CA2037422A1 - Braided suture exhibiting reduced tissue drag - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
A braided suture exhibits one or more improved properties, e.g., reduced chatter, greater flexibility and/or better hand, than that of a braided suture of known, or standard, construction and of substantially equivalent size.

Description

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(1086 CIP IV) 1 ERAID~D SUIY~E OF IM~QVEP CHAR~CTERISTICS
BA~GRQ~ND Q ~ ~HE INVENTIO~
This invention relates to a braidsd suture exhibiting one or more improved characteristics, e.g., reduced t~sue drag, reduced chattar, greater flexibility and/or better hand tban ~ known, or ~standard", ~uture of ~ubstantially equivalent ~iz~.
Sutures intended for ~h~ repair of body tissues ~ust ~eet certain requir~ment~: they ~ust be ~ub~t~ntially non-toxic, capable of being r~adily ~terilized, they must bave good tensile 3trength and have acceptable Xnot-tying and knot-holding (knot ~ecurity) characteristics and if the sutures are of the absorbable or biodegradable variety, the absorption or biodegradation of t~e ~uture ~ust be closely controlled.
Sutures have been constructed from a wide variety of ~aterials including surgical gut, ~ilk, cotton, a polyolefin such as polypropyIen2, polyamide, polyglycolic acid, polyesters such a6 polyethylene terephthalate and glycolide-lactide copolymer, etc. Although the optimum structure of a uture i~ that of a monofilament, ~ince certain materials of con~truction will only result in a stiff monofilament lacking acceptable knot-tying and knot-holding properties, 6utures manufactured from such materials are preferably provided as braided ~tructureq. Thus, ~or example, suture6 manufactured fro~ ~ilk, polyamide, polyester and bio-absorbable glycollde-lactide copolymer are usually provided as multifilament braids. Co~mercial examples of BUCh ~uture~ ~nclude tho8e ~arketed under the DEXON (Davis & Geck, Inc.,) and VICRY~ (Ethicon, Inc.) brands.

1 Currently available braided suture products are acceptable in terms of their knot-tying and knot-holding properties. However, as removed from the package, they tend to be fitiff a~d wiry and retain a ~et" or ~emoryn ~uch that at the ti~e of usa, it i~ usually necessary for the sur~eon or assistant par~onnel to ~lex and 6trQtch the ssture to ~ake it more readily hand~ble. Further~ore, the 6urfaces of known ~utures are percepti~ly rough. Thus, if one passes one'G hand or fingers along the braid, ~urface irragularities will be readily detected. The result of this rough sur~ace i8 that the ~uture will exhibit tissue drag and/cr chatter as it is drawn through tissue, characteristics which ~ilitate against smooth, neat, accurately placed wound approximation, the hallmarks of excellence in surgical practice.
In the case of one braided suture now on the market, due to the necessity of ha~ing to meet fiber 6trength reguirements while at the ~ame time retaini~g acceptable knot-tying and knot-holding properties~ the 8uture i6 constructed ~rom a greater amount o fiber and consequently i8 of larger diameter than the acc~pted industry sta~dard.
It is an object of thi~ invention to provide a braided suture possessing one or ~ore i~proved characteri~tics, e.g., reduced tis~ue drAg, reduced chatter, greater ~lexibility andjor bett~r hand than that o~ a known, or Nstandard", fiuture o sub6tanti~11y ~quivalent 6ize.
It is ~nother object of th~ 8 i~vention to provide a braid~d suture which exhibit~ 6igni~icantly ~ettar knot secur$ty, e.g., expressed ~n t~rm6 of knot pull ~trength d 1 andJor loop pull Btrength, compared with the knot s~curity of a standard suture of suhstantially eguivalent size.
It is a particular ob~ect of the invention to provide a braided 6uture exhibiting one or more o~ the foreqoing improved characteristics po~sessing a greater number of sheath yarns, ~ ~ner denier for the individual filaments making up an individual sheath yarn and a greater pick count for a 6uture of ~ny given overall denier.
SUMM~RY ~E $~e~1r~5LIa~
By way of satisfying the ~ore~oing ob~ects as well ~s other objects of the invention, there i8 provided in accordance with this invention a braided su~ure exhibiting at least one improved property relative tD a standard ~uture of substantially equivalent size, the improved property being that of reduced tissue drag, reduced chatter, grea er flexibility, greater knot security ~nd/or better hand.
As a result of it~ po~se6sing ~ greater pick count and/or a greater number of sheath yarns for a suture of given overall denier and in some cases, a finer denier for the individual filaments ~aking up ~ sheath yarn, the braided suture of the present invention exhibit~ ~ewer ~urf~ce discontinuities thereby providing a ~uture which is considerably smoother than a ~tandard braided ~uture. This smoother ~tructure i~ believed to be responsible ~or the aforementioned improved characteristic(s).
The term ~suture" i~ intanded to embra~e both the non-ab~orbable as well a~ the bioabsorbable varieties.
The term ~braid" or ~braided~ as applied to the suture of ~hi3 invention refers to ~n arrange~ent of disc~ets units, or bundles, deno~inated ~heath yarnsn~ ~ade -4- f ~ ?, .;''!~ ' 1 up of individual filaments with individual ~heath yarns interlocking or interlacing each other in a regular pattern, e.g., of cri~s-cro~ configur~tion.
The ~xpres6isn plck count" refers to the number of crossovers or interlocks of ~heath yarn~ per linear inch of ~uture ~nd, together with ~he ovsrall denier o~ the ~uture, the denier of the individual fila~ent~ Gonstituting a sheath yarn and the nu~ber of ~hea~h yarns ~mploy~d, define~ the principal con~truc~ion characteri ~iC8 of the braided suture herein.
The expression "standa(rd ~uture" i6 intended to designate ~ny o~ the heretofore known braided ~utures, e.g., t~ose described in U.S. Patent No. 3,S65,077, the contents of which are incorporated by re~erenoe herein, and in particular, braided suture product6 marketed by Ethicon, Inc. under its Vicryl brand and those ~arXeted by Davis &
Geck, InG. (American Cyanamid Company) under it~ Dexon brand.
BRIEF ~ESCRIPTIQN Q~ H~_~R~WINGS
The present invention will become ~ore apparent from the following detailed da~criptl3n taken in onjunction with the accompanying illu trations in which:
Figs. l, 2, 5 ~nd 6 ~r~ photomicrographs of cros~-sectional and linear views (Figs. 2 and 6~ o~ ~tandard 6utur~ which are pre~ented for comparison purpose ;
Fig~. 3, 4 ~nd 7 to lO are photomicrogr~phfi of cross-section~l (Fig~. 3, 7 and 9) and line~r ~i~ws (Fi~s.
4, 8 ~nd lO) of br~ded ~utures ~n ~ccor~ancQ with the pre~ent invention;
Figs. 11-16 are graphi~l comp~ri~on~ o~ the measured tis~ue drag performance o~ br~ided ~utures oP thiC

v~ J

1 invention compared with that o~ standard suturee o~
sub~tantially equivalent size: ~nd, F~ g. 17 ~llu~trat~6 th~ ~or~ation o~ tha X~ot which was ~ployed in th~ knot ~ecurity ~easurement test of S Examples 22-31, ~nL~-In a pre~err~d e~bodiment, the bra~ded ~uture o~
the pre6ent invention iB ~abr~cated ~r~ ~ blo-absorbable or bi~degradable resln ~uch a~ o~e derived from polyglycolic acid, glycolide, lactic Acid, lactide, dioxanone, tri~ethylene carbonate, etc., and various comblnations of these and related monomers. Sutures prepared from resins o~
thiC type are known in the art, e.g., a8 discloæed in U.S.
Patent Nos. 2,668,162t 2,703,316; 2,758,987; 3,225,766;
3,297,033; 3,422,181; 3,~31,561 3,56~,~77; 3,56~,869;
3,620,218: 3,626,948: 3,636,956; 3,73~,646; 3,772,420;
3,773,919: 3,79~,010; 3,797,499; 3,839,297; 3,867,190;
3,878,284; 3,982,543; 4,047,533; 4,0~0,089; 4,137,921;
4,157,437; 4,234,775; 4,237,920; 4,300,565; ~nd, 4,523,591:
U.X. Patent No. 779,291; D. ~. Gilding ~t al., ~Biodegrad-able polymers for use in ~urgery - polyglycolic/poly(la~tic acid) homo- ~nd co-polymers: 1, Polymer, Volume 20, pages 1459-1464 (1979), and D.F. WilliaD5 (~d.), ~okY~Y~ CL~LY
25 Qf Clinical I~lan~ Materials, Vol. II, ch. 9: ~8iodegrad-able Polymers~ (1981).
The defining characteri~tic~ o~ a br~ided ~uture, apart ~rom the material of it~ aonstruction, ar~:
(1) o~erall suture deni~r;

