively, disclosed in certain embodiments is a process
for preparing an article having a functional surface, the process
comprising depositing functional organophosphorus compounds or
functional oligomers or polymers on a surface of the article to
form a functional layer, where depositing the functional
organophosphorous compounds or oligomers or polymers on the article
surface comprises anodization.
[0060] For example, compounds such as (6-hexylphosphonic
acid)triethylammonium bromide may be obtained and deposited on an
article surface by a process comprising anodization.
[0061] For example, an organophosphorous compound containing a
suitable substituent on the organo group may be reacted with a
functional compound to provide a functional organophosphorous
compound. The functional organophosphorous compound is then
deposited on an article surface by a process comprising
anodization.
[0062] For example, an organophosphorous compound containing a
suitable substituent on the organo group may be reacted with a
compound to provide an intermediate organophosphorous compound. The
intermediate organophosphorous compound may be deposited on an
article surface by a process comprising anodization. The deposited
intermediate compounds are then modified to provide functional
compounds; providing a functional layer.
[0063] For example, an organophosphorous compound containing a
suitable substituent on the organo group may be reacted with a
compound to provide an intermediate organophosphorous compound. The
intermediate organophosphorous compound may be further reacted to
provide a functional organophosphorous compound, which is then
deposited on an article surface by a process comprising
anodization.
[0064] In certain embodiments, a functional oligomer or polymer may
be prepared containing an organophosphorous moiety, which oligomer
or polymer may be deposited on an article surface by a process
comprising anodization. For example, 6-hydroxyhexyllphosphonic acid
may be reacted with an ATRP initiator such as alpha-bromoisobutyryl
bromide. This organophosphorous initiator compound may then be
reacted under ATRP conditions with an unsaturated functional
monomer such as MDPB. The functional polymer containing phosphonic
acid groups is then deposited on an article surface by a process
comprising anodization.
[0065] An example of this is to react 6-hydroxyhexylphosphonic acid
with a cross-coupling agent such as (p-nitrophenyl) chloroformate,
followed by reaction with a diamine or aminoalcohol to provide a
free distal amino group. This compound may be quaternized to
provide a quaternary ammonium moiety. The quaternary ammonium
compound is then deposited on an article surface by a process
comprising anodization. Provided is a functional antimicrobial
quaternary ammonium layer.
[0066] Alternatively, the compound containing the free distal amino
group may be deposited on an article surface by a process
comprising anodization. The deposited compound may then be
quaternized to provide a functional antimicrobial quaternary
ammonium layer.
[0067] Present articles are for instance medical devices such as
implantable or percutaneous medical devices. Medical devices
include endoscopic, arthroscopic, laproscopic, cardiac,
cardiovascular, vascular, non-woven mesh, woven mesh, foam, cloth,
fabric, orthopedic, orthopedic trauma, spine, surgical, drainage
catheter, shunt, tape, mesh, rope, cable, wire, suture, skin and
tissue staple, burn sheet, external fixation and
temporary/non-permanent implant devices.
[0068] In certain embodiments the article is a medical implant
device or component thereof. Suitable medical implant devices and
components thereof include, but not limited to, orthopedic
prostheses for the hip, knee, ankle, shoulder, elbow, and spine.
