Note: Descriptions are shown in the official language in which they were submitted.
1 3 3 7 0 0 4 (1088)
1 ABSORBABLE COATING COMPOSITION, COATED SUTURES
AND METHOD OF PREPARATION
BACKGROUND OF THE INVENTION
This invention relates to an absorbable coating
composition for surgical sutures and more particularly to
coated, surgical sutures having, among other desirable
characteristics, improved knot tie-down properties.
Monofilament synthetic absorbable suture materials
are generally stiffer than their catgut or collagen
counterparts and therefore synthetic absorbable sutures are
usually employed in a multifilament, such as a braided or
twisted construction, in order to provide the suture with
the desired degree of softness and flexibility.
Multifilament sutures, however, exhibit a certain degree of
undesirable roughness, in what is generally referred to as
tie-down performance, i.e. the ease or difficulty of sliding
a knot into place down the suture.
Thus, the problem of improving knot tie-down
performance of multifilament surgical sutures has been the
subject of considerable research. For example, U.S. Patent
No. 4,027,676 relates to an absorbable coated multifilament
suture disclosed to have improved tie-down properties. In
particular, the absorbable coated suture of this patent
consists of a synthetic absorbable suture coated with an
absorbable composition consisting of an absorbable
film-former, an absorbable lubricant and an absorbable
hydrophobic material. Suitable film formers according to
this patent include homopolymers of lactide and glycolide,
i.e. polylactide, polyglycolide and copolymers of lactide
3 and glycolide with each other and with other reactive
monomers, copolymers of vinyl acetate with unsaturated
. -2- 1 3 3 7 0 ~ 4
1 carboxylic acids such as crotonic, acrylic and methacrylic
acids; water soluble or dispersible cellulose derivatives
such as methyl cellulose, hydroxymethyl cellulose and
carboxymethyl cellulose; natural gums; high molecular weight
crystalline ethylene oxide polymers; polyacrylamide;
collagen; gelatin; polyamino acids; polyvinyl alcohol;
polyvinyl pyrrolidone and absorbable conjugated unsaturated
triglycerides, such as dehydrated castor oil. The lubricant
of the composition is disclosed to be a polyethylene glycol
having a molecular weight of less than about 200,000, such
as copolymers of ethylene oxide and propylene oxide.
Particularly preferred is polyethylene glycol at a molecular
weight of from about 4,000 to about 200,000 and more
preferably from 5000 to 50,000. The hydrophobic material
is disclosed as a higher fatty acid having more than about
12 carbon atoms such as stearic acid or an ester of such a
fatty acid such as sorbitan tristearate and hydrogenated
castor oil.
Similarly, U.S. Patent Nos. 4,043,344 and
4,047,533 disclose that the handling characteristics,
particularly knot run down and tissue drag of non-absorbable
and absorbable sutures can be improved by a coating of a
lubricating film of a bioabsorbable copolymer having
polyoxyethylene blocks and polyoxypropylene blocks, e.g.
Pluronics.
U.S. Patent No. 3,942,532 discloses that the
tie-down performance of braided sutures may be improved by
coating the surface with a polyester derived from the
polymerization of lactones as a polyester obtained by
esterifying low molecular weight glycols with a dimeric
acid.
U.S. Patent No. 4,080,969 discloses improved knot
tie down properties may be imparted to a suture by coating
1 33700~
1 the suture with a hydrolyzable polyester resin of a
diglycolic acid and an unhindered glycol, such as ethylene
glycol or diethylene glycol.
Numerous other patents disclose sutures and/or
coated sutures having improved handling characteristics.
These include, U.S. Patent No. 4,452,973, U.S. Patent No.
4,201,216, U.S. Patent No. 4,224,946, U.S. Patent No.
4,314,561, U.S. Patent No. 4,105,034, U.S. Patent No.
4,185,637, U.S. Patent No. 4,532,929, U.S. Patent No.
4,608,428, U.S. Patent No. 3,867,190, U.S. Patent No.
3,540,452, U.S. Patent No. 3,527,650, U.S. Patent No.
3,379,552 and U.S. Patent No. 3,655,927, among others.
Notwithstanding the extensive research in
attempting to improve the tie-down characteristics of
surgical sutures, sutures having even further improved knot
tie-down properties are still desirable.
-
SUMMARY OF THE INVENTION
Accordingly, it is one object of the present
invention to provide an absorbable coating composition forsurgical sutures, particularly multifilament synthetic
sutures.
Another object of this invention is to provide a
coated surgical suture having improved knot tie down
Properties.
Still another object of the present invention is
to provide an absorbable, coated synthetic suture having
improved knot tie-down properties under both wet and dry
conditions.
A further object of this invention is to provide
an absorbable, coated synthetic suture having an improved
coated which is not readily susceptible to wash off under
wet conditions.
1 3370~
1 A still further object of the present invention is
to provide a method for imparting improved knot tie-down
properties to synthetic absorbable multifilament sutures.
These and other objects are achieved herein by
providing an absorbable polymeric coating composition
comprising either (i) a copolymer derived from the
copolymerization of a low molecular weight polyalkylene
glycol, a glycolide monomer and a lactide monomer or (ii) a
copolymer derived from the copolymerization of a low
molecular weight polyalkylene glycol and a preformed
copolymer of lactide and glycolide. Coated sutures, having
improved knot tie-down properties, under dry and wet
conditions, are provided by depositing a coating of the
afore-described coating composition on the suture.
DETAILED DESCRIPTION OF THE INVENTION
It has been discovered herein that the knot
tie-down characteristics of multifilament sutures, such as
braided or twisted sutures, are improved by applying a
surface coating of a non-toxic, physiologically inert
absorbable coating composition derived from the (i)
copolymerization of a low molecular weight polyalkylene
glycol with small quantities of glycolide monomer and
L-lactide monomer or tii) the copolymerization of low
molecular weight polyalkylene glycol with a copolymer of
lactide and glycolide.
Suitable low molecular weight polyalkylene glycols
useful in the practice of the present invention include
those, for example, having the general formula:
3o
HO-~RO ~yH
1 33700~
1 wherein R is alkylene having from 2-4 carbon atoms,
preferably 2 carbon atoms, and y is an integer from about
100 to about 350, preferably from about 100 to about 250.
Thus, suitable molecular weights for the polyalkylene
glycols of the present invention range from about 3500 to
about 25,000 and preferably from about 4,000 to about
10, 000.
In preparing the coating compositions of the
present invention, the afore-described polyalkylene glycol
is copolymerized with small amounts of glycolide monomer and
L-lactide monomer in the presence of a suitable catalyst.
In another embodiment of the present invention, the coating
composition is prepared by copolymerizing the polyalkylene
glycol polymer with a preformed copolymer of lactide and
glycolide. Suitable copolymerization catalysts for both of
these copolymerization processes, include stannous chloride,
stannous octoate and the like. It should be understood,
however, that the copolymerization scheme employing a
pre-made copolymer may be carried out with or without a
copolymerization catalyst.
In the copolymerization process wherein glycolide
monomer and lactide monomer are employed, suitable amounts
of glycolide monomer include from about 10% to about 35~, by
weight, based on total weight of glycolide and lactide
monomers, while suitable amounts of lactide monomer include
from about 90 to about 65% by weight, based on total weight
of glycolide and lactide monomers. In the copolymerization
process employing the preformed copolymer of lactide and
glycolide, the preformed copolymer generally comprises from
about 10 to about 35 mole ~, glycolide and 90 to about 65
mole %, lactide. The preferred preformed copolymer
composition is comprised of 18 mole ~ glycolide and
1 3370~
82 mole % lactide. Suitable preformed copolymers of
glycolide and lactide which are used in the practice of the
present invention and their method of preparation are
described in U.S. Patent No. 4,523,591.
In general, however and notwithstanding the
utilization of glycolide and lactide monomer or preformed
lactide/glycolide copolymer in the preparation of the
coating compositions of the present invention, the weight
ratio of polyalkylene glycol to combined lactide and
glycolide monomer or lactide/glycolide copolymer utilized
in the copolymerization process is from about 4:1 to about
1:4, preferably 2:1 to about 1:2, respectively. Typically,
copolymerization is carried out in an inert atmosphere,
e.g., nitrogen, at temperatures, for example, of from about
125-200C, preferably 150C to about 160C, for a period
of from about 10 to about 24 hours.
The absorbable, coating compositions of the
present invention are non-toxic and physiologically inert
and are applied to the multifilament suture surface as a
solution and/or dispersion of the polymeric coating
composition in a volatile solvent, such as methylene
chloride or acetone. Solidification of the coating on the
suture surface is accomplished by volatilizing the solvent.
The coating composition may be applied to the
multifilament suture by any suitable process, such as
passing the suture through a solution of the coating
composition or past a brush or applicator melted with the
solution or past one or more spray nozzles dispensing the
solution as droplets. The suture wetted with the coating
solution is subsequently passed through or held in a drying
oven for a time and at a temperature sufficient to
volatilize the solvent.
The coating composition may, if desired, also
contain components other than those discussed above for
1 337~4
other purposes such as, for example, dyes, antibiotics,
antiseptics, anaesthetics, anti-inflammatory agents.
The amount of coating composition applied to the
suture, will vary depending upon the construction of the
suture, e.g., the number of filaments, tightness of braid
or twist, and the size of the suture and the composition
thereof. In general, the coating composition applied to an
"unfilled" (i.e. not containing a storage stabilizing
agent) braided suture will constitute from about 1.0 to
about 3.0 percent by weight of the coated suture, but the
amount of coating add on may range from as little as about
0.5 percent, by weight, to as much as 4.0 percent or
higher. For a preferred "filled" (i.e. containing a
storage stabilizing agent) braided suture, amounts of
coating composition generally comprise from about 0.5% to
2.0% with as little as 0.2% to as much as 3.0%. As a
- practical matter and for reasons of economy and general
performance, it is generally preferred to apply the minimum
amount of polymeric coating composition of the present
invention consistent with good tie-down performance and
this level of coating add on is readily determined
experimentally for any particular suture-coating system.
Preferred filled sutures, such as glycerin filled
braided sutures, which can be coated in accordance with the
present invention, are described in commonly assigned,
copending Canadian patent application Serial No. 575,700,
filed concurrently herewith. As disclosed in said
copending application, in addition to glycerin and its
mono- and diesters derived from low molecular weight
carboxylic acids, e.g. monoacetin and diacetin, other water
, .. . .
1 3370~4
1 soluble hygroscopic polyhydroxy compounds or esters thereof
which are useful in these "filled" sutures include ethylene
glycol, diethylene glycol, triethylene glycol,
1,3-propanediol, trimethylolethane, trimethylolpropane,
pentaerythritol, sorbitol, and the like. Glycerin, however,
is especially preferred. Mixtures of these storage
stabilizing agents, e.g., sorbitol dissolved in glycerin,
glycerin combined with monoacetin and/or diacetin, etc., are
also useful.
In the preparation of a filled suture which is
suitable to be coated with the absorbable polymeric coating
composition of the present invention, application of the
storage stabilizing agent to the suture can be carried out
in any number of ways. Thus, for example, the suture can be
submerged in the storage stabilizing agent or solution
thereof until at least a storage stabilizing amount of agent
is acquired or otherwise retained by the suture. In many
cases, contact times on the order of from just a few
seconds, e.g., about 10 seconds or so, to several hours,
e.g., about 2 hours and even longer, are sufficient to
impart a substantial improvement in the storage stability of
the suture.
The foregoing submersion method of contacting the
suture with storage stabilizing agent can be conducted
continuously or in batch. Thus, in the case of an
absorbable suture, a running length of the suture can be
continuously passed through a quantity of the stabilizing
agent at a velocity which has been previously determined to
provide the necessary degree of exposure, or contact time,
of the suture with the storage stabilizing agent. As the
suture emerges from the storage stabilizing agent, it can be
passed through a wiper or similar device to remove excess
agent prior to the packaging operation. In a batch
operation, a quantity of suture is merely submerged within
1 3370~4
1 the storage stabilizing agent for the requisite period of
time with any excess agent being removed from the suture if
desired.
Alternatively, the storage stabilizing agent can
be applied by spraying, brushing, wiping, etc., on the
surfaces of the suture such that the latter receive and
retain at least a storage stabilizing amount of the agent.
Yet another procedure which can be used to apply the storage
stabilizing agent involves inserting the suture in a package
containing an effective amount of the agent such that
intimate contact between the suture and the agent will be
achieved.
Whatever the contacting procedure employed, it is
necessary that the article being treated acquire a storage
stabilizing amount of the storage stabilizing agent. In
general amounts of from about 2 to about 25, and preferably
from about 5 to about 15 weight percent, of storage
stabilizing agent(s) (exclusive of any solvent) by weight of
the suture contacted therewith is sufficient to provide
significantly improved storage stability.
The term "filled" as used herein refers to the
association of the suture with a storage stabilizing amount
of storage stabilizing agent whether this association be one
in which the storage stabilizing agent is absorbed by the
suture, is present on the surface thereof or is a
combination of the two.
The polymeric coating composition of the present
invention may be applied to any suture material where it is
desired to improve fiber lubricity, suture tie-down
characteristics or the like. The coating compositions of
the present invention are particularly useful with
synthetic, absorbable multifilament sutures, braided or
unbraided, comprised of, for example, polylactide,
1 3370~4
polyglycolide, copolymers of lactide and glycolide, poly(p-
dioxanone) and mixtures of such polymers with each other
and other compatible absorbable compositions. Particularly
preferred absorbable, multifilament sutures for the
purposes of the present invention are comprised of
copolymers of lactide and glycolide, said copolymers, for
example, being disclosed in U.S. Patent No. 4,523,591.
Moreover, as described hereinbefore, absorbable, braided
sutures filled with glycerin or other water soluble
hygroscopic polyhydroxy compound, in amounts of from about
2 to about 25%, are also preferred herein. In addition to
stabilizing the suture, the glycerin filling improves the
handleability of the coated suture as well as allows lower
levels of coating to be applied to the suture. As stated
hereinbefore, these filled sutures are described in
Canadian patent application Serial No. 575,700.
Non-absorbable sutures are also contemplated
within the scope of the present invention. Typically these
include braided or unbraided silk, cotton, nylon,
polyester, polypropylene, polyethylene and linen sutures.
To measure improvement of tie down properties
imparted to sutures, for example, synthetic absorbable
sutures, in a quantitative fashion, an Instron tensile
tester is used to simulate knot slide down and the
resistance a surgeon might experience.
Suture tie down properties are evaluated dry
after the sutures are conditioned for at least 24 hours in
vacuum at room temperature, and wet after being immersed in
water at 37C for 1 minute.
1 33ioo4
1 A suture sample is tested for knot run down
performance using the following method. The suture to be
tested is cut to approximately 30 cm. lengths. A length of
suture is wrapped once around a 2.5 cm diameter tube and
tied in a simple sliding one over one knot (square knot) and
snugged down on the tube. The suture is then removed from
the tube and the ends of the suture are clamped in 1 inch
square rubber coated flat grips mounted on an Instron Model
1011 Tensile tester. The Instron is equipped with a 5 kg
load transducer with load range set at 5000 grams and
crosshead speed 10-50 mm/min.
As the suture passes over itself, a curve is
plotted on the graph paper. Since a braided suture has
braid protrusions and is somewhat elliptical in cross
section, a smooth curve does not appear. The "stick"
portion of the stick-slip curve is produced when it is
easier for the suture to stick to itself and elongate than
to slip. As the suture is elongated more and more, the
tension continues to build-up until either the yield point
of the suture is reached or until the cohesive force is
overcome and the suture knot slips. This cycle is repeated
producing a saw tooth pattern on the chart, the magnitude of
which gives a measure of braid "chatter" or the smoothness
of tie down.
The surface lubricity of the suture may be
determined from the maximum and minimum friction peaks on
the graph in accordance with the following equation:
average lubricity = minimum peak
+ (maximum peak - minimum peak)
1 337004
1 In order that those skilled in the art may better
understand how the present invention may be practiced, the
following examples are given by way of illustration and not
by way of limitation.
3o
1 3370~
1 EXAMPLE 1
Fifty (50) grams of polyethylene glycol (MW 7500,
available from BASF) was placed in a 250 ml. three necked
flask equipped with a stirrer and inlet/outlet nitrogen gas
lines. The polyethylene glycol in the flask is stirred and
heated at about 150C for about 3 hours while maintaining a
low level dry nitrogen purge. After 3 hours, 0.02 grams of
stannous chloride catalyst is added and stirring is
increased to homogenize the catalyst/block copolymer
mixture. A dry mixture of 83.2 grams of L-lactide and 16.8
rams of glycolide is added to the catalyst/block copolymer
mixture in the flask under increased stirring conditions to
dissolve the monomer. After polymerization is allowed to
proceed for about 24 hours, the resultant polymer is allowed
to cool to about 100C at which time about 75 ml. methylene
chloride is added in two portions: 50 ml. then 25 ml and
stirred until homogeneous. The resultant solution is then
poured into a clean dry crystallizing dish. The mixture is
allowed to evaporate until solidified (about 24 hours). The
solid polymer is placed in a vacuum over for three days (the
first day at 80C for 24 hours, second day at 100C for 24
hours, third day at 120C for 24 hours) after which time the
product is allowed to cool to room temperature and then
removed from the oven. NMR Analysis of the product
identifies it to be a copolymer of about 75 wt.%
polyethylene oxide with 25 wt.% glycolide/lactide wherein
the glycolide/lactide is in a 58:42 weight ratio,
respectively.
A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90~ glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
-14-
1 337004
1 leaving glycerin (about 10% by weight) in the braid. The
polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
apparatus was a standard lab coater. The braid was dried in
vacuum to remove methylene chloride. The knot tie down
characteristics of the filled braided suture after coating
are summarized in Table 1.
An unfilled (i.e. not soaked in glycerin) braided
suture comprised of filaments of a glycolide/lactide
copolymer containing 90~ glycolide units was also coated
with the polymeric coating composition prepared above
dissolved in methylene chloride. The solution was pumped to
a capillary to form a droplet. The braid was drawn through
the droplet wetting the braid. The coating apparatus was a
standard lab coater. The braid was dried in vacuum to
remove methylene chloride. The knot tie down
characteristics of the unfilled braided suture after coating
are summarized in Table 1.
3o
1 337~a~
1 EXAMPLE 2
Fifty (50) grams of polyethylene glycol, (MW 7500
available from Polysciences) and 25 grams of a preformed
glycolide/lactide copolymer comprised of (18 mole %
glycolide and 82 mole % lactide units) are placed in a dry 3
neck flask. The flask and contents are heated in a vacuum
oven to about 100C and maintained at that temperature for
about 24 hours. The oven is then allowed to cool to room
temperature and the vacuum broken with dry nitrogen only.
The flask and contents are again heated under nitrogen purge
to about 160C. After the mass in the flask has melted,
slow stirring is commenced. When the mass is completely
melted, 0.02 gram of stannous chloride catalyst is added
under rapid stirring for about one minute to evenly disperse
the catalyst. Slow stirring is continued for about 47 hours
after which the mass is allowed to cool. 75 ml. in two
portions: 50 ml., then 25 ml. of methylene chloride are
added to the mass and stirred until homogeneous. The
solution is then poured into a crystallizing dry dish and
allowed to stand until all the methylene chloride has
evaporated and the polymer has solidified. Post-treatment
of the polymer is carried out as in Example 1. The
copolymer product is made in virtually 100% conversion. NMR
Analysis of the product identifies it to be a copolymer
consisting of polyethylene glycol and glycolide/lactide
blocks with virtually the same ratio in the finished product
as in starting material.
A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90% glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
leaving glycerin (about 10% by weight) in the braid. The
-16-
1 337004
1 polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
apparatus was a standard lab coater. The braid was dried in
vacuum to remove methylene chloride. Approximately 1.1%
coating by weight was added to the braid. The
characteristics of the filled braided suture after coating
are summarized in Table 1.
An unfilled braided suture comprised of filaments
of a glycolide/lactide copolymer containing 90% glycolide
units was also coated with the polymeric coating composition
prepared above dissolved in methylene chloride. The
solution was pumped to a capillary to form a droplet. The
braid was drawn through the droplet wetting the braid. The
coating apparatus was a standard lab coater. The braid was
dried in vacuum to remove methylene chloride. The knot
tie-down characteristics of the braided suture after coating
are summarized in Table 1.
3o
1 337~
1 EXAMPLE 3
Fifty (50) grams of polyethylene glycol (MW 7500,
available from Polysciences) and 25 grams of a preformed
glycolide/lactide copolymer comprised of 18 mole % glycolide
and 82 mole % lactide units are placed in a dry 3 neck
flask. The flask and contents are heated in a vacuum oven
to about 100C and maintained at that temperature for abut
24 hours. The oven is then allowed to cool to room
temperature and the vacuum broken with dry nitrogen only.
The flask and contents are again heated under nitrogen purge
to about 160C. After the mass in the flask has melted,
slow stirring is commenced. When the mass is completely
melted, 0.02 gram of stannous chloride catalyst is added
under rapid stirring for about one minute to evenly disperse
the catalyst. Slow stirring is continued for about 24 hours
after which the mass is allowed to cool. 75 ml. in two
portions: 50 ml. then 25 ml. of methylene chloride are
added to the mass and stirred until homogeneous. The
solution is then poured into a crystallizing dry dish and
allowed to stand until all the methylene chloride has
solidified. Post-treatment of the polymer is carried out as
in Example 1. NMR Analysis of the product identifies it to
be a copolymer consisting of polyethylene glycol and
glycolide/lactide blocks with virtually the same ratio in
finished product as in starting material.
- A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90% glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
leaving glycerol (about 10% by weight) in the braid. The
polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
-18-
1 33700~
1 apparatus was a standard lab coater. The braid was dried in
vacuum to remove methylene chloride. Approximately 1.6%
coating by weight was added to the braid. The
characteristics of the filled braided suture after coating
are summarized in Table 1.
An unfilled braided suture comprised of filaments
of a glycolide/lactide copolymer containing 90% glycolide
units was also coated with the polymeric coating composition
prepared above dissolved in methylene chloride. The
solution was pumped to a capillary to form a droplet. The
braid was drawn through the droplet wetting the braid. The
coating apparatus was a standard lab coater. The braid was
dried in vacuum to remove methylene chloride. The knot tie
down characteristics of the braided suture after coating are
summarized in Table 1.
3o
--19--
1 33700~
1 EXAMPLE 4
Fifty (50) grams of polyethylene glycol (MW 7500
available from Polysciences) and 25 grams of a preformed
glycolide/lactide copolymer comprised of 18 mole % glycolide
and 82 mole ~ lactide units are placed in a dry 3 neck
flask. The flask and contents are heated in a vacuum oven
to about 100C and maintained at that temperature for abut
24 hours. The oven is then allowed to cool to room
temperature and the vacuum broken with dry nitrogen only.
The flask and contents are again heated under nitrogen purge
to about 160C. After the mass in the flask has melted,
slow stirring is commenced. Slow stirring is continued for
about 24 hours after which the mass is allowed to cool. 75
ml. in two portions: 50 ml. then 25 ml. of methylene
chloride are added to the mass and stirred until
homogeneous. The solution is then poured into a
crystallizing dry dish and allowed to stand until all the
methylene chloride has solidified. Post-treatment of the
polymer is carried out as in Example 1. NMR analysis of the
product identifies it to be a copolymer consisting of
polyethylene glycol and glycolide/lactide blocks with
virtually the same ratio in finished product as in starting
material.
A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90% glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
leaving glycerol (about 10~ by weight) in the braid. The
polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
apparatus was a standard lab coater. The braid was dried in
-20-
1 3370~
1 vacuum to remove methylene chloride. The physical
characteristics of the filled braided suture before and
after coating are summarized in Table 1.
An unfilled, braided suture comprised of filaments
of a glycolide/lactide copolymer containing 90% glycolide
units was also coated with the polymeric coating composition
prepared above dissolved in methylene chloride. The
solution was pumped to a capillary to form a droplet. The
braid was drawn through the droplet wetting the braid. The
coating apparatus was a standard lab coater. The braid was
dried in vacuum to remove methylene chloride. The knot tie
down characteristics of the braided suture after coating are
summarized in Table 1.
3o
-21-
1 33700~
1 EXAMPLE 5
37.5 grams of polyethylene glycol (MW 7500,
available from Polysciences) and 37.5 grams of a preformed
glycolide/lactide copolymer comprised of 18 mole % glycolide
and 82 mole % lactide units are placed in a dry 3 neck
flask. The flask and contents are heated in a vacuum oven
to about 100C and maintained at that temperature for about
24 hours. The oven is then allowed to cool to room
temperature and the vacuum broken with dry nitrogen only.
The flask and contents are again heated under nitrogen purge
to about 160C. After the mass in the flask has melted,
slow stirring is commenced. When the mass is completely
melted, 0.02 gram of stannous chloride catalyst is added
under rapid stirring to evenly disperse the catalyst for
about one minute. Slow stirring is continued for about 2
hours after which the mass is allowed to cool. 75 ml. in
two portions: 50 ml. then 25 ml. of methylene chloride are
added to the mass and stirred until homogeneous. The
solution is then poured into a crystallizing dry dish and
allowed to stand until all the methylene chloride has
evaporated and the polymer has solidified. Post-treatment
of the polymer is carried out as in Example 1.
A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90% glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
leaving glycerin (about 10~ by weight) in the braid. The
polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
apparatus was a standard lab coater. The braid was dried in
vacuum to remove methylene chloride. The physical
characteristics of the filled braided suture before and
after coating are summarized in Table 1.
-22-
1 33700~
1 An unfilled braided suture comprised of filaments
of a glycolide/lactide copolymer containing 9o~ glycolide
units was also coated with the polymeric coating composition
prepared above dissolved in methylene chloride. The
solution was pumped to a capillary to form a droplet. The
braid was drawn through the droplet wetting the braid. The
coating apparatus was a standard lab coater. The braid was
dried in vacuum to remove methylene chloride. The knot tie
down characteristics of the braided suture after coating are
summarized in Table 1.
3o
-23-
1 33700~
1 EXAMPLE 6
25 grams of polyethylene glycol (MW 7500,
available from Polysciences) and ~0 grams of a preformed
glycolide/lactide copolymer comprised of 18 mole % glycolide
and 82 mole % lactide units are placed in a dry 3 neck
flask. The flask and contents are heated in a vacuum oven
to about 100C and maintained at that temperature for about
24 hours. The oven is then allowed to cool to room
temperature and the vacuum broken with dry nitrogen only.
The flask and contents are again heated under nitrogen purge
to about 160C. After the mass in the flask has melted,
slow stirring is commenced. When the mass is completely
melted, 0.02 gram of stannous chloride catalyst is added
under rapid stirring to evenly disperse the catalyst for
about one minute. Slow stirring is continued for about 24
hours after which the mass is allowed to cool. 75 ml. in
two portions: 50 ml. then 25 ml. of methylene chloride are
added to the mass and stirred until homogeneous. The
solution is then poured into a crystallizing dry dish and
allowed to stand until all the methylene chloride has
evaporated and the polymer has solidified. Post-treatment
of the polymer is carried out as in Example 1. NMR analysis
of the product identifies it to be a copolymer consisting
of polyethylene glycol and glycolide/lactide blocks with
virtually the same ratio in the finished product as in the
starting materials.
A braided suture comprised of filaments of a
glycolide/lactide copolymer containing 90~ glycolide units
was prepared for coating by soaking in glycerin/methanol
solution. Methanol is dried from the braid under vacuum
leaving glycerin (about 10% by weight) in the braid. The
polymeric coating composition prepared above was dissolved
in methylene chloride. The solution was pumped to a
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1 capillary to form a droplet. The filled braid was drawn
through the droplet wetting the braid. The coating
apparatus was a standard lab coater. The braid was dried in
vacuum to remove methylene chloride. The characteristics of
the filled braided suture after coating are summarized in
Table 1.
An unfilled, braided suture comprised of filaments
of a glycolide/lactide copolymer containing 90% glycolide
units was also cited with the polymer coating composition
prepared above dissolved in methylene chloride. The
solution was pumped to a capillary to form a droplet. The
braid was drawn through the droplet wetting the braid. The
coating apparatus was a standard lab coater. The braid was
dried in vacuum to remove methylene chloride. The knot tie
down characteristics of the braided suture after coating are
summarized in Table 1.
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1 COMPARATIVE EXAMPLE 7
To demonstrate the superior results obtained by
the copolymerized coating composition of the present
invention, a non-copolymerized admixture was prepared for
testing. That is, two parts, by weight polyethylene glycol
(MW 7500, from Polysciences) and one part by weight
preformed copolymer (20 mole % glycolide and 80 mole %
lactide units) were dissolved in methylene chloride. This
admixture was applied to unfilled braided sutures comprised
of filaments of glycolide/lactide copolymer containing 90~
glycolide units using a lab coater in similar conditions to
those described in the previous examples. After initial
stretching and tightening of the knot, the samples broke at
the knot as shown by the data in Table 1.
~5
W W r~
TABLE 1
Weight Knot Run Down Knot Run Down
polyethylene Weight Weight glycolide/lactlde % by weight(Avg.)Instron (Avg.)Instron
Example glycol glycolide lactide copolymer coating on (Dry) (Wet)
(grams)(grams)(grams) (grams) suture (grams) (grams)
1 50 16.8 83.2 __ 2.1(U); 0.6(F)2 200
2 50 -_ __ 25 l.l(U);<1.5(F) 50-500(F); S00-lOOO(F)
250(U)500-lOOO(U)
3 50 -- -- 25 1.6(U):<1.5(F) 100-200tF) 500-l500(F)
200-400(U) 500-lOOO(U)
4 50 25 l.l(U);<l.O(F) 100-200(F) 200-2000(F)
250-500(U) 1000-3000(U)
5 37.5 -- -- 37.5 1.5(U);l.O(F) lso(F) <lOOO(F)
400-lOOO(U) 1000-2000(U)
6 25 ~- ~~ 50 2.9(U);1.6(F) 400-lOOO(F) 1000-3000(F)
1000 (U)500-1500 (U)
Comparative
7 50 25 1-1.5% 8roke at knot with no run-down
lAll sutures size 1/0. Uncoated sutures break without knot run-down at approximately 4000-4300 grams. ~J~
2In this table (U) refers to sutures not prepared for coating by contact with glycerin; (F) refers to sutures with the O
the glycerin pretreatment. O
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1 The above data show the improved knot tie down
properties achieved by the absorbable polymeric coating
compositions provided by the present invention.
Obviously, other modifications and variations of
the present invention are possible in light of the above
teachings. It is, therefore, to be understood that changes
may be made in the particular embodiments of this invention
which are within the full intended scope of the invention as
defined by the appended claims.