(2) the pattern of ~he interlocking yarns expressed as the pick count, which i8 to ~ay, th~ nu~ber of --6-- ~,f ~ ~ ~ 5 !.s 1 1 interlocks ox crossovers o~ individual sheath yarns per linear inch of suture:

(3) the number of cheath yarn~ comprising the braid;

(4) the denier of the individual ~ilaments comprising each sheath yarn; and, ~5~ the denier o~ the cor~, where pra~ont.
In ~ preferred braid~d ~uture ~ccording to thi6 invention, the ~oregoing cons~ruction characteristics are as follows:
(1) Overall Denier of the Su~u~e The overall denier of the uture can ~ary from about 50 to about 400Q. ~ithin this range, the ranges of overall denier for particular sutures ar~ ~rom about 50 to about 125 denier; fro~ above ~bout 125 to about 200 denier;
15 ~rom above about 200 to about 300 denier; from above about 300 to about 500 denier; from i~bove about 500 to about 800 deni~r; from above about 800 to about 1500 denier; ~rom above about 1500 to about 2000 denier: and, from above about 2000 to about 3600 denier.
(2) Pattern of the Interlockin~ Shea~h Ya~ns ~PicX CQunt) For a suture of any ~ange of overall denier, pick count can vary from about 50 to about 100 crossovers/lnch with about 55-80 crossovers/inch ~eing preferred. For suturss constructed within any range of overall denier, as larger numbers of sheath yarns are Qmployed, the pick-count for the sutures will al80 increase within th~ a~oYe ranges.
For a suture of a particular range of denier ~nd number of sheath yarn , pick count i~ ~dvantageously established to ~chieve a balance in the propertie desired.
In general, with increasing piok count, 6ur~ace roughnes6 of 1 the suture tends to increase and with decrea~ing pick count, the ability of the external braided sheath to contain the core (if preæent) tend~ to decrease even reaching the point wh~re the braid may become ~o loose ~ to result in the core protruding therethrough.
For suture~ of any ~pecific denier range and number of sheath yarns, it i~ pref~rable to have a~ low a picX count a~ possible in order to achieve opti~um surface ~moothness, consis~en~, of cour~e, with the need to provide a compact braid which prevents the core (~f pr~sent) from protruding through the exterior ~heath ya-n ~tructure.
(3) The Number o~ Sheath ~arn~
The number of ~heath yarns bears some relation to overall suture denier/ the number generally increasing with the weight of the suture. Thus, ~cros~ the ranqe of ~uture weight (denier) indicated above, the preferred suture of this invention can be constructed with from about 4 up to as many as about 36 individual sheath yarns constructed from individual filaments having ~h~ denl~rs discussed below.
Table I below sets forth broad and preferred ranges for the number~ of sheath yarn~ which are ~uitable for the construction of preferred braided ~utures cf various ranges of overæll denier. The p~ck counts o~ the ~utures vary from about 50 to about 100 and deniers of ~ndividual filament~ vary from about 0.2 to about 6.0 for the broad range of number of ~heath yarns and the pick counts vary from about 55 to about 80 and tha deniar~ of individual ~ilaments vary ~rom about 0.~ to ~bout 3rO~ and advantageously fro~ about 1.0 to ~bout 1.8, for t~e preferred range of number oP ~heath yarn~.

-8~

1 Table I: Sh~ath Yarns R~ ed_to Su~ure ~enier Number Or Nu~ber of Overall Suture Suture Sheath Yarns eheath Yarns Denier ~ Broad R~nae3 lPree~red Ranae) greater than about 50 to about 1257/0,8/0 4-16 6-14 greater than ahout 125 to ~bout 200 6/0 4-16 6~14 greater than about 200 to abou~ 300 5/o ~-16 6-14 greater than about 300 to about 500 4/0 10-?0 12-14 graater than about 500 to about 800 3/0 14-20 - 14-18 greater than about 800 to about 1200 2/0 18-32 20-30 greater than about .
1200 to about 2000 0 20-36 24-34 ~reater than about 200~ to ~bout 4000 1,2 20-36 24-34 While the ~heath yarns need not be twi~ted, it is generally preferred that they be provided with a:twist 80 as to minimize ~nagging during bra~d ~onstruction.
(4) I~ l~J~b~ e~
The individual fila~nt~ co~prising each ~heath yarn can vary in weight from about 0.2 to about 6.0 denier, preferably from about 0~8 to about 3.0 denier ~nd ~ore preferably from about 1~0 to about 1.8 dani2r. The number of ~uch ~ila~ents pre~ent in a p~rticular sheath yarn will 3n depend on the overall denier of the ~utur~ a8 well a~ the number of sheath y~rn~ utilized in the cons~ruc~ion o~ the 6~ ~ J

1 sutur~. Table II sets forth some typical numbers of filaments per 6heath yarn ~or both the broad and prefexred ranges of fila~ent weight~
Table II: ~umber o~ Filam~n~s per S~eath Yarn ~pproxL~ate ~pproximate Filament _ ~Yi~Q D~nier_ 450 0.2 0 15 150 0.5 1.5 3 40 1.8 1 15 6.0 (5) ~ore (Qptionall For all bu~ t~e lowest range o~ overall denier, the prePerr~d suture can optionally be ~onstructed around a filamentous core which itself can be braided or which can be provided in some other configuration Euch as a~twist, ply, cable, etc. The filament(s) compri~ing the core need not be as fine as those comprising the 6hea~h yarns. ~t :ie particularly advantageous ~or ~uture~ of heavier denier to possess a core~ Where a core i~ provided, it i generally preferrad that it posse~s a weight whlch i8 ignificantly greater than that of a core of a ~tandard sutur~ of equivalent overall denier.
TAble III below provid~s 80me typical core deniers for ~utures of various deniers.

--~ -- 6~ r~ ' ~

1 ~able III Ç~ ~enier Rçlat~d to Suture Denier Denier of Denier oP
Overall Suture Suture Optional Core Opt~onal Core Denier ~ Q9~ E~D51 ~Pr~fexred Ranae~
from about 50 to about 125 8/0,7/0 none none gre~tar than about 125 to about 200 6/0 20-80 25-50 greater than about 10 200 to ~bout 300 5/0 30-100 59-80 greater than about 300 to ~bout 500 4/0 80-50 80-120 g~rQater than about 500 to about 800 3/0 150-300 1~0-280 greater than about 800 to about 1200 2/0 250-700 ~50-650 greater than about 1200 to about 2000 0 400-1200 500-1000 greater than about 20 2000 to about 4000 1,2 800-2400 1000-2200 When a suture of thi8 invention i5 ~abrlcated from a ~aterial which is susc~ptible to hydrolysis, e.g., any of the absorbable resins previously mentioned, care ~ust be take to rigorously exclude moisture ~ro~ contacting the ~uture during storage or to otherwise preserve the su~ure fro~ ~xce~sive hydrolytic attack which would compro~ise its YiYQ strength to thQ point where th~ ~uture would no longer ~a ~erviceable.
30 According to U.S. Patent Nos. 3,728,839 and 4,135,622, the ~a yivQ strength o~ polyglycolic ac~d s~ .~. ro. <`/! "` ', ~V
1 ~urgical elemen~s cUch as sutures undergoes significant deterioration on long term storage in the package even on exposure of the contents to very ~mall amounts o~ water ~or very short periods of time, 9.g., 20 minutes or leEs, ~ust prior to packaging due to the tendency of a ~oisture imperviou~ pac~age to seal the DOistUre in with the suture.
To prevent or ~inimize exce~ive hydrol~tic degradation of ~n absorbable suture durlng ~torage, U.S. Patent NOG.
3,728,839 and 4,135,622 dl~close ramoving ~oisture from the suture before sealing the pac~age ~o that no more than about 0.5 percent of water by weight of suture remains in the package once the pacXage is ~ealed. This approach to i~proving the suture's storage ~tability, while effective, is in practice difficult and expensive to carry out. Prior to ~ealing the suture within itG moisture impervious package, it is es~ential that the suture be "bone dry", a condition achieved by heating the suture for a sufficient period to remove the water therefrom, e.g., 180-188F
(82-87-C) for 1 hour under a 26 inch vacuum. However, once the water is removed, the suture cannot be allowed to contact a moisture-containing environment even~for a li~ited:
duration since as previously noted, ~en brie~ exposure to moisture can ~ause severe d~t~rioration oP sutur~ in v~vo strength. It therefore becom~ nece~sary following the water removal 6tep to temporarily ~tore the suture in a dry area, i.e., an environment which i~ e~sentially ~ree of moisture, where the possibility oP con~act with moi~ture is largely eliminated. These op~rations ~or improving ~he ~toraga ~tability of an absorb~ble ~uture are ti~e con3uming, ~xpens~ve and constitut~ a relztl~ely complex ~olution to tha storage ~tab~lity probl~m.

.
' 1 In an entirely different approach to improving the ~torage stability o~ an absorbable 6uture, one ~hat avoids the foregoing drawbacko a~sociated with the method of U.S.
~atent No~. 3,728,839 and 4,135,~22, the 6torage ~tability S of an ~bsorbable braided ~uture which i~ ~u~ceptible to hydrolysi~ i8 i~prov~d by applying to the suture a storage stabilizing a~ount of at least one wat~r soluble liquid polyhydroxy conpound and/or e~tQr ~hereof. In ~ddition to imparting an ~nhanced degree of ~torage atability to the suture, practice of ~hi8 embodiment of the pre~ent invention confers other benefits as well. So, for example, a braided ~uture which has been ~illed with a ~torage stabili2ing amount of, e.g., glycerol, exhibits better ~lexibility and "hand" characteristics ~han the untreated ~uture. ~oreover, since the polyhydroxy compounds are generally capable of dissolving a variety o~ ~edico-~urgically userul ~ubstances, they can be used as vehicles ~o deliver ~uch substances to a wound or surgical site at the ti~e the suture i6 introduoed into the body.
The u~eful storage ctabilizing agents are generally ~elected ~rom the water soluble liquid polyhydroxy co~pounds and/or e~ters o~ such compounds, preferably ~ho~e having no appreciable toxicity for the body at the levels present. The expression ~liquid polyhydroxy compound"
~5 conte~plates ~ho8e polyhydroxy compounds which in the essent~ally pure state are liquids, ~6 opposed to solids, at or ~bout ambient temperature, e.g., at from about 15C to About 40C. The preferr3d polyhydroxy compounds pos~ess up to ~bout 12 carbon atoffls and where ~he esters are concerned, are p~eferably the monoe~ter~ and diesters.

--13-- G ~

1 Among the ~peci~ic storage stabiliziny agents which can be used with generally good re6ults are glycerol and ~ts mono- and diester~ derived ~rom low molecular weight carboxyllc acids, e.g., ~onoacetin and diacetin (re~pectiYely, glyceryl ~onoacetate and glyceryl diacetate), ethylene glycol, diethylene glycol, triethylene glycol, 1,3-propanediol, trise~hylolethane, trl~ethylolpropane, penta~rythritol, sorbitol, and the like. Glycerol i8 ~specially pr~ferr~d. ~ixtur~s o~ ~torage ~tab~lizing ~gents, e.g., sorbitol dis601ved in glyc~rol, glycerol combined with monoacetin and/or diacetin, etc., are also useful.
To prevent or minimize run-off or ~eparation of the storage 6tabilizing agent from the cuture, a tendency:to which relatively low visco~ity compounds such as glycerol are somewhat prone, it can be advantageous to combine the agent with a thickener. ~any kinds of pharmaceutically acceptable non-aqueous thickener6 can be:utilized including water-soluble poly6accharides, ~ , hydroxypropyl methylcellulose (HPMC) and similar cellulosic ~aterials, polysaccharide gu~ ~uch a6 guar, xanthan, and the like, gelatin, colIagen, ~tc. An e~pecially pr~ferred class of thicXeners are the ~aturated aliphatic hydroxycarhoxylic acids of up to about 6 carbon atom~ and the alkali ~etal and alkaline earth metal salts and hydrates ~hereof. Within 3~

1 this prererred class of compound~ are those o~ the general formula 0~
R _ ~ (CH2)~ C~OR' whsrein R iB hydrogen or a ~ethyl group, ~' i8 hydrogen or a m~tal ~el~cted fro~ the group con6i6ting of alkali ~etal and alkaline ear~h metal and n 1~ o or 1 and hydrate~ thereo~. -Specific examples of ~uch compound~ include alts of lactic acid such as calcium lactate and potas~ium lactate, sodium lactate, salts of glycolic acid uch a~ calcium glycolate, potassium glycolate and sodium glycolate, ~alts of 3-hydroxy propanoic acid ~uch as the calcium, pota~ium a~d 60dium salts thereof, &alts of 3-hydroxybutanoic acid 6uch a~ the calcium, potassium and sodium salt~ thereof, ~nd the like.
As stated hereinbefore, hydrates of these compounds can also be used. Calcium laotate, especially calcium l~ctate pentahydrate, i8 a particu~arly preferred thickener.
Where a thickener is utilized, it will ke incorporated in the storage ~tabilizing composition in at least that amount required ~o incre~e the overall vi~cosity of the compocition to the point where it no longer readily dralns away from the suture in a relati~ely ~hort period.
In the case of a preferred storage stabilizing agent-thickener combination, na~ely, glycerol ~nd calciu~lactate, th~ weight ratio of glycerol to ~lciu~ lact~te can vary from about 1:1 to ~bout 10:1 and preferably i~ ~rom about 6:1 to about 8:1.
~f nece~sary or de~ir~ble, th~ storage stabi}izing agent together with optional thickener can be di~olved in 1 any suitable non-aqueous ~olvant or combination of ~olvents prior to use. To b~ auitable, the solvent must (1~ be miscible with ~he storage stabil~z~ng agent and optional thic~ener, ~2) have a sufficiently high vapor pressure to be S readily removed by evaporation, (3) not appreciably aff~ct ~he integrity of ~he ~uture and (4) ~e capable of wettlng the surface o~ the sutur~. ~pplying ~hese criteria to preferred ~torage ~tabilizing agent, glycerol, advantageously in admixture with a pre~erred thickener, calcium lactate, lower alcohol~ ~uch a~ ~ethanol ~nd othanol are ~ntirely 6uitable solvent carriers. When a ~olvent i8 utilized in the preparation of the storage stabilizing agent, ~uch solvents, ~.g., ~Qthanol, can be employed in amounts providing a solution concentration of ~rom about 20%
to about 50%, preferably about 30% to about 45%, by weight of the storage ~tabilizing agent (including any optional thickener) b~sed on the total weight o~ the ~olution.
Preparing the ~torage stabilizing agent for appl~cation to the ~uture i6 ~ relatively ~imple procedure.
For example, in the case of a ~ixture of glycerol and calcium lactate, the de~ired ~mount of glycerol ~5 fir~t introduced to ~ suitable vessel followed ~y the addition thereto of th~ desired amount of oalcium lactate. I~ no solvent i9 u~ed, the mixture i~ then thoroughly mixed.
Where a ~olvent ~uch a ~ethanol i~ employed, th~ solvent i~
addQd to the mixture o~ glycerol and calcium lactate and the ~olution i6 then thoroughly mixed to dis~olve the oompounds.
Application of the atorage ~tabilizing ngent to the suture can ~e carr~ed out in any nu~ber of way~. Thu~, for exa~ple, the ~uture can be ~ub~erged in the ~torage ~tabilizing ~gent or ~olution thereo~ until ~t least a ; . , --1 6 ~ s 1 ~torage stabilizing amount of agent i6 acquired or otherwise retained by the suture, ~ven after the optional removal of any exces~ agent and/or &ccompanying solvent ~f pre6ent) such ~s by drainage, wiping, ev~poration, etc. In many cases, contact tiDes on the order o~ from just a few ~econds, e.g., ~bout lO 3econds or ~o, to ~everal hour6, e.g., about 2 hourfi and even longer, are sufficient to impart a substantial improvement in the storage stability o~
the trsated ~uture compared to ~he s~me duture ~hich ha~ not been treated with ~toraga ~tnbilizing agent. It ha~ been found that calendering the suture prior to ~illing, such as by passing the suture through at le~st two pairs of transversely mounted calender roll~, can improve the receptivity of the suture to filling and improves the suppleness of the resulting filled suture. It i6 believed that calendering the suture separates ~he individual ~uture filaments to open up ~paces ther~between which ~re conducive to ensuring that the filling compo~ition penetrates within, and fills, the inter tices o~ the br~ided suture.
The foregoing submersion method of contacting the suture with ~torage ~tabilizing ~gent can be conducted continuously or in batch. Thu~, a running length of khe ~uture can be continuously pasaed throu~h a quantity :of the stabilizing ~gent at a velocity which has been previously determined to provide the nece~ary degree of exposure, or ~ontact time, of the suture wl~h the storage ~tabilizing agent. As the ~utur~ emerges from the storage stabilizing agent, it can be pa~ed through a wiper or ~imilar devl~e to remove excess agent prior to the pacXaging operation.
30 Preferably, the suture i 8 pa~sed through a ooating head ~upplie~ by a ~etering pump with ~ con~tant ~upply of -17- ,; "~s~

