Note: Descriptions are shown in the official language in which they were submitted.
CA 02162801 2006-03-06
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COATED GUT SUTURE
CROSS-REFERENCE TO RELATED APPLICATION
BACKGROUND
1. Technical Field
The present disclosure relates to a coated gut
suture and, more particularly, to a coated gut suture
which is capable of being dry packaged.
2. Background of the Related Art
Absorbable sutures are manufactured from
natural or synthetic materials. Some of the earliest
absorbable sutures were made of collagenous material
taken from sheep intestines. Such sutures are still in
use today and are commonly referred to as "catgut" or
simply "gut" sutures or ligatures. In the present
specification, the term "catgut" or "gut" suture refers
to a collagen based suture or ligature of any type or
origin. Gut sutures may be prepared in the form of
threads or strands that are undesirably stiff before
subsequent treatment which renders them flexible or
pliable.
A suture having a good degree of flexibility
and pliability can conform closely to body tissue
without undue pressure. Good flexibility and pliability
enhance the degree to which a suture can be tied down,
knotted and securely placed in a desired position.
Various attempts have been made to modify and
optimize the physical characteristics of gut sutures.
For example, tubing fluids, i.e., liquids which are used
to condition gut sutures to achieve or enhance
flexibility and pliability, have been used to preserve
gut sutures. Tubing fluids typically contain an alcohol
such as isopropyl alcohol and a relatively small
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percentage of water. Examples of tubing fluids are found
in U.S. Patent Nos. 1,239,690, 2,394,054, 2,519,404,
2,524,772, and 2,694,487. Ideally, the tubing fluid aids
the gut suture to retain its flexibility and pliability
without adversely affecting the strength and overall
integrity of the suture.
Commercially available gut sutures are
immersed in tubing fluid, sterilized and supplied to
surgeons in packages or tubes which contain tubing
fluid. The alcohol and water present in the tubing
fluid keep the suture flexible and pliable as long as
they remain in contact with the suture. As the tubing
fluid evaporates, the suture loses its flexibility and
pliability which may affect handling characteristics.
In addition to tubing fluids, various suture
coatings which adhere to the surface of the suture have
been developed in an attempt to maintain flexibility and
control swelling and fraying. Such coatings are also
intended to improve the handling characteristics of
sutures and maximize run-down performance. For example,
U.S. Patent No. 3,942,532 discloses a suture coating
composition obtained by polymerizing lactones such as
epsilon-caprolactone in the presence of a
polymethylenediol. U.S. Patent No. 4,624,256 discloses
a suture coating composition containing a high molecular
weight epsilon-caprolactone homopolymer, or a copolymer
derived from a major amount of epsilon-caprolactone and
a minor amount of a comonomer or a blend of such an
epsilon-caprolactone polymer with a lubricating agent
(e.g., sterol esters of fatty acids).
Copolymers derived from epsilon-caprolactone
and at least one other monomer such as glycolide,
lactide, p-dioxanone and trimethylene carbonate are
disclosed in U.S. Patent Nos. 4,605,730, 4,624,256,
4,700,704, 4,788,979, 4,791,929, 4,994,074, 5,076,807,
5,080,665, 5,085,629 and 5,100,433.
U.S. Patent No. 3,896,814 discloses a dry-
packaged gut suture which is coated with a treatment
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agent such as polyoxyethylene glycol. U.S. Patent No.
4,027,676 discloses a gut suture coated with a three-
component coating composition. This patent discloses
polyalkylene glycol as one ingredient of the three-
component coating composition. U.S. Patent No. 4,506,672
discloses a gut suture coated with a cured isocyanate-
capped polyester which can be packaged either dry or in
alcohol-containing wrappers. U.S. Patent No. 4,649,920
discloses an absorbable surgical suture coated with a
high molecular weight poly(alkylene oxide).
The aforementioned U.S. Patent Nos. 3,896,814,
4,027,676, 4,506,672 and 4,649,920 do not disclose a gut
suture which is coated with an epsilon-caprolactone-
containing bioabsorbable copolymer.
SUNIIKARY
A gut suture is coated with a composition
comprising a bioabsorbable copolymer obtained by
polymerizing a major amount of epsilon-caprolactone and
a minor amount of at least one other copolymerizable
monomer in the presence of a polyhydric alcohol
initiator.
The use of a polyhydric alcohol initiator,
i.e., an alcohol possessing three or more hydroxyl
groups, provides a copolymer having a branched, or
"star", configuration. The branched structure of the
bioabsorbable copolymer exerts a characteristic
influence on its bioabsorption behavior making it useful
as a coating material for gut sutures.
The gut suture coated with the bioabsorbable
copolymer can optionally be packaged in the dry state,
i.e., in the absence of tubing fluid, and yet still
maintain substantially the same degree of flexibility,
pliability and resistance to fray exhibited by a gut
suture which is stored in tubing fluid. Thus, a gut
suture coated with a coating composition in accordance
with this disclosure can be packaged in a manner which
is typical for conventional surgical sutures and, when
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removed from its package, be immediately employed by the
surgeon.
In an alternative embodiment, a pre-coating
composition is applied to the gut suture prior to being
coated with a bioabsorbable copolymer in accordance with
this disclosure. A preferred pre-coating composition
includes poly(alkylene oxide) such as polyethylene
glycol.
BRIEF DESCRIPTION OF THE DRAWING
Fig. 1 schematically illustrates a fray
testing system for sutures.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Conventional polymerization techniques that
are well known and disclosed in the prior art can be
utilized in preparing the bioabsorbable copolymer
employed as a coating composition for a gut suture. The
bioabsorbable copolymer is obtained by polymerizing a
major amount of epsilon-caprolactone and a minor amount
of at least one other copolymerizable monomer or mixture
of such monomers in the presence of a polyhydric alcohol
initiator. The polymerization of these monomers
contemplates all of the various types of monomer
addition, i.e., simultaneous, sequential, simultaneous
followed by sequential, sequential followed by
simultaneous, etc.
Suitable monomers which can be copolymerized
with epsilon-caprolactone include glycolide, lactide, p-
dioxanone and trimethylene carbonate.
Suitable polyhydric alcohol initiators include
glycerol, trimethylolpropane, 1,2,4-butanetriol, 1,2,6-
hexanetriol, triethanolamine, triisopropanolamine,
erythritol, threitol, pentaerythritol, ribitol,
arabinitol, xylitol, N,N,N',N'-tetrakis(2-
hydroxyethyl)ethylenediamine, N,N,N',N'-tetrakis(2-
hydroxypropyl)ethylenediamine, dipentaerythritol,
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allitol, dulcitol, glucitol, altritol, iditol, sorbitol,
mannitol, inositol, and the like.
The copolymer can contain from about 70 to
about 98, and preferably from about 80 to about 95,
5 weight percent epsilon-caprolactone-derived units, the
balance of the copolymer being derived from the other
copolymerizable monomer(s). The inherent viscosity of
the copolymer generally ranges from about 0.10 to about
0.60, and preferably from about 0.20 to about 0.50, dl/g
when measured in chloroform at a concentration of 0.2500
g/dl at 30 C. The polyhydric alcohol initiator is
generally employed in small amounts, e.g., from about
0.5 to about 5, and preferably from about 0.1 to about
2, weight percent of the total monomer mixture.
The bioabsorbable copolymer can be applied to
a gut suture by any suitable process, e.g., by passing
the gut suture through a solution of the copolymer,
e.g., in acetone, methylene chloride, etc., past a brush
or other coating solution applicator, or past one or
more spray nozzles dispensing the gut suture coating
solution. The gut suture wetted with the coating
solution is subsequently air dried and/or passed through
or held in a drying oven for a time and at a temperature
sufficient to vaporize and drive off the solvent.
Preferably, the coated gut suture is first air dried and
then dried in an oven maintained at a temperature of
about 50 C. The solution of bioabsorbable copolymer can
contain a suitable amount of water or other moisturizing
agent which swells the gut suture and imparts a
desirable degree of flexibility and pliability to the
suture. The bioabsorbable copolymer will entrap the
moisture within the suture and/or enhance the retention
of the moisture within the suture. If desired, the gut
suture coating composition can optionally contain
additional components, e.g., dyes, antibiotics,
antiseptics, growth factors, anti-inflammatory agents,
etc. The amount of coating composition applied to a gut
suture will vary depending upon the structure of the
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suture, e.g., the number of filaments, tightness of
braid or twist, the size of the suture and its
composition.
In an alternative embodiment herein, a gut
suture is pre-coated with a pre-coating composition
prior to being coated with the bioabsorbable copolymer
disclosed herein. Examples of pre-coating compositions
which can be employed herein include compositions
containing fatty acids, esters and ethers of fatty
acids, polyalcohols, fatty alcohols, glycerine, glycols
and derivatives thereof and poly(alkylene oxides). Pre-
coating compositions containing poly(alkylene oxides)
are preferred. Particularly preferred are poly(alkylene
oxides) or derivatives thereof having molecular weights
ranging from about 300 to about 5000. Examples of
poly(alkylene oxides) which can be employed include
polyethylene glycol, polypropylene glycol and
polyethylene glycol methyl ether. Such pre-coating
compositions can generally be applied to the gut suture
at a level of from about 0.1 to about 10 weight percent
or more and preferably from about 0.5 to about 5 weight
percent, based on the final weight of the coated gut
suture. The pre-coating composition can be applied to a
gut suture by simply immersing the suture in a solution
or suspension containing the pre-coating composition and
drying the suture. The solution or suspension can
contain water which swells the gut suture and becomes
entrapped therein by virtue of the coating of the pre-
coating composition. Optionally, the gut suture can be
immersed in water and/or moisturizing agent to render
the suture flexible and pliable prior to contacting the
suture with the solution/suspension containing pre-
coating composition.
The bioabsorbable copolymer can be applied to
the suture after application of the pre-coating
composition. The amount of bioabsorbable copolymer
applied to a gut suture which has been pre-coated can
range from about 0.2 to as much as about 3 weight
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percent or more and preferably from about 0.5 to about 2
weight percent. For a gut suture which has not been
pre-coated, the bioabsorbable copolymer can be applied
at a level of from about 0.5 to about 4 weight percent
or more and preferably from about 1 to about 3 weight
percent. As a practical matter, it is generally
preferred to apply the minimum amount of coating
composition consistent with good tie-down performance.
This level of coating can be readily determined
employing routine experimental procedures.
The following examples should be considered as
illustrative and not as limitations of the present
description. The examples demonstrate that coating
formulations containing bioabsorbable copolymer and pre-
coating composition as disclosed herein enhance the
properties of gut sutures coated therewith.
Formulation 1
Dry glycolide (300g), epsilon-caprolactone
(2760g), stannous octoate as catalyst (0.3g) and dry
mannitol as initiator (39.Og) were mixed under N2 for
one hour. The mixture was heated in a reactor at a
temperature of 160 C for 24 hours. A solution of the
resultant copolymer was prepared by dissolving the
copolymer (5g) in toluene (95cc) and stirring the
resultant mixture.
Formulation 2
A solution of polyethylene glycol methyl ether
350 (PEGME 350) (number average molecular weight of 350
and viscosity of 4.1 centistokes at 210 F) was prepared
by mixing PEGME 350 (50cc) in isopropyl alcohol (50cc)
and stirring the resultant mixture.
Formulation 3
A solution of polyethylene glycol methyl ether
350 was prepared by mixing PEGME 350 (as used in
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Formulation 2) (70cc) in isopropyl alcohol (30cc) and
stirring the resultant mixture.
Formulation 4
A solution of polyethylene glycol methyl ether
350 was prepared by mixing 60 cc of PEGME 350 (as used
in Formulation 2) with 40 cc of a solution made.from 20%
water and 80% isopropyl alcohol.
Formulation 5
A solution of polyethylene glycol 600 (PEG
600) (number average molecular weight of 600 and
viscosity of 10.5 centistokes at 210 F) was prepared by
mixing 60 cc of PEG 600 in 40 cc of a solution made from
20% water and 80% isopropyl alcohol.
EXAMPLE 1
Chrome gut sutures of size 1 are passed
through a 10% solution of the copolymer of Formulation 1
in methylene chloride. The sutures are then air dried
to remove the solvent, leaving a coating of the
copolymer on the suture.
EXAMPLE 2
A chrome size 1 gut suture was dipped in the
solution of Formulation 2 for 30 minutes, air dried and
thereafter dried in an oven at 50 C for 5 minutes. The
suture was then dipped in the solution of Formulation 1
for about 1 minute, air dried for 120 minutes and oven-
dried at 50 C for 5 minutes. The resulting suture was
then packaged dry and tested for number of cycles to
break.
EXAMPLE 3
A chrome size 1 gut suture was dipped in the
solution of Formulation 3 for 30 minutes, air dried and
thereafter dried in an oven at 50 C for 5 minutes. The
suture was then dipped in the solution of Formulation 1
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for about 1 minute, air dried for 120 minutes and oven-
dried at 50 C for 5 minutes. The resulting suture was
then packaged dry and tested for number cycles to break.
EXAMPLE 4
A chrome size 1 gut suture was immersed in the
solution of Formulation 4 for 30 minutes at 50 C, air
dried for 60 minutes and thereafter immersed in the
solution of Formulation 1 for about 1 minute. The
suture was then removed, air dried for 120 minutes and
oven-dried at 50 C for 5 minutes. The resulting suture
was then packaged dry and tested for number of cycles to
break.
EXAMPLE 5
A chrome size 1 gut suture was immersed
in the solution of Formulation 5 for 30 minutes at 50 C,
air dried for 60 minutes and thereafter immersed in the
solution of Formulation 1 for about 1 minute. The
suture was removed, air dried for 120 minutes and oven-
dried at 50 C for 5 minutes. The resulting suture was
then packaged dry and tested for number of cycles to
break.
COMPARATIVE EXAMPLE 1
A chrome size 1 gut suture was immersed in
isopropyl alcohol for 30 minutes at 50 C, air dried for
60 minutes and thereafter immersed in toluene for one
minute. The coated suture was removed, air dried for 120
minutes and oven-dried at 50 C for 5 minutes. Thus,
this gut suture contains no polymeric coating
composition. The suture was packaged dry and tested for
number of cycles to break.
Table I below presents the data which resulted
from tests conducted on the coated gut sutures of
Examples 2-5 and Comparative Example 1. Tensile
strength was tested in accordance with the test
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procedure described in ASTM D-2256. Percent elongation
was tested in accordance with the test procedure
described in ASTM D-2256. Young's Modulus, which is a
measurement of flexibility, is the initial modulus as
5 determined from the slope of the stress-strain curves
produced in straight-pull strength tests carried out in
accordance with the test procedure described in ASTM D-
2256. Young's Modulus is the ratio of applied stress to
strain in the elastic region.
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Table I
Tensile
Young's
Number of Standard Strength Percent
Modulus
Example Cycles to Break Deviation {kpsi) Elongation
k si
2 52.7 11.0 75 21.3
178
3 28.4 34.0 76 21
89.7
4 17.7 13.0 83 20.5
208
5 44.5 12.0 81 21.6
207
Comparative 0.3 0.2 79.2 18.9
199.7
Example 1
Af`T
The number of cycles needed to break each of
the sutures of Examples 2-5 and Comparative Example 1
was determined using the fray resistance test
schematically illustrated in Fig. 1. A static suture 10
is wound around rollers 12 and tied into a knot 14. A
dynamic suture 20 is placed into a grip 23 and extended
to reach the static suture 10 where it is wrapped twice
at point 25 around the static suture 10. The dynamic
suture 20 is extended around roller 26 and attached to a
weight 24 which supplies tension to the dynamic suture
20. The grip 23 and dynamic suture 20 move up and down
to cause the sutures to rub against each other at point
25. One cycle is a complete up and down movement of the
grip 23 and dynamic suture 20. Testing conditions
included a preload weight which is 15% of the USP limit
on average knot pull strength for gut sutures. The
travel distance for the grip was 50mm for each cycle at
a speed of 500mm/minute. The test is dependent on the
number of cycles needed to break a suture due to the
fraying which occurs when one strand of suture, under
applied load, slides against another static strand. A
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modified Sintech 1/G MTS system tester is used to
conduct the fraying test. The bottom grip is removed
from the tester, the load calibrated and gage set to
zero. The static suture 10 is tied with sufficient
tension around the rollers 12 of the fixture, forming a
square. The fixture is adjusted so the point 25 where
the static suture 10 and dynamic suture 20 interface is
in line with the center line of the upper grip. The
preload weight for these examples was 0.550 (15% of USP
knot pull, kg.). The test is initiated with cycling
observed until one of the sutures breaks to stop the
test. If strands should lock themselves in a knot and
do not slide against each other it is considered a
break. The average number of cycles (Xave.) is Xave. -
(X1 + X2 +.... + Xn)/n wherein Xn is the number of
cycles to break each pair of strands and n is the number
of pairs. The standard deviation s is calculated as
I
i
s= L1=xl?
n - i.
It can clearly be seen from the data of Table
I that the average number of cycles to break the dry
packaged gut sutures coated in accordance with this
disclosure (Examples 2-5) were much higher relative to
the uncoated dry packaged gut suture of Comparative
Example 1. Furthermore, it can be seen from these data
that the tensile strength, percent elongation and
Young's modulus of each of the dry packaged coated
sutures of Examples 2-5 remained comparable to that of
the uncoated dry packaged suture of Comparative Example
1.
It will be understood that various
modifications may be made to the embodiments disclosed
herein. For example, the pre-coating composition can be
applied to a gut suture after the bioabsorbable
copolymer described herein has been applied to the
suture. Therefore, the above description should not be
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construed as limiting, but merely as exemplifications
within the scope and spirit of the claims appended
hereto.
