Surgical suture abstract
A surgical suture material of absorbable, synthetic polymer is
formed from glycolide-trimethylene carbonate copolymer with a glycolide
content higher than 76 wt. % and with a statistical distribution
of the monomers. Within 9 to 21 days, the suture material has a
complete breaking strength loss and is completely absorbed in vivo
after 35 to 91 days.
Surgical suture claims
1. A process for the production of a surgical suture material of
an absorbable, synthetic, random copolymer which comprises simultaneously
reacting glycolide and trimethylene carbonate monomers to form the
2. Process according to claim 1 characterized in that the copolymer
is extruded to a monofilament.
3. Process according to claim 2 wherein the monofilamnent has a
diameter of 0.001 to 0.8 mm, a crystallinity of 15 to 40%, an inherent
viscosity of 1 to 2 dg/l, a tensile strength of 250 to 900 N/m.sup.2
and an elongation at break of 25 to 45%.
4. Process according to claim 1 wherein the glycolide content of
the copolymer is at least 76 wt. % such that the suture material
has complete breaking strength loss in vivo within 28 days.
5. Process according to claim 1 wherein a plasticizer is added
during formation of the copolymer in an amount sufficient to reduce
the elastomeric properties of the suture material.
6. Process according to claim 1 wherein the glycolide content of
the copolymer is 80 to 99% by weight, and the suture material retains
50% of its tensile strength after 3 to 10 days and has complete
breaking strength loss in vivo within 9 to 21 days.
7. Process according to claim 1 wherein an oligomer of .epsilon.-caprolactone
is added during formation of the copolymer in an amount sufficient
to reduce the elastomeric properties of the suture material.
8. Process according to claim 1 wherein an oligomer of TMC is added
during formation of the copolymer.
9. Process according to claim 1 wherein the copolymer is prepared
from 14-dioxin-25-dione and 13-dioxin-2-one monomers.
Surgical suture description
The present invention relates to surgical suture material made
from absorbable, synthetic polymer, its use in surgery and process
for its production.
Surgical suture material usable for wound closure comprises non-absorbable
and absorbable materials. Absorbable surgical sewing threads based
on natural biological materials, particularly cat gut and absorbable
synthetic sewing threads are known. Absorbable synthetic suture
material can inter alia be produced from polyglycolic acid (PGA).
In the physiological environment the sewing threads undergo a hydrolysis.
The 50% breaking strength loss, also known as the half-life period,
serves as a measure for the hydrolytic decomposition of the polymer
material. Surgical sewing threads formed from braided PGA multifilaments
(e.g. obtainable under the trademark Dexon) within 21 days have
a 50% breaking strength loss and an absorption of hydrolyzates within
100 to 120 days. A multifilament sewing thread produced from a glycolide-lactide
copolymer with a comonomer ratio of 90:10 has similar characteristics
(obtainable under the trademark Vicryl). In vivo, after 25 days
it loses 50% of its initial strength and is absorbed after more
than 80 days.
Hitherto known absorbable synthetic suture material in the form
of multifilament sewing threads suffers from a number of disadvantages,
such as e.g. poor fabric passage, sawing action or capillarity.
Monofilaments made from the described polymers have a high stiffness
and a poor knotting behavior, which is disadvantageous for the use
thereof as surgical suture material.
Monofilament sewing threads based on polyglycolic acid are also
known, which contain softening components in the PGA matrix. From
a copolymer of glycolide and trimethylene carbonate in a ratio of
68:32 (available under the trademark Maxon), it is possible to produce
a surgical monofilament thread, whereof up to 50% of the initial
strength is maintained for more than about 5 weeks and which is
completely absorbed after about 7 months. Flexible, usable monofilaments
can also be extruded from polydioxanone (available under the trademark
PDS). The breaking strength loss and absorption time are comparable
with glycolide/trimethylene carbonate (trademark Maxon) threads
(cf. following table).