1 ~illing ~olution, with the suture emerging from the coating head and passing through an eYapOratiOn oven to remove the ~illing solution ~olvent prior to any further sur~cP
contact, i.e., wi~h rollerc~ etc. In a batch oparation, a guantity oP suture i8 ~erely ~ubmerged within the ~torage stabilizing agent for th2 regui~ite period of time with any excess agant being removed fro~ the ~utur0 if de~ired.
Alternatively~ the ~torag2 stabiliziny agent and ~olutionfi thereof can be applied to th~ ~uture by ~praying, brushing, wiping, ~tc., such that the ~uture receiveR and retains at least a 6torage stabilizing ~mount of ~he agent.
Yet another procedure which can be used to apply the storage stabilizing agent involve~ inserting the 6uture in a package containing an e~fective amount of the ~gent such that intimate contact between the suture and the agent i5 achieved.
Whatever the contacting procedure 2~ployed, it is necessary that the ~utuxe being treated acguire ~ storage stabilizing amount of the ~torage stabilizing agent. In general, amount8 of from ~bout 2 to ~bout 25, and preferably from ~bout 5 to ~bout 15 we~ght percent, of ~torage stabilizing agent(~) (exclusive of any ~olvent) by weight of the suture contacted ther~with ~ 8 fiufficient to provide significantly i~proved ~tor~ge ~tability Gompared to that of the untreated ~uture.
As previously pointed out, ~ filled braided 3uture in accordance with the i~ventlon need not be pack~ged and ma~nt~ined under ~he very dry conditiGns r~guir~d ~or prior Bynth~tiC ab~orb~ble ~utures. Instead, it i~ pre~erred that thQ ~illed ~utures be aguilibr~t6d ~o that ~he l~v~l of moisture or other ~tabilizing agent ~olvent iB ~uf~icient to ~ 7, f ;;

1 result in an appropriate viscosity level for the ~tabilizing agent and thickener in order to keep the ~tabilizing agent on the suture. In the preferred Qmbodiment of a braided ~uture filled with ~ ~ixture of glycerol and calcium lActate, the moisture l~vel ~ay be equili~rated to ~8 low as about 0.2% by weight o~ the ~utur~, ~nd i~ pre~erably above 0.3~ or, even more prefer~bly, about 0.5% by weight of the ~utu~.
Indeed, it has besn found that ~ braided 6uture fillod with a glycerol/calciu~ lact~te co~po~ition tends to undergo undesirable changes if exposed to a very dry envir~nment. ~or~ particularly, i~ such ~illed suture i~
exposed to a very dry envirohment, the sur~ace~of the ~uture may accumulate a fla~ed or powdered substance which could possibly interfere with, or render more di~ficult, the removal of the suture ~rom it8 package. Equilibrating the filled suture, such as in ~ dew point controlled environment, ~o that the ~uture contain6 ~ relatively high moisture lev~l, e.g., in exces6 of 002~ and preferably in excess of 0.5% by weight o~ the suture, prevents ~uch accumulation of flaked or powdered sub~tance whlch ~ight otherwise re~ult were the suture exposed to an extremely dry environment. Conver~ely, the pre~ence of too much ~oisture can also have deleterious e~fects, 6uch AS causing ~he glycerol ~illing to run. Therefore, it ~5 preferable to control the ~oisture level within a range having presat upper nnd lower ll~its.
It $6 al~o wi~hin th~ ~cope of thi~ ~n~antion to impregnate the bralded sutu~e w$th, or otherwlfie apply thereto, one or ~ore medico-~urgically u~eful ~u~stances, e.g., those which accelerate or ~eneficially ~odi~y the 1 healing process when ~he suture is applied to a wound or surgical site. So, for example, the suture herein can be provided wi~h a therapautic agent which will be depo6ited at the sutured sit2. The therapeutic agent can be chosen for 5 its antimicrobial properties, capability for promoting wound repair ~nd/or tiBsue growth or for ~peci~ic indication~ ~uch a~ ~hrombosis~ Antimicrobial ~gents such as broad ~pectrum antibiotics (gentamicin sulphate, ~rythromycin or derivatized glycopeptides) which are ~lowly ralea~ed into the ti~sue can be applied in th~s ~a~ner to aid in combating clinical and sub-clinical lnfections ln a ~urgical or trauma wound site.
To pro~ote wound repair ~nd/or ti~ ue growth, one or more biolo~ically active ~aterials known to ~chieve either or both of these objective~ can be applied to the spiroid braided suture of the present invention. Such materials include any of ~everal ~u~an Growth Factor~
(~GFs), magainin, tis~ue or ki~ney plAsminogen activator to cause thro~bosis, superoxide dismutase to ~cavenge tissue damaging free radicals, tumor necrosi~ ~actor for cancer therapy, colony stimulating factor, interferon, int~rleukin-2 or other ly~phokine to Qnhance the i~une ~y~tem, and ~o ~orth.
The ter~ ~Human Growth Factor" or "HGF~ ~braces those materials, known in the llterature, which ~re re~erred to A~ such ~nd ~ncludes their ~ologically scti~e c~osely related derivativ2s. The HGF~ can be derived fro~ n~turally occurring sources including h~An ~nd non-human ~ources, ~.g., bovln2 ~ourc2s, and are pre~erably produced by re~ombinant DNA tachniques. 8p~cifically, ~ny of the HGFs which are ~itogenically activ~ ~nd as such are e~fective in ,.,. 7.

