CA1213797A - Composite sutures of silk and hydrophobic thermoplastic elastomers - Google Patents

Abstract

COMPOSITE SUTURES OF SILK AND HYDROPHOBIC THERMOPLASTIC
ELASTOMERS

ABSTRACT
Composite suture of multifilament silk embedded in a highly flexible, hydrophobic highly deformable matrix made of thermoplastic elastomer. This suture exhibits minimal irritation to living tissue and retains its strength in vivo for extended periods of time and also retains the desirable handling qualities of silk. The suture is prepared by treating a multifilament silk suture with a solution of a suitable polymer in a solvent and heating the moving suture to obtain a continuous impregnation of the silk with the elastomer.

Description

~12~37~7 COMPOSITE SUTURES OF SILK AND HYDROPHOBIC THERMOPLASTIC
~LASTOMERS

Background of the Invention , . , ~ . _ This invention relates to a non-irritating composite suture of silk and hydrophobic thermoplastic elasto~ers containing at least 25% soft segments which composite suture retains the handling qualities of silk and is also capable of retaining at least thirty-two percent of its initial mechanical strength ln vivo after eight weeks~
This composite suture has surface barrier properties of a monofilament and tissue reaction conparable to co~on synthetic sutures. This invention also relates to the process for preparing the composite suture.

Many natural and synthetic materials are presently used as surgical sutures. These materials may be used as single filament strands, i.e., monofilament sutures, or as multi-filanlent strands in a braided, twisted or other multifila-~ent construction. Silk does not lend itself to the fabrication of monofilament sutures and is accordingly generally use~ in one of the multifila~ent constructions, preferably the hraided form. This results in a silk suture having desirahle handling characteristics, being sufficiently flexible and having good knot~tying ability and knot security. However, presently availahle untreated silk sutures are known ~a) to provoke a significant tissue reaction in the biologic environ~ent, (b) have a signifi-cant strength loss in living tissues (typically a 2-0 s~lk suture retains about twenty percent of its original strength after eight weeks, post-implantation), and (c) to lack the surface barrier properties needed for retarding cellular infiltration into the suture interior in living tissue.

137~

The composite suture of the present invention displays equivalent handling properties to those of the untreated braided silk suture, it elicits reduced tissue reaction after seven days and later post-implantation intervals, and when implanted intramuscularly, is more effective in retarding cellular infiltration due to the monofilamentous geometry of the composite suture and it is characterized by improved strength retention after fifty-six days post-implantation.
n The prior art discloses a number of methods for coating sutures in general. Coating material for sutures normally would require low surface friction characteristics so as to facilitate the knot-tying ability of the resultant coated suture. Contrary to such expectations, the present invention utilizes an elastomer (which has high surface friction characteristics) in preparing the present composite suture.

Rraided silk sutures are desirably flexihle due to the interlocking geometry of the fibers. In accordance with the present invention, a multifilament silk suture is treated with a hydrophobic~ limp thermoplastic elastomer in order, not only to coat the suture, but to substantial-ly fill all the interstices between the silk filaments.It has heen found, surprisingly, that the particular elastomers utilized in accordance with the present invention, when filling the spaces between the silk fibers, do not adversely affect the flexihility of the 3n suture as a whole.

Description of the Prior Art IJ.S. Patent No. 3,527,650 teaches that multifilament non-absorhable sutures can he improved with respect to ~37~7 tie-down performance by depositing solid particles of polytetra~luoroethylene and a bin~er resin on the extern~l surface. No infiltration of this coating to the suture interior was described in this patent. Further-more, the coating flakes off during use, especially duringknot tie-down.

According to U.S. Patent No. 3,942,532, non-absorbable sutures can be improved with respect to tie-down performance by coating them with a linear polyester having a molecular weight between about 1,000 and about 15,000 and at least two carbon atoms between the ester linkages.

This patent pertains to simple linear thermoplastic polyesters which are highly crystalline, low melting materials. These are expected to impart lubricity and are not (a) segmented in structure, (b) elastomeric or (c) significantly capahle of contributing to the mechanical properties of braided sutures (including silk) to any discernable extent.

U.S. Patent No. 3,297,033 discloses that synthetic absorbable sutures can be coated with coating materials used on conventional sutures, such as a silicone or beeswax to modify handling. However, it does not describe any material or system that can be combined with braided silk sutures to form the uni~ue composite sutures subject of the present invention.

30 U.S. ~atent No. 4,043,34~ shows that the handling charac-teristics and particularly tlle knot run down and tissue drag characteristics of non-absorbable sutures are improved by a coating with a lubricating film of bioabsorhahle copolymer having copolyoxvethYlene blocks ~L;213~7 and polyoxypropylene bloc~s. The copolymer has a molecular weight such that it is pasty to solid at 25C.
This lubricant coating is described as absorbable (in vivo) in less than two days which results in improved long term knot security.

The lubricant coating as descrihed should (a) have a low molecular weight, about 8350 Dalton, and low Tm and hence would be expected to have hardly any integrity at usual levels of stress; (b) it is soluble in the biologic environment and likely to migrate to the surrounding tissue in two days to cause additional foreign body reaction; (c) it is water-soluble and hence would be expected to provide minimum lubricity during wet tie-down and (d) would not be expected to render a commercial silk suture less irritatins to tissue and more resistant towards losing its breaking strength, for the coating does not act as a hydrophobic inert barrier about the braid components and does not mask effectively the undesirable morphological features of a braided suture.

U.S. Patent No. 4,1~5,637 discloses a multifilament suture having improved tie-down properties, said suture being coated with from about 1 to 5 percent by weight of the dry residue of a composition comprising a gel of a polyvalent metal ion salt of C6 or higher fatty acid in a volatile organic solvent.

The coating described by this patent can only serve as a lubricant, for it is a low molecular weight system that cannot impart any discernable physical changes to the mechanical integrity of the suture braid construction. If used for silk sutures, this absorbahle coating would not be expected to decrease the tissue reaction or increase the strength retention.

_5_ According to U.S. Patent Mo. 4,105,03~ the tie-down properties of a multifilament surgical suture are improved by coating the suture with an absorbable composition comprising a low molecular weight polyalkylene oxalate.

If silk sutures were to be treated with such a coating, the latter would be expected to only impart desirable surface lubricity, without affecting the tissue reaction or hreaking strength retention of the implanted suture in any positive sense. This is simply because the coating is an absorbable low molecular weight material which limits the residence time about the fibers and the effect on the suture properties of the braid.

Canadian Patent No. 9~2~39 describes a polyfila~entary silk suture having a plurality of fine solid particles of insoluble synthetic polymeric material incorporated in the interstices thereof, in an amount sufficient to embue the suture with substantially the properties of a monofila-ment. However, these particles cannot be expected to actas a hydrophobic inert barrier about the braid co~ponents and accordingly, the method of said reference is not likely to decrease the tissue reaction or increase the strength retention of the suture.
In view of the above discussion it will be seen, with respect to non-absorbable sutures such as braided silk sutures, that the prior art does not disclose any effec-tive method for reducing tissue reaction a~ later post-3n implantation periods, retarding cellular infiltration orbringing about improved strength retention after eight weeks post-i~plantation. It is accordingly an object of the present invention to prepare a composite suture which is non-irritating and retains the handling qualities of silk, and which is capable of retaining a higher propor-tion of the initial mechanical strength, ln vivo, after 12~3~t7 ei~ht weeks, than in the case of an untreated silk suture per se. I~ is a further object of the present invention to provide a composite suture having surface barrier properties comparable to those of a monofilament and S tissue reaction comparable to common synthetic sutures.
It is a further object of the invention to provide a composite silk-elastomer suture in which the elastomer substantially fills all the interstices between the silk filaments and having properties such that the elastomer nevertheless permits the individual components of the silk to flex in such a way that the flexibility of the silk suture, as a whole, is not impaired. It is yet a further object of the present invention to provide a composite silk-elastomer suture wherein the primary strength is provided by the silk (since the elastomer matrix is much less strong).

Summary of the Invention In accordance with the present invention there is provided a non-irritating composite suture retaining the handling qualities of silk, which, in the case of size 5-n, is capable of retaining at least 32% of its initial mechani-cal strength, 1n vivo, after eight weeks; said suture having surface barrier properties against cell infiltra-tion comparable to those of a monofilament and tissue reaction comparable to common synthetic sutures; compris-ing multifilament silk embedded in a hy~rophobic, limp thermoplastic elastomer; said elastomer comprising copoly~
mers having hard and soft components, said soft components comprising about 25-80~ by weight of said elastomer, depending upon the melting temperature and crystalliz-ability of the hard components, said elastomer having a suitable molecular weight sufficient to provide a solution viscosity that is consistent with optimum diffusion into the interior of the suture structure, resulting in a high ~TH-531 ~2~L37~

integrity matrix which does not flake when the suture is subjected to mechanical stress.