______________________________________ 50% breaking Resorption
Trade strength loss time Polymer name Thread (weeks) (months) ______________________________________
Polyglycolic acid Dexon.sup.R braided 3* 3-4* Glycolide/lactide
Vicryl.sup.R braided 3-4* 3* copolymer (90:10) Glycolide/TMC Maxon.sup.R
monofilament 5** 7** copolymer (68:32) Polydioxanone monofilament
5*** 6*** ______________________________________ *P. F. Nockermann:
Die chirurgische Naht, Georg Thieme Verlag Stuttgart, 3rd edition,
p 42 **A. R. Katz, D. P. Mukberjec, A. L. Kaganov and S. Gordon
in: Surg. Gynecol. Obstet. 161 213 (1985) ***J. A. Ray, N. Doddi,
D. Regula, J. A. Williams and A. Melveger in: Surg. Gynecol. Obstet.
153 497 (1981)
However, these monofilament threads have a very slow decomposition
behavior in living tissue and are only completely absorbed by the
body after several months. Their absorption time is twice as long
as known filament threads. Thus, more recent developments cover
monofilament sewing threads made from absorbable polymers with shorter
half-life periods and faster absorption.
U.S. Pat. No. 4653497 describes the two-stage production of crystalline
copolymers from 14-dioxanone and glycolide, as well as the characteristics
of the monofilament threads produced therefrom. After 4 weeks in
vivo, said monofilaments still have 10 to 30% of their initial strength
and are absorbed after about 4 to 5 months.
U.S. Pat. No. 4700704 claims copolymers of glycolide and .epsilon.-caprolactone
and the monofilaments produced therefrom. These surgical, monofilament
sewing threads, after 7 days implantation, have 44 to 62% of their
strength and after 14 days 11 to 37% thereof.
According to U.S. Pat. No. 4441496 it is possible to process
to monofilaments copolymers comprising 14-dioxanone and 25-morphalinodiones
which, after 28 days, have up to 50% of the initial strength and
which are completely absorbed after 90 to 180 days.
DE-OS 2206144 discloses copolymers of glycolide as the main component
and other cyclic comonomers such as e.g. ethylene carbonate and
trimethylene carbonate. With an ethylene carbonate proportion of
15 to 25%, the absorption time is 30 to 60 days (with 15%) or 15
to 30 days with a higher ethylene carbonate content.
U.S. Pat. No. 4243775 and U.S. Pat. No. 4300565 describe the
successive polymerization of glycolide and trimethylene carbonate
leading to block polymers. The monofilament threads produced from
this sequential copolymer have in the case of a trimethylene carbonate
content of 15 wt. %, after 21 days in vivo, a linear breaking strength
of 45% of the initial value and with a weight proportion of 45%
have a linear breaking strength of 38% after 21 days.
GB-A-2033411 also claims sequential copolymers of glycolide and
trimethylene carbonate (TMC), with a preferred TMC content of 10
to 20%. The residual strength of extruded monofilaments is 45% 21
days after implantation.
In certain areas of surgical wound closure long absorption times
and a long maintenance of the breaking strength are unnecessary,
because the tissue rapidly recovers its strength and consequently
the thread loses its function. Examples of such indications are
intestinal sutures, sutures in the vicinity of the mucous membranes
of the tooth-mouth-jaw area and gynecological applications. In the
case of surgical sewing threads for such applications an accelerated
hydrolytic decomposition and consequently a faster absorption are
desired. It is sufficient if there is an adequate suture strength
for a few days. A good knot breaking strength and good knottability
are consequently necessary for a reliable, safe use. At present,
for such indications, there are only synthetic material multifilament
sewing threads, which suffer from the disadvantages referred to
The problem therefore arises of making available a surgical suture
material of absorbable synthetic polymer in the form of a monofilament
having an accelerated decomposition behavior and improved absorption,
which overcomes the disadvantages of the known suture materials,
is easy and inexpensive to manufacture, as well as easy and reliable
This problem is solved by a surgical suture material of absorbable
synthetic polymer, which is characterized in that it is formed from
glycolidetrimethylene carbonate copolymer with a glycolide content
above 76 wt. % with a statistical distribution of the monomers.
A copolymer having a statistical distribution of monomer units is
known in the art as a random copolymer. Preferably, the suture material
according to the invention is in the form of a monofilament with
a diameter of 0.001 to 0.8 mm. In such a material according to the
invention the glycolide content, based on the total copolymer is
preferably more than 78 wt. %. Based on the total copolymer, its
glycolide content can in particular be 80 to 99 wt. %. In a preferred
embodiment of the invention its glycolide content can be 83 to 93
wt. %, based on the total copolymer.