t ~timulating, accelerating, potentiating or otherwise enhancing the wound healing proce3~ can be use~ully applied to the ~uture herein, e.g., hEGF (urogastrone), TGF-beta, IGF, PDGD, FGF, etc. The~e and G~her useful HGFs and 5 clo6ely related ~GF derivatives, method~ by which ~hey can be obtained and ~ethods and co~position~ featuring the use of HGFs to enhance wound healing are ~ariously disclosed, inter ~ , in U.S. Patent No~. 3,883,497, 3,917,824, 3,948,875, 4,338,397, 4,418,691, 4,528,186, 4,621,052, 4,743,67~, 4,717,717, 4,861,757, ~,874,746 and 4,944,948, European Patent Applicat~on No~. 046,039, 128,733, 131,868, 136,490, 147,178, 150,572, 177,91S ~nd 267,015, PCT
International AppliGations ~0 83/04030, W0 85/003698, W0 85/01284 and W0 86/02271, UK Patent Applications GB 2 092 155 A, 2 162 R51 A and GB 2 172 890 A and, "Growth Factors in Wound Heallng", Lynch, et al., J rlin l~_ s~ , Vol. 84, pages 640-646 (Augu~t 1989~, all of which are incorporated by reference herein. O~ the Xnown HGFs, ~EGF, TGF-beta, IGF, PDGF and FGF are preferred, elther ingly or in com~ination-In a preferred e~bod$ment o~ the ~raided ~uturedevice of this invention, a filling co~position co~prising a surgical wound healing enhancing ~ount of at lea~t one HGF
and as carrier thers~or at lea~t one water ~oluble, liquid 2~ poly~ydroxy compound and/or e~ter thereof such a~ any o~
those previou~ly ~entioned i5 ~pplied to the ~uture. The carrier protect~ the HGF component of the filling compo~ition from ~xces3iv2 degradation or 106~ of ~iopotency during ~torage and as disclo~ed above, when ~he su~ure is fabricated from an nb~orbable resin whlch i~ susceptible to hydrolysi~, the carrier i~proves ~he storage stability of 1 the suture as well. In additio~ to carrier, the HGF can contain a thickener such a6 any oP those previously mentioned in order to reduce or limit the ~endency of caxrier run-off.
The filling compositlon can contain one or more additional components wh~ch promotQ or enhance the wound healing effectivene~s of the ~GF co~ponent. Thus, e.g., sit2-~peciflc hybrid proteins c~n be incorporated in the filling composition to maxi~ize the availability of the HGF
at the wound ~ite and/or to potent~ate wound h~aling. See, Q-g~ r Tomlinson ~Ciba-Geigy Pharmaceutical~, West Su~ex, U.K.), "Selective Delivery and Targeting of Therapeutic Proteins", a paper pre6ented at ~ ~ymposiu~ held June 12-14, lg89 ln Boston, ~A, the contents of which ar~ incorporated by ref~rence herein. The ~GF~ can ~180 be ~s~ociated with carri~r protein~ (CP~), e.g., in ~he ~orm of CP-bound HGF(s), to further enhance a~allability o~ ~he ~GF~ at a wound ~ite a~ disclosed in ~Carrier Pr3tein-Based Delivery of Protein Pharmaceuticals~, ~ paper of BioGrowth, Inc., Ri¢hmond, CA presented at the aforemention~d ~ymposiu~, the contents oS ~aid paper beinq ~corpor~ted by reference herein. The ~GFs can al~o b~ incorpor~t~d in liposomes to provide ~or their release over ~n Qxtendod period. Lactate ion can be pre~ent to augment the wound healing actiYity of the HGF. Prote~tants for ~he ~GF can al80 be utilized, e.g., polyethylene ylycol~, aceto~yphenoxy polyetho~y ethanols, polyoxye~hylene sorbitans, d~xtrans, ~lbu~in, poly-D-alanyl peptide6 and N-(2-hydroxypropyl)-methacryla~ide (HPMA).
The amounts of HGF, ca~r~er and optional component(s~ ~uch as thickener, ~ite-~pecific hybrid -22; ~J ~' .5 iJ ~

1 prot~in, carrier protei~, etc., identified above can vary widely and in general will be a~ least that amount of a particular component which i8 rRgUired to per~orm its xespective function in an effective way. Tho~e ~killed in the ~rt employing known or conv~ntional procedures can readily determine optimum a~ounts of each component for a particular filling compo~ition And particular braided ~uturs filled therewith.
In g~neral, the ~GF(~) can be present in the total composition at a level r~nging fro~ about 0.1 to about 25,000 micrograms per gram of such compositisn, preferably ~ro~ about 0.5 to about 10000 micrograms per gram of composition and most preferably from about 1 to ~bout 500 micrograms per gram of composition.
lS Application of the HGF-containiny co~position to the ~uture can be carried out by any suitable technique, e.g., by any of the procedures de~cribed above ~or applying a storage ~tabilizing agent to the ~uture.
It can also be advantageous to apply one or more coating compositions to the ~uture where particular functional propertie6 are deRired. For ~xample, the ~uture can be coated with a material which l~proves its surface lubricity and/or knot tie-down characteri~tics. Material~
of this kind are known, e.g., tho8e described in U.S. Patent Nos. 3,942,532, 40406,533 and 41716,203, the content~ of which ~re incorporated by reference herein. Particularly suitable materials which impart elther or both improved lubricity ~nd knot-tie down characteri~tics ar2 ~he bioab~orbable coating co~position~ obtain~d by copolymerizing in ~ccordance with known procedures ~
polyether glycol sel~ct~d from the qroup con~i~ting of --2~ C~, 1 relatively low molecular weight polyalkylene glycol, e.g., one corresponding to the general formula HO(R0)~ wherein R
is an alkylene group of ~rom 2-4 carbon atoms and y 1~ an integer of Pro~ about 100-350, and polyethylene oxide-S polypropylenQ oxide blocX copoly~er, s.g., one corre6ponding~0 thQ ganeral ~ormula ~(OC~ÇH~)x(SK~Hs)r(OCH~H2~aOX wherein X ~8 an integer o~ from about 45-90, y ~ an int~ger of from about 60-85 ~nd z iB an in~ger o~ ~ro~ about 45-90 with (2) a ~ixture o~ lactide ~ono~er and glyco~id~ monomsr or a prefor~ed copoly~er of lactid~ and glycolide, ~he weight ratio of (1) to (2) preferably ranging from about 4:1 to about 1:4 and more preferably ~rom about 2:1 to about 1:2.
The ratio of lactide to glycolide in the monomer mix*ure or in the copolymer of these monomers preferably varies fro~
about 65-90 mole percent lactide and 10-35 ~ole percent glycolide. Polyether glycol~ which can be u ed to prepare the bioabsorbable coating compo~itions advantageously include polyethylene glycols having ~olecul~r weights o~
about 3, 500-25, 000 and preferably ~rom about 4, 000-10, 000 and polyethylene oxide-polypropylene oxide ~lock copolymers having molecular weight~ of îro~ about 5, 000-10, 000 &nd preferably from about 7 , 500 to about 9 , 000 , e . g ., those disclo~ed in U.S. Patent Nos. 2,674,619, 3,036,118, 4, 043, 344 ~nd 4, 047, 533 and commercially avail~le ~ the Pluronics SBASF-Wyandotte). Wher~ preformed copoly~er~ of lactide and glycolide ~ro employ~d in prep~ring the ~ bioab~orbable coating CO;llpO6itiOn8, they may be prepared described in U.S. Pa~ent No. 4,523,591. ~he amount~ of bioab~orbable coating co~po~ition to be applied to the ~utur~, e.g., by coating, dlpping, ~praying or other appropriate technique will vary dQpending upon the ~pecific 1 construction 9~ the suture, its 8ize and the material of its construction. In general, the coating compositlon applied to àn unfilled suture will constitute from about l~0 to about 3.0 percent by weight of the coated ~uture, but the amount of coating add on ~ay range fro~ a~ little ~s about 0.5 percent, by weight, to ~ ~uch a~ ~.0 percent or higher.
For a preferred ~lled (i.e. cont~ining a 6torage stabilizlng agent) ~raided ~uture, amounts o~ coa ing composition will generally vary from about 0.5~ to 2.0~ with a~ little a~ 0.2% to s ~uch ~ 3.0%. A~ a practical ~atter and for reason6 of economy and general performance, it i6 generally pre~erred to apply the minlmum a~ount of coating composition con~istent with good ~urface lubricity and/or knot tie-down characteristics ~d thi8 level o~ coat$ng add on i~ readily deteroined experimentally ~or any particular suture.
The following ~xamples are illustrati~e of the braided suture of thi~ invention.

2 5 , ., 1 Çompa~ison~xa~lçs 1-7 The following braided ~uture configurations ar~
disclosed in U.S. Patant No. 3,565,077:
O~erall ~enier of Comparison Suture Pick Number of Individual Denier Exa~le ~e~ ÇQ~n~ ~h~ L~n~ ula~_ o~ core 2 309 46 8 6 lQ0 1~ 6 1500 50 12 5 600 Sutures possessing ~pproxi~ately these configurations are rel~tively lnflexible, rough-surfaced and ~xhibit a relatively high level of chatter and drag.

~26 1çomParison ~x~Eples 8~
The following braided euture configurations are `those of four commercially available ~uture~:
Number 5Overall of Denier 9~ Denier Compar~ 80n Suture Suture PicX Sheath Individual o~
~xampl~ Denier ~S~U~ Y~n~ mç~ ore 8 259 5~0 47 8 2.1 29 9 698 3/0 52 12 2.1 55 1566 0 50 16 2.1 252 11 2122 1 ~4 16 2.~ 330 Photomicrographs obtained by scanning electron microscopy (SEM) of the suture of Comparison Example 10 ~Figures 4 and 5: cro~s-sectional view at 200x and llnear ViQW at 50x, respectively) clearly show th~ st~uctural details of the suture. Th~ uture braid iB made up of relatively few sheath yarns and the ciroumfer~ntial indentations, plainly evident i~ Figure 4, ause the braid surface to be relatively rough.