In accordance with the preferred emhodiment of the present invention, the silk is of braided construction and the elastomer is selected from the group consisting of copolymers having the following recurring units:
O O O
Il 11 11 11 P) ~C-Z-C-O-G-O~e ~C-Z-C-O-(G-O)p~f A B
wherein each G individually represents an alkylene group of from 2 to 6 carbon atoms, and p is 9 to 15, e and f each represent a number having a value greater than 1 such that the B units comprise 50 to 80 weight percent of the copolymer and the A units co~prise the remainder; wherein Z represents l,~-phenylene, 1,3-phenylene or trans-1,4-cyclohexylene;

Q) a copolymer consisting essentially of a multiplicity of recurring A 1PO1Y ( alkylene terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate)] and ~ [poly(alkylene dimerate)] units having the following general formula:
CH3 C~3 25 O O ~ ~ ~ O
Il 11 11 ~ 11 ~C-Z-C-O-G-O~X ~C~ ~ ;S C-O-G~-O~y A B
wherein x and y are integers, such that the B units comprise 50 to 80 weight percent of the copolymer, and the ,~
A units conprise the remainder; denotes a branched hydrocarbon chain containing from 24 to 32 carbon atoms and Z and G are as hereinabove defined;

R) a copolymer consi.sting essentially of a ~ultiplicity of recurring poly(alkylene) terephthalate, isophthalate or ~ :~2~L3~37 cyclohexane-1,4-dicarboxylate, anc~ poly(alkylene) alkyl or alkenyl succinate units having the following general formula:
O O O

fC~Z~C~O~G~O~g ~C-fH-CH2C-O-G-o~h Alk A
wherein Alkl is a linear or hranched alkyl or alkenyl radlcal with a chain length of about 4 to 3~ carbon atoms and g and h are integers such that the ~ units co~prise 5n to 30 weight percent of the copolymer and the A units comprise the remainder; and Z and G are as hereinabove defined;

S) a rando~ copoly~er having the following general formula:
O
~C ~ O~G~O~e~ -Jf-A n wherein J is either:
O
Il 11 (l) ~C-CH-CHzC-O-G-A~ 2 or C~3 CH3 35~ ~ ~ O
Il ~ 11

(2) ~C ~ C-O-G-O~

wherein Alk2 is alkyl or alkenyl moieties with a chain length of ~ to 30 carhon atoms; ~ ~enotes a branched hydrocarhon chain with an estimated formula of C32H60~ or ~TH-531 ~2~ ;~7~37 g o o Il 11

(3) ~C-R'-C-O-(G-O)p-G-O~f wherein p is 9 to 15 and G is as hereinahove defined and R' is an aliphatic or aromatic disubstituted moiety and wherein e and f are such that the ~ units comprise about 25 to 50% by weight of the copolyester and the A units comprise the remainder.
The elastomer o the present invention possesses an inher-ent viscosity which ranges between about n.2 and 1.4, and has a melting temperature by thermal microscopy of between about 80 and 180C. The elastomer comprises hetween S and 50% by weight of the total composite system and preferably has a molecular weight of at least 2000 Dalton, and most preferably at least 10 ,noo Dalton. Preferably the soft segments of the elastomer of the formulae P), Q) and R) comprise between 55% and 75% by weight thereof and in the instance wherein the elastomer has the above formulae P), Q) or R), the soft segments comprise between 60 and 70~
thereof. Furthermore, in the instance wherein the elasto-mer has the formula .5), the soft seg~ents preferably comprise between 30 and 5n% thereof.
In the instance wherein the elastomer has the formula P), the inherent viscosity in ~FIP (hexafluoro-2-propanol) is preferably between 0.~ and 1.3. In the instance wherein the elastomer has the formula Q) or R), the inherent viscosity in hexafluoro-2-propanol is preferably between n.2 and 0.7; and in the instance wherein the elastomer has the formula S) the inherent viscosity in hexafluoro-2-propanol is preferably between n .3 and 0O6~

Within the scope of the present invention is a composite suture, having a surgical needle attached to at least one end, preferahly in a sterile condition.

~2~3~7 In this connection, it is important that sutures be pre-sented to the operating room in sterile condition.
Several methods of achieving sterility are known. ~f these the ~ost commonly employed method for silk sutures consists of exposure to 2.5 Mrads of y irradiation derived from a Cobalt 60 source. It is i~portant therefore that the thermoplastic elastoners used in this invention be capable of resisting exposure to this level of irradiation without significant change in their physical properties.
In accordance with the present invention, there is also provided a method of preparing a non-irritating and strength retaining composite s lk thermoplastic elastomer suture comprising the steps of a) treating a multifilament silk suture with a hydrophobic, limp thermoplastic elastomer dissolved in a solvent therefor at a temperature between 2no and ~0C but preferably between 30 and 50C
in order to coat said suture, said elastomer co~prising copolymers having hard and soft components, said soft conponents comprising about 25-80% by weight of said polymer; said elastomer having a suitable molecular weight sufficient to provide a solution viscosity that is consisten-t with optimum diffusion into the interior of the suture structure, resulting in a high integrity matrix which does not flake when the suture is subjected to mechanical stress; and optionally, b) rapidly heating the treated suture at a temperature between about 340 and 500C to obtain a continuous and consistent impregnation of the multifilament silk suture, and to substantially fill all the interstices hetween the silk filaments.

Description of Preferred Embodiments . .

mhe preferred synthetic matrix P), used to prepare the composite suture of the present invention, is a segmented polyether-ester made by the condensation of dimethyl E~i_531 37~

terephthalate, polyoxytetramethylenediol (molecular weight 650 to 10,000 Dalton and preferably 1000 Dalton) and butanediol in the presence of a typical polyesterification catalyst [e.g. Ti(oBu)4, Ti(O~u)4 + Mg(~Ac)2~, optionally, an antioxidant of the hindered phenol type (e.g. Irganox 1098 [N,N'-hexamethylene bis (3,5-ditert~butyl-4-hydroxy-hydrocinnamide] at 0.1 to 1~) or aromatic secondary amine type (e.g. ~augard 445 [4,4'bis(~ dimethylhenzyl)-diphenylamine] at 0.2 to 1%). The polymerization can be achieved under conventional conditions of temperature, pressure and stirring. The resulting polymer is characterized by having long se~uences of crystallizahle polybutylene terephthalate (4GT) units linked to low Tm or liquid (at room temperature) poly(polyoxytetramethylene) terephthalate (POTMT); these units are commonly referred to as hard and soft segments, respectively. The structure of the matrix material can be represented as follows:

O O O
11 ~ C-O-CH2CH2CH2CH2-O~e ~C ~ l-O-(CH2CH~CH2CH2~O)p~f ~ - hard segment 4~,T- > < soft segment P~TMT- >

Although some of these segmented copolyesters are avail able commercially and disclosed broadly in U.S. Patent ~o.
3,n23l192 (sold in the U.S. under the trademark Hytrel) the relatively high proportion of hard segments and high molecular wei~ht of the commercially avaiable products render them less suitable for use in the present inven-tion, and accordingly special compositions are made in order to provide optimum matrixes for the composite sutures of this invention. The composition and physical properties of two typical matrix materials are shown in Table I. If tested in the appropriate physical form (e.g.
compression molded film Die C) these polymers are 12- ~2~
expected* to have an ultimate elongation of 300~, ultimate tensile strength of 5000 psi and a flex. modulus of <10,000 psi.

TAB
Properties of Two Typical Matrix Materials .
Polymer No.: 135 137 10 .Soft Segment Content 63 71 Wt. % ~determined by ~lMR) Inherent Viscosity in HFIP 1.27 1.12 (hexafluoro-2-propanol) Melting Temperature by ~icroscopy 126-143 138-145C
~ Crystallinity, by X-ray - 15-20 ~ased on available physical data* on compositions other than those described in Table I, the glass transition temperature of polymers #135 and 137 are expected to be well below -40lC irrespective of the analytical procedure used for the Tg measurement.
The crystallinity detected in sample #137 is shown to be due to the hard 4GT segments. Considering the available data on Hytrel-type polymers* the molecular weight of polymers #135 and 137 can he equal to or exceed 10,000 Dalton.

The synthetic matrix ~) is prepare~ by the polycondensa-tion of dimethyl terephthalate, di~er acid, or preferably its diisopropyl ester and a polymethylene diol (n = 4 to 8, and preferably 4~.

*See A. Lilconitkul ~ S. L. Cooper, Rubber Chem. Tech. 50 (1), 1 (1977) and references therein.

ET.-531 -13- ~%~37~

C~3 O O CH
~ 1l 1 3 CH3OOC ~ -COOCH3 + HO(CH2)n OH + Hf-C-C34H66-C-C~
C~3 c~3 catalyst ~ > polymer stabilizer 10 ( optional ) The preferred parent dimer acid of the diisopropyl ester utilized in the polymerizations is derived from high purity oleic acid and is formed by a clay catalyzed high pressure dimerization of the oleic acid in the presence of water. The ~echanism of formation of the dimer acid is probably free radical in nature and the product is believed to consist of a mixture of acyclic unsaturated C36 acids. The unsaturated materials are then hydrogen-ated and the dimer ester used in the present polymeriza-tions possesses a slight degree of unsaturation as evidenced by an Iodine number of 5. In addition to the C36 acids that make up the dimer acid there is present some monofunctional acid (iso-stearic) and a certain ~uantity of trifunctionality in terms of a "Trimer (Cs4) acid." The former may act as a chain terminator and the latter as crosslinking agent. Detailed structures of the C36 components of the dimer acid have not been elucidated as yet and the diaci~ is someti~es represented graphically 3~ as shown below (with four almost equal branches).

