U.S. patent application number 10/274813 was filed with the patent office on 2003-08-14 for absorbable e-caprolactone polymers and medical devices.
Invention is credited to Shalaby, Shalaby W..
Application Number | 20030152546 10/274813 |
Document ID | / |
Family ID | 27379478 |
Filed Date | 2003-08-14 |
United States Patent
Application |
20030152546 |
Kind Code |
A1 |
Shalaby, Shalaby W. |
August 14, 2003 |
Absorbable E-caprolactone polymers and medical devices
Abstract
Crystalline, low melting .epsilon.-Caprolactone polymers which
undergo accelerated hydrolysis, and their use as lubricant coatings
and/or as coatings containing bioactive agents, as carriers of
viable cells, and as coatings for open-cell microporous template or
constucts for tissue regeneration; the polymers bearing basic
functionalities can be linked tonically or covalently to the ester
chain which induces autocatalyzed hydrolysis.
Inventors: |
Shalaby, Shalaby W.;
(Anderson, SC) |
Correspondence
Address: |
LAW OFFICES OF NANCY A. BIRD
231 WALTON AVENUE
SO. ORANGE
NJ
07079
US
|
Family ID: |
27379478 |
Appl. No.: |
10/274813 |
Filed: |
October 21, 2002 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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10274813 |
Oct 21, 2002 |
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09713860 |
Nov 16, 2000 |
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6485749 |
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09713860 |
Nov 16, 2000 |
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09103142 |
Jun 29, 1998 |
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6197320 |
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09103142 |
Jun 29, 1998 |
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08660089 |
Jun 3, 1996 |
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5773563 |
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08660089 |
Jun 3, 1996 |
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08212174 |
Mar 11, 1994 |
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5522842 |
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Current U.S.
Class: |
424/78.08 ;
514/2.3; 514/7.6 |
Current CPC
Class: |
A61L 29/085 20130101;
C08L 67/04 20130101; C08L 67/04 20130101; C08L 67/04 20130101; C08L
67/04 20130101; A61L 27/34 20130101; C08G 63/912 20130101; A61L
27/50 20130101; A61L 24/046 20130101; A61L 27/18 20130101; A61L
27/18 20130101; A61L 27/34 20130101; A61L 17/145 20130101; A61L
29/085 20130101; A61L 17/12 20130101; A61L 24/046 20130101 |
Class at
Publication: |
424/78.08 ;
514/12 |
International
Class: |
A61K 038/18; A61K
031/74 |
Claims
We claim:
1. A bioabsorbable, lubricant coating for medical devices such as
surgical staples; facia fasteners and other surgical closure
devices; trocars, syringes; endoscopes and endoscopic catheters,
instruments and devices; surgical implants; vascular grafts;
shunts; and stents; an open cell, microporous template for tissue
regeneration; a matrix for peptides and proteins; a matrix for
vaccines and growth factor; and a bioabsorbable carrier for viable
cells, said coating comprising crystalline nitrogenous polyesters
comprising predominantly .epsilon.-caprolactone polymer sequences
linked ionically or covalently to amine-bearing structures which
represent 1 to 20 percent of the total weight.
2. A lubricant coating as in claim 1, further comprising a
bioactive agent.
3. A lubricant coating as in claim 2, wherein the bioactive agent
is an anti-microbial.
4. A bioabsorbable, lubricant coating for a surgical closure device
as in claim 1, wherein the device is a suture, and the coating
comprises a crystalline nitrogenous polyester comprising
predominantly .epsilon.-caprolactone polymer sequences linked
tonically or covalently to amine-bearing structures which represent
1 to 20 percent of the total weight, and wherein the polyester
chain is terminated with a carboxyl group and wherein the polyester
is tonically linked to arginine.
5. A bone wax comprising crystalline nitrogenous polyesters
polymers comprising predominantly .epsilon.-caprolactone polymer
sequences linked tonically or covalently to amine-bearing
structures which represent 1 to 20 percent of the total weight.
6. A tissue sealant comprising crystalline nitrogenous polyesters
polymers comprising predominantly .epsilon.-caprolactone polymer
sequences linked ionically or covalently to amine-bearing
structures which represent 1 to 20 percent of the total weight.
7. A bioabsorbable carrier as in claim 9, further comprising a
growth factor.
8. A hemostatic agent comprising crystalline nitrogenous polyester
polymers comprising predominantly .epsilon.-caprolactone polymer
sequences linked ionically or covalently to amine-bearing
structures which represent 1 to 20 percent of the total weight.
9. A hemostatic agent as in claim 8, further comprising multivalent
metal ions.
10. A component for therapeutic or prophylactic system for managing
orthopedic, vascular or dental infection, said component comprising
nitrogenous polyester polymers comprising predominantly
.epsilon.-caprolactone polymer sequences linked ionically or
covalently to amine-bearing structures which represent 1 to 20
percent of the total weight.
Description
BACKGROUND OF THE INVENTION
[0001] This invention relates to crystalline, low melting,
.epsilon.-caprolactone polymers bearing basic amine functionalities
which are linked to the ester chain ionically or covalently to
induce catalyzed hydrolysis. The ester components can be derived
from .epsilon.-caprolactone with or without small amounts of
glycolide, and/or similar lactones. Such polymers with accelerated
absorption profiles are especially adapted for use as transient
coatings for absorbable multifilament surgical sutures and other
medical implants.
[0002] Multifilament surgical sutures such as Dexon.RTM.
polyglycolide multifilament suture typically require a surface
coating to improve their handling and knotting characteristics.
Capitalizing on the desirable low melting temperature,
crystallinity, and Theological properties of polycaprolactone and
its copolymers as coating materials, several compositions based on
this polymer were investigated as coatings for surgical sutures.
Recognizing the fact that the .epsilon.-caprolactone homopolymer is
essentially non-absorbable led to the development of copolymers of
.epsilon.-caprolactone with variable amounts of more absorbable
monomers to improve the coating absorbability. U.S. Pat. No.
4,624,256 discloses a suture coating copolymer of at least 90
percent .epsilon.-caprolactone and a biodegradable monomer and
optionally a lubricating agent. Examples of monomers for the
biodegradable polymers disclosed include glycolic acid and
glycolide, as well as well-known monomers typically used to prepare
absorbable polymer fibers or coatings for multifilament sutures.
U.S. Pat. No. 4,788,979 and U.S. Pat. No. 4,791,929 disclose a
bioabsorbable coating of a copolymer of at least 50 percent
.epsilon.-caprolactone and glycolide. Sutures coated with such
polymers are reported to be less stiff than sutures coated with
other materials and the physical properties of the coated suture
are also reported to be acceptable. U.S. Pat. No. 4,994,074
discloses copolymers of a predominant amount of
.epsilon.-caprolactone, the balance being glycolide and glycolic
acid. The use of glycolic acid as a comonomer into the copolymers
of this invention was reported to increase the rate of-absorption
of the copolymer when used as a coating for multifilament surgical
sutures.
[0003] Unfortunately, the problem of adequate bioabsorbability of
.epsilon.-caprolactone-based polymers without detrimental effects
on their desirable properties as coatings still remains.
Specifically, the use of sufficient amounts of glycolide to achieve
sufficient absorbability of the copolymeric coating can compromise
its crystallinity and melting characteristics, for it may become
amorphous or liquid near room temperature. On the other hand, the
strategy of using glycolic acid to achieve the reported results in
coating absorbability does limit the ability to produce
sufficiently long chain molecules to achieve optimum frictional
properties, due to glycolic acid's known properties as both a
ring-opening initiator or chain terminator. Thus, a totally new
approach to modifying the absorbability of polycaprolactone and its
copolymers without affecting their desirable properties as suture
coatings or coatings for surgical devices would be a more desirable
goal.