Exemplary medical implant devices include a full or partial knee
arthroplasty prosthesis, full or partial hip arthroplasty
prosthesis, full or partial elbow arthroplasty prosthesis, full or
partial wrist arthroplasty prosthesis, full or partial shoulder
arthroplasty prosthesis, full or partial ankle arthroplasty
prosthesis, and full or partial articulating spinal segment
arthroplasty prosthesis. Exemplary components of medical implant
devices include a femoral component (e.g., for replacing one or
more femoral condyles) or a tibial component (e.g., for replacing
at least a portion of a proximal tibial plateau) of a knee
prosthesis (e.g., a uni-compartmental or total knee arthroplasty
prosthesis), a femoral component (e.g., for replacing at least the
proximal portion or head of the femur) or an acetabular cup (e.g.,
for replacing the hip bone's femoral socket) of a hip prosthesis, a
humeral component (e.g., for replacing the distal portion of the
humerus) or an ulnar component (e.g., for replacing the proximal
portion of the ulna) of an elbow prosthesis, a metacarpal component
(for replacing at least a portion of one or more metacarpal bones)
or radial component (for replacing the distal portion of the
radius) of a wrist prosthesis, a humeral component (e.g., for
replacing the proximal portion or head of the humerus) or glenoid
component (e.g., for replacing the glenoid or socket portion of the
scapula) of a shoulder prosthesis, a tibial component (e.g., for
replacing the distal portion of the tibia) or talar component
(e.g., for replacing the proximal portion of the talus) of an ankle
prosthesis, and an endplate component (e.g., for contacting the
superior or inferior portion of a cervical, lumbar or thoracic
vertebra) or spacer component (e.g. for insertion between endplate
components) of a vertebral disc prosthesis.
[0069] Present articles also include for example household articles
such as cutting boards, sinks, utensils, counter tops, packaging,
food storage containers, refrigerator parts, coolers and the
like.
[0070] Present articles also include for example articles employed
in hospital and/or nursing home environments such as walls, floors,
bed-pans.
[0071] Following are some embodiments of the invention.
[0072] In a first embodiment, a process for preparing an article
having a functional surface, the process comprising depositing
organophosphorous compounds on a surface of the article to form an
organophosphorous layer and attaching one or more functional
compounds or functional oligomers or polymers to the
organophosphorous layer to form a functional layer, wherein
depositing the organophosphorous compounds on the article surface
comprises anodization.
[0073] In a second embodiment, a process according to the first
embodiment wherein the organophosphorous compounds comprise
organophosphonic acids.
[0074] In a third embodiment, a process according to the first or
second embodiments, wherein the organophosphorous compounds
comprise organophosphinic acids. In a fourth embodiment, a process
according to any of the preceding embodiments, wherein the
organophosphorous compounds comprise organophosphoric acids.
[0075] In a fifth embodiment, a process according to any of the
preceding embodiments, wherein the article comprises a surface
comprising titanium, a titanium alloy, stainless steel, a cobalt
chrome alloy, nickel, molybdenum, tantalum, zirconium, magnesium or
an alloy containing one or more of nickel, molybdenum, tantalum,
zirconium and magnesium. In a sixth embodiment, a process according
to any of the preceding embodiments, wherein the article comprises
a surface comprising titanium.
[0076] In a seventh embodiment, a process according to any of the
preceding embodiments, wherein the organo group is a
C.sub.2-C.sub.12 or C.sub.2-C.sub.9 hydrocarbyl group. In an eighth
embodiment, a process according to any of the preceding
embodiments, wherein the organo group is a C.sub.2-C.sub.6
hydrocarbyl group. In a ninth embodiment, a process according to
any of the preceding embodiments, wherein the functional compounds,
functional oligomers or functional polymers comprise anti-infective
compounds, for example antimicrobial compounds.
[0077] In a tenth embodiment, a process according to any of the
preceding embodiments, wherein the functional compounds, functional
oligomers or functional polymers comprise ammonium salts,
pyridinium salts or phosphonium salts. In an eleventh embodiment, a
process according to any of the preceding embodiments, wherein the
organo groups are reacted with a diamine or an aminoalcohol to
provide a distal amine which is subsequently quaternized to provide
a functional layer containing quaternary ammonium compounds.
[0078] In a twelfth embodiment, a process according to the eleventh
embodiment, wherein the organo groups contain an amino, hydroxy or
thiol substituent which is reacted with a cross-coupling reagent
followed by reaction with a diamine or aminoalcohol. In a
thirteenth embodiment, a process according to any of the first
through tenth embodiments comprising depositing unsaturated
organophosphorous monomer compounds.
[0079] In a fourteenth embodiment, a process according to the
thirteenth embodiment, wherein the unsaturated organophosphorous
monomers are reacted with unsaturated functional monomers to form a
functional layer comprising functional oligomers or polymers. In a
fifteenth embodiment, a process according to the fourteenth
embodiment comprising free-radical polymerization, anionic
polymerization or cationic polymerization.
[0080] In a sixteenth embodiment, a process according to any of
embodiments 13 to 15 where the unsaturated organophosphorous
monomer compounds are selected from the group consisting of vinyl
phosphonic acid, allyl phosphonic acid, 2-methyl allylphosphonic
acid, 2-butenyl phosphonic acid, allyl phosphate and ethyleneglycol
methacrylatephosphate.
[0081] In a seventeenth embodiment, a process according to any of
the first through tenth embodiments comprising attaching functional
oligomers or polymers to form an oligomeric or polymeric functional
layer by a process comprising atom transfer radical polymerization
(ATRP) of unsaturated functional monomers.
[0082] In an eighteenth embodiment, a process according to the
seventeenth embodiment, wherein the organo group of the water
soluble organophosphorous compounds is a C.sub.2-C.sub.40 or
C.sub.2-C.sub.24 hydrocarbyl having 1 to 3 substituents selected
from hydroxy, amino and thiol. In a nineteenth embodiment, a
process according to any of embodiments 14-18 where the unsaturated
functional monomers are antimicrobial monomers comprising ammonium
salts, pyridinium salts or phosphonium salts.
[0083] In a twentieth embodiment, a process according to any of
embodiments 14-19 where the unsaturated functional monomers are
antimicrobial monomers selected from the group consisting of
methacryloyloxydodecylpyridinium salts, diallyldimethylammonium
chloride (DADMAC), methacryloyloxyhexadecylpyridinium salts,
methacryloyloxydecyltriethylammonium salts,
4-hexadecylmethacryloyloxyethylpyridinium salts,
methacryloyloxyethylhexadecylbipyridinium salts,
methacryloyloxydodecyltrimethylphosphonium salts,
methacryloyloxyoctadecyltriethylphosphonium salts,
4-methacryloyloxyethyldodecylpyrldinium salts,
di(4-vinylbenzyl)hexadecylmethylammonium salts,
di(methacryloyloxyethyl)dodecylmethylammonium salts and
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halides.
[0084] In a twenty first embodiment, a process according to any of
embodiments 14-20 where the unsaturated functional monomers are
antimicrobial monomers containing ammonium salts. In a twenty
second embodiment, a process according to any of embodiments 14-21
where the unsaturated functional monomers comprise two or more
different monomers. In a twenty third embodiment, a process
according to any of embodiments 14-22 comprising also reacting
non-functional unsaturated monomers.
[0085] In a twenty fourth embodiment, a process according to any of
the preceding embodiments, wherein the functional layer is formed
in a pattern or micropattern. In a twenty fifth embodiment, a
process according to any of the preceding embodiments, wherein the
organophosphorous layer is covalently bonded to an oxide layer
through phosphinate, phosphonate or phosphate moieties.
[0086] In a twenty sixth embodiment, a process according to any of
the preceding embodiments, comprising preparing an aqueous solution
containing organophosphorous compounds, placing an article having a
metal surface in the aqueous solution, connecting the metal surface
to a positive terminal of an electric power supply and connecting a
counter electrode to a negative electrode of the power supply.
[0087] In a twenty seventh embodiment, a process according to the
twenty sixth embodiment, comprising applying a voltage of from
about 1 to about 400 volts or from about 30 to about 90 volts for a
time period of from about 1 sec to about 60 seconds or from about 1
second to about 30 seconds. In a twenty eighth embodiment, a
process according to any of embodiments 1-26 where the article is
selected from the group consisting of endoscopic, arthroscopic and
laproscopic medical devices.
[0088] In a twenty ninth embodiment, a process according to any of
embodiments 1-26 where the article is selected from the group
consisting of cardiac, cardiovascular, vascular, orthopedic,
orthopedic trauma and spine medical devices. In a thirtieth
embodiment, a process according to any of embodiments 1-26 where
the article is selected from the group consisting of catheters,
shunts, tapes, meshes, ropes, cables, wires, sutures, skin or
tissue staples, burn sheets, external fixation devices and
temporary implants.
[0089] In a thirty first embodiment, a process for preparing an
article having a functional surface, the process comprising
depositing functional organophosphorous compounds or functional
oligomers or polymers on a surface of the article to form a
functional layer, wherein depositing the functional
organophosphorous compounds, oligomers or polymers on the article
surface comprises anodization.
[0090] In a thirty second embodiment, a process according to the
thirty first embodiment, wherein the organophosphorous compounds
comprise organophosphonic acids.
[0091] In a thirty third embodiment, a process according to
embodiments 31 or 32 where the organophosphorous compounds comprise
organophosphinic acids. In a thirty fourth embodiment, a process
according to any of embodiments 31 to 33 wherein the
organophosphorous compounds comprise organophosphoric acids. In a
thirty fifth embodiment, a process according to any of embodiments
31-34 where the article comprises a surface comprising titanium, a
titanium alloy, stainless steel, a cobalt chrome alloy, nickel,
molybdenum, tantalum, zirconium, magnesium or an alloy containing
one or more of nickel, molybdenum, tantalum, zirconium and
magnesium.
[0092] In a thirty sixth embodiment, a process according to any of
embodiments 31-35 where the article comprises a surface comprising
titanium. In a thirty seventh embodiment, a process according to
any of embodiments 31-36 where the organo group is a
C.sub.2-C.sub.12 or C.sub.2-C.sub.9 hydrocarbyl group. In a thirty
eighth embodiment, a process according to any of embodiments 31-37
where the organo group is a C.sub.2-C.sub.6 hydrocarbyl group.
[0093] In a thirty ninth embodiment, a process according to any of
embodiments 31-38 where the functional compounds, functional
oligomers or functional polymers comprise anti-infective compounds,
for example antimicrobial compounds. In a fortieth embodiment, a
process according to any of embodiments 31-39 wherein the
functional compounds, functional oligomers or functional polymers
comprise ammonium salts, pyridinium salts or phosphonium salts.
[0094] In a forty first embodiment, a process according to any of
embodiments 31-40 wherein organophosphorous compounds are reacted
with a diamine or an aminoalcohol to provide a distal amine which
is subsequently quaternized to provide functional organophosphorous
compounds containing quaternary ammonium moieties and depositing
the functional organophosphorous compounds.
[0095] In a forty second embodiment, a process according to any of
embodiments 31-40 where the organophosphorous compounds are reacted
with a diamine or an aminoalcohol to provide an intermediate
compound having a distal amine, depositing the intermediate
compound on the surface and quaternizing the distal amine.
[0096] In a forty third embodiment, a process according to the
forty first or forty second embodiments, wherein the organo groups
contain an amino, hydroxy or thiol substituent which is reacted
with a cross-coupling reagent followed by reaction with a diamine
or aminoalcohol.
[0097] In a forty fourth embodiment, a process according to any of
embodiments 31-40 comprising preparing a functional oligomer or
polymer and depositing the oligomers or polymers on the surface. In
a forty fifth embodiment, a process according to embodiment 44
where the functional oligomers or polymers are prepared by a
process comprising atom transfer radical polymerization (ATRP) of
unsaturated functional monomers.
[0098] In a forty sixth embodiment, a process according to
embodiments 44 or 45 where an organophosphorous compound having one
or more substituents suitable for reacting with an ATRP initiator
on the organo group is reacted with an ATRP initiator.
[0099] In a forty seventh embodiment, a process according to the
forty sixth embodiment, wherein the organo group of the
organophosphorous compounds is a C.sub.2-C.sub.12 or
C.sub.2-C.sub.9 hydrocarbyl having 1 to 3 substituents selected
from hydroxy, amino and thiol.
[0100] In a forty eighth embodiment, a process according to any of
embodiments 45-47, wherein the unsaturated functional monomers are
antimicrobial monomers comprising ammonium salts, pyridinium salts
or phosphonium salts.
[0101] In a forty ninth embodiment, a process according to any of
embodiments 45-48, wherein the unsaturated functional monomers are
antimicrobial monomers selected from the group consisting of
methacryloyloxydodecylpyridinium salts, diallyldimethylammonium
chloride (DADMAC), methacryloyloxyhexadecylpyridinium salts,
methacryloyloxydecyltriethylammonium salts,
4-hexadecylmethacryloyloxyethylpyridinium salts,
methacryloyloxyethylhexadecylbipyridinium salts,
methacryloyloxydodecyltrimethylphosphonium salts,
methacryloyloxyoctadecyltriethylphosphonium salts,
4-methacryloyloxyethyldodecylpyrldinium salts,
di(4-vinylbenzyl)hexadecylmethylammonium salts,
di(methacryloyloxyethyl)dodecylmethylammonium salts and
methacryloyloxyethyl(4-N-hexadecylpyridinylmethyl) succinate
halides.
[0102] In a fiftieth embodiment, a process according to any of
embodiments 45-49, wherein the unsaturated functional monomers are
antimicrobial monomers containing ammonium salts. In a fifty first
embodiment, a process according to any of embodiments 45-50,
wherein the unsaturated functional monomers comprise two or more
different monomers.
[0103] In a fifty second embodiment, a process according to any of
embodiments 45-51 comprising also reacting non-functional
unsaturated monomers. In a fifty third embodiment, a process
according to any of embodiments 31-52 where the functional layer is
formed in a pattern or micropattern.
[0104] In a fifty fourth embodiment, a process according to any of
embodiments 31-53, wherein the functional organophosphorous
compounds, oligomers or polymers are covalently bonded to an oxide
layer through phosphinate, phosphonate or phosphate moieties.
[0105] In a fifty fifth embodiment, a process according to any of
embodiments 31-54 comprising preparing an aqueous solution
containing functional organophosphorous compounds, oligomers or
polymers, placing an article having a metal surface in the aqueous
solution, connecting the metal surface to a positive terminal of an
electric power supply and connecting a counter electrode to a
negative electrode of the power supply.
[0106] In a fifty sixth embodiment, a process according to
embodiment 55 comprising applying a voltage of from about 1 to
about 400 volts or from about 30 to about 90 volts for a time
period of from about 1 sec to about 60 seconds or from about 1
second to about 30 seconds.
[0107] In a fifty seventh embodiment, a process according to any of
embodiments 31-56, wherein the article is selected from the group
consisting of endoscopic, arthroscopic and laproscopic medical
devices. In a fifty eighth embodiment, a process according to any
of embodiments 31-57 where the article is selected from the group
consisting of cardiac, cardiovascular, vascular, orthopedic,
orthopedic trauma and spine medical devices.
[0108] In a fifty ninth embodiment, a process according to any of
embodiments 31-57, wherein the article is selected from the group
consisting of catheters, shunts, tapes, meshes, ropes, cables,
wires, sutures, skin or tissue staples, burn sheets, external
fixation devices and temporary implants.
[0109] In a sixtieth embodiment, an article having a functional
surface, the article comprising a surface having a functional layer
disposed thereon, the article prepared according to any of the
preceding embodiments.
[0110] In a sixty first embodiment, an article having a functional
surface, the article comprising a surface having a functional layer
disposed thereon, the functional layer comprising an
organophosphorous layer and functional oligomers or polymers bonded
to the organophosphorous layer, where the functional oligomers or
polymers contain a --O(CO)C(CH.sub.3).sub.2--,
--NH(CO)C(CH.sub.3).sub.2-- or a --S(CO)C(CH.sub.3).sub.2--
moiety.