~27-mples 1-8 These example6 illustrat~ various ~ize of braided sutur~ constructed in accordance wlth the present invention.
Nw~ r Overall of Denier of ~eni~r Suture Sutur~ Pick ~heath ~ndividual of E~ le ~ ~ æ~_ ÇQ~a~ Y~aa~_ E111L~GI~a_ Co~e 1 9~ 7/0 82 8 1.2 ---2 173 6/0 75 12 l.Z 2g 3 240 5/0 65 8 1.2 48 4 3~9 4/0 75 12 1.2 ~l 600 3~0 65 16 1.2 216 6 1080 2/0 72 24 1.2 504 7 1378 0 ~5 28 1.2 706 8 202~ 1 ~5 32 1.2 1260 Comparing the details of construction of the foregoing braided sutures with tho~e of the known braided sutures a6 set forth in Comparioon Examples 1-11, it will bs noted that ~or sutures of compar~ble overall ~enier, the suture of this invention po ~s~e~ a s~gnificantly greater pick count and number o~ ~heath yarns:and a significantly finer deniar Por he individual filaments making up a sheath yarn than the eguivalent characteristic of the known suture.
A8 a result o~ their unigue con tructio~ :
oharacteristics, the 8UtUrQ 0~ ~hi~ ~nvention ~xhiblts perceptibly improved flexibility and hand~and r~duced chatter and drag compared with the Xnown, or standard, sutures o~ Compari~on ~xampl~ 11. For a gi~en ~uture ~ize, a br~ided suture: of thi~ ~nvention will typically exhibit a level of ti~sue drag not ~xceeding about 60%, preferably not exceeding about ~0% and ~ore prefsrably, not exceeding about 20%, of th~ ti~ue ~r~g of a stand~rd braidsd ~uture of comp~rabl~ ~iz~.

., -~8 1 Exa~pl~ 9~
The following braided ~uture~ were fabricated in ~ccordance with the pre~ent invention:
Number Overall o~ Denier of Denier Suture Suture Pick hoath Individual o~
E~mIiLe E~$L~ ~ S~Y~rns Fila~ents Çore .
9 2~0 5/0 6~8 1.2 40 600 3/0 7116 1.2 lao 11 1374 0 6728 1.2 702 12 2230 1 5732 1.2 975 In contrast to the suture of Comparl60n Example 10, ~upr~, SEM photomicrographs of the ~uture of Example 11 (Figures 6 and 7: cross-sectio~al view at 200x and linear view at 50x, respect~vely) 8how a ~mooth circumferential ~ur~ace ~s the re6ult of ~he increased number o~ ~heath yarns and smaller diameter of individual filaments~
Figure 4 as compared to Figure ~ shows the relatiYely larger core present in the ~uture of Example 11 as co~pared to ~hat o~ Co~pari~on Exa~ple 10.
Comparison between Figures 5 and 7 show~ the increased number of pic~s (cros~overs/inch) of ~he ~uture of Example 11 a~ compared to that o~ Compari60n Example 10.
.

1 EXAMP~ES 13-15 The following suture braids were fabricated in accordance with thQ present invention:
Nu~er Overall o~ Denier of Denier Suture Suture Pick Sheath Individual of 21~ ~enie~ Ç__ S~ Yarns Fila~nt~ 5~
13 1442 0 70 28 2.01 ~82 14 1621 o 70 ~8 1.~ 882 1554 o 78 2B 1.2 882 D~nior o~ ~he~h fll~n~; cor- t~lJ~lt8 ~er~ l.Z ~pf.
The suture braids ~ere coated to improve suture lubric~ty and knot tie-down charact0ri6ti~s and compared for physical properties for diameter USP knot-pull and suture ticsue drag with the coated com~ercial suture of Comparison Example 10.
In thl~ tissue dray test, ~utures were needled with identical tapered needles to normalize any effect of ~`
needle diameter on the test.
Sutures were passed through live animal abdominal fascia tissue. The r~sults of ~he tis~ue drag study are ~hown in Table IV as follows:

-30~

le Xv: Ti#sue Draa Re~ul~s Tissue Drag Exa~le Dlameter ~min~ ~not-Pull~g~ ~Q~ç~.... ~aximumL
Comparison ~xample 10 0.419 4.72 257 13 0.413 5.27 3~
14 0.428 5.35 ~6 0.444 5.~ 50 TheGe d~ta d early ~how that th~ ~moother ourface of the braided sutures fabricated in ~ccordance with this invention provides smoother, more resistance-free passage of the suture through t~ssue thereby resulting in lower tissue drag and chatter. High drag forces ~ake it ~ore difficult for the surgeon to align tissue neatly and increase the time to complete the closure. A vi~ual compari~on of the suture of Comparative Example 10 and tho5e of ~xa~ples 13 and 14 of this invention are consistent with the ti~ue drag observations set forth aboveO Thu~, it i~ evident from a visual comparison of the SEM photo~icrographs of Flgs. 8 and 9 (suture of Co~parison Example 10 shown in cross-sectional view at 150x and linear view at 70x, r~6pectively) with those of Figs. 10 and 11 (suture o~ Example 13 ~hown in cro~s-section at 150x and linear view ~t 70x, raspQctively) and Figs. 12 and 13 (~uture of Exa~ple 14 ~hown in cros~-~ection at 150x and linear view ~t 70x, re~pacti~ely) that the extarnal surface6 of the ~uturQs of the present $nvent~on, i.~., tho~e o~ Exampl~ 13 and 14, ~re perceptibly ~moother than the ~ur~a~e~ of S~he ~uture of Comparison Exa~ple 10.

- 3 1- f , ',, ~ ~ j, .. .

~EI~!
Measurement of ti~sue drag in accordance with this example employed a Chatillon Ten~ e~ter (~erial no.
06279~ quipped with ~ load cell (Full Scale Load 1.72g) for recording ten~ile ~nd compre~sion loads, ~ ~tripchart recorder (Omega Eng. serial no~ 211347) for constantly recording th~ ten~ load~ and crossh~ad moveQent, a S00 gra~ calibration weight ~nd n~edle holders ~iltex Straight-6n) .
Each suture ~a~pl~ which was tQ~ted was armed with the same ne~dle ~or 61ze and type) to reduce the potential for error resulting from vary~ng punctures by different needles. For each test, the armed ~uture was pa6sed through the ~ascia tis~ue in a ~W" pattern thus a~surin~ that an approximately l inch spacing would be maintain~d betweenentries and exits of the 6uture. In each pas~age of the suture, care was taken to insure ~ntry of the ~uture into all fascia layer~ (excluding the skin~. Following:passage o~ an adequate length of ~uture khrough the ~ascia ti~sue to accommodate the test ~etup, the needle wa~ pl~ced ~nto ne~dle holders. The suture was pa~ed und~r a ringst~nd bar cre~ting a 90- angle directly aligned with the load cell and the ~pecimen. The~ne~dle holder was auspended ~rom the load cell fixture. Tension in the 3uture was reli~ved ~nd the zero 6ettings on the ten~ile tester were rechecked prior to testing.
The cro6shead wa~ then ~ngaged in the te~t diraction (t~n~ile, upward) at ~ rate of 30 ~m/~ln tl2 in/~in) and the ~tripchart r2corder W~8 m~nually engaged at a rate of 30 cm/min (12 in/min). During the te~ting of the suture, load and crosshead ~o~Qm~nt wer~ recorded until the --32~ ," s-s 1 entire ~uture sample had been withdrawn from the tissue or complete crosshead ~ravel had been achieved. The crosshead was then disengaged ~nd return2d to its zero ~etting, the ~tripchart was di~engaged and ~ny r~ain~ng length of suture wa~ removed ~rom th~ ~ascia.
The foregoing procedure wa~ rQp~ated for ~ach armed ~uture within a test groupO
In this example, a rilled and coated size 2/0 braided 6uture con tructed in accordance with the inYention tO (Suture A) was compared ~ith a coated ~ze 2/0 braîded silk suture of Davis & Geck, Inc. S~D & G Silk": Sutur~ B) and a coated 6ize 2/0 braided ab60r~able ~uture o~ Ethicon, ~nc.
(nVicryl~: Suture C) for ti~sue drag a~ de cribed. ~he tissue drag proile~ of the ~hree sutures ~ppear in Fiy. 11 as the plot of force (kg~ required to pull each suture through animal fascia ti~sue through a distance of somewhat great2r than 10 cm. As the graphically represented data show, the braided suture constructed in accordance with the principles of thi~ invention, i.e., Exhibit A, exhlbited a dramat~cally reduced level of ti~ue drag compared with that o~ the two standard suture~, i.e., Suture~ B and C.