SUMMARY OF THE INVENTION
[0004] One aspect of the invention are low melting, crystalline,
basic nitrogenous polyesters, or polyesteramides, where the amine
functionality represents between 1 and 20 percent of the total
weight, while the repeat units of the polyester chain originate
predominantly from .epsilon.-caprolactone. The balance ester
sequences can be derived from glycolide, lactide, p-dioxanone
and/or one or more of the corresponding hydroxy acids. The amine
functionality can be linked to the polyester chain ionically or
covalently.
[0005] In another aspect, the invention is a coating for a surgical
suture which displays autocatalyzed hydrolysis and improved
absorbability over polyester coatings of the prior art which are
devoid of any basic amine functionality. This coating comprises a
low viscosity melt or a solution in an organic solvent, of the
amine-bearing polyesters described above. Surprisingly, the
incorporation of 1 to 10 percent of the amine functionality
increased the polyester absorbability substantially, without
compromising its desirable physical properties such as those
associated with crystallinity and melting profile.
[0006] Polyesters bearing the amine-functionalities subject of this
invention and coating derived therefrom can be used for coating
bioabsorbable multifilament surgical sutures, as well as other
surgical closure devices and indwelling devices. In addition, they
may be used alone or as carriers or matrices for viable cells and
vaccines, or as a coating containing bioactive agents such as
growth factors, antimicrobials and antibiotics.
DETAILED DESCRIPTION OF THE INVENTION
[0007] Polyesters comprising predominantly .epsilon.-caprolactone
polymer sequences generally refers to polymers with
.epsilon.-caprolactone-based sequences of greater than 80 mole
percent, the monomer compositions from which the polymers of this
invention are derived. .epsilon.-Caprolac-tone is the predominant
component of the polyester because of its low melting,
exceptionally low glass transition temperature (Tg) and its ability
to enhance the surface physical properties of coated multifilament
sutures. Preferably, the amount of .epsilon.-caprolactone used in
the synthesis of the polyester ranges from 90 to 99, more
preferably 96 to 99 mole percent. For copolyesters of this
invention, the remaining comonomers are preferably glycolide and/or
glycolic acid. Other lactones such as lactide and p-dioxanone
and/or their corresponding hydroxy acids can be used. The hydroxy
acids can be used, specifically, as chain initiators to control the
polyester molecular weight, as determined in terms of their
inherent viscosities (I.V.) as approximately 0.1 g/dl solutions in
chloroform, and/or to provide chains with a carboxylic end group.
The basic nitrogenous polyesters which are the subject of this
invention, are to have I.V. of 0.05 to 0.35 dl/g and, preferably,
0.05 to 0.25 and, more preferably 0.10 to 0.20 dl/g.
[0008] Two major types of amine functionalities can be introduced
into the polyester chain to accelerate its absorption through
autocatalyzed hydrolysis. Excluded from the amine-bearing
functionalities are bio-active polypeptides. The weight percent of
the amine functionalities in the polyesters subject of this
invention can be between 1 and 20 and, preferably, 1 to 10. The
first type of amine functionality comprises an ionically linked
mono- or poly-functional amine which is capable of forming a
carboxylate salt with an acid-terminated polyester chain. This can
entail, for instance, a caprolactone/glycolide copolymer made using
catalytic amounts of stannous octoate and glycolic acid as the
chain initiator, and following a typical reaction scheme
established for caprolactone polymerization. The resulting acid
terminated polyester is then allowed to form carboxylate salts with
amine-bearing molecules: lysine, 1-lysine, potassium lysinate, or
an alkane diamine as depicted by structures A and B,
respectively.