It has surprisingly been found that monofilaments can be produced
from statistical copolymers of glycolide and trimethylene carbonate
(TMC) with a glycolide content of more than 76 wt. %, which have
the very good characteristics necessary for a surgical suture material,
particularly with respect to the physical characteristics and practical
handling, and which are much more rapidly degraded and absorbed
than the prior art monofilaments formed from the same comonomers,
which are sequentially polymerized, i.e. reacted to block copolymers.
Suture material of statistical copolymer according to the invention
is advantageously characterized by an accelerated absorbability
in living tissue. Preferably, its absorbability is less than 100
days. In particular, its absorption time is in vivo 35 to 91 days.
Preferably its absorption time in vivo is 42 to 56 days.
The decomposition of the polymer according to the invention takes
place in the body of an animal or human by metabolic processes.
Body and tissue fluids participate in the reaction. Through hydrolysis
the polymer chain is split into smaller and more readily soluble
fragments. The fragments are further decomposed, optionally accompanied
by the participation of enzymatic processes. The decomposition products
are transported away by the metabolic system and are expelled from
the organism in the same way as other metabolic waste. It is important
for good compatibility of the absorbable suture material with the
patient, that during the decomposition process no harmful metabolites
can be formed or concentrated. Polyglycolic acid is in particular
characterized in that during its decomposition in vivo no toxic
decomposition products are formed. The trimethylene carbonate used
as a comonomer according to the invention is also characterized
by good compatibility and the avoidance of toxic reactions.
The statistical glycolide-TMC copolymer according to the invention
differs from the conventional, sequential glycolide-TMC copolymers
hitherto used for producing surgical suture material through the
modified sequence of the monomer units in the macromolecule chain.
This also influences the interactions between the individual chain
molecules in an already formed filament. As is known to the experts
in the field of fibre technology, the physical and mechanical properties
of a fibre are dependent on the orientation and structure of the
chain molecules, particularly the formation of amorphous and crystalline
regions. As has been revealed by analyses of the microstructure,
the inventive suture material of statistical glycolide-TMC copolymer
can have a crystallinity of 15 to 40%. It is also characterized
by an inherent viscosity (limit viscosity) of 1.0 to 2.0 dl/g, particularly
1. to 1.6 dl/g, measured in 0.1% hexafluoroisopropanol (HFIP) at
The material according to the invention has advantageous mechanical
characteristics. Thus, the monofilament suture material according
to the invention can have a tensile strength of 250 to 900 N/mm.sup.2
particularly 300 to 650 N/mm.sup.2. These tensile strength values
correspond to those for recognized, readily absorbable, surgical
sewing threads according to the prior art and which are required
by pharmacopoeias, or even significantly exceed these values. The
surgical suture material according to the invention can have an
elongation at break of 25 to 45%, particularly 30 to 40%. Thus,
the monofilament according to the invention is particularly suitable
for surgical applications.
The decomposition of polymer chains during absorption is linked
with a reduction in the mechanical strength of the filament material.
After 3 to 10 days, particularly 4 to 6 days, the surgical suture
material according to the invention can still have 50% of its tensile
strength. The degradation of the suture material means that, in
vivo, within 7 to 28 days it can have a complete breaking strength
loss. In particular, a material according to the invention, in vivo,
within 9 to 21 days can have a complete breaking strength loss.
Investigations of the behavior of the mechanical characteristics
over a period of time and therefore the decomposition behavior of
the suture material according to the invention reveals significant
differences compared with the behavior of known, absorbable, surgical
suture materials. The investigations are described in greater detail
in the following examples and in the accompanying drawings. As has
been mentioned hereinbefore, surgical suture materials formed from
statistical glycolide-TMC copolymers according to the invention
have a higher initial strength than known, resorbable, multifilament
materials. Filaments from from 84 wt. % glycolide and 16 wt. % trimethylene
carbonate can give good results. Both in vitro and in vivo tests
have revealed that the strengths of the samples according to the
invention only decrease slowly during the first 3 days and remain
above the values of the known multifilament materials. Subsequently
there is an accelerated reduction of strength. This decomposition
behavior is particularly pronounced in the case of the glycolide-TMC
copolymer with a monomer ratio of 92:8.
Advantageously the surgical suture material of absorbable, synthetic
polymer is in the form of a monofilament of glycolide-trimethylene
carbonate copolymer with a statistical distribution of the monomers
and is suitable for use for wound closure with accelerated absorption.
The aforementioned advantageous, mechanical characteristics of monofilament
sewing threads of statistical glycolid-TMC copolymer permit a simple
handling of the suture material during the sewing of tissue in an
animal or human body, e.g. when fixing organs, closing tears in
the body tissue or closing surgical incisions. In particular as
a result of the construction of a monofilament with a smoother thread
surface than a multifilament sewing thread, the tissue to be treated
can be protected against damage during suture application. This
limits the risk of side-effects for the patient, such as e.g. delayed
healing and tissue granuloma formation. The good knottability and
knot strength in conjunction with the high initial tensile strength
and extensibility permit a reliable fixing and stabilization of
the joined wound edges during the first days following surgery.
In particular, during said first days, regenerative, endogenic tissue
can be used in reliable manner for natural wound healing, because
the risk of a tearing apart of the wound edges during movement of
the patient is reduced by the secure fixing.
A process for the production of surgical suture material of absorbable
synthetic polymer is characterized in that glycolide and trimethylene
carbonate monomers are simultaneously reacted to a statistical copolymer.
The monomers can be 14-dioxan-25-dione and 13-dioxan-2-one in
proportions necessary for the desired copolymer. To the monomer
mixture can be added a suitable catalyst, e.g. tin octoate, in the
quantity normally required. The reaction is carried out as a melt
polymerization in a suitable reactor, which is heatable and provided
with a stirrer. The polymerization reactor must in particular be
designed in such a way that the highly viscous melts obtained are
homogenized, the necessary temperature ranges maintained and the
raw polymer can be substantially completely removed from the reactor.
Reactors of this type are inter alia offered for sale by Werner
& Pfleiderer, Stuttgart, AMK in Aachen or Haake in Karlsruhe.
The copolymerization reaction can be performed in accordance with
conventional, known procedures for the production of statistical
copolymers. Preferably the reaction mixture is heated accompanied
by constant thorough mixing, particularly at a temperature of 170
to 190.degree. C. and preferably 175 to 185.degree. C. During a
reaction of 30 to 100 minutes, the monomers can be reacted to a
At the end of the reaction the raw copolymer is heated for a short
time beyond the reaction temperature and discharged as a melt and
after cooling is granulated in the usual way. By extraction, e.g.
with ethyl acetate or some other suitable solvent, low molecular
weight fractions and residual monomers can be separated. The resulting
polymer granules are then dried. Drying can take place according
to conventional processes, particularly at elevated temperature
and/or under reduced pressure. Any extractant residues still adhering
to the raw copolymer can be removed by evaporation during drying.
In the same way monomer residues can be optionally eliminated during
drying. Optionally a further purification stage can be performed
for obtaining a high-purity copolymer according to the invention.
Preferably such a purification takes place before the drying stage.
The statistical glycolide-TMC copolymer with a composition ratio
according to the invention is characterized by a melting range of
170 to 215.degree. C. This melting range can be at higher temperatures,
particularly with a higher glycolide proportion. The glycolide-TMC
copolymers produced according to the invention are also characterized
by a melting enthalpy in the range 40 to 65 J/g. In the case of
copolymers with a higher glycolide proportion, the melting enthalpy
can be in a higher value range.
The copolymer according to the invention has a partially crystalline
structure. This results from the high glycolide content of more
than 76 wt. %. Due to the high glycolide content the polymer material
has increased stiffness which affects its properties in the use
as suture material in practice. Advantageously the suture material
can include a plasticizer. The plasticizer can be present in an
amount of 1-25 wt. %, based on the total weight of the copolymer
and plasticizer, in the suture material. The plasticizer is characterized
in that it is physically dissolved in the copolymer. The plasticizer
is biocompatible and/or biodegradable. Advantageously, glyceryl
triacetate, butyl citrate, triethyl citrate, or acetyltributyl citrate
can be used for glycolide-TMc copolymers according to the invention.
Preferably can be used oligomers of .epsilon.-caprolactone as plasticizers.
Further also oligomers of TMC are appropriate as plasticizers in
the copolymer according to the invention. Advantageously the oligomers
to be used according to the invention have a maximum molecular weight
of 22000 particularly of 20000 which corresponds to about 400
units of caprolactone. Preferably the plasticizer has a viscosity
in the range of viscous flowing to solid. The intrinsic viscosity
at 25.degree. C. is particularly in the range of 0.05 to 0.5 dl/g.
As to the interrelation of viscosity and molecular weight of polymers
see Schindler, A. et al. in: Journ. Polym. Sci., Vol. 20 p. 319-326
(1982), and Rafler, E. in: Acta Polym. 44 p. 168-170 (1993). Admixing
of the plasticizer to the copolymer can be done with the molten
polymer or in solution. The amount of plasticizer added can be about
inversely proportional to the amount of TMC in the copolymer. The
TMC in the copolymer acts as a so-called internal plasticizer. An
additionally included plasticizer acts as a so-called external plasticizer.
The copolymer with a plasticizer content according to the invention
does not exhibit elastomeric properties.
Surgical suture material can be produced by known processes from
the polymer material produced according to the invention. In particular,
the statistical glycolide-TMC copolymer according to the invention
can be spun to monofilaments in a melt spinning process. For example,
the polymer material according to the invention, can be heated to
its melting point in a conventional extruder installation, e.g.
a single-screw extruder and extruded through suitable spinnerets
to monofilaments. In a preferred embodiment, dried glycolide-TMC
copolymer can be melted at a temperature in the range 170 to 235.degree.
C. For extrusion purposes, use is preferably made of a spinneret
with a diameter of 0.5 to 1.5 mm. Advantageously the filament formed
is extruded in a cooling bath, preferably water at ambient temperature.
In order to obtain the requisite mechanical properties, the extruded
filament can be stretched or drawn for orienting the molecule chains.
Advantageously it is stretched or drawn with a stretch or draw ratio
of 1:4 to 1:10. In order to ensure that the orientation, mechanical
properties and dimensional stability of the filaments are permanently
maintained, the stretched polymer material can be fixed. Fixing
takes place at temperatures between ambient temperature and 95.degree.
C., preferably between 40 and 80.degree. C. It is particularly preferred
that stretching and fixing take place immediately following extrusion,
more especially in a combined process. Advantageously use is made
of an apparatus constituted by combined, appropriate means.
The diameter of the monofilaments produced in this way is in the
standard range 0.001 to 0.8 mm. Advantageously, the monofilaments
according to the invention are characterized by the aforementioned
Glycolide-TMC copolymer filaments produced according to the invention
can be processed to surgical suture material by conventional methods,
e.g. cut to suitable lengths. In particular the polymer material
according to the invention can be appropriately sterilized. An appropriate
sterilization process can be chosen from among standard physical
or chemical methods for deactivating microorganisms or a combination
of such methods. Preferably, the suture material according to the
invention is sterilized using ethylene oxide.
Advantageously the surgical suture material, cut to appropriate
lengths is appropriately packed ready for use. In a preferred embodiment
the sewing threads according to the invention can be provided with
Due to the hydrolytic decomposability of the polymer material according
to the invention, the suture materials must be protected from moisture
and elevated temperatures during storage, so that the strength characteristics
are fully maintained up to the time of use. Advantageously the surgical
suture materials according to the invention are dried in the ready
for use state and appropriately packed. This appropriately takes
place in a pack protected against moisture intrusion and in particular
in moisture-proof film material, more especially a vacuum pack.
In addition, a dry, cool storage location should be chosen.
According to a particularly preferred embodiment surgical suture
threads of glycolide-TMC copolymer can be cut to length ready for
use, provided with surgical needles and sterilized and placed in
a sterile pack protected against moisture and suitable for simple
Further features and details of the invention can be gathered from
the following exemplified description of preferred embodiments.
The individual features can be implemented individually or in subcombinations.
Reference is also made to the attached drawings, wherein show:
FIG. 1 The change to the tensile strengths in vitro over an incubation
time of 14 days of two suture materials according to the invention
and a comparison, prior art material.
FIG. 2 The change to the tensile strengths in vivo over an implantation
time of 10 days of two suture materials according to the invention
and a comparison, prior art material.
The examples merely serve to illustrate the invention, which is
in no way limited thereto.