EX~MPLE~ 17-2 1 Example 16 was repeated with di~ferent size6 OI
Suture~ A, B and C, na~ely, 8iZQ8 0 ~Example 17), 1 (Example 18), 2/0 (Example 19), 4~a t~:XUllpl0 20) and 5~0 (Example 5 21). As shown in Fig~. 12-16, 2~ch ~iæe o~ Suture A
exhibited far lower ti88UI~ drag t~han ~tandard Sutuxe~ B and C of ~ tant~ally equivz~ nt ~ize.

34~

Knot security was measured in terms of the amount of force which, when appli~d to a loop pos~essing the knot shown in F~g. 17, c~u6es ~he knot to ~lip or the loop to break.
The d~tails of the knot ~ecurity test are as follows:
Each ~uture in the t~t ~et was approximately 7 inches in length. A knotted loop w~ ormed in a test suture in three 8tep5 ~3 tllustratad in Fig. 17. A~ ~hown in Step 1 of Fiq. 17, each ~uture wa~ given a douhle ~hrow (left over right) around a 2c~ diameter cylinder. In Step 2, ~he free ends of the suture were ~et with a single throw ~right over lef~) onto the initial tXrow of Step 1.
Finally, in Step 3, another double throw (left over right3 was ~et onto the single throw o~ Step 2 to co~plete the knot. The free end~ of the ~uture were cut to approximately inch and the loop was carefully ~a~ed from ~he cylinder.
Testing of each loop was carried~out e~ploying a calibrated Instron ~achine operated in a conventional ~anner. For each size suture, up to 20 test samp}e~ were prepared and measured for loop pull ~trength. The test ~5 ' : -' ; r 3 5 ~

results for all of the ~;U~ures in all 8ize6 are ~et forth in Tabl~ V as follows:
Table V: }~not S~curity oS Bioab~orbDble Sutur~s __ 0~~rolt~n Loop ~3) or 13.5 2 13.8 3 16.1 4 1~
13.9 7 1~ a 13.2 9 13.3 B
13.2 1~

11 13.6 B

12 13.2 B

13 14.3 ll 14 13.a 13.6 1~ 14.0 11 17 l~i-3 18 1~i.2 19 14.0 a 13.3 e ~x~ 5~2e ~
G~ ~rok~n LOQP t8j G~pe ot ~h~8 Invention ~e-ding or S~ or Sl~pp6g~
T~ttka? of l~n~ ~52~ISilL
2. 1 S
2 13.1 8 17.4 3 12.5 B 16.8 B
~ 13.9 a ~7.4 a 3.s s 15.3 a 12.13 S 16.Z
7 3.6 S 15.9 8 3 1 S 1?.2 B
9 73 S llS.~, -10 13.5 B 17.5 11 11 13.4 17.0 12 14.5 11 17.6 13 12.8 ~ 16.7 14 9.~ S lr.S

15 13.6 11 lr.5 lo~13.5 ~ 17.1 5 lr 11.8 ~ 14.6 a 1~ ~.0 S 17.6 19 1~.3 ~ 1~.6 1-.. 1 9 18.1 . ' ~

.
, fi ~ J~. ,ri ~, ~3 6--EJ~PIDle 24: Sfze 0 St~rd Suturo S~turo of ~h!~ Ir~rntion c ~ge Drok~n Loop tB) Cff~o a-r~8n Lrop ~B) r~ or 51~pp~o ~dir4 ot Sl~w~ge tkr,) o~ t (C~ _~9L Ot ~
9.6 ~ 11.0 3 2 9.6 ~ 10.~S a 3 4.2 ~; t0.8 10.5 0 3.5 3 8.3 6 5.~ 1.0 8 6.5 5 10.~ B
9 6.4 9.~ ~ 11.0 11 9.2 ~ ~0 5 0 12 5.7 3 1~ ~ -13 6.~ ~ 10.8 C
1~. 6.0 5 10.3 B
5.7 5 lû.~ 5 16 f.2 8 1~.3 1J 4.1 S 10.8 11 18 9.~ 1~ 10.~1 ~
19 ~.1 i; ~.0 3 S.9 S lO.a E~ e 25- S~2~ 2-0 Stu~dard Sutur~ eure o- ~8 Ir~enei~n C~ge 8r*en Lr~p t3) C-~ Brol~ Lr,cp tB) Ro~ir~ or Slfpp 9~ R~iin~ or ~Slipp~
? rtt Itr~t (s~ _~;L rtf ~t ~5? -2.~ s ~ ~.5 2 3.5 S 9.3 3 1.~ S 8.7 ~ $-1 S 8.6 2.~. 5 a.7 6 ~.. 1 S 8.6 7 1.5 S 8.
2.2 5 8.9 ~ ~
9 3.1 s 8.~ B
lo ~ 8.
11 6.0 1~ ~ 2 12 ~ 8 13 2.5 s U 2.f. 5 9 0 D
2.S S 9.3 6 16 S.9 ~ ~.2 1r 2.1 S l~.f. B
1~ 2.1 S 9 1 19 4.4 S 9 1 ~.B 5 9.1 .

., ~ 3 7 ~ G"

s4tur~ of thlr ~rvent~on ~p Orok~n LCAP t3) 6~ 9rok~n LrAP t9) ll~dlr~ or 511~ B~dSr~ or SllW2g~
uf ~t (S) _~L 0- I~not ~S~
1.5 S S.
2 3.~ 5.
3 1.2 S 5.3 2.~ S 5.3 5 3.7 ~ S.O
3.9 ~ 5.0 7 1.2 ~ 5.0 8 ~.. 0 ~ 5.5 1.4 ~ 5 1 10 ,.0 ~ 5 3 11 2.~ .. 8 12 2.~ ~ 6.5 D
13 2.2 5 o.3 14 2.~ S 5.3 3 15 2.9 5 S.3 16 3.2 S ~.. 8 17 3.9 ~ 5.6 B

18 3.7 11 ~ 8 19 2.1 S 5.0 B

20 2.ô S 5.3 ~;~lç 27~ 0 _~tu~brd SUtYr~ _ ~ =~L8 ~eBrok-n Loop ~0)~ rok~n Loop ~a) B~odirgor SlS~oo i~adSr~ or SiSpp~oe ot~not.~S~ ~ ot ~r,o~ lS)_ 2.g ~ 3.
2 1.5 S 3.2 -3 1.9 ~ 3.0 4 2.~ ~ 3,3 ~ :
S 2.Y ~ 3.3 ~ :
6 2.0 : S 3.3 1 7 0.6 S ~.0 11 11 1.0 S 3.3 9 2.6 ~ . 3.3 10 ~.0 ~ 3.5 11 1.4 S 3.ô B
12 0.8 S 3.3 ~ :
13 ~.0 S 3.~ 1~
1~ 2.b 11 2.~ 9 15 2.~ 9 3.3 ~ :
16 1.7 S
17 2.~ ~ 3.3 11 1D 1.8 i 2.8 19 3.0 ~ 3.0 20 2.~ ~ 2.A

3~i EJ~Ple 28~ e 5-0 sssr~brd Suture Ro, 1 ~_ ___ ~turc of thi~ ention 6OoesrOg~en Lsop S3) C~o Srr,k~n Loop ~ rok~n Loop tB) 4INdinoor Sli~geIt--dlr~or Slip4~ r SliW~ge 5 ~ ~illL ~t Ynot ~S) ~8L ot i~no~ ~5) I~? f Itnot (S) 0.5 i 1.0 ~ 2.0 2 0.7 S l.~ ~ 2.2 3 0.~ S 1.6 9 2.2 0-7 ~ 0.5 S 2.2 1.~. S 0.3 S 2.3 6 1.2 S 0.4 s 2.
7 0.7 ~ 0.6 S 2.5 t 2.0 ~ 0.2 ~ 2.3 9 l . S 0.5 ~ 2.
10 0.6 S 1.5 8 2.6 3 1~ 1.4 S 1.3 S 2.6 12 ~ ~ 1.6 S 2.
13 - ~ 1.1 S 2.2 14 - ~- - - 2.~ ~
- - - - 2.5 gl 16 ~ - - - 2.2 17 ~ - ~ - 2.2 18 - - ~ - Z.~ Il 519 ' ' - - 2.5 ~ ~ - - 2.4 ~grd~rd $uturç 11~,_, St~rd~rd juture !lo. ~ Suture o- th~ Ir,vention G~gearokm Loop ~B) C-ge 3-ok n Loop ~0) Ca~e Ird~n Loop ~) Rlt~or Slippr92R~ædin~or Sli~ge ~dingor Sliw~ge _~Lof l~rlo~ tS~ o~ rrC~ ~5 0.7 S 0.1 S 0.8 B
2 0.7 S 0.7 B 1.0 B
3 0.3 S 0.7 1 1.0 B
4 0.8 1~ 0.8 ~ 1.0 9 5 0.2 S 0.9 0 1.0 6 0.~ Il o.a 1l 1.0 a 7 ~ ~ 0.7 11 ~.0 ~1 ~1 . . 0.3 S 1.0 ~ -9 - - 0.~ ~ i.0 1 ~ 1.0 1.0 11 12 - - - - 1.0 il 13 - - - ~ 1.0 B
14 - - - ~ 1.1 a - - - - 1.1 1~ - - - - 1.0 17 - - - - 1.0 1.0 19 ~ - ~ - l.o . , , , o.

.

--3 9-- ~ J ;, f, Ex~le ~0. Ske 7-0 _~ ~ tur~ of th~s Im~ntlon 6-ge BroRen Loop ~3~ ~ Urr~k~n Loop ~B~
ReKiir~or 511pp~2 ~iira r,r Slippr~e hL o~ ~s) ~ t l~ O
0.4 2 0.3 ~ 0.4 B
3 0.~ .3 4 0.4 1~ 0.2 s o.~ s o.~ a 0.3 ~ 0.4 7 0 ~ ~ 0.~ J
03 ~ 0.4 9 Q.4 ~ 0.6 0.3 ~ O.f, 11 U.3 3 0.5 12 0.4 0 0.4 D
13 0.4 S 0.2 B
1~ 0.~ ~ 0.
.3 1l 0.
o.3 s o.6 0.4 a 0 4 1~ 0.2 S 0 4 EL~le 31. 5~2~ ~-0 Suture ot ~his tm~ntioQ
C-~e ~roken Loop lEi~
Re-dir~ or Slipp~oe f ~noS
0~3 B
2 0.3 ~ :
3 0.3 3 4 0.3 11 0.3 6 03 a ti 0.3 9 0.3 B
~.3 ~ :
11 0.3 B
12 0.2 3 13 0.3 B
1$ 0.2 0.
1~ 5.
~7 o.
1~ 0.3 19 0.3 ao 0.3 B

Asthedata for 13xa~pl~s 23~30 fihow, the loop pull strength o~ uture of thi8~ invention wa8 GOn81~ilkently .

1 higher for all sizes o~ suture than that of the comparably sized ~tandard ~utures. ~oreover, only in relatively few cases did slippage o~ ~he knot occur prior to loop breakage where the ~utures of thi~ invention ~re concerned whereas slippage was a frequent occurrsnce in ~he case of ~he standard suture For ~ given sze o~ bioab20r~able suture in accordance with th~ 3 i~vention, prsferr~d av~r~ge minimum loop pull force values at ~reak in kg ~re as ~et ~orth in Table VI b~low:
VI: Preferred Average ~1nimum Loop 2ull Values ~or th~ Bioab~orbable cutures o~ thi~-~nve~l~n --Preferred Suture Minimum Loop __~L~ ull Fo~e ~ka) 0 ~0 4-0 l.5 7-0 0.4 8-0 0.25 This example i6 illustrative of a 6ize 2~0 braided glycolide-lactide copoly~er ~uture sf this invention ~illed with a wound healing enhancing a~ount of an ~GF- and ci~rrier/storage stabiliz$ng agent-con~aining filling compo6ition.
A ~olution of glycerol t278 g~), calcium lactate (43 gm) and sterile water (370 g~ prapared. ~man Growth Fac~or HEGF-51 (152.6 ~g) ~reativ~ Biomolocules, Inc., Hopk~nton, MA) was di3sol~ed vol~etrically to 25 ml wit~ the ~bove solution to provide a braided ~uture ~illing composition. The composition was plac~d in ~he ~yringe pump of a suture co~ting apparatus. The syringe pump was ~et to provide the filling compo~ition at a constant r~te ~nd the suture ~peed was adjusted to apply 17ml o~ filling composition to 200 meters of braid. The tsrget concentration of HGF on ~he br~id i~ 0.52 mg h~GF/meter or approximately 1.8 ~g hEGF/gram:of braid. A~ter filling, the braid was immediately pa~sed through a 50 drying column.
After fi}ling, the ~pool2d braid wa~ removed to a small chamber ~nd ~tored under a ~lowing dry nitrogen atmosphere to remove the water from the ~olution.
* * *
While the foregoing descri~tion contain~ many ~pecifics, these specific~ ~hould not~b¢ con~trued as limitations on the ~cope of ~he invention, ~ut ~rely ~s ~xemplification5 of preferred ~bodi~ents ~her@of. ~hose skilled in the art vill envi~ion ~i~ny other po~ible variations th~t are ~ithin the acope and ~pirit of the inv~ntion as de~ined by th~ ~cco~p~nying olai~6.

Claims (20)

1. A braided suture of improved construction possessing a greater pick count and/or a greater number of sheath yarns for a suture of given overall denier than the pick count and/or number of sheath yarns of a standard braided suture of substantially the same overall denier.

2. A braided suture exhibiting reduced tissue drag compared with the tissue drag of a standard suture of substantially equivalent size.

3. The braided suture of Claims 1 or 2 characterized in that, for a given overall suture denier, the range of pick count, number of sheath yarns and denier of individual filaments comprising a sheath yarn for a given size of braided suture are related to each other as follows.

4. The braided suture of Claims 1 or 2 characterized in that, for a given overall suture denier, the range of pick count, number of sheath yarns and denier of individual filaments comprising a sheath yarn for given size of braided suture are related to each other as follows:

5. The braided suture of any of Claims 1 to 4 characterized in that the suture further possesses a core.

6. The braided suture of Claim 5 characterized in that the overall suture denier and core denier are related to each other as follows:

7. The braided suture of Claim 6 characterized in that the overall suture denier and core denier are related to each other as follows:

8. The braided suture of any of Claims 1 to 7 characterized in that the braided suture is fabricated from a non-absorbable material.

9. The braided suture of Claim 8 characterized in that the non-absorbable material is cotton, silk, polyamide or polyolefin.

10. The braided suture of any of Claims 1 to 7 characterized in that the individual filaments of the braided suture are fabricated from a bio-absorbable polymer.

11. The braided suture of Claim 10 characterized in that the individual filaments of the braided suture are fabricated from a polymer derived at least in part from one or more monomers selected from the group consisting of glycolic acid, glycolide, lactic acid and lactide.

12. The braided suture of Claims 10 or 11 characterized in that the suture is fabricated from a material which is susceptible to hydrolysis, the suture being filled with a filling composition comprising at least one water soluble, liquid polyhydroxy compound and/or ester thereof,

13. The braided suture of Claim 12 characterized in that the water soluble, liquid polyhydroxy compound is glycerol.

14. The braided suture of Claim 12 characterized in that the water soluble, liquid polyhydroxy compound and/or ester thereof is admixed with a thickener.

15. The braided suture of Claim 14 characterized in that the thickener is a saturated aliphatic hydroxycarboxylic acid or salt of the general formula wherein R is hydrogen or a methyl group, R' is hydrogen or a metal selected from the group consisting of alkali metal and alkaline earth metal and n is 0 or 1, and hydrates thereof.

16. The braided suture of Claim 15 characterized in that the saturated aliphatic hydroxycarboxylic acid salt is calcium lactate.

17. The braided suture of any of Claims 1 to 18 characterized in that the braided suture is surface-coated with a composition enhancing one or more functional properties of the suture.

18. The braided suture of Claim 19 characterized in that the composition is a bio-absorbable coating composition obtained by copolymerizing a polyether glycol with a mixture of lactide monomer and glycolide monomer or a preformed copolymer of lactide and glycolide.

19. The braided suture of any of Claims 1 to 20 characterized in that the suture contains at least one medico-surgically useful substance.

20. The braided suture of Claim 12 characterized in that the filling composition includes at least one Human Growth Factor.