1 Polyester 1 2(A) K.sup.+ Polyester 3 4(B) Polyester 5 6(C)
Polyester X = alkane or cycloalkane group, R' = H or alkyl
group
[0009] The second type of amine functionality is covalently
incorporated into the polyester chain. This can be achieved by
amidation of preformed polyester with di- or poly-functional amine
or using di- or poly-amine with at least one reactive hydrogen as
the chain initiator, such as 1-methyl 4-aminomethyl-piperidine and
3,3'-diamino N-methyl-diproppylamine. The ring opening
polymerization can be achieved using catalytic amounts of stannous
octoate. Typical polyesters covalently linked to the amine
functionalities can be illustrated by structures D and E shown
below.
R.sub.2N--X--NH--CO--(CH.sub.2).sub.n--O--CO-Polyester (D)
[0010] n=1 or 5
[0011] R=CH.sub.3 or C.sub.2H.sub.5
[0012] X=alkane or cycloalkane group
R.sub.2N--[X--NH--CO--(CH).sub.n--O--CO-Polyester].sub.2 (E)
[0013] n=1 or 5
[0014] R=CH.sub.3 or C.sub.2H.sub.5
[0015] X=Alkane or cycloalkane group
[0016] Although this invention addresses low melting crystalline
polyesters made predominantly of .epsilon.-caprolactone, those
skilled in the art can foresee the use of other aliphatic
polyesters as the base materials and incorporate the amine
functionality to the acid terminated polyester chains by salt
formation or the amidation of pre-formed polyester chains using
amino compounds similar to those associated with structures D and E
above.
[0017] The coating can be applied to the braided suture as a low
viscosity melt at temperatures between 70.degree. C. and
100.degree. C. and, preferably 70.degree. C. and 90.degree. C.
Excess coating can be removed by passing through a pad of non-woven
fabric, e.g., polypropylene or a sizing die. More traditional
methods of coating application can entail the use of 1 to 15
percent solution and, preferably, 2 to 10 percent in an organic
solvent such as toluene at room temperature or between 25.degree.
C. and 50.degree. C. The solvent can then be evaporated by
air-drying at room temperature or between 25.degree. C. and
75.degree. C. Other solvents or mixture of solvents can be used as
substitutes for toluene or acetone. The coated suture can be
further treated thermally to insure even distribution of the
coating on the braid components. Typical sutures which can be
coated with compositions subject of this invention include those
made of polyglycolide and polyethylene terephthalate. Depending on
the suture size, the percent add-on of the coating can be varied
between 1 and 10 percent and, preferably, 1.5 to 4.5 percent as the
suture decreases from say size #1 to size #6-0. At such level of
coating, the suture handling and tie-down characteristics are
improved substantially without compromising other properties such
as visibility, surface appearance, and knot strength and
security.
[0018] The absorption profile of the coating is such that it will
not affect that of an absorbable suture to any discernable extent.
Typically, when representative coatings subject of this invention
are used on polyethylene terephthalate sutures incubated in a
phosphate buffer at 37.degree. C. and pH of 7.26 lose 50 to 100
percent of their original mass in two to six months.
[0019] The following examples illustrate the claimed invention and
are in no way intended to limit its scope.
EXAMPLE 1
[0020] Synthesis of Acid-Terminated Polycaprolactone Polymer A
[0021] .epsilon.-Caprolactone (57.1 g, 0.5 mole) glycolic acid (7.6
g, 0.1 mole) and stannous octoate (0.5 ml of 0.1 M solution in
toluene, 20 mg, 5.times.10.sup.-5 mole) were added to a glass
reactor. The reactor was purged with dry nitrogen gas. The reactor
was heated in an oil bath at 180.degree. C., under nitrogen, for 12
hours while the contents were magnetically stirred. The resultant
homopolymer has a Tg of -60.degree. C. and Tm of 39.degree. C. as
measured by DSC. The resultant polymer inherent viscosity is 0.1
dl/g at 30.degree. C. in hexafluoroisopropyl alcohol.
EXAMPLE 2
Preparation of Potassium L-Lysinate Salt of Polymer A
[0022] Potassium L-lysinate (1.25 ml of 2.0 M solution in methanol,
25 mmole), is slowly added with stirring to Polymer A (4.4 g) in
100 ml tetrahydrofuran at room temperature. The tetrahydrofuran is
then removed by vacuum. The structure of the resultant coating as
an onium salt was determined by IR and NMR.