[0111] The articles "a" and "an" herein refer to one or to more
than one (e.g. at least one) of the grammatical object. Any ranges
cited herein are inclusive. The term "about" used throughout is
used to describe and account for small fluctuations. For instance,
"about" may mean the numeric value may be modified by .+-.5%,
.+-.4%, .+-.3%, .+-.2%, .+-.1%, .+-.0.5%, .+-.0.4%, .+-.0.3%,
.+-.0.2%, .+-.0.1% or .+-.0.05%. All numeric values are modified by
the term "about" whether or not explicitly indicated. Numeric
values modified by the term "about" include the specific identified
value. For example "about 5.0" includes 5.0.
[0112] Unless otherwise indicated, all parts and percentages are by
weight.
[0113] All U.S. patent applications, published patent applications
and patents referred to herein are hereby incorporated by
reference.
EXAMPLES
Example 1 Attachment of Antimicrobial Functional Polymers by
Free-Radical Polymerization
[0114] A clean metal titanium strip is placed in a 15 weight %
aqueous solution of vinyl phosphonic acid. A titanium counter
electrode is attached to the negative terminal of a DC power
supply. The voltage is adjusted to between 1 and 300V and a
titanium rod connected to the positive terminal of the power supply
is contacted with the titanium strip for a period of from 1 to 30
seconds.
[0115] Anodization occurs, resulting in formation of a titanium
oxide layer and vinyl phosphonic acid bonded to the oxide layer via
phosphonate moieties. Ti--O--P fragments are observed via TOF-SIMS
surface analysis. The titanium surface having an attached
unsaturated organophosphorus layer is represented as below.
##STR00001##
[0116] A solution of 12-methacryloyloxydodecylpyridinium bromide
(MDPB) in ethanol (1 g/70 mL) is sprayed onto the titanium surface
containing the vinylphosphonate layer (unsaturated organophosphorus
layer). The titanium strips are placed in a nitrogen purged UV
ozone cleaner chamber and exposed to UV light with a lambda max of
ca. 260 nm with continuous purging for 15 minutes, resulting in
polymerization of the vinyl groups with the methacrylate
groups.
[0117] A titanium strip containing an antimicrobial layer is
formed. The antimicrobial layer attached to a titanium surface
contains an oxide layer, an organophosphorus layer and an
antimicrobial polymer containing antimicrobial monomer units, as
represented below, where * is a terminal end group.
##STR00002##
Example 2 Antimicrobial Efficacy
[0118] Titanium strips according to Example 1 and untreated samples
are cut into 1.times.1 cm squares, sanitized with 70% alcohol and
dried with argon. The sanitized samples are aseptically transferred
individually into the wells of a sterile 24-well polystyrene dish.
An overnight culture of MSSA 29213 is diluted in ASTM E2149 working
buffer (0.3 mM KH.sub.2PO.sub.4, pH 7.2) to OD.sub.600=0.005
(.about.1-4E+06 CFU/mL).
[0119] A 330 mL portion of the bacterial dilution is pipetted into
each of the wells to cover the samples. A sample of the bacterial
dilution is also serially diluted in 1.times.DPBS (Dulbecco's
phosphate-buffered saline) and drop plated in triplicate on a TSA
plate to ensure the bacterial challenge is on target. The TSA
(tryptone soya agar) plates are incubated overnight at 37.degree.
C.
[0120] The polystyrene dish is placed into the 37.degree. C.
incubator at 500 RPM on a IKA MS3 digital shaker with a microtiter
plate attachment overnight (18.+-.2 hours). After the overnight
incubation, the 24-well plate containing the sample buffer is
removed from the incubator and the buffer samples are pipetted into
a 96-well plate and serially diluted 1:10 in 1.times.DPBS. Each
dilution is drop plated in triplicate for each sample on TSA
plates. The plates are incubated overnight at 37.degree. C. Against
MSSA 21293, treated coupons show a reduction vs. control of 99.92%
this assay.
* * * * *