CH3 ~ ~ CH3 ~ ~ ~
HOOC COOH

The reaction may be run in the ahsence or preferably in the presence of stabilizers taken from the types of 37~3~

hindered phenols or secondary aromatic amines. An example of the forner is Irganox 109~ sold by ~iba-Geigy [N,N'~
hexamethylene bis (3,5~ditert-butyl~4-hydroxy hydrocinna-mide)] and an example of the latter is Maugard 445 sold by ; 5 Uniroyal [4,4'-bis(a,~-dimethylbenzyl)diphenyl amine)].
Oxides and alkoxides of numerous polyvalent metals may be employed as catalysts~ A preferred catalyst for the poly-merization is a mixture of about 0.1~ tetrabutyl orthoti-tanate and about 0.005% magnesium acetate (percentages based on total charge weight).
.~
The polymerization is run in two staqes. In the first stage, run under nitrogen at temperatures ranging from 160 to 250C, polycondensation via transesterification and esterification occurs resulting in oligomeric chains.
These are converted to materials having high degree of polymerization in the subsequent step run at 240 to 255C, at pressures of less than 1 mm of mercury.

; 20 The resulting polymers exhibit inherent viscosities (measured in hexafluoroisopropyl alcohol) of 0.5 to 0.9.
The Tm of the polyners, depending on composition, varies from 100 to 1~0C.
;'' PolYmerization Procedure for Preparing Matrix Q
_._ For each mole of the desired amounts of dimethyl terephthalate and diisopropyl dimerate (obtained from Emery Industries as E~erest 2349), a 1.3 to 2.2 molar excess of a polymethylene diol and a given stabilizer are placed under nitrogen into a dry reactor fitted with an efficient mechanical stirrer, a gas inlet tube and a i takeoff head for distillation. The system is heated under nitrogen to 160 and stirring is begun. To the honogeneous stirred solution the required amount of catalyst is added. The mixture is stirred and heated under nitrogen for given time periods at 19nC
E~H 531 ~ Trademark ?i~ ~i ~3~7 (2-4 hours) and 220C (1-3 hours). The tenperature is subsequently raised to 250 to 255C and over a period of n.4-0.7 hours, the pressure is reduced in the system to below 1 mm/~g (preferably in the range of 0.05 mm to 0.1 mm). Stirring and heating under the above conditions is continued to the completion of the polymerization. The endpoint is determined by either a) estimating visually the attainment of maximum melt viscosity, b) measuring inherent viscosity or melt indices of samples removed from the reaction vessel at intermediate time periods, and c) using a calibrated torquemeter immersed into the mixture.
In practice, depending on the terephthalate/di~erate ratio, in vacuo reaction times vary from 2 to 13 hours.

At the end of the polymerization cycle the hot mixture is equilibrated with nitrogen and allowed to cool slowly.
The reaction product is isolated, chilled in liquid nitrogen and ground. The ground chips are dried at 80 to 110C for 8 to 16 hours under vacumm of 1 mm or less.
Copolyesters Q) of aromatic diacids (e.g. terephthalic acid) and "dimer acids" of C18 unsaturated fatty acids have been known for some time in the technical and patent literature.
Hoeschele ~Angew.Makromol.Chem. 58/59, 229(1977)]
disclosed the preparation of thermoplastic PBT
(polybutylene terephthalate)/dimerate systems.

According to a number of patents [U.S. Patent Mo.
3,390,108 (1968), U.S. Patent No. 3,091,600 (1963) and ~ritish Patent No. 994,4~1 (1965)], P~T (polyethylene terephthalate) copolymers were disclosed containing small amounts of dimerate moieties.

~TH 531 ~37~

In a few instances higher concentrations of dimerates are disclosed as being incorporated into PET copolymers [Belgium Patent No. 649,158 (1964?, U.S. Patent No.
3,383,343 (1968) and French Patent No. 1,398,551 (1965)]~

The general structure of the poly[polymethylene terephthalate-co-(2-alkenyl or alkyl) succinate] R), useful in forming the composite sutures of the present invention, may be expressed as follows:
1 0 0 01 l ~ g ~C-C7-C~2~-0 ~ ~h Alkl wherein Z and G are as defined hereinabove.

; The structure belongs to the copolymer type and g and h can be predicted from the quantities of starting materials;

"G" is preferably 1,4-butylene, and "Alkl" is a linear or branched alkyl, or alkenyl (preferably a 2-alkenyl) group with a chain length of about 4 to 30 carbon atoms with the preferred range lying between about 12 and 22 carbon atoms.

The preferred polymers R) useful in the present invention are prepared by the polycondensation of dimethyl terephthalate, an alkyl (or 2~alkenyl) succinic anhydride and a polymethylene diol: O

CH300C- ~ -COOCH3 + HO(CH2)40H + ~ O $atalyst ~ polymer ~ stabilizer R

~, ~! ~

-17~ 3~

The required diols are commercially available. The substituted succinic anhydrides can be prepared by the "ene" reaction of maleic anhydride and an olefin (preferably a terminal olefin):

R-CH2CH=CH + ~ RCU=CN CH2 ~ o The reaction may be run in the absence or, preferably, in the presence of stabilizers such as hindered phenols, (e.g., Irganox 1098) or secondary aromatic amines, (e.g., Naugard 445). Acetates, oxides and alkoxides of numerous 15 polyvalent metals may be employed as the catalyst such as, for example, zinc acetate, or magnesium acetate in combi-nation with antimony oxide, or zinc acetate together with antimony acetate. However, the preferred catalyst for the polymeriæation is a mixture of about 0.1~ (based on total 20 charge weight) tetrabutyl orthotitanate and about 0.005 magnesium acetate.

The polymerization is run in two stages. In the first stage, run under nitrogen at temperatures ranging from 25 160 to 250C, polycondensation via transesterification and esterification occurs, resulting in lower molecular weight polymers and oligomers. These are converted to higher molecular wieght materials in the subsequent step run at 240 to 255C, at pressures of less than 1 mm of 30 mercury. The resulting polymers, exhibit inherent viscosities (measured in hexafluoroisopropyl alcohol) of 0.3 to 0.9. A representative molecular weight determina-tion of one of the polymers by light scattering gives a value of 78x103 Daltons. The Tm of the polymers, depending 35 on composition varies from about 100 to 180C.

. ~
.~1 ~ ~37~

Polymerization Procedure for Preparation of Polymer R

The desired amounts of ~imethyl terephthalate, a 2-alkenyl succinic anhydride (or an alkylsuccinic anhydride), a 1.3 to 2.0 molar excess of a polymethylene diol and a given stabilizer are placed under nitrogen into a dry reactor fitted with an efficient mechanical stirrer, a gas inlet tube and a takeoff head for distillation. The system is heated under nitrogen to 160C and stirring is begun. To ln the homogeneous stirred reaction mixture the required amount of catalyst is addefl. The mixture is then stirred and heated under nitrogen for given time periods at 190C
;~(2-4 hours) and 22noc (1-3 hours). The temperature is subsequently raised to 250 to 25SC and over a period of ;15 0.4 to n.7 hours, the pressure is reduced in the system to about 1 mm/Hg ~preferably 0.05 m~ to 0.1 mm). Stirring and heating under the above conditions is continued to complete the polymerization. The endpoint is ~etermined hy either (a) estimating visually the attainment of maximum melt viscosity, (b) measuring inherent viscosity or melt indices of samples removed from the reaction vessel at intermediate time periods, or (c) using a ;cali~rated tor~uemeter (attached to the stirrer of the reactor).
At the end of the polymerization cycle the molten polymer is extruded and pelletized (or slow cooled in the glass reactor, isolated and ground in a mill). The polymer is dried at 8n to 110C for 8-16 hours under reflucefl pressure. One alternate method of polymerization is set forth in t7.S. Patent Mo. 3,890,279.

Said U.~S. Patent No. 3,890,279 and tJ.S. Patent No.
3,891,~04 flisclose copolymer R).

~L3~

The flexible polyesters S) useful in the present invention have rigid AB type ester units of an alkylene oxybenzoate and one of the following flexible AA-BB type ester sequen-ces of (1) an alkylene, 2-alkenyl (or alkyl) succinate, (2) an alkylene Aimerate (from a dimer of a long chain unsaturated fatty acid), (3) a Aicarboxylate of poly(oxy-tetramethylene) glycol~ Preferred copolymers ~S) have the following general formula:
o ~Ç ~ O-(-G-O~e...Jf wherein G is defined hereinbefore and e and f can be fletermined by the a~ount of starting materials and J is either:
O O
Il 11 (1) ~C-CH-CH2C-O-G-O-}
Alk2 or O
Il 7~J 11 (2) ~C~- ~ C-O-G-O~

wherein Alk2 is alkyl or alkenyl with a chain length of 8 to 30 carhon atoms; ~ denotes a branched hydrocarbon chain with an estimated formula of C32H60, or O
Il 11 ~3) ~C-R'-C-O-~-G-O)p-G-O~f wherein R' is an aliphatic, cycloaliphatic or aromatic Aisubstituted moiety and p is about 10. The J units comprise about 25-50% by weight of the copolyester.

The general structures of the preferred copolymers S) useful in the present invention may be expressed as follows:
ETH^531 7:~

I. ~ ~ -G-}e........ ~C I -CH2-C 0-G O~f Alk2 C ~ o-G-o~e-~ O-G-O~

III. ~C ~ o-G-o~e~ -R'-c-o-tG~otp-G-o~f Copolymers 5) of type I are prepared typically by the polycondensation of p-(4-hy~roxy-n-butoxy) benzoic acid (i'lB-03) (or its methyl ester) (~B-0~), an alkenyl (or alkyl) succinic anhydride ~or the corresponding dialkyl succinate) and a polymethylene diol in the presence of a suitable catalyst and preferably an antioxidant. '~ypical illustration of the reaction can be given as follows:

i'O-(Ci'2)4-0~-.OOCH3 ~ HO-(CH2)6'0H ~ R ~ Cdtalyst~ Sta~ili2er MB-oB
2() Pol~ymer I ~

'.nhe M3-OB can be prepared accor~in~ to the following tpical reaction scheme:

~ ~ CH3-C03r _nC~ Br-(cH2)4-o-c-cH3 (8~A) HO~).COOH ~ (8-A) Base ~ HO-(CH2)4-0-~-COCH (I~-C~) (HB-OB) ~ CH3-OH Catalyst (MB-OB) Copolymers S) of type II are prepared typically by the polycondensation of p-(~-hydroxy-n-hutoxy) ben~oic acid (or its methyl ester), the dialkyl ester of di~er acid (or the free acid) and a polymetllylene diol in the presence of a suitahle catalyst and preferahlY an antioxidant. ',~ypi-cal illustration of the reaction can be ~ en as follows:
ErlnHr~31 3~7 HO-(CH2)4-o-~COOCH3 ~ HO-(CH2)6-011 ~ CH(cH3)2o-c-~c34H66--C-GCH(CH3)2 polym~r II ~5t~ 2er The parent dimer acid of the diisopropyl ester utilized in the polvmerization is derived by a catalyzed 'nigh pressure dimerization of high purity oleic acid.

Copolymers S) of type III are prepared typically by the polycondensation of p-(4-hydroxy-n~butoxy) benzoic aci~
(or its alkyl est~r), di~ethyl terephthalate, and polyoxybutylene ~iol (Mol. Wt. = about ln00 Daltons), a suitable catalyst and stabilizer. ~y~ical illustration of the reaction can be given as follows:

Ho(cH2)4-- ~ C0~CH3~[(CH2)~-o-]n-cH2cH2cY2C~H~C~ 5C ~ -~

The polymerization may be conducted either in the absence or preferably in the presence of stabilizers of the hindered phenol or secondary aromatic amine tvpe. ~n 3n example of the former is Irganox 109~ and an example of the latter is rlaugard ~5. As catal~st, oxide.s and al]coxides of numerous polyvalent ~etals may be employed.
E~owever, the preferred polymerization catalysts are combinations of (a) tetrabutyl orthotitanate and/or magnesium acetate, (h) r1~(OAc)2 and/or Sb2O3, ancl (c) combinations oE tin an.l antimony catalysts, such as ~uSnO
(Ol~) and Sb2O3.
~TH 531 L37~

The polymerization is conducted in two stages. In the first stage, run unfler nitrogen at temperatures ranging from 160 to 250C polycondensation via transesterifica-tion and esterification occurs resulting in lower molecu-lar weight polymers and oligomers. These are converted tohigher molecular weiqht materials in the subsequent step run at 240 to 260C, at pressures of less than 1 mm of mercury.

Polymerization Procedure for Preparation of Polymer S) The clesired amounts of monomers (and prepolymers as in system III) and a given stabilizer (optional) are placed under nitrogen into a dry reactor fitted with a mechanical stirrer, a gas inlet tube and a take-off head for distillation. The system is heated under nitrogen at 100 to 160C and stirring is begun. To the homogeneous stirred solution the required amount of catalyst is added.
The mixture is then stirred and heated under nitrogen for given time periods at 190C (2-4 hours) and 220C (1-3 hours). The temperature is subsequently raised to 25no to 260C and over a period of n.4~0.7 hours the pressure is reduced in the system to helow 1 mm/Hg (preferably in the range of 0.05 mm to n.l m~). Stirring and heating under the above conditions is continued to the completion of the polymerization. The end point is determined hy either (a) estimating visually the attainment of maximum melt viscosity, (b) measuring inherent viscosity or melt indices of samples removed from the reaction vessel at 3n intermediate time periods, and (c) using a calibrated torquemeter immersed into the reaction mixture. In practice, depending on the copolymer composition, in vacuo reaction times varies from 2 to 8 hours.

At the end of the polymerization cycle the hot mixture is equilibrated with nitrogen and allowed to cool slowly.

~3~
~23~
The reaction product is isolated, cooled in liquid nitrogen, and then ground. (In the case of metal reactors the hot melt is extruded at the bottom of the vessels into Teflon covered metal trays.) The ground chips are dried at 60 to llnC for 8-32 hours under a vacuum of 1 mm or less.

In accordance with the present invention, pure silk filaments of braided construction are preferably used (a wide range of sizes being available). ~ddition of the elastomer to the silk does not significantly alter the - 15 dia~eter thereof. The elastomers utilized in accordance with the present invention are designed to be soft, duc-tile and elastomeric but capable of retaining their mechanical integrity under the ordinary mechanical stres-ses that the composite suture may be subjected to during end use. Retention of physical form and mechanical integrity is achieved by having quasi-crosslinks due to the crystallites of the crystaline phase in this system.
This constitutes about S to 35% of the weight of the polymer. The low modulus and "soft handle" of the polymer are associated with the soft component of the polymer which comprises between about 25% and 30% by weight there-of [for polymers P), Q) and R), the soft components comprise between 50% and 30% by weight thereof, preferably between 55% and 75~, and for polymer ~S), the soft 30 component comprises between 25~ and 50~, preferably 30% to 50% by weight]~ By virtue of their compositions, these quasi-crosslinked systems can be made to flow above the melting temperature (Tm) of the hard block. These thermal characteristics of the matrix material are of importance in connection with the optimal development of the composite suture, for it is then possible to rapidly ~LZ~37~7 ~24-sinter the matrix about the fibers of the silk braid at a temperature of above 200C, without causing thermally induced degradation of the silk.

Suitable solvents for applying the elastomer matrix mater-ial to silk are halocarbons or mixtures of halo carbons with aromatics, methylene chloride being preferred.
Methylene chloride was selected for (aJ i~s ability to induce certain amounts of swelling of the silk braid so as to ensure an ultima-te strong joint between the braid components and the elastomeric matrix; (b) its ability to provide polymer solutions in a preferred case, with 20 to 5% concentrations having low ~rookfield viscosities; this facilitates the impregnation of the braid with these solutions and (c) its high fugacity under mild devolatili-zation conditions, for drying the composite suture.

The elastomer is applied to the silk suture from a warm solution in a suitable solvent, as discussed above, 2n especially dichloromethane. The temperature of the solu-tion and the concentration of the polymer in the solution are not critical but it is preferred to have a temperature close to the boiling point of the solvent (ahout ~0C in the case o dichloromethane) and a concentra-tion which will not substantially increase the viscosity of the solution.

In order to carry out the process of the present inven-tion, the braided silk suture is passed in a continuous 3n process through a warm solution of elastomer, then immediately above the solution surface through a felt wipe, then vertically upward to air dry the treated suture over a short distance (e.g. 2 to 3 feet). The treated suture is then submitted to a rapid heating process in which the suture travels through a hot air ~one to momentarily melt the elastomer layer inside the braided ET~-531 ~Z~3t7~

silk suture in order to substantially fill all interstices hetween the silk filaments. The temperature of the heated zone is adjusted for optimum polymer infiltration and depends upon the polymer used, the speed of the threadline and the suture diameter.

Typical temperatures of the hot air medium used for sin-tering during the rapid heat treatment range hetween 340C
and 500C. This temperature ranqe is not necessarily the same as that of the suture itself. In the instance wherein the polymer has the structure P) and the silk suture is size 2/0 travelling at 14 feet per minute, the temperature is preferably 415C, the length of the heated zone being 22 centimeters.
The composite sutures of the present invention are extremely inert and have a minimal to very slight tissue reaction and are impervious to cellular ingrowth. They also exhibit a greater strength retention after eight 2n weeks than silk coated with beeswax. These properties are demonstrated by the following studies:

In Vivo Performace of the Composite Suture Needle Attachment and Sterilization Needles are attached by hand swaging with a crimping tool and all samples are Cobalt sterilized.

In Vivo Implantation Tissue Reactions of Polymer P) Coated Silk Implanted in Rats Materials _ 1. Materials of the following description are implanted, Polymer P) being the product of ~xample 2:
ET~-531 ~Z~3'7~7 -~6-Sample No. Size Coat1ng Treatment 1 2~0 Polymer P) coating 2 2-0 Wax coated control 3 5-0 Polymer P) coating

4 5-0 Wax coated control 2. Amount of Material Required for Tissue Reaction Twenty-two needled strands at least eight inches long for each sample; strands are fitted with drilled straight tapered needles.

3. All samples are sterilized by Cobalt60.

Procedures 1. Tissue Reaction Study A. Animals - Rats, female, Sprague Dawley, weight 150 to 200 grams. Fifty-four animals are used.

B. Implantation Periods - 7, 28 and 56 days.

C. Experimental Design:

Implantation of samples for tissue reaction are carried out according to the following design:

Sample No_. Periods in Days/No. of Rats ~2~3~
~27 D. Standard conditions of anesthesia and ase~tic procedures are observed during suture preparation and -surgical implantation.

Utilizing one strand per side, 2 cm segrnents of each su~ure are implanted in the right and left ~luteal muscles, two implants per side. ~Strands from the same suture sample are implanted on both sides of each rat.

Rats are sacrificed according to ex~erimental design after period of 7, 28, and 56 days. The gluteal muscles containing implants are excised and preserved in formalin fixative. A single block is cut transversely from each gluteal muscle and a sin~le cross section of the two implant sites are stained with Hematoxylin and Eosin for microscopic evaluation. This procedure yields twelve sites per sample per period for evaluation.

E. Evaluation 1. Tissue Reaction Evaluation A method modified from that descrihed by ~Sewell, Wiland and Craver, (Surg., Gynecol. and Obstet. 10n:483-494, 1955) is utilized to assess responses to implanted sutures~ In this scheme the width of the reaction zone measured along the radius from the center of the suture cross section, is graded as:

3n Assigned Grade 0 - 25 ~icrons 0 5 25 - 50 microns 1. n 50 - 200 microns 2. n 200 - 400 microns 3.0 35400 - 600 microns 4.0 37~7 28~
Cellular response is graded from 0 to ~ based on increasing concentrations of cells in the reaction zone.
A grade of 0.5 is assigned where only a few cells are widely scattered in the reaction zone, while a grade of 4 is assigned where a high cellular concentration is present in the site.

Weighting factors are assigned to zone of reaction and inflammatory cells in computing reaction score as follows:

Characteristic Weighting Factor _ .
Width of Zone 5 Overall cell density 3 Neutrophils fi G7iant cells 2 Lymphocytes/plasma cells Macrophages Eosinophils Fibrohlasts/Eibrocytes A sample score is computed as follows:

Parameter Grade x Weightinq factor = Score Zone 2 5 10 Cell densitv 2 3 6 Macrophages 2 1 2 Giant cells 1 2 2 Fihroblasts 2 1 2 Total Score 22 Adjectival ratings assigned to reaction scores are arbitrarily assigned within the following limits: 0-none:
1-~ minimal; 9-24 slight; 25-40 moderate; 41-56 ~arked;
over 56, extensive.

2. Cellular Invasion of Strands The extent of cellular invasion of suture fibrils is estimated subjectively as: none, minimal, slight, moder-ate or marked; these ratings correspon~ approximately to0, 25, 50, 75 and 100 percent of suture invaded.

Determlnation of Tissue Reaction The implants are recovered after the designated intervals and fixed in buffered formalin. Using standard histologic techniques, Hematoxvlin and Eosin stained slides of the muscle cross-sections are prepared and examined nicroscop-ically, twelve sites per sample per period. Tissue reac-tions are evaluated according to the modified Sewell-Wiland method as described above (See Tahles 2 and 3).

In addition, the muscle cross-sections containing the polymer P) treated silk are stained with Oil Red 0 to visualize the presence of the polymer inside the silk braid.

Calculation of the tissue reaction area is accomplished by measuring the reaction diameters using an ocular micro-meter. Since the shape of the tissue reaction tends to beelliptical, the ormula for the area of an ellipse, A=(Dl x D2)/4 x ~ is used to calculate these areas. The suture is included in these diameter measurements (See Tables 2 and 3).
3~
The measurements of cellular invasion inside the silk hraids are estimated subjectively as a percentage of suture area invaded.

~2~L3~

Determination of In Vivo Tensile Streng h Loss Breaking Strength Evaluation of Coated Silk Sutures After ntation in Rats The purpose of this study is to determine the breaking strength of silk sutures coated with a Polymer P) coating (product of Example 2) at baseline (0 days), 7, 28 and 56 days in the rat subcutis.
Materials .

Seventy-two young (approx. 200 gm) female Long-Evans (Blue Spruce Farms) rats.
Test Material One lot each of sizes 2-0 and 5-0 sterile silk, coated as follows:
A. Standard Wax Coating B. Polymer P) Coating Eight strands 18 inches each are used for each coating group.

Methods Eight 18 inch strands of each coating type are divided int four groups of eight segments each. One segment from each of the strands is placed in each of three implanted groupso (7, 28, 56 days) and one unimplanted (0 day) group. Each segment to be implanted is clamped at each end in a hemostatic forcep.

--~Z~L3~7~7 The rats are prepared for surgery by clipping fur from the dorsal scapular region of the skin. They are anesthetized using METOFAME* and swabbed in the operative area with an antiseptic solution.

A transverse incision approximately 2 cm. long is centered in the shaved area. Two segments of test material are implanted in the posterior dorsal subcutis through this single incision, one left and one right. The wound is ln closed with stainless steel wound clips.

Sutures are so implanted in four rats for each time period previously listed, thus yielding eight replicate segments/period.
The animals are sacrificed at the designated time periods and suture segments are gently and carefully removed from their respective sites. The recovered segments are stored in prelabeled moist paper towels for subsequent breaking strength testing.

All suture segments for this study are tested on an Instron Universal Testing Unit using the following machine parameters~
Jaw Face: Coplanar rubber faced steel ~,age Length: l inch Crosshead distraction rate: 2 inches/minute Chart speed: 2 inches/minute Jaw Pressure: 70 PSI
Baseline day sample condition: Dry *Trademark of Pitman-Moore 3~
~32-Data Handl1ng The results of the hreaking strength tests are summarized for each sample lot as follows:

Averages ~tandard Deviation 95% upper and lower confidence limits Conversion of all numbers to kilograms Calculation of percent remaining of baseline These data are listed for each time period including baseline.

Results Biological response, tensile strength loss and other physical test data are summarized in Tables 2, 3 and 4.

~iscussion ~ .

The cellular responses to all the tested suture samples are foreign body in nature. However, the polymer P) treated silk is extremely inert, provoking minimal to very slight tissue reaction scores and preventing cellular ingrowth inside the silk braid.

Oil Red 0 stained cross sections reveal that the polymer is infiltrated throughout the braid. In the case of the size 2-0 material, distribution of polymer tends to be higher in the peripheral carriers than in the central core. The extent of the polymer infiltration is similar after the 7, 28 and 56 day implantation periods, and comparable to the non-implanted suture cross sections.

~%~37~
~3-The silk filaments of the polymer P) treated samples have a less intense black coloration than the beeswaxed (control) silk filaments, but this can only be seen in the cross-sections and is not apparent grossly.

The waxed silk elicits a moderate tissue reaction. The primary cell types seen in these reaction zones are macro-phages, multinucleated foreign body giant cells and fibro blasts. Individual filaments or bundles of filaments of the waxed silk sutures are separated and surrounded by inflammatory cells.

The cross-sectional areas of the waxed controls show considerable cell infiltration and consequent "explosions"
of the silk braid.

After four and eight week implantation periods the polymer P) treated silk exhibits increasingly greater strength retention compared with beeswaxed controls.
Infiltration of braided silk with the polymer P) results in a tissue-inert silk suture with an excellent "silk hand" and an improved strength retention. Both tissue inertness and ln vivo strength retention are rated significantly better than standard silk controls.

A further study, similar to the above is conducted utilizing 54 female Long Evans rats, rather than Sprague Dawley rats, and the results are summarized in Tables 5, 6, 7 and 8. Table 5 sets forth Average Breaking Strength values for polymer P) coated Sutures after subcutaneous implantation in rats, whereas Tables 6, 7 and 8 relate to tissue response evaluation.

_34_ ~2~37~7 Results ~ ~ . .. _ The reactions elicited by the sutures are foreign body in nature. In implant sites of Polymer P) sutures the reac-tions are primarily confined to the periphery of thesuture. The reactions consist mostly of fibroblastic/
fibrocytic cells and macrophages on the suture surface.
Other inflammatory cells are absent or present in minimal numbers. Cellular reaction in polybutilate coated suture implant sites tend to be composed of fibroblasts/
fibrocytes, macrophages, glant cells and scattered neutro-phils especially at the seven day interval. Neutrophilic leukocytes are prominent in implant sites oE wax coated sutures especially at seven days post implantation. Giant cell and fibroblast/fibrocyte cellular reaction are dominant in the 28 and 56 day waxed suture implant sites.

Fibrous encapsulation of Polymer P) sutures is well-defined at 56 days while encapsulation of wax coated sutures is poorly defined at this interval.

With respect to overall reactions elicited by size 2-0 sutures, it is noted that Polymer P) coated sutures tend to evoke less tissue reaction than wax coated silk at seven days post-implantation (see Table 6).

The areas of reaction zones for sizes 2-0 and 5-0 Polymer P) coated sutures are significantly smaller than are observed for the control samples at 7, 28 and 56 days (see Table 7). The smaller tissue reaction areas observed for Polymer P) coated sutures are due mainly to lesser amounts of interfibrillar cellular infiltration.
.

Polymer P) coating is highly effective in preventing cellular invasion of both sizes of silk sutures at all three periods (7, 28 and 56 days) as shown in Table 8.

ET~.531 3~

In hematoxylin and eosin stained sections of implant sites of paraffin/beeswax, coatings are not visihle due to their solubility in histoprocessing solutions. Polymer P) coating is faintly visible in ordinary transmitted light and is readily seen in polarized transmitted light.
Sections of Polymer P) coated suture sites stained with oil red O reveal the coating to be uniformly distributed at the periphery of the suture and variably dispersed around filaments near the center of the suture.

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AVERAGE BREAKING ~STRENGTH VALUES FOR POLYMER P) SUTURES

DATA ÆXPRÆSSED IN POUMDS
.
TIME IN DAYS

~ 0 7 2856 DESCRIPTIOrlS

SIZE:2-08.60 5.00 4.27 3.n2 PARAFFIN/BEESWAX
% REMAINING 100 58 50 35 .SIZE:2-08.315.13 4.37 3.88 POLYMER P) COATED
% REMAINING 100 62 53 47 SIZE:5-01.82 1.17 0.88 0.68 PARAFFIN/8EÆSWAX
% REMAINING 100 64 49 37 ~SIZÆ:5-0 1.. 65 n.ss 0.79 0.74 POLYMER P) COATE~
% REMAINING 100 60 4~ 45 ~231 3~
-40~

MEDIAN TISSUE OVERALL REACTION SCORES FOR COATED
SILK SUTURES AFTER INTRAMUSCULAR IMPLANTATION
IN LONG EVANS RATS*

. . ~
DAYS POST- MPLANTAmION
SIZE DESCRIPTIO~l 7 28 56 2-0 Pol~mer P) Coated 14.5 8 11 (8-17) (6-14) (7-14) 2-0 Paraffin/~eeswax 3~.5 31 25.5 Coated (13-42) (17-52) (15-40)

5-0 Polymer P) Coated lfi 7.5 10.5 (13-23) (5-15) (8-14) 5-0 Paraffin/~eeswax 2fi 17 16 Coated (20-30) (14-34) (15-23) ,, _ . . . ._ *Data represent the medlan of 10-12 cross section in three rats per period. Arbitrary assignment of scores are as follows: 1-8 minimal, 9-24 slight, 25-40 moderate, 41-56 marked, 56+ extensive.

**( )=range of tissue reaction scores for the period.

ETH-'31 121~7~7 TABL

AVERAGE TISSUE REACTION AREAS FOR COATED SILK SUTURES
AFTER INTRAMUSCULAR IMPLANTATION IN LONG EVANS R~TS*

DAYS POST-IMPLANTATION

~ _ . . .... . .
2-0 Polymer P) Coated .204++ .196++ .170 (.026) (.026) (.030) 2-0 Paraffin/Beeswax .857 .768 .539 Coated (.200) (.41S) (.331) 5-0 Polymer P) Coated .112~ .049++ .053++
(.036) (.009) (.013) 5-0 Paraffin/Beeswax .280 .161 .143 Coated (.074) (.040) (.041) *Data represent the mean of 10-12 cross sections per period and are presented in square millimeters (mm~).

**( ) = Standard deviation.

++Significantly different from polybutilate and paraffin/
beeswax.

+Significantly different from paraffin/beeswax.

ETfi 531 ~Z~3~9~
~42-TAB

DEGREE OF INTEREIBRILI,AR CELL~JLAX IMEILTRATION INTO
COATED SII.K SUTURES AFTER INTRAMUSCULAR IMPLANTATION
IN LONG EVANS RATS*

DAYS POST-IMPLANTATION

2-n Polymer P) Coated 0.6** 0.7 0.9 2-0 Paraffin/~eeswax 4.0 3.8 3.8 Coated 5-0 Polymer P) Coated 0.5 0.7 n . 8 5-0 Paraffin/~eeswax 3.9 3.9 4.0 Coated *Data represent the average of 10 12 cross sections per period.

**Arhitrary assignment of scores is as ollows:

0 = no infiltration l = slight infiltration 2 = moderate infiltration 3 = marked infiltration 4 = complete infiltration E~--531 ~Z~37~7 Example 1: Polymer P) Poly[tetramethylene terephthalate-Co-Poly(oxytetramethylene terephthalate)]~

Under a dry nitrogen atmosphere, the following materials are placed into a flame and vacuum dried 300 ml two-neck, round-hottom flask equipped with a stainless steel paddle stirrer~ a short distilling head fitting with a receiver, and a gas inlet nozzle:
27.9 g 1,4 dimethyl terephthalate (0.1439 mol) Z4.6 g 1,4 butanediol (0.2730 mol) 53.1 g (Poly tetramethylene oxide diol).
(Molecular Weight 1000 Dalton) (0.0531 mol) 0.16 g Irganox 1093 After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at 165C is performed for 15 minutes.
Mext, the catalyst consisting of a mixture of tetrabutyl orthotitanate (0.24~ g) and magnesium acetate (0.01 g) dissolved in a mixture of methanol and butanol, is quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogent the melted reaction mixture is then subjected to -the following heating sequence: 190C for 2.5 hours, 220C for 2.5 hours.

As the distillation of volatile by~products slows, after 2.5 hours at 220C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction ~ ~37~

flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 230C for 4.5 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil hath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.
Example 2: Polymer P) Poly[tetramethylene terephthalate-Co-Po~y-(oxytetramethylene terephthalate)]-~29/71 P~T/POTM-T) Under a flry nitrogen atmosphere, the following materials are placed into a flame and vacuum dried 500 ml two-neck, round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:
~0 38.8 g 1,~ dimethyl terephthalate (0.1998 mol) 37.7 g 1,4 hutanediol (0.4183 mol) 65.4 g (Poly tetramethylene oxide diol) Molecular Weight 1000 Dalton (n.0654 mol) 0.0331 g dibutyl tin oxide (0.000133 mol) After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer ETt-531 ~3~

and thorouqh l~ixing at 165C is performed for 15 minutes.
Still under a continuous flow of nitrogen~ the melted reaction Mixture is then subjected to the following heat-ing sequence: l90~C for 3.0 hours, 23~C for 4.0 hours.

As the distillation of volatile by-products slows, after 4.0 hours at 230C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask is reduced to O.n5 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 230C for 6.0 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil bath, equilihrated with nitrogen, and then allowed to cool to room temperature. mhe polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.

Analytical Data: Tm(microscopy) 140 - 15nC
I.V.(in HFIP) 1.2 Exa~ple 3: Polymer P) Poly[tetramethylene terephthalate-Co-Poly(oxytetramethylene terephthalate)]-(45/55 P~T/P~TM-T) Under a dry nitrogen atmosphere, the following ~aterials are placed into a flame and vacuum dried 300 ml two-neck, round-botto~ flask equipped with a stainless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

39.3 g 1,4 dimethyl terephthalate (0.2024 mol~
44.1 g 1,4 butanediol (0.4~93 mol) 35 38.9 g (Poly tetramethvlene oxide diol) Molecular Weight lOnO Dalton (~.0389 mol) 0.16 g Irganox ln98 ~l%1~3~7~

After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at 165C is performed for lS minutes.
Next, the catalyst consisting of a mixture of tetrabutyl orthotitanate (~.244 g) and magnesium acetate (0.01 g) dissolved in a mixture of methanol and butanol, is quickly syringed into the reaction vessel via the side ar~. .Still under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the following heating sequence: 190C for 2.n hours, 22noc for 2.5 hours.

As the distillation of volatile by-products slows, after 2.5 hours at 220C, the receiver containing the distillate is re~laced with an empty receiver. Then, gradually over the course of ~.75 hours the pressure in the reaction flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 230C for 3.5 hours.

At the end of this heating cycle, the reaction vessel is removed fro~ the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.
Example 4: Polymer R) Poly[tetramethylene terephthalate-Co-(2-octadecenyl)succinate](40/6n PBT/Cl8-succinate) Under a ~ry nitrogen atmosphere, the following materials are placed into a flame and vacuum dried 300 ml two-neck, ~3~7 round-bottom flask equipped with a stalnless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

28.2 g 1,4 dimethyl terephthalate (n.1453 mol) 39.~ g 2-octadecenyl succinic anhydride (0.1136 mol) 69.9 g 1,4 butanediol (0.7756 mol) 0.16 g Irganox 1098 After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at 165C is performed for 15 minutes.
~lext, the catalyst consisting of a mixture of tetrahutyl orthotitanate (0.244 g) and magnesium acetate (0.01 g) dissolved in a mixture of methanol and butanoll is quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the ~ollowing heating sequence: 190C for 3.0 hours, 220C for 3.0 hours.
As the distillation of volatile by-products slows, after 3.0 hours at 220C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction 3n flask is reduced to 0.05 mm. Under redllced pressure the reaction mi~ture is suhjected to the following heating scheme: 2~0C for 2.0 hours, 250C for 2.0 hours.

At the end of this heating cvcle, the reaction vessel is removed from the oil hath, equilibrated with nitrogen, and then allowed to cool to room te~perature. The polymer is ET:-531 -4~
isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.

Analytical Data: Tm(microscopy) 113 - 118C
I.V.(in HFIP) 0.46 Example 5: Polymer S) Poly[poly(tetramethylene oxyben-zoate)-Co-poly(hexamethylene-2-octadecenyl succinate)](40/6~ PB~/C succinate) Under a dry nitrogen atmosphere, the following materials are place~ into a fla~e and vacuum dried 300 ml two-neck, round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

37.3 g meth~l para(4~hydroxy butoxy)benzoate (0.166~ mol) 37.3 g 2-octadecenyl succinic anhydride (0.1065 mol) 13.9 g 1,6 hexanediol (0.1176 mol) 0.16 g Irganox 1098 After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitro~en, and the reactants are melted by heatin~ to 100C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at lnOC is performed for 15 minutes.
Next, the catalyst consisting of a mixture of tetrahutyl orthotitanate (0.305 g) and magnesium acetate (0.0125 g) dissolved in a mixture of methanol and butanol, is quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the following heating sequence: 190C for 2.5 hours, 220C for 3.0 hours, 240C
for 2.25 hours.

~2~37 As the distillation of volatile by-products slows, after - 2.25 hours at 240C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is sub~ected to the following heating scheme: 240C for 2.5 hours, 250C for 2.75 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. mhe polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.
Analytical Data: Tm(microscopy) 50 - 70C

Example h: Polymer S) Poly[poly(tetramethylene oxyben-zoate)-Co-poly(hexamethylene-2-octadecenyl succinate)]t50/50 P~B/ClRsuccinate) Under a dry nitrogen at~osphere, the following materials are placed into a flame and vacuum dried 300 ml two-neck, round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

46.7 g methyl para(4-hydroxy butoxy)~enzoate (n.?n82 mol) 31.1 g 2-octadecenyl succinic anhydride (0.~888 mol) 11.6 g 1,6 hexanediol (O.n981 mol) 0.16 g Irganox 1098 After stoppering the open neck of the flask, the entire charge-containing assembly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then ~37~

vented with nitrogen, and the reactants are melted by heating to ln0C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at 100C is performed for 15 minutes.
Next, the catalyst consisting of a mixture of tetrabutyl orthotitanate (0.305 g) and magnesium acetate (n.~125 g) dissolved in a mixture of methanol and butanol, is quickly syringed into the reaction vessel via the side arm. ~till under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the following heating sequence: 190C for 3.0 hours, 22noc for 2.3 hours, and 240C for 1.25 hours.

As the distillation of volatile by-products slows, after 1.25 hours at 240C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 2~0C for 4.5 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.

Analytical nata: Tm(microscopy) 93 - 101C
I.V.(in HFIP) 0.38 ~xample 7: Polymer Q) Poly~tetramethylene terephthalate-Co-dimerate](30/70 PBT/dimerate) .
Under a dry nitrogen atmosphere, the following materials are placed into a flame and vacuum dried 300 ml two-neck, round-bottom flask equipped with a stainless steel paddle ~TH-531 .

-51~ 37~7 stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

21.2 g 1,4 dimethyl terephthalate (0.1090 mol) 5~.7 ~ diisopropyl dimerate (0.0903 mol) 53.7 g 1,4 butanediol (0.5959 mol) 0.16 g Irganox 109~

After stoppering the open neck of the flask, the entire charge-containing assenbly i5 re~oved from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. Once the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrerand thorough mixing at 165C is performed for 15 minutes.
Next, the catalyst consisting of a mixture of tetrabutyl orthotitanate (0.244 g) and magnesium acetate (0.01 g) dissolved in a mixture of methanol and hutanol, is quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the following heating sequence: 190C for 2.0 hours, 220C for 2.5 hours.

As the distillation of volatile by-products slows, after 2.5 hours at 220C, the receiver containing the distillate is replaced with an empty receiver. ~hen, qradually over the course of 0.75 hours the pressure in the reaction flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 2~0C for 3.5 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. mhe polymer is EmH--531 ~Z~37~
~52-isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.

Analytical Data~ Tm(microscopy) 151 - 156C
I.V.( in HFIP) 0.36 Example ~: Polymer Q) Poly[tetramethylene terephthalate-Co-dimerate](40/60 PBT/dimerate) Under a dry nitrogen atnosphere, the following materials are placed into a flame and vac~lum dried 300 ml two-neck, round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitting with a receiver, and a gas inlet nozzle:

2~.2 g 1,4 dimethyl terephthalate (0.1~53 mol) 50 3 g diisopropyl dimerate (0.0774 mol) 60.3 g 1,4 butanediol (0.6691 mol) 0.16 g Irganox 1098 After stoppering the open neck of the flask, the entire charge-containing assemhly is removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel is then vented with nitrogen, and the reactants are melted by heating to 165C. ~nce the charge is liquified, the reac-tion flask is connected to an efficient mechanical stirrer and thorough mixing at 165C is perfor~ed for 15 minutes.
~lext, the catalyst consisting of a mixture of tetrabutyl orthotitanate (0.244 g) and magnesiun acetate (0.01 g) dissolved in a mixture of methanol and butanol, is quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reaction mixture is then subjected to the following heating sequence: 190C for 2.5 hours, 220C for 3.0 hours.

~53~ 3~7~
As the distillation of volatile by-products slows, after 3.0 hours at 220C, the receiver containing the distillate is replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask is reduced to 0.05 mm. Under reduced pressure the reaction mixture is subjected to the following heating scheme: 240C for 2.0 hours.

At the end of this heating cycle, the reaction vessel is removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer is isolated after chilling in liquid nitrogen, ground, and then dried under vacuum.

Analytical Data: Tm(microscopy) 148 - 151C
I.V.(in HFIP) 0.23 Example 9: Impregnation of_Silk Suture with Polymer The laboratory coating line consists of the conventional spool let-off, solution treatment, drying and suture take-up operations, arranged se~uentially. Two black dyed silk sutures, sizes 2 0 and 5-0 are treated. The suture material is passed through a 15-20~ w/v solution of polymer P) prepared in accordance with Example 2 in dichlormethane, maintained at 40 ~ 5C.

On emerging from the polymer solution, excess solution is removed by passage through a felt wipe. Solvent is evaporated by running the sutures past a hot air blower (150C).

Both polymer solution temperature and concentration are important in achieving the desired polymer add-on in a single pass. ~esirable polymer add-on is in the 7-15%
range, with a value of 9~ for size ?-0 and 12% for size 5-n.

ETH-~31 ~2~3~7~7 At this stage of the process, the polymer encapsulates the suture and does not appreciably penetrate the interior of the braid. The hand of this material is very stiff.
Desirable suture properties of hand and knot-tying are achieved by causing the polymer to infiltrate and penetrate the interior of the braid by subjecting the polymer sheathed suture to a short duration, high temperature heating stage.

The polymer sheathed suture is passed in a vertical mode centrally through a 0.5 cm diameter hole bored in a 22 cm electrically heated aluminum block. Conditions of block temperature and suture speed for achieving optimum infiltration are given helow:
Suture Size Block Temperature Suture Speed 2~0 ~15 + 5C 7.1 cm/sec 5-0 345 ~ 5C 9.6 cm/sec The above conditions are found to confer a soft, supple hand, as contrasted to the stiff, wiry hand of the encapsulated suture.

ETH~531

Claims (29)

We Claim:

1. A composite suture essentially retaining the handling qualities of silk, which, in the case of size 5-0, is capable of retaining at least 32% of its initial mechani-cal strength, in vivo, after eight weeks; said suture having surface barrier properties against cell infiltra-tion comparabe to those of a monofilament and tissue reac-tion comparable to common synthetic sutures; comprising multifilament silk embedded in a hydrophobic, limp thermo-plastic elastomer, substantially all the interstices between the silk filaments being filled by said elastomer;
said elastomer comprising copolymers having hard and soft components, said soft components comprising about 25-80%
by weight of said elastomer, depending upon the melting temperature and the crystallizability of the hard compo-nents, said elastomer having a suitable molecular weight sufficient to provide a solution viscosity that is consis-tent with optimum diffusion into the interior of the suture structure, resulting in a high integrity matrix which does not flake when the suture is subjected to mechanical stress.

2. A suture according to Claim 1 wherein the elastomer is selected from the group consisting of copolymers having the following recurring units:

wherein each G individually represents an alkylene group of from 2 to 6 carbon atoms, and p is 9 to 15, e and f each represent a number having a value greater than 1 such that the B units comprise 50 to 80 weight percent of the copolymer and the A units comprise the remainder; wherein Z represents 1,4-phenylene, 1,3-phenylene or trans-1,4-cyclohexylene;

Q) a copolymer consisting essentially of a multiplicity of recurring A [poly(alkylene terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate)] and B [poly(alkylene dimerate)] units having the following general formula:

wherein x and y are integers, such that the B units comprise 50 to 80 weight percent of the copolymer, and the A units comprise the remainder; denotes a branched hydrocarbon chain containing from 24 to 32 carbon atoms and Z and G are as hereinabove defined;

R) a copolymer consisting essentially of a multiplicity of recurring poly(alkylene) terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate, and poly(alkylene) alkyl or alkenyl succinate units having the following general formula:

wherein Alk1 is a linear or branched alkyl or alkenyl radical with a chain length of about 4 to 30 carbon atoms and g and h are integers such that the A units comprise 20 to 50 weight percent of the copolymer and the B units comprise the remainder and Z and G are as hereinabove defined;

S) a random copolymer having the following general formula:

wherein J is either:

(1) or (2) wherein Alk2 is alkyl or alkenyl moieties with a chain length of 8 to 30 carbon atoms; denotes a branched hydrocarbon chain with an estimated formula of C32H60, or (3) wherein p is 9 to 15, G, is as hereinabove defined and R' is an aliphatic or aromatic disubstituted moiety and wherein e and f are such that the B units comprise about 25 to 50% by weight of the copolyester and the A units comprise the remainder.