2 The Tg and Tm were shown by DSC to be -62.degree. and 44.degree.
C., respectively. Elemental analysis data were consistent with the
proposed chemical structure: % N % K Pound 1.52 2.23 Calculated
1.45 2.05
EXAMPLE 3
Synthesis of Random Copolymer of 98.5/1.5 caprolactone-glycolide,
Copolymer B
[0023] .epsilon.-Caprolactone (57.1 g, 0.5 mole), glycolide (1.1 g,
9.5 mmole), glycolic acid (7.6 g, 0.1 mole) and stannous octoate
(0.5 ml of 0.1 M solution in toluene, 20 mg, 5.times.10.sup.-5
mole) were added to a glass reactor. The reactor was purged with
dry nitrogen gas. The reactor was heated in an oil bath at
180.degree. C. under nitrogen for 12 hours, while the contents were
magnetically stirred. The final composition was determined by
.sup.1H NMR is shown to be essentially the same as the theoretical.
The Tg is -62.degree. C., and the Tm is 37.degree. C.
EXAMPLE 4
Preparation of Potassium L-Lysinate Salt of Copolymer B
[0024] Potassium L-lysinate (1.25 ml of 2.0 M solution in methanol,
25 mmole), is slowly added with stirring to Polymer B (4.4 g) in
100 ml tetrahydrofuran at room temperature. The tetrahydrofuran is
then removed by vacuum. The structure of the resultant coating as
an onium salt was determined by IR and NMR. The Tg and Tm were
shown by DSC to be -60.degree. and 39.degree. C., respectively.
Elemental analysis data were consistent with the proposed chemical
structure:
3 % N % K Found 1.31 2.03 Calculated 1.45 2.05
EXAMPLE 5
Synthesis of Random Copolymer of 95/5 .ang.-Caprolactone/Glycolide,
Copolymer C
[0025] Following a procedure similar to that used for the synthesis
of Copolymer B, copolymer C was made and shown to have an inherent
viscosity of 0.1 dl/g in HFIP at 25.degree. C. It has a Tg of
-60.degree. C., and Tm of 40.degree. C.
EXAMPLE 6
Preparation of Potassium L-Lysinate Salt of Copolymer C
[0026] The salt is prepared following a procedure similar to that
used for the preparation of the salt of Copolymer B. The
composition of the resultant coating was consistent with its
elemental analysis and NMR data. The Tg and Tm were shown by DSC to
be -53.degree. C. and 36.degree. C., respectively.
EXAMPLE 7
Synthesis of Acid-Terminated Polycaprolactone, Polymer D
[0027] .epsilon.-Caprolactone (57.1 g, 0.5 mole) lactic acid (9.0
g. 0.1 mole) and stannous octoate (0.5 ml of 0.1 M solution in
toluene, 20 mg, 5.times.10.sup.-5 mole) were added to a glass
reactor. The reactor was purged with dry nitrogen gas. The reactor
was heated in an oil bath at 180.degree. C., under nitrogen, for 12
hours, while the contents were magnetically stirred. The resulting
Polymer D was removed and shown to have an inherent viscosity of
0.1 dl/g in hexafluoro-isopropyl alcohol.
EXAMPLE 8
Preparation of Amine-Trerminated Polycaprolactone, Polymer E
[0028] .epsilon.-Caprolactone (57.1 g, 0.5 mole),
1-methyl-4-aminomethyl piperidine (2.5 g, 0.02 mole) and stannous
octoate (0.5 ml. of 0.1 M solution in toluene, 20 mg, 5.times.10
mole) were transferred to a predried glass reactor under
oxygen-free dry nitrogen atmosphere. The reaction mixture was
heated to 170.degree. C. under dry nitrogen. The polymerization was
continued for 12 hours while the contents were magnetically
stirred. The resulting Polymer E was removed and shown to have an
inherent viscosity of 0.15 dl/g in hexafluoroisopropyl alcohol.
EXAMPLE 9
Preparation of Polycaprolactone with Internally Placed Amine
Functionality, Polymer F
[0029] Using the same polymerization scheme as in Example 8 and all
reagents except 1-methyl-4-aminomethyl piperidine, which was
replaced by 3,3'-diamino-N-methyldipropylamine (2.32 g, 0.016 mole)
to produce a polymer having as inherent viscosity of 0.13 dl/g.
EXAMPLE 10
Preparation of Potassium L-Lysinate Salt of Polymer D
[0030] This is done following a procedure similar to that used for
the preparation of the coating in Example 2.
EXAMPLE 11
Solution Coating of Size 2-0 Polyglycolide Braided Suture
[0031] The suture is dipped 5-10 times in a 2 percent solution of
the coating (from Examples 2, 4, or 6) in methylene chloride, with
each coat dried in between dips. This yields a very thin
homogeneous coating layer (typically 2.5 to 5 weight percent of the
suture) which gives excellent knot tie-down properties both wet and
dry, with no visible flaking.
EXAMPLE 12
[0032] Application of Molten Coating Polymer to Size 2-0
Polyglycolide Braided Suture
[0033] The suture is passed through the molten coating (from
Examples 2, 4, or 6) in a temperature of 5.degree. C. to 50.degree.
C. above the melting temperature of the coating material, and then
threaded through two non-woven Teflon.RTM. pads under slight
compression to remove excess coating. This yields a thin, uniform
coating layer (typically 5 weight percent of the suture). The
coated suture exhibited excellent knot tie-down properties both wet
and dry, with no visible flaking.
EXAMPLE 13
[0034] Absorption Profiles of Coatings
[0035] Depending on the composition of the polyester component as
in Examples 4 and 6 of the coating, and the level of amino groups,
the mass loss ranges from 10 to 20 at three weeks, 40 to 50 at ten
weeks, and 55 to 65 at thirteen weeks. To obtain accurate weight
loss, a size 2-0 non-absorbable suture braid made of polyethylene
terephthalate was used.
EXAMPLE 14
Synthesis of a 95/5 .epsilon.-Caprolactone/Glycolide Copolymer
(J)
[0036] .epsilon.-Caprolactone (456.6 g., 4 mole), glycolide (24.4
g, 0.21 mole), glycolic acid (30.4 g, 0.4 mole), and stannous
octoate (4 ml. of 0.2 M solution in toluene, 0.8 mmole) were
transferred to a predried, stirred reactor. The polymerization
charge was treated as follows: (1) after purging with dry argon,
the charge was heated to 50.degree. C. under reduced pressure
(about 0.1 mm Hg) for 30 min.; (b) the reaction pressure was
returned to atmospheric and the polymerization charge was heated to
150.degree. C. while stirring, and kept at this temperature for 14
hours; .COPYRGT. the temperature of the polymer was lowered to
120.degree. C. and vacuum was applied for about 35 min. before
cooling to 80.degree. C. and bringing the pressure to one
atmosphere with argon; and (d) the polymer was transferred to a
predried jar for storage at room temperature and reduced pressure.
The final composition was determined by NMR and shown to be
essentially the same as expected.
EXAMPLE 15
Preparation of L-Lysinate Salt of Copolymer G
[0037] Copolymer G (5.0 g.) was dissolved in 50 ml. acetone. A
solution of 1-lysinate (0.5 g. in 1.5 ml. water) was added dropwise
(5 min) to the copolymer solution under argon atmosphere, while
stirring. Upon completing the addition, the solution was stirred
further for about 30 min.; then 5 g of anhydrous sodium sulfate
were added, and the mixture was stirred at room temperature for at
least 4 hours. The mixture was then filtered and the filtrate was
transferred for storage under dry argon atmosphere at about
4.degree. C. Part of the filtered solution of the 1-lysine salt was
evaporated under reduced pressure at 25.degree. C. and then at
40.degree. C. The infrared spectra of the resulting solid were
consistent with the expected structure.
