CA2046095A1 - Packaged synthetic absorbable surgical elements - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

Synthetic absorbable sutures are filled with a stabilizing agent, preferably a mixture of glycerol and calcium lactate, and inserted into a retainer having a narrow convoluted passageway. The retainer is inserted into an open foil pouch with a package stabilizing element, such as a paper sheet filled with stabilizing agent. The package containing the suture, retainer and package stabilizing element is sterilized, aerated, equilibrated to a relatively high moisture level, and sealed. Long lengths of suture and doubled-over and tripled-over suture may be withdrawn from the retainer with low force without damaging the suture. Bends and kinks in the suture are prevented so as to provide a snythetic absorbable suture having highly desirable out of package hand and feel.

Description

I'ECHNICAI, FIELD

The pre~ent invention relate~ to packaging of ~ynthetic absorbable ~urgLcal elements and, more particularly, to an improved package and method of providing packaged syntbetic absorbable ~utu~es having improved out of package handling characteristic~.

BACKGROUND AND OBJECTS OF THE INVENTION

This invention relates to a packaged 0ynthetic absorbable suture having improved out of package handling characteri~tics and to a method of packaging polymeric article~ having an inherent tendency to ~nderga degradation when expoaed to water or a humid atmo~phere, probably as a result of hydroly~is. More particularly, the invention i~ directed to improving the out of package flexibility and hand of synthetic absorbable sutures and to the packaging of articles and devices such a~ absorbable surgical sutures, clips, staple~, implants, prosthe es and the like, fabricated from polymer~ which are susceptible to hydrolytic degradation, notably, polymers and copolymers of glycolic acid (i.e., hydroxyacetic acid)/ the cyclic dimer of glycolic acid ("glycolide"), lactic acid, the cyclic dimer of lactic acid (nlactide") and related monomers, polydioxanone, polytrim0thylene carbonate, polyalkylene glycol, polycaprolactona, their copolymers, etc. Polymerc and copolymer0 of the foregoing kind and ab~orbable ~urgical devices made therefrom are well known. See, e.g., U.S. patent No~. 2,668,162; 2,703,316; 2,7S~3,987;

3,225,766; 3,297,033; 3,422,181; 3,531,561; 3,565,869; 3,620,218; 3,626,948;
3,636,956, 3,736,646; 3,772,420; 3,773,919; 3,792,010; 3,797,499; 3,~39,297;
3,867,190; 3,878,284; 3,982,543; 4,060,089; 4,137,921; 4,157,437; 4,234,~75;
4,237,920; 4,300,565; and 4,523,591; U.K. Patent No. 779,291; D. R. Gilding et al., ~siodegradable polymers for uae inaurgery -- polyglycolic/poly(lactic acid) homo- and co-polymers: 1, Poly~, Volume 20, page~ 1459-1464 (1979), and D.F. Williams (ed.), Biocom3atibilitv of Clinical rm~lan-t Materials, Vol.
II, ch. 9: "Biodegradable Polymers" l1981). The biodegradability of theae polymera/copolymers is believed to be due to the hydrolytic attack of their e~ter linkages by agueous body fluid~ although the exact mechanism involved has been a matter of sp~culation. The present invention also extends to other ~urgical articles such aa suturea baaed in whole or in part on a polyester polymer or copolymer such as polyglyaolic acid, lactide-glycolide copolymer, polydioxanone, polytrimethylene carbonate, polyalkylene glycol, polycaprolactone, their copolymerA, etc.

Numerous patents, including United States Patent~ 3,636,956;
3,728,839; 3,839,297; and 4,135,622 teach that synthetic absorbable surgical element~, particularly sutures, must be packaged and maintained under extremely dry conditions in order to be storage stable. Indeed, the preferred packaging and storage conditions de~cribed in the foregoing patenta and used for commercialiy available ~ynthetic absorbable sutures have a moisture level at or less than about 0.05~ by weight of the suture, and preferably no more than about 0002~. According to the patents, such conditions are attained by heating the ~uture and package to a high temp~rature under vacuum immediately prior to sealing, ~uch a~ by heating to 180-188F for 1 hour under a 26 inch vacuum. United States Patent~ 4,412,617 and 4,519,501 are consiatent. The latter patents disclose a package for synthetic absorbable ligating clip~

packaged under the aforementioned extremely dry conditions and further including a pre-dried paper de~icant. In addition, synthetic absorbable staplea and clip~ made primarily of lactide have been available for ~everal year~ from United 5tates Surgical Corporation, Norwalk, CT. Such clip~ and staple3 are not as ~usceptible to hydroly~is as other commercial}y available absorbable ~urgical materiala, and are not packaged under the very dry conditions deacribed in any of the foregoLn~ U.S. Patents, but rather are packaged in foil envelope3 including a de~sicant, such as a silica pouch.
United States Patent 3,382,141 disclose~ a des~icant paper.

Synthetic absorbable ~utures typically are packaged in moisture impervious foil lamlnate envelopes with the suture wound in a so-called "figure 8" pattern on a paper card retainer. Typical retainer~ are sho~n in United States Patent 4,249,656 entitled "Suture Packagen; United States Patent 4,253,563 entitled "Multistrand Suture Packagen; and United States Patent 4,063,638 entitled "Direct Dispen~ing Packaging of Surgical Sutures." Longer lengths of ~uch sutures or ligatures are sold on a ~uture reel, such a~
disclo~ed in United States Patents 3,648,949 and 3,749,238. Unfortunately, heretofore known synthetic abaorbable 3utures packaged under very dry conditions are relatLvely stiff and Lnflexible. Such sutures typically exhibit "memory" wh~ah cause~ the ~uture to retain and have a tendency to re~ume the figure 8 or coiled shape a~sumed by the packaged suture. The fiyure 8 configuration haa alao been found to introduce undesirable kinks and bend~ in the auture. The~e e~fects are highly undesirable since the suture muat be ~traightened prlor to u~e, and does not exhibit particularly good "feel" or ~hand" characteristics important to the end user.

Molded 3uture packages having convoluted passagaway~ ara al~o known.
By way of example, Unlted States Patent 3,338,401 entitled "Molded suture PacXage" and United Stata~ Patent 3,490,192 entitled "Method of Packaging Sutura3" disclose a molded suture package wherein one or more elongated utura3 are contained in a coiled narrow pas~ageway having a plurality of convolution3. The foregoing patente teach that the ~uture may be drawn into the paqsageway by vacuum. The convoluted pa~aagoway desirably eliminates the introduction of kinka and bends to the suture but, despite the de~irable characteri~tics of molded suture packages, such package~ have not been adopted for use in packaging synthetic absorbable sutures. It is speculated that the extremely dry conditions raquLred for packaging prior synthetLc absorbable suturea, together witb the suture memory effect such very dry packaging condition3 create, may combine to make it impossible to withdraw prior synthetic absorbable sutures from a molded ~uture package without breaking tha suture.

Therefore, it would be highly desirable to provide a packaged synthetic ab~orbable auture having superior flexibility, "hand" and "feal~' when removed from the package.

SUMM~RY OF T~E INVENTION

The present invention provides a sterile packaged synthetic ab~orbable suture filled with a ~tabil~zing agent, preferably a mixture of glycerol and calcium lactate, pac~aged in ~ suture retainer disposed within a subatantially moi~ture impervious foil pouch. The preferred retainer is a molded retainer having at lea~t one convoluted pa~aageway, with one or more ~uturas di~posed in the pa~ageway. The preferred pouch is a peelable foil pouