GB2096627A - Flexible copolymers and surgical products therefrom - Google Patents

Abstract

Novel flexible polyesters comprising copolymers made from p- hydroxy oxy alkylene benzoate and one of the following sequences: (1) an alkylene 2-alkenyl (or alkyl) succinate; (2) an alkylene dimerate (from the dimer of a long chain unsaturated fatty acid); (3) a dicarboxylate of polyoxytetramethylene glycol, and pliant surgical products, particularly monofilament surgical sutures, therefrom.

Description

SPECIFICATION Flexible copolymers and surgical products therefrom Background of the Invention The novel polyesters of the present invention comprise copolymers made from rigid AB type (made from selfcondensing hydroxy acid moiety) ester units of an alkylene oxybenzoate and one of the following flexible AA-BB type (made from a diacid moiety and a diol) ester sequences: (1) an alkylene, 2-alkenyl (or alkyl) succinate, (2) an alkylene dimerate (from the dimer of a long chain unsaturated fatty acid), (3) a dicarboxylate of polyoxytetramethylene glycol.

Two p-(hydroxyalkoxy) benzoic acids; p-(hydroxybutoxy) benzoic acid and -p(hydroxypropoxy) benzoic acid, have been used in the production of modified poly(trimethylene terephthalate) fibers and films with improved strength and dimensional stability with no mention of a change in flexibility [Jap. Pat. Appl. No. 20474/69; Chem. Abstracts 72, 4277e (1 970)]. The p (hydroxypropoxy) benzoic acid was also used to modify poly(ethylene terephthalate) to study isomorphism in the system. [J. Polym. Sci. A-2, 4361(1964)] The prior art does not disclose the use of AB type polyesters as the precursor of crystalline hard sequences or combining the AB oxybenzoate moieties with sequences bearing flexible chain components to product the unique flexible copolyesters of the present invention.

The homopolymer of p-(hydroxyethoxy) benzoic acid has been converted into fibers which exhibit lower crystallinity and tensile strength when compared to PET. The fibers of the homopolymer exhibit a high modulus and rigidity compared to other known monofilament sutures and seemingly preclude the use of the ethylene oxybenzoate moieties in copolymers used to produce strong but flexible fibers. [Angew. Makromol. Chem. 40/41, 41 (1974)] U.S. Patents 3,542,737; 3,651,014; 3,682,863; and 3,890,279 and copending Application Serial No. 218,998, as well as Angew. Makromol.Chem. 58/59, 229 (1977), disclose the use of polyether, dimerate, and 2-alkenyl succinate in the production of thermoplastic copolyester elastomers, but do not disclose their use with an AB type polyester such as the poly(alkylene oxybenzoates) of the present invention, not do they suggest that the copolyesters of the present invention could produce the unexpectedly strong but pliant monofilaments of the present invention.

Monofilament sutures are preferred by surgeons for many surgical applications due to their inherent smoothness and noncapillarity to body fluids. Most synthetic monofilament sutures are relatively stiff. Besides making the material more difficult to handle and use, suture stiffness or low compliance can adversely affect knot tying ability and knot security.

In addition, high compliance under low stress allows the suture or other wound closure or approximation device to yield as a wound swells, so that the suture or device do not place the wound tissue under tension, which might cause tearing, cutting or necrosis of the tissue.

The problems associated with the use of low compliance sutures in certain applications were recognized in U.S. Patent No. 3,454,011, where it was proposed to fabricate a surgical suture composed of Spandex polyurethane. Such sutures, however, were too elastic and did not find general acceptance by the medical profession.

Recently issued U.S. Patent No. 4,224,946 describes a monofilament suture with good flexibility and knot strength, which suture is composed of block polyether-esters which contain (1) a polymeric block of polyalkene esters and (2) a polymeric block of aromatic dicarboxylic acids or cycloaliphatic acids with short chain aliphatic or cycloaliphatic diols. In addition, copending application SN 318,998 discloses high complicance monofilament sutures of poly(tetramethylene terephthalate-CO-(2-alkenyl or alkyl)succinate.

Accordingly, it is an object of the present invention to provide novel flexible polysters which can be melt processed at moderately low temperatures to produce useful surgical sutures and allied surgical products and more particularly strong but pliant monofilament sutures having unique handling and knot tying characteristics.

Summary of the Invention The novel flexible polyesters of the present invention have rigid AB type ester units of an alkylene oxybenzoate and one of the following flexible AA-BB type ester sequences of (1) an alkylene, 2-alkenyl (or alkyl) succinate, (2) an alkylene dimerate (from a dimer and a long chain unsaturated fatty acid), (3) a dicarboxylate of poly(oxytetramethylene) glycol.The novel copolymers have the following general formula:

wherein m = 2, 3, 4, 5 or 6 and x and y can be determined by the amount of starting materials and A is either:

or

wherein n = 2 to 12, and R = alkyl or alkenyl with a chain length of 8 to 30 carbon atoms;

denotes a branched hydrocarbon chain with an estimated formula of C32H60, or

wherein R' = an aliphatic, cycloaliphatic or aromatic disubstituted moiety and p is about 10. The A units comprise about 1-50% by weight of the copolyester.

The copolymers may be melt processed at low to moderate temperatures to produce useful surgical sutures and allied surgical products such as clips and staples, and more particularly, may be extruded to yield oriented fibers having the following unexpected combination of physical properties: Knot Strength greater than about 30 x 1 03psi Tensile Strength greater than about 50 x 103psi Young's Modulus less than about 150 x 103psi Monofilament sutures having physical properties in accordance with the present invention are particularly useful in many surgical procedures where the suture is used to close a wound which may be subject to later swelling or change in position. The low Young's modulus provides the suture with an appreciable degree of compliance under low applied force.As a result, the suture is able to "give" to accommodate swelling in the wound area. The combined low modulus and high tensile strength of the suture allows the suture to reversibly stretch during knot tie-down so that the knot "snugs down" for improved tying ability and provides knot security with a more predictable and consistent knot geometry regardless of variations in suture tying technique or tension.

The fact that copolymers of p-(hydroxyalkoxy) benzoic acid can be processed at temperatures generally below 220"C results in less thermal degradation of the polymer in the products formed therefrom as compared with similar known thermoplastics; a distinct advantage in medical and surgical applications. In addition, the copolymers exhibit excellent melt stability at these low temperatures resulting in greater uniformity in the products formed and specifically yielding improved monofilaments having uniform diameter and physical properties.

In the preferred copolymer compositions, m = 4, n is 4 or 6, and R has a chain length of 16-24 carbon atoms. In the most preferred copolymer compositions, m = 4, R has a chain length of 1 8 and the A units comprise 10-30% by weight of the copolymer.

Description of the Invention The general structures of the copolymers of the present invention may be expressed as follows:

The structure belongs to the random copolymer type and x and y can be determined by the quantities of the starting materials used.

The term "m" in copolymers I, II and Ill is confined to about 2 to 6 and preferably is 4.

The term "n" in copolymers I and II is confined to about 2 to 1 2 and preferably is 4 or 6.

The term "R" in copolymer I may be alkyl, branched alkyl or alkenyl (preferred 2-alkenyl) with a chain length of about 8 to 30 carbon atoms with the preferred range lying between about 16 and 24.

The term "p" in copolymer Ill varies between 9 and 1 5.

The term R' in copolymer Ill may be an aliphatic or aromatic disubstituted moieties such as the tetramethylene or p-phenylene.

Copolymers of type I are prepared typically by the polycondensation of p-(4-hydroxy-n-butoxy) benzoic acid (or its methyl ester), an alkenyl (or alkyl) succinic an hydroxide (or the corresponding dialkyl succinate) and a polymethylene diol in the presence of a suitable catalyst and preferably an antioxidant. Typical illustration of the reaction can be given as follows:

0 Catnst & Szer ()4 Ocooc+ + R R4o CatalMst & SFi\izer ffs oe o Po\5fmer I s The MB-OB can be prepared according to the following typical reaction scheme:

o ZnC Ca + CW3-CoBr -fL-, lr-(CUL4'0''CHS (13-A) Cco 3-A) . ease o so-(cu2)4-0Scoos4 (b-o) + c3ro fCWbOH Copolymers of type Il are prepared typically by the polycondensation of p-(4-hydroxy-n-butoxy) benzoic acid (or its methyl ester), the dialkyl ester of dimer acid (or the free acid) and a polymethylene diol in the presence of a suitable catalyst and preferably an antioxidant. Typical illustration of the reaction can be given as follows:

0 0 II (t uo -b2)- COOC3 + lso -(c)6O+ O((a43)2MCS9HLCC -OCHCCHS)2'1 Polymer < SSS\\arzL The parent dimer acid of the diisopropyl ester utilized in the polymerization is derived by a catalyst high pressure dimerization of high purity oleic acid.

Copolymers of type Ill are prepared typically by the polycondensation of p-(4-hydroxy-nbutoxy) benzoic acid (or its alkyl ester)m, dimethyl terephthalate, and polyoxybutylene diol (Mol.

Wt. = about 1000 Daltons), a suiable catalyst and stabilizer. Typical illustration of the reaction can be given as follows:

o.(C4-o Couch3+ UO t(CH 2)4 -o-]n-CH2CR2 > lC2 > +CU3-00C-(O)C00 Polymer m ~ catalya e Stabiizer The polymerization may be conducted either in the absence or preferably in the presence of stabilizers of the hindered phenol or secondary aromatic amine type. An example of the former is Irganox 1098 and an example of the latter is Naugard 445. As catalyst, oxides and alkoxides of numerous polyvalent metals may be employed.However, the preferred polymerization catalysts are combinations of (a) tetrabutyl orthotitanate and/or magnesium acetate, (b) Mg(OAc)2 and/or Sb203, and (c) combinations of tin and antimony catalysts, such as BuSnO(CH) and Sb203. If a dyed end product is desired, a compatible dye or pigment such as, for instance, DBC Green &num; 36 can be added in concentrations of up to 0.5% based on expected polymer yield.

The polymerization is conducted in two stages. In the first stage, run under nitrogen at temperatures ranging from 1 60 to 250"C polycondensation via transesterification and esterification occurs resulting in lower molecular weight polymers and oligomers. These are converted to high molecular weight materials in the subsequent step run at 240-260"C, at pressures of less than 1 mm of mercury.

For the three types of polymers, useful compositions for molded articles and fiber formation may contain the poly(alkylene-4-oxybenzoate) chain component at 50 to about 100% by weight.

Specifically, the preferred composition that is useful for fiber formation may contain poly (nbutylene-4-oxybenzoate) moieties at about 70 to 90% by weight of the total system.

The polymers can readily be extruded at temperatures usually exceeding the polymer Tm by 10-50"C. The resulting extrudate can be drawn, usually in a two-stage process using either two consecutive heated glycerine baths or by using a hot shoe followed by a subsequent glycerine bath. Drawing may also be conducted over suitable heated rolls. The draw ratio may vary from about 300 to 700%.

The copolymers of this invention provide oriented fibers exhibiting properties that are quite unexpected in view of the prior art. Typical size 3/0 strands possessed knot strengths in the 35-40 x 103 psi range, tensile strengths in the 60-80 X 103 psi range and a Young's modulus of less than 150 x 103 psi. Elongations ranged from 20 to 35%.

In summary, the polymers described in this patent application lend themselves to ready extrusion and drawing to strong and supple fibers which are useful as flexible monofilament sutures. A survey of fiber properties is shown in Table II.

Fibers made from polymers prepared in the presence or absence of a stabilizer upon Co60 sterilization (2.5 megarads) suffer minimal losses in physical properties as judged by a comparison of inherent viscosities and tensile strength before and after sterilization. The unexpected retention of physical properties following irradiation sterilization provides a distinct advantage of these copolymers over the highly accepted polypropylene surgical sutures which undergo degradation and considerable loss in tensile properties when subjected to similar treatment. For this reason polypropylene sutures are sterilized by ethylene oxide and not by Co60.

General Polymerization Procedure The desired amounts of monomers (and prepolymers as in system Ill) and a given stabilizer (optional) were 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 was heated under nitrogen at 100 to 160"C and stirring was begun. To the homogeneous stirred solution the required amount of catalyst was added. The mixture was then stirred and heated under nitrogen for given time periods at 190"C (2-4 hours) and 220"C (1-3 hours). The temperature was subsequently raised to 250-260"C and over a period of 0.4-0.7 hours the pressure was reduced in the system to below 1 mm/Hg (preferably in the range of 0.05 mm to 0.1 mm).Stirring and heating under the above conditions was continued to the completion of the polymerization. The end point was 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 reaction mixture. In practie, depending on the copolymer composition, in vacuo reaction times varied from 2 to 8 hours.

At the end of the polymerization cycle the hot mixture was equilibrated with nitrogen and allowed to cool slowly. The reaction product was isolated, cooled in liquid nitrogen, and then ground. (In the case of metal reactors the hot melt was extruded at the bottom of the vessels into Teflon covered metal trays.) The ground chips were dried at 80-110"C for 8-16 hours under a vacuum of 1 mm or less prior to extrusion.

Analytical and Instrumental Testing Methods Inherent viscosity (ninh) was obtained for polymer solutions in hexafluoro-2-propanol (HFIP) (1g/1). The NMR spectra of the polymer solutions in hexafluoroacetone sesquideuterium oxide were recorded in a Jeol FX-100. A DePont 990 DSC apparatus was used to record the melting (Tm) temperature of the polymers in nitrogen. A Mettler hot-stage microscope was used to determine the melting behavior of the polymers. Fiber tensile properties were measured on an Instron, Model &num;1122. For the measurement of the Young's modulus, line contact jaws were applied. For tensile measurements a strain rate of 100 mm/min., was employed.

p-(4-Hydroxy-n-butoxy)benzoic acid In a 22 1. stirred reactor, 1.1 6 kg. of p-hydroxy-benzoic acid (M.W. 138) in 4 1. of water are neutralized by the addition of 0.5 1. of 40% sodium hydroxide. The temperature is adjusted to 50"C and over a period of one hour, 1 200 ml. of 4-bromobutyl acetate are slowiy added. The temperature is then raised to 90"C + 1 0'C and the hot reaction mixture kept at pH 10 by continuous titration with a 40% sodium hydroxide solution. When no change in pH is noted for a period of 45 minutes the reaction is considered compiete, an additional liter of water is then added, and sufficient 40% sodium hydroxide solution to raise the pH to 11.While still hot, concentrated hydrochloric acid is added in large enough quantities to lower the pH to 1.2. The mixture is allowed to cool overnight while stirring and the precipitate collected on a filter. The precipitate is then thoroughly washed with water to remove excess acid until the wash has attained a pH of at least 5. The precipitate is then dried and dissolved in hot methanol (15% solution), and the solution filtered to remove any insolubles (usually about 6-7%). While the clear methanol solution is still hot, hot water is added to adjust the solvent ratio to 10:1 methanol/water, and set aside to let the product crystallize out overnight yielding p-(4-hydroxyn-butoxy) benzoic acid having a melting point of 146"-148"C.

Methyl p-(4-hydroxy-n-butoxy)benzoate was obtained by refluxing a solution of p-hydroxybenzoic acid (90 g., 0.43 mol.) in methanol (540 ml) in the presence of concentrated sulfuric acid (32 g.) for about 4-8 hours. The reaction mixture was cooled, poured into ice water and the product was then extracted with ether. The ether extract was dried and evaporated to give a semi-solid crude ester. This was purified by crystallization from toluene and the pure ester (65% yield) melted at 52-54"C. The infrared spectra of the pure ester were consistent with the expected structure.

General Extrusion Procedure Extrusion through an Instron rheometer was geared towards producing an extrudate which upon drawing (5x to 7x ratio) yielded a fiber in the 8-10 mil diameter range (size 3/0 suture).

The polymers were compacted at 110-130"C in the extrusion chamber and extruded after a dwell time of about 9 to 1 5 minutes through a 40 mil die. The ram speed was about 2 cm/minute. Extrusion temperatures depended both on the polymer Tm and on the melt visosity of the material at a given temperature; usually extrusion proceeded at temperatures of 10-50"C above the Tm. The extrudate was taken up at a speed of 1 8 feet per minute.

General Drawing Procedure The extrudate (diameter range, 19-22 mm) was passed over take-off rollers at an input speed of four feet per minute onto a hot shoe or into a draw bath of glycerine. The temperatures of the hot shoe or draw bath varied from 50 to 100"C. The draw ratio in this first stage of operation varied from about 4x to 6x. The drawn fibers were then placed over another set of rollers into the second stage draw bath kept at temperatures ranging from about 70-95"C. Draw ratios for the second stage operation varied from about 1.1 x to 1.25x. Finally, the fiber was passed through a water wash bath and taken up on a spool.

Example for polymer Formation Example 1: Under a dry nitrogen atmosphere, the following materials were placed into a flame and vacuum dried 100 ml two-neck, round-bottom flask, equipped with a stainless steel paddle stirrer, a short distilling head fitted with a receiver and a gas inlet nozzle: 20.5 g. p-(4-Hydroxybutoxy)benzoic acid (0.0976 mol 4.5 g. 2-Dodecenylsuccinic anhydride (0.0170 mol) 2.1 g. 1,6-Hexanediol (0.0171 mol) 0.271 g. 4,4'-bis(cY,Lu-Dimethylbenzyl)diphenyl amine 0.271 g. Antimony trioxide After stoppering the open neck of the flask, the entire charge-containing assembly was removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel was then vented with nitrogen, closed off, and subsequently placed in an oil bath.Under a continuous flow of nitrogen, the reaction mixture was then melted at 165"C. Once the charge was liquidfied, the reaction flask was connected to an efficient mechanical stirrer and thorough mixing at 165"C was performed for 1 5 minutes.

Still under a continous flow of nitrogen, the melted reaction mixture was then subjected to the following heating sequence: 190"C for 2.5 hours, 220"C for 2.5 hours, 240"C for 1.5 hours.

As the water distillation slowed after 1.5 hours at 240"C, the receiver containing the distillate was replaced with an empty receiver. Then gradually over the course of 0.75 hours the pressure in the reaction flask was reduced to 0.05 mm. Under reduced pressure the reaction mixture was subjected to the following heating scheme: 240"C for 2.5 hours, 255"C for 2.5 hours, 260"C for 1.5 hours. At the end of this heating cycle, the reaction vessel was removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer was isolated and ground after chilling in liquid nitrogen. The resulting polymer chips were dried for 8 hours at 80"C under high vacuum (less than 1 mm).Properties of this polymer (II) and of other similarly prepared polymers are presented in Table I.

Example 2: Under a dry nitrogen atmosphere, the following materials were placed into a flame and vacuum dried 100 ml two-neck, round-bottom flask, equipped with a stainless steel paddle stirrer, a short distilling head fitted with a receiver and a gas inlet nozzle: 20.5 g. p-(4-Hydroxybutoxy)benzoic acid (0.0976 mol) 4.9 9. 2-Octadecenylsuccinic anhydride (0.0139 mol) 2.1 9. 1,6-Hexanediol (0.0144 mol) 0.250 g. 4,4'-bis(a,a-Dimethylbenzyl)diphenyl amine 0.271 9. Antimony trioxide 0.05 9 D & Green &num;6 dye After stopperirig the open neck of the flask, the entire charge containing assembly was removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours.The charged reaction vessel was then vented with nitrogen, closed off, and subsequently placed in an oil bath. Under a continuous flow of nitrogen, the reaction mixture was then melted at 165"C. Once the charge was liquified, the reaction flask was connected to an efficient mechanical stirrer and thorough mixing at 165"C was performed for 1 5 minutes.

Still under a continuous flow of nitrogen, the melted reaction mixture was then subjected to the following heating sequence: 190"C for 2.5 hours, 220"C for 2.25 hours, 240"C for 1.0 hours.

As the water distillation slowed after 1.0 hours at 240"C, the receiver containing the distillate was replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask was reduced to 0.08 mm. Under reduced pressure the reaction mixture was subjected to the following heating scheme: 240"C for 1.5 hours, 255"C for 1.5 hours, 260"C for 1.5 hours, 250"C for 2.0 hours. At the end of this heating cycle, the reaction vessel was removed from the oil bath, equilibrated with nitrogen and then allowed to cool to room temperature. The polymer was isolated, chilled in liquid nitrogen and ground. The resulting polymer chips were dried for 8 hours at 80"C under high vacuum (less than 1 mm).

Properties of this polymer (IV) and of similarly prepared polymers are presented in Table I.

Example 3: Under a dry nitrogen atmosphere, the following materials were 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 gas inlet nozzle: 91 .Og. Methyl p-(4-hydroxybutoxy)benzoate (0.4060 mol) 18.3 g. 2-Octadecenylsuccinic anhydride (0.0521 mol) 5.9 9. 1,4-Butanediol (0.651 mol) 1.0 9. 4,4'-bis(a,a-Dimethylbenzyl)diphenyl amine 0.2 g. DBC Green &num;6 dye After stoppering the open neck of the flask, the entire charge containing assembly was removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel was then vented with nitrogen, closed off, and subsequently placed in an oil bath. Under a continuous flow of nitrogen, the reaction mixture was then melted at 100"C. Once the charge was liquified, the reaction flask was connected to an efficient mechanical stirrer and thorough mixing at 100"C was performed for 1 5 minutes.

Next, the catalyst (1.60 ml), consisting of a mixture of tetrabutyl orthotitanate and magnesium acetate dissolved in a mixture of methanol and butanol, was quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reactor mixture was then subjected to the following heating sequence: 190"C for 2.5 hours, 220"C for 2.5 hours, 240"C for 1.25 hours. As the water-methanol distillation slowed after 1.5 hours at 250"C, the receiver containing the distillate was replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask was reduced to 0.05 mm.Under reduced pressure the reaction mixture was subjected to the following heating scheme: 240"C for 3.25 hours and 250"C for 4.25 hours. At the end of this heating cycle, the reaction vessel was removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer was isolated, chilled with liquid nitrogen and ground.

The resulting polymer chips were dried for 8 hours at 80"C under high vacuum (less than 1 mm). Properties of this polymer (VIII) and other similarly prepared polymers are presented in Table I.

Example 4: Under a dry nitrogen atmosphere, the following materials were placed into a flame and vacuum dried 100 ml two-neck round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitted with a receiver, and a gas inlet nozzle: 23.2 g. p-(4-Hydroxybutoxy)benzoic acid (0.1106 mol) 3.8 g. Diisopropyl ester of the acid dimerate (0.0058 mol) 0.8 9. 1,6-Hexanediol (0.0068 mol) 0.2780 9. 4,4'-bis(a,eY-Dimethylbenzyl)diphenyl amine 0.2780 g. Antimony trioxide After stoppering the open neck of the flask, the entire charge containing assembly was exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel was then vented with nitrogen, closed off, and subsequently placed in an oil bath.Under a continuous flow of nitrogen, the reaction mixture was then melted at 165"C. Once the charge was liquified, the reaction flask was connected to an efficient mechanical stirrer and thorough mixing at 165"C was performed for 1 5 minutes. Still under a continuous flow of nitrogen, the melted reaction mixture was then subjected to the following heating sequence: 190"C for 2.3 hours, 220"C for 2.3 hours, 240"C for 2.0 hours. As volative formation slowed after 2.0 hours at 240"C, the receiver containing the distillate was replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask was reduced to 0.06 mm.Under reduced pressure the reaction mixture was subjected to the following heating scheme: 240"C for 2.25 hours, 255"C for 2.25 hours and 260"C for 2.0 hours. At the end of this heating cycle, the reaction vessel was removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer was isolated, nitrogen chilled and ground. The resulting polymer chips were dried for 8 hours at 80"C under high vacuum (less than 1 mm). Properties of this polymer (X) and other similarly prepared polymers are presented in Table I.

Example 5: Under a dry nitrogen atmosphere, the following materials were placed into a flame and vacuum dried 100 ml two-neck, round-bottom flask equipped with a stainless steel paddle stirrer, a short distilling head fitted with a receiver, and a gas inlet nozzle: 21.9 g. Methyl p-(4-Hydroxybutoxy)benzoate (0.0976 mol) 5.5 g. Poly(oxybutylene)glycol (Teracol 1000) (0.0055 mol) 1.1 9. Dimethyl terephthalate (0.0055 mol) 0.1 9. 1,6-Hexanediol 0.2860 g. 4,4'-bis(a,a-Dimethylbenzyl)diphenyl amine After stoppering the open neck of the flask, the entire charge containing assembly was removed from the nitrogen atmosphere and exposed to a high (less than 1 mm) vacuum for several hours. The charged reaction vessel was then vented with nitrogen, closed off and subsequently placed in an oil bath.Under a continuous flow of nitrogen, the reaction mixture was then melted at 100"C. Once the charge was liquified, the reaction flask was connected to an efficient mechanical stirrer and thorough mixing at 100"C was performed for 1 5 minutes.

Next, the catalyst (0.32 ml), consisting of a mixture of tetrabutyl orthotitanate and magnesium acetate dissolved in a mixture of methanol and butanol, was quickly syringed into the reaction vessel via the side arm. Still under a continuous flow of nitrogen, the melted reaction mixture was then subjected to the following heating sequence: 190"C for 2.0 hours, 220"C for 2.5 hours, 240"C for 1 hour. As the water-methanol distillation slowed after 1 hour at 240"C, the receiver containing the distillate was replaced with an empty receiver. Then, gradually over the course of 0.75 hours the pressure in the reaction flask was reduced to 0.05 mm.Under reduced pressure the reaction mixture was subjected to the following heating scheme: 240"C for 2 hours, 250"C for 1.5 hours, 255"C for 1 hour. At the end of this heating cycle, the reaction vessel was removed from the oil bath, equilibrated with nitrogen, and then allowed to cool to room temperature. The polymer was liquid nitrogen chilled and then ground. The resulting polymer chips were dried for 8 hours at 80"C under high vacuum (less than 1 mm). Properties of this polymer (XIII) are presented in Table I.

Example 6: The copolymers of the present invention also may be spun as multifilament yarn and woven or knitted into fabrics or gauze, or used as prosthetic devices within the body of a human or animal where it is desirable that the structure have high tensile strength and desirable levels of compliance and/or ductility. Useful embodiments include tubes, including branched tubes, for artery, vein or intestinal repair, nerve splicing, tendon splicing, sheets for supporting damaged kidney, liver and other abdominal organs, protecting damaged surface areas such as abrasions, particularlly major abrasions, or areas where the skin and underlying tissues are damaged or surgically removed.

In more detail, the medical uses of polyesters subject of this invention include, but are not necessarily limited to: 1. Solid products molded or machined a. orthopedic pins, clamps, screws and plates b. clips c. staples d. hooks, buttons, and snaps e. bone substitutes (e.g., mandible prosthesis) f. intrauterine devices 9. draining or testing tubes or capillaries h. vascular implants or supports 2. Fibrillar products, knitted, woven, or nonwoven including velours a. burn dressing b. hernia patches c. medicated dressings d. facial substitutes e. gauze, fabric, sheet, felt or sponge for liver hemostasis In combination with other components 1. Solid products, molded or machined a. reinforced bone pins, needles, etc.

2.Fibrillar products a. arterial graft or substitutes b. bandages for skin surfaces c. burn dressings (in combination with polymeric films) It will be understood by those skilled in the art that variations and modifications of the specific embodiments described above may be employed without departing from the scope of the invention as defined in the appended claims.

TABLE I SYNTHESIS # PHYSICAL PROPERTIES OF POLYMER TYPES I, II # III Monomer Polymer Flexible Ratio %D #C Polymerization Scheme ninh Polymer Melting Sample Segment Soft/Hard %Stabilizer Green #6 Temp. Pres. Time. # 25 C Range ( C) No. Source (moles) # Type (by Wt.) C (mm) hrs. (HFIP) (by microscopy) I - 0/100a None 0 160 N2Atm. .3 .71 178-179 190 " 2.5 220 " 2.0 240 1.5 240 .03 3.0 255 .03 2.0 260 .03 1.0 II Dodecenyl 14.8/85.2a 1% Naugard 0 165 N2Atm. .3 .70 132-138 succinic 445 190 " 2.5 anhydride 220 " 3.3 240 " 2.0 240 .05 2.5 255 .05 2.75 260 .05 1.5 III Hexadecenyl 13.2/86.8b 1% Naugard 0 100 N2Atm. .3 .94 137-145 succinic 445 190 " 2.5 anhydridec 220 " 2.5 240 " 1.25 240 .05 1.75 255 .05 1.75 IV Octadecenyl 12.5/87.5a 1% Naugard .2 165 N2Atm. .3 .66 135-142 succinic 445 190 " 2.5 anhydridec 220 " 1.25 240 " .75 240 .1 1.5 255 .1 1.5 260 .05 1.5 250 N2Atm..5 250 .03 2.0 Monomer Polymer Flexible Ratio %D #C Polymerization Scheme ninh Polymer Melting Sample Segment Soft/Hard %Stabilizer Green #6 Temp. Pres. Time. # 25 C Range ( C) No. Source (moles) # Type (by Wt.) C (mm) hrs. (HFIP) (by microscopy) V Octadecenyl 12.5/87.5b 1% Naugard .2 165 N2Atm. .3 .69 138-144 succinic 445 190 " 2.25 anhydridec 220 " 2.25 240 " 1.5 240 .05 2.0 255 .05 2.0 260 .05 2.0 VI Octadecenyl 12.4/87.6b 1% Naugard .2 160 N2Atm. .3 .91 138-146 succinic 445 190 " 2.25 anhydridec 220 " 2.25 240 " 1.25 240 .08 2.25 255 .05 1.75 260 .05 1.25 VII Octadecenyl 10.8/89.2b 1% Naugard .2 165 N2Atm. .3 .81 138-144 succinic 445 190 " 2.5 anhydridec 222 " 3.0 240 .05 2.5 240 .05 2.5 260 .05 .5 VIII Octadecenyl 11.4/88.6b 1% Naugard .2 100 N2Atm. .3 .69 139-144 succinic 190 " 2.5 anhydrided 220 " 2.5 240 " 1.5 240 .05 3.25 250 .05 3.25 240 N2Atm..5 250 .05 1.0 IX Diisopropyl 6.9/93.1a 1% Naugard 0 165 N2Atm. 3 .74 154-156 dimeratec 445 190 " 2.5 220 " 2.0 240 " 1.25 240 .04 2.0 255 .05 2.0 260 .06 1.25 Monomer Polymer Flexible Ratio %D #C Polymerization Scheme ninh Polymer Melting Sample Segment Soft/Hard %Stabilizer Green #6 Temp. Pres. Time. # 25 C Range ( C) No. Source (moles) # Type (by Wt.) C (mm) hrs. (HFIP) (by microscopy) X Diisopropyl 5.0/95.0a 1% Naugard 0 165 N2Atm. .3 .80 159-160 dimeratec 445 190 " 2.3 220 " 2.3 240 " 2.25 240 .08 2.25 255 .08 2.25 260 .05 2.0 XI Diisopropyl 10.3/89.7a 1% Naugard 0 165 N2Atm. .3 .47 140-144 dimerate 445 190 " 2.5 220 " 2.5 240 " 2.0 240 .03 2.5 255 .03 2.25 260 .03 2.0 XII Teracol 5.3/94.7b 1% Naugard 0 100 N2Atm. .3 .50 148-162 1000e 445 190 " 2.0 220 " 2.5 240 " 1.0 240 .05 2.0 250 .05 1.5 255 .05 1.0 XIII None 0/100f None 0 165 N2Atm..3 .44 219.222 190 " 3.0 220 " 2.0 250 .05 2.0 230 N2Atm. 1.0 250 .05 4.25 a = Hard segment produced from para(4-hydroxybutoxy)benzoic acid.

b = Hard segment produced from methyl-para(4-hydroxybutoxy)benzoate.

c = Used with 1,6-hexanediol.

d = Used with 1,4-butanediool.

e = Used with 1,4-DMT.

f = Hard segment produced from methyl-para(2-hydroxyethoxy)benzoate.

Table II EXTRUSION # DRAWING CONDITIONS AND ULTIMATE TENSILE PROPERTIES OF MONOFILAMENTS DERIVED FROM TYPE I, II AND III POLYMERS Extrusion Draw. Conditions Tensile Properties Polymer Conditions Ratio/Temp ( C) Knot Str.

Poly. % PB nappc First Second Diam. psi psi Elong. Y. Mod.

No. Type Felxa ninh Tmb, C. C. poise Stage Stage mil x10-3 x10-3 % psi X 10-3 I (d) 0 insol. 180 195 6.984 5/70 1.05/95 7.9 55.4 84.9 15 641 II I 25 .70 132-138 155 6,070 5.0/55 1.2/80 8.6 38.2 54.0 24 71.4 III I 25 .94 137-145 200 8,488 5.0/82.2 1.2/70 8.9 33.3 70.4 35 52.0 IV I 25 .65 135-142 165 5,587 5.0/75 1.2/90 9.1 36.0 57.3 32 77.8 V I 25 .69 138-144 160 6,285 5.0/75 1.2/90 9.4 34.3 68.2 35 77.3 VI I 25 .91 138-146 190 9,401 5.0/75 1.2/90 9.3 35.2 65.0 32 61.1 VII I 22 0.81 146* 185 6,608 5.0/75 1.2/90 8.7 41.4 68.6 27 110.5 VIIIf I 22 0.69 142* 180 4,996 5.5/75 1.09/80 8.9 37.3 64.3 29 96.9 IX II 20 0.74 155-160 190 8,004 5/53 1.075/75 9.5 38.1 62.3 32 172 X II 15 0.80 159-160 220 6,017 5.0/52 1.2/75 9.3 45.6 69.6 26 231 XI II 28 0.47 140-145 155 3.814 5.0/52 1.2/70 9.1 26.7 41.5 35 52.4 XII III 28 .50 148-162 - - - - - - - - XIII (e) 0 0.44 219-222 225 537 4/75 - 6.9 38.0 44.1 23 2,451 a = Wt. percent of flexible moieties in copolymers.

b = by microscopy except those with an asterisk.

c = at a shear rate of 212.6 sec-1.

d = Homopolymer.

e = poly(ethylene-4-oxybenzoate).

f = All Polymers Type I were made with 1,6-hexanediol except #VIII (made with 1,4-diol).

Claims (17)

1. A surgical filament comprising a random copolymer having the following general formula:

wherein m = about 2 to 6 and A is either:

or

wherein n = about 2 to 1, and R = alkyl or alkenyl moieties with a chain length of about 8 to 30 carbon atoms;

denotes a branched hydrocarbon chain with an estimated formula of C32H60, or

wherein p is 9 to 1 5 and R' = an aliphatic or aromatic disubstituted moiety and wherein the A units comprise about 1-50% by weight of the copolyester.

2. A filament as in Claim 1 having a surgical needle attached to at least one end and useful as a surgical suture.

3. A filament of Claims 1 or 2 in a sterile condition.

4. A filament of any preceding Claim wherein the A units comprise about 10-30% by weight of the copolymer.

5. A filament of any preceding Claim wherein m = 4.

6. A filament of any preceding Claim wherein n = 4 or 6.

7. A filament of any preceding Claim wherein R has a chain length of about 16-24 carbon atoms.

8. A filament of any preceding Claim wherein R has a chain length of about 1 8.

9. A filament of any preceding Claim wherein R is 2-alkenyl.

10. A filament of any preceding Claim characterized by the following physical properties: Knot Strength greater than about 25 X 1 O3psi Tensile Strength greater than about 45 X 103psi Young's Modulus less than about 1 50 X 103psi

11. A woven or knitted surgical fabric comprised of filaments of any of Claims 1 to 10.

1 2. A fabric of Claim 11 in a seamless tubular construction.

1 3. A method of closing a wound by approximating and securing the wound tissue with a surgical fiber of Claims 1 or 10.

14. A solid surgical aid molded or machined from a copolymer having the following general formula:

wherein m = about 2 to 6 and A is either

or

wherein n = about 2 to 12, and R = alkyl or alkenyl with a chain length of 8 to 30 carbon atoms:

denotes a branched hydrocarbon chain with an estimated formula of C32 H60, or

wherein p is 9 to

1 5 and wherein R' = an aliphatic or aromatic disubstituted moiety wherein the A units comprise about 1-50% by weight of the polyester.

1 5. A fibrillar surgical aid comprising knitted, woven or nonwoven, fibers comprising a random copolymer having the following general formula:

wherein m = about 2 to 6 and A is either:

or

wherein n = 2 to 12, and R = alkyl or alkenyl with a chain length of 8 to 30 carbon atoms;

denotes a branched hydrocarbon chain with an estimated formula of C32H60, or

wherein p is 9 to 1 5 and wherein R1 = an aliphatic or aromatic disubstituted moieties wherein the A units comprise about 1-50% by weight of the copolyester.

1 6. The surgical aid of Claims 14 or 1 5 in a sterile condition.

17. A flexible copolyester which can be processed at low temperatures of less than 220"C to produce strong but pliant surgical products, produced by the polycondensation of a flexible chain component and 50% to about 100% by weight of p-(4-hydroxy-n-butoxy) benzoic acid.

1 8. A copolymer as claimed in claim 17, produced by a procedure substantially as described in any of the foregoing Examples 1-5.

1 9. A filament as claimed in claim 1, produced by a procedure substantailly as indicated in any row of the foregoing Table II.