EXAMPLE 16
Solution Coating of Size 2-0 Polyglycolide Braided Suture
[0038] The suture was threaded through a 10% acetone solution of
the 1-lysine salt of copolymer G. The coated suture was dried at
room temperature, and displayed similar characteristics to those
described in Example 11.
[0039] Similarly, coating solutions for monofilament,
multi-filament and braided sutures may be made using 90 to 99% by
weight of the acid terminated caprolactone polymer of Example 14
and 1 to 10% by weight 1-arginine following a procedure similar to
that used for the preparation of the coating in Example 15. The
suture, such as a size 2-0 polyglycolide braided suture, may be
coated as described in Example 16.
[0040] The polymers of the present invention have other important
uses, as absorbable lubricious coatings. As such, these polymers
may be used as coatings for surgical staples and other surgical
closure devices such as facia fasteners. In addition, the polymers
of the present invention may also be used to coat percutaneous
surgical devices, such as trocars, endoscopes, and endoscopic
catheters, instruments and devices. For the needles of syringes and
catheters, and for catheters in general, these polymers may replace
silicone and teflon lubricants.
[0041] An example of an antibiotic, lubricant coating for a
catheter can be made by mixing a 5% acetone solution of the polymer
salt of Example 17, at 85 to 90% by weight, with a 20% aqueous
solution of cephalexin hydrochloride monohydrate, at 1 to 15% by
weight. The mixed system may then dried with anhydrous sodium
sulfate and kept at 40 C in a dark container under dry argon until
used. The intravenous catheter may be dipped into the mixed
solution for 1 to 20 minutes and air dried in a laminar-flow
hood.
[0042] In fact, the polymers of the present invention may be used
to coat most surgical implants. In this regard, it is to be noted
that coatings of the polymers of the invention may incorporate
bioactive agents such as growth factors, antimicrobials and
antibiotics, especially useful to combat implant-induced infection.
In a similar manner, coatings of the polymers of the present
invention may be used to coat synthetic vascular grafts and similar
graft devices such as stents, and shunts. They may also be used to
coat open-cell microporous templates or constructs, such as those
made of open-cell sponge, for use in tissue regeneration.
[0043] The speed of the hydrolysis of the nitrogenous polyesters of
the present invention may be modulated to suit the many uses of the
polymer. Polymers with the amine-bearing structures at the chain
ends, linked ionically to the polyester sequences, will
autocatalyze more slowly than if the amine-bearing structures are
covalently linked to the chain ends, as the residence time of the
catalytic component of the tonically linked amine structure will be
shorter than the residence time of the catalytic component of the
covalently linked amine structure. Similarly, if the amine-bearing
structure is internally placed, the projected residence time of the
catalytic component will be greater, and these nitrogenous
polyesters will undergo autohydrolysis faster.
[0044] The nitrogenous polyesters of the present invention are
pliable and waxy. They may be used to replace bone wax, and, With
or without a solvent, may be used as a tissue sealant spray or a
compliant barrier. The polymers of the present may also be used to
form a matrix for peptides and proteins for use in modulating
certain biological events, such as cell division; and as a matrix
for vaccines and growth factors. They may also be used as a carrier
for viable cells, such as chondrocytes cells for cartillage, and
osteoblasts, and/or growth factors, such as insulin, and platelet
derived growth factor.
[0045] The nitrogenous polyesters of the present invention are also
useful as hemostatic agents. In this use, its performance may be
augmented by certain metal ions known for hemostatic use, such as
multivalent ions of calcium, iron, zinc, chromium and magnesium.
The polymers of the present invention may also be put to use as
components of therapeutic or prophylactic systems for managing
orthopedic, vascular, or dental infection. For example,
osteomyelitis.
* * * * *