U.S. patent application number 16/195886 was filed with the patent office on 2019-03-21 for medical devices having activated surfaces.
The applicant listed for this patent is Covidien LP. Invention is credited to Ferass Abuzaina, Nadya Belcheva, Amin Elachchabi, Ahmad Robert Hadba, Mbiya Kapiamba.
Application Number | 20190085143 16/195886 |
Document ID | / |
Family ID | 42634221 |
Filed Date | 2019-03-21 |
United States Patent
Application |
20190085143 |
Kind Code |
A1 |
Belcheva; Nadya ; et
al. |
March 21, 2019 |
Medical Devices Having Activated Surfaces
Abstract
Implantable biocompatible polymeric medical devices include a
substrate with an acid or base-modified surface which is
subsequently modified to include click reactive members.
Inventors: |
Belcheva; Nadya; (Essex
Junction, VT) ; Abuzaina; Ferass; (Shelton, CT)
; Elachchabi; Amin; (Hamden, CT) ; Kapiamba;
Mbiya; (Cromwell, CT) ; Hadba; Ahmad Robert;
(Fort Worth, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Covidien LP |
Mansfield |
MA |
US |
|
|
Family ID: |
42634221 |
Appl. No.: |
16/195886 |
Filed: |
November 20, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15342488 |
Nov 3, 2016 |
10167371 |
|
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16195886 |
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|
14621493 |
Feb 13, 2015 |
9517291 |
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15342488 |
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13202373 |
Oct 26, 2011 |
8968818 |
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PCT/US10/24737 |
Feb 19, 2010 |
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14621493 |
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61154376 |
Feb 21, 2009 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61L 31/06 20130101;
A61L 31/148 20130101; A61L 31/043 20130101; Y10T 442/20 20150401;
C08J 2300/16 20130101; A61L 31/14 20130101; A61L 31/042 20130101;
A61L 31/04 20130101; C08J 7/12 20130101; C08J 7/14 20130101; A61L
31/16 20130101; A61L 31/044 20130101; A61L 2400/18 20130101; A61L
31/048 20130101; A61L 33/06 20130101 |
International
Class: |
C08J 7/12 20060101
C08J007/12; A61L 31/16 20060101 A61L031/16; A61L 33/06 20060101
A61L033/06; C08J 7/14 20060101 C08J007/14; A61L 31/14 20060101
A61L031/14; A61L 31/04 20060101 A61L031/04; A61L 31/06 20060101
A61L031/06 |
Claims
1-3. (canceled)
4. A medical device having an acid or base-treated surface that is
functionalized with one or more click reactive members to provide
an activated surface on the medical device.
5. The medical device of claim 4, wherein the medical device
comprises a biodegradable polymer selected from collagen,
cellulose, poly (amino acids), polysaccharides, hyaluronic acid,
gut, copolymers and combinations thereof.
6. The medical device of claim 4, wherein the medical device
comprises a non-degradable polymer selected from fluorinated
polymers, polyolefins, nylons, polyamides, polyurethanes,
silicones, ultra high molecular weight polyethylene, polybutesters,
polyaryletherketone, copolymers and combinations thereof.
7. The medical device of claim 4, wherein the one or more click
reactive members are selected from the group consisting of thiols,
azides, alkynes and alkenes.
8. The medical device of claim 4, wherein the one or more click
reactive members comprise a thiol.
9. The medical device of claim 4, wherein the one or more click
reactive members comprise an azide.
10. The medical device of claim 4, wherein the one or more click
reactive members comprise an alkyne.
11. The medical device of claim 4, wherein the one or more click
reactive members comprise an alkene.
12. The medical device of claim 4, wherein the medical device is
selected from the group consisting of monofilament sutures,
multifilament sutures, surgical meshes, ligatures, sutures,
staples, slings, patches, foams, pellicles, films, barriers,
stents, catheters, and inflatable balloons.
13. The medical device of claim 4, wherein the medical device
comprises a surgical mesh.
14. The medical device of claim 4, wherein acid or base-treated
surface is hydrolyzed prior to being functionalized with the at
least one click-reactive member.
15. The medical device of claim 4, wherein the acid treated surface
is treated with an acid selected from the group consisting of HCl,
HCl.sub.3, HCl.sub.4, H.sub.2SO.sub.3, H.sub.2SO.sub.4,
H.sub.3PO.sub.4, HI, HIO.sub.3, HBr, lactic acid and glycolic
acid.
16. The medical device of claim 4, wherein the base treated surface
is treated with a base selected from the group consisting of LiOH,
Ba(OH).sub.2, Mg(OH).sub.2, NaOH, KOH, Na.sub.2CO.sub.3,
Ca(OH).sub.2, and NH.sub.4OH.
17. The medical device of claim 4, further comprising a drug
functionalized with one or more complementary click reactive
members, wherein the one or more click reactive members of the
medical device and the one or more complementary click reactive
members of the drug interact to covalently bond the drug to the
activated surface of the medical device.
18. The medical device of claim 17, wherein the one or more click
reactive members comprise a thiol and the one or more complementary
click reactive members comprise an alkene.
19. The medical device of claim 17, wherein the one or more click
reactive members comprise an alkene and the one or more
complementary click reactive members comprise a thiol.
20. The medical device of claim 17, wherein the one or more click
reactive members comprise an alkyne and the one or more
complementary click reactive members comprise an azide.
21. The medical device of claim 17, wherein the one or more click
reactive members comprise an azide and the one or more
complementary click reactive members comprise an alkyne.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This Application claims priority benefit of U.S. Application
No. 61/154,376 filed Feb. 21, 2009, the entire disclosures of which
are incorporated herein by reference.
BACKGROUND
Technical Field
[0002] The present disclosure relates to surface-activated polymers
and to a methods for preparation thereof. Medical devices made from
or containing such surface-activated polymers are also described
herein.
Related Art
[0003] Biocompatible and biodegradable materials have been used for
the manufacture of prosthetic implants, suture threads, and the
like. A relative advantage of these materials is that of
eliminating the need for a second surgical intervention to remove
the implant. The gradual biodegradability of such materials favors
regeneration of the pre-existing tissues. There has been recent
interest in using such devices for delivery of bioactive
agents.
[0004] It would be advantageous to provide reactive functional
groups on the surface of such biodegradable medical devices for a
variety of purposes.
SUMMARY
[0005] Implantable biocompatible polymeric medical devices in
accordance with the present disclosure include a substrate with an
acid or base-modified surface which is subsequently functionalized
to include click reactive members. The substrate of the medical
devices described herein may be made from any biocompatible polymer
and can be part of any medical device of being implanted at a
target location. Acid or base treatment of the substrate may result
in chemical modification of the material from which the substrate
is made thereby facilitating functionalization of the surface or
attachment of a linker compound which can be functionalized with
click reactive members.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0006] Implantable biocompatible polymeric medical devices in
accordance with the present disclosure include a substrate with an
acid or base modified surface which is subsequently functionalized
to include click reactive members.
The Polymeric Substrate
[0007] The substrate of the medical devices described herein may be
made from any biocompatible polymer. The biocompatible polymer may
be a homopolymer or a copolymer, including random copolymer, block
copolymer, or graft copolymer. The biocompatible polymer may be a
linear polymer, a branched polymer, or a dendrimer. The
biocompatible polymer may be bioabsorbable or non-absorbable and
may be of natural or synthetic origin.
[0008] Examples of suitable biodegradable polymers from which the
substrate of the medical devices described herein may be made
include, but are not limited to polymers such as those made from
alpha-hydroxy acids (e.g. lactic acid, glycolic acid, and the
like), lactide, glycolide, .epsilon.-caprolactone,
.delta.-valerolactone, carbonates (e.g., trimethylene carbonate,
tetramethylene carbonate, and the like), dioxanones (e.g.,
1,4-dioxanone), 1,dioxepanones (e.g., 1,4-dioxepan-2-one and
1,5-dioxepan-2-one), ethylene glycol, ethylene oxide, esteramides,
hydroxy alkanoates (e.g. .gamma.-hydroxyvalerate,
.beta.-hydroxypropionate, 3-hydroxybuterate, and the like), poly
(ortho esters), tyrosine carbonates, polyimide carbonates,
polyimino carbonates such as poly (bisphenol A-iminocarbonate) and
poly (hydroquinone-iminocarbonate), polyurethanes, polyanhydrides,
polymer drugs (e.g., polydiflunisol, polyaspirin, and protein
therapeutics) and copolymers and combinations thereof. Suitable
natural biodegradable polymers include collagen, cellulose, poly
(amino acids), polysaccharides, hyaluronic acid, gut, copolymers
and combinations thereof.
[0009] Examples of suitable non-degradable polymers from which the
substrate of the medical devices described herein may be made
include, but are not limited to fluorinated polymers (e.g.
fluoroethylenes, propylenes, fluoroPEGs), polyolefins such as
polyethylene, polyesters such as poly ethylene terepththalate
(PET), nylons, polyamides, polyurethanes, silicones, ultra high
molecular weight polyethylene (UHMWPE), polybutesters,
polyaryletherketone, copolymers and combinations thereof.
[0010] The biocompatible polymeric substrate may be fabricated into
any desired physical form. The polymeric substrate may be
fabricated for example, by spinning, casting, molding or any other
fabrication technique known to those skilled in the art. The
polymeric substrate may be made into any shape, such as, for
example, a fiber, sheet, rod, staple, clip, needle, tube, foam, or
any other configuration suitable for a medical device. Where the
polymeric substrate is in the form of a fiber, the fiber may be
formed into a textile using any known technique including, but not
limited to, knitting, weaving, tatting and the like. It is further
contemplated that the polymeric substrate may be a non-woven
fibrous structure.
[0011] The present biocompatible polymeric substrate can be part of
any medical device of being implanted at a target location. Some
non-limiting examples include monofilaments, multifilaments,
surgical meshes, ligatures, sutures, staples, patches, slings,
foams, pellicles, films, barriers, stents, catheters, shunts,
grafts, coil, inflatable balloon, and the like. The implantable
device can be intended for permanent or temporary implantation.
Treatment of the Substrate
[0012] Surface activation of the substrate is provided by acid or
base hydrolysis.
[0013] In embodiments, the process of hydrolysis is conducted in
the presence of an aqueous solution of a base or an acid to
accelerate surface reaction, inasmuch as excessively long processes
of activation can induce a reduction in molecular weight and thus
in the mechanical properties of the material. Suitable bases for
use in the present hydrolysis processes include, for example,
strong alkalis, such as LiOH, Ba(OH).sub.2, Mg(OH).sub.2, NaOH,
KOH, Na.sub.2CO.sub.3, Ca(OH).sub.2 and the weak bases, such as for
example NH.sub.4OH and the amines such as methylamine, ethylamine,
diethylamine and dimethylamine. Acids suitable for surface
hydrolysis treatments can be chosen, for example, from among HCl,
HClO.sub.3, HClO.sub.4, H.sub.2SO.sub.3, H.sub.2SO.sub.4,
H.sub.3PO.sub.3, H.sub.3PO.sub.4, HI, HIO.sub.3, HBr, lactic acid,
glycolic acid.
[0014] Surface activation by means of hydrolysis can be conducted
at temperatures preferably comprised between 0 degrees Celsius and
the material softening temperature or glass transition
temperature.
[0015] Surface hydrolysis treatment is followed by careful washing
to remove all traces of acid or base.
[0016] The present surface treatment can generate COONa groups
which can be subsequently converted into COOH groups by treatment
with strong mineral acids.
[0017] Further, the surface freeing of alcoholic groups by means of
a hydrolysis process can be followed by reaction by means of the
addition of a compound provided with functional group or groups
able to react with surface alcoholic groups, such as for example by
means of the addition of an anhydride such as succinic anhydride,
with the conversion of --OH groups into
--O--CO--CH.sub.2--CH.sub.2--COOH groups.
Addition of Reactive Members to the Treated Substrate
[0018] Once a surface of the substrate is acid or base treated,
click reactive functional groups are provided on the surface.
[0019] Examples of the types of reactions that are known to have
click reactivity include cycloaddition reactions. Cycloaddition
reactions can be used to activate the substrates of the present
disclosure. These reactions represent highly specific reactant
pairs that have a chemoselective nature, meaning that they mainly
react with each other and not other functional groups. One example
of a cycloaddition reaction is the Huisgen 1,3-dipolar
cycloaddition of a dipolarophile with a 1,3 dipolar component that
produce five membered (hertero)cycles. Examples of dipolarophiles
are alkenes, alkynes, and molecules that possess related heteroatom
functional groups, such as carbonyls and nitriles. Specifically,
another example is the 2+3 cycloaddition of alkyl azides and
acetylenes. Other cycloaddition reactions include Diels-Alder
reactions of a conjugated diene and a dienophile (such as an alkyne
or alkene).
[0020] Other examples of the types of reactions that are known to
have click reactivity include a hydrosilation reaction of H--Si and
simple non-activated vinyl compounds, urethane formation from
alcohols and isocyanates, Menshutkin reactions of tertiary amines
with alkyl iodides or alkyl trifluoromethanesulfonates, Michael
additions, e.g., the very efficient maleimide-thiol reaction, atom
transfer radical addition reactions between --SO2Cl and an olefin
(R.sup.1, R.sup.2--C.dbd.C--R.sup.3, R.sup.4), metathesis,
Staudinger reaction of phosphines with alkyl azides, oxidative
coupling of thiols, many of the procedures already used in
dendrimer synthesis, especially in a convergent approach, which
require high selectivity and rates, nucleophilic substitution,
especially of small strained rings like epoxy and aziridine
compounds, carbonyl chemistry like formation of ureas, and addition
reactions to carbon-carbon double bonds like dihydroxylation.
Therefore, attached functionality may be chosen from acetylene
bond, an azido-group, a nitrile group, acetylenic, amino group,
phosphino group. The click chemistry reaction may results in the
addition of a functional group selected from amino, primary amino,
hydroxyl, sulfonate, benzotriazole, bromide, chloride,
chloroformate, trimethylsilane, phosphonium bromide or
bio-responsive functional group including polypeptides, proteins
and nucleic acids, to the polymer.
[0021] Thus, suitable reactive members that may be applied to the
treated substrate include, for example, an amine, sulfate, thiol,
hydroxyl, azide, alkyne, alkene, carboxyl groups aldehyde groups,
sulfone groups, vinylsulfone groups, isocyanate groups, acid
anhydride groups, epoxide groups, aziridine groups, episulfide
groups, groups such as --CO.sub.2N(COCH.sub.2).sub.2,
--CO.sub.2N(COCH.sub.2).sub.2, --CO.sub.2H, --CHO, --CHOCH.sub.2,
--SO.sub.2CH.dbd.CH.sub.2, --N(COCH).sub.2,
--S--S--(C.sub.5H.sub.4N) and groups of the following structures
wherein X is halogen and R is hydrogen or C.sub.1 to C.sub.4
alkyl:
##STR00001##
[0022] The treated substrate can be provided with click reactive
members using any variety of suitable chemical processes. Those
skilled in the art reading this disclosure will readily envision
chemical reactions for activating treated substrate to render them
suitable for use in the presently described devices/methods.
[0023] For example, in embodiments, the acid or base treated
substrate is functionalized with a halogen group to provide a
reactive site at which a click reactive member can be attached. The
halogenated sites on the surface of the treated substrate can be
functionalized with a click reactive member, for example, by
converting pendant chlorides or iodides on the core into azides by
reaction with sodium azide. See, R. Riva et al., Polymer 49, pages
2023-2028 (2008) for a description of suitable reaction
conditions.
[0024] Alternatively, the polymer or copolymer backbone may be
halogenated using methods similar to those described by Nottelet et
al., Biomaterials, 27, pages 4948-4954 (2006). Once halogenated,
the backbone can be functionalized with a click reactive
functionality by reacting it with a hydroxyacid under condition
described by Shi et al. Biomaterials, 29, pages 1118-1126 (2008)
followed by reaction with sodium azide. The halogen can also be
converted directly to the alkyne by reacting it with an alcoholic
alkine suck as propargyl alcohol.
Uses of Medical Devices Having an Activated Surface
[0025] Medical devices having an activated surface in accordance
with the present disclosure can be used for a variety of purposes.
For example, in embodiments they may be used for drug delivery. In
such embodiments, the drug to be delivered is functionalized with
one or more reactive member that are complementary to the reactive
members provided on the surface of the substrate. By
"complementary" it is meant that the reactive members on the drug
to be delivered are able to interact with the reactive members
provided on the surface of the substrate to covalently bond the
drug to be delivered to the surface activated substrate.
[0026] In other embodiments, the medical device having an activated
surface in accordance with the present disclosure can be attached
to biological tissue by functionalizing tissue with one or more
reactive member that are complementary to the reactive members
provided on the surface of the substrate. Biological tissue can be
provided with reactive member that are complementary to the
reactive members provided on the surface of the substrate by
conjugation of such groups to various components of tissue such as
proteins, lipids, oligosaccharides, oligonucleotides, glycans,
including glycosaminoglycans. In embodiments, the complementary
groups are attached directly to components of the tissue. In other
embodiments, the complementary groups are attached to components of
the tissue via a linker. In either case, situating the
complementary groups on the tissue can be accomplished by
suspending the reactive member in a solution or suspension and
applying the solution or suspension to the tissue such that the
reactive member binds to a target. The solution or suspension may
be poured, sprayed or painted onto the tissue, whereupon the
reactive members are incorporated into the tissue.
[0027] Those skilled in the art reading this disclosure will
readily envision other uses for the activated medical devices
described herein.
[0028] It will be understood that various modifications may be made
to the embodiments disclosed herein. Therefore, the above
description should not be construed as limiting, but merely as
exemplifications within the scope and spirit of the claims appended
hereto.
* * * * *