3. A composite suture, comprising multifilament silk embedded in a hydrophobic, limp thermoplastic elastomer, said elastomer being selected from the group consisting of copolymers having the following recurring units:

wherein each G individually represents an alkylene group of from 2 to 6 carbon atoms, and p is 9 to 15, e and f each represent a number having a value greater than 1 such that the B units comprise 50 to 80 weight percent of the copolymer and the A units comprise the remainder; wherein Z represents 1,4-phenylene, 1,3-phenylene or trans-1,4-cyclohexylene;

Q) a copolymer consisting essentially of a multiplicity of recurring A [poly(alkylene terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate)] and B [poly(alkylene dimerate)] units having the following general formula:

wherein x and y are integers, such that the B units comprise 50 to 80 weight percent of the copolymer, and the A units comprise the remainder; denotes a branched hydrocarbon chain containing from 24 to 32 carbon atoms and Z and G are as hereinabove defined;

R) a copolymer consisting essentially of a multiplicity of recurring poly(alkylene) terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate, and poly(alkylene) alkyl or alkenyl succinate units having the following general formula:

wherein Alk1 is a linear or branched alkyl or alkenyl radical with a chain length of about 4 to 30 carbon atoms and g and h are integers such that the A units comprise 20 to 50 weight percent of the copolymer and the B units comprise the remainder and Z and G are as hereinabove defined;

S) a random copolymer having the following general formula:

wherein J is either:

(1) or (2) wherein Alk2 is alkyl or alkenyl moieties with a chain length of 8 to 30 carbon atoms; denotes a branched hydrocarbon chain with an estimated formula of C32H60, or (3) wherein p is 9 to 15, G is as hereinabove defined and R' is an aliphatic or aromatic disubstituted moiety and wherein e and f are such that the B units comprise about 25 to 50% by weight of the copolyester and the A units comprise the remainder.

4. A suture according to Claim 3 wherein Z is 1,4-phenylene, G is 1,4 butylene, and the elastomer has an inherent viscosity of between 0.2 and 1.4 and has a melting temperature, by thermal microscopy of between about 80° and 180°C.

5. A suture according to Claim 4 wherein the elastomer comprises 5-50% by weight of the total composite system and has a molecular weight of at least 2000 Dalton.

6. A suture according to Claim 4 wherein the elastomer has the formula P), Q) or R) and the soft segments comprise between 55% and 75% thereof.

7. A suture according to Claim 6 wherein the soft segments of the elastomer comprise between 60% and 70% by weight thereof.

8. A suture according to Claim 4 wherein the elastomer has the formula S) and the soft segments comprise between 30% and 50% thereof.

9. A suture according to Claim 4 wherein the elastomer has the formula P) and the inherent viscosity in hexafluoro-2-propanol is between 0.8 and 1.3.

10. A suture according to Claim 4 wherein the polymer has the formula Q) and the inherent viscosity in hexafluoro-2-propanol is between 0.3 and 0.9.

11. A suture according to Claim 4 wherein the polymer has the formula R) and the inherent viscosity in hexafluoro-2-propanol is between 0.2 and 0.7.

12. A suture according to Claim 4 wherein the polymer has the formula S) and the inherent viscosity in hexafluoro-2-propanol is between 0.3 and 0.6.

13. A suture according to Claim 2 wherein the silk is of braided construction.

14. A suture according to Claim 2 having a surgical needle attached to at least one end.

15. A suture according to Claim 2 or 14 in a sterile condition.

16. A composite suture essentially retaining the handling qualities of silk, which is capable of eliciting a tissue reaction comparable to common synthetic sutures and having barrier properties against cell infiltration comparable to these of a monofilament; comprising a multifilament silk embedded in a hydrophobic, limp thermoplastic elastomer, substantially all the interstices between the silk filaments being filled by said elastomer.

17. The composite suture of Claim 16 in which the elasto-mer comprises a copolymer having hard and soft components, said soft components comprising about 25-80% by weight of said elastomer, depending upon the melting temperature and the crystallizability of the hard components, said elasto-mer having a suitable molecular weight sufficient to pro-vide a solution viscosity that is consistent with optimum diffusion into the interior of the suture structure, resulting in a high integrity matrix which does not flake when the suture is subjected to mechanical stress.

18. A method of preparing a non-irritating and strength retaining composite silk-thermoplastic elastomer suture, comprising the steps of:

a) treating a multifilament silk suture with a hydrophobic, limp thermoplastic elastomer dissolved in a solvent therefor at a temperature between 20° to 80°C in order to coat said suture; said elastomer comprising copolymers having hard and soft components, said soft components comprising about 25-80% by weight of said polymers; and said elastomer having a suitable molecular weight sufficient to provide a solution viscosity that is consistent with optimum diffusion into the interior of the suture structure, resulting in a high integrity matrix which does not flake when the suture is subjected to mechanical stress; and b) heating the treated suture at a temperature between 340° to 500°C to obtain a continuous and consistent impregnation of the multifilament silk suture, so that substantially all interstices between the silk filaments are filled.

19. A method of preparing a non-irritating and strength retaining composite silk-thermoplastic elastomer suture, comprising the steps of:

a) treating, in a continuous process, a multifilament silk suture with a warm solution of a hydrophobic, limp thermoplastic elastomer at a temperature between 20° and and 80°C; said elastomer comprising segmented copolymers having hard and soft segments, said soft segments comprising about 25-80% by weight of said polymer; said elastomer having a suitable molecular weight sufficient to provide a solution viscosity that is consistent with optimum diffusion into the interior of the suture structure, resulting in a high integrity matrix which does not flake when the suture is subjected to mechanical stress;

b) passing said treated suture through a felt wipe, and then upwards to air dry same; and c) rapidly passing the suture through a hot air zone at a temperature between 340°C and 500°C to sinter the elastomer in order to coat said suture and substantially fill all interstices between the silk filaments.

20. The method of Claim 19 wherein the suture is of braided construction and the elastomer is selected from the group consisting of copolymers having the following recurring units:

wherein each G individually represents an alkylene group of from 2 to 6 carbon atoms, and p is 9 to 15, e and f each represent a number having a value greater than 1 such that the B units comprise 50 to 80 weight percent of the copolymer and the A units comprise the remainder; wherein Z represents 1,4-phenylene, 1,3-phenylene or trans-1,4-cyclohexylene;

Q) a copolymer consisting essentially of a multiplicity of recurring A [poly(alkylene terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate)] and B [poly(alkylene dimerate)] units having the following general formula:
wherein x and y are integers, such that the B units comprise 50 to 80 weight percent of the copolymer and the A
units comprise the remainder; denotes a branched hydrocarbon chain containing from 24 to 32 carbon atoms and Z and G are as hereinabove defined;

R) a copolymer consisting essentially of a multiplicity of recurring poly(alkylene) terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate, and poly(alkylene) alkyl or alkenyl succinate units having the following general formula:

wherein Alk1 is a linear or branched alkyl or alkenyl radical with a chain length of about 4 to 30 carbon atoms and g and h are integers such that the A units comprise 20 to 50 weight percent of the copolymer and the B units comprise the remainder and Z and G are as hereinabove defined;

S) a random copolymer having the following general formula:

wherein J is either:

(1) or (2) wherein Alk2 is alkyl or alkenyl moieties with a chain length of 8 to 30 carbon atoms; and denotes a branched hydrocarhon chain with an estimated formula of C32H60, or (3) wherein p is 9 to 15, G is as defined hereinabove and R' is an aliphatic or aromatic disubstituted moiety and wherein e and f are such that the B units comprise about 25 to 50% by weight of the copolyester and the A units comprise the remainder.

21. The method of Claim 20 wherein Z is 1,4-phenylene, G
is 1,4 butylene, and the elastomer has an inherent visco-sity of between 0.2 and 1.4 and has a melting temperature, by thermal microscopy of between about 80° and 180°C.

22. The method of Claim 21 wherein sufficient elastomer is utilized so that it comprises 5 to 50% by weight of the resultant total composite system.

23. The method of Claim 21 in which the elastomer is dissolved in methylene chloride, the solution of elastomer being kept at about 40°C, and at a concentration of 10% to 30% by weight.

24. The method of Claim 23 in which the braided silk su-ture is passed in a continuous process through said solu-tion of elastomer in methylene chloride, then, above the solution surface, through a felt wipe, then upwards to air dry the treated suture, which is then submitted to a heat-ing process in which the suture travels through a hot air zone to sinter the elastomer layer inside the silk suture.

25. The method of Claim 23 in which the temperature in the heated zone ranges between 340°C and 500°C.

26. The method of Claim 25 in which the polymer has structure P).

27. The method of Claim 25 in which the polymer has structure Q).

28. The method of Claim 25 in which the polymer has structure R).

29. The method of Claim 25 in which the polymer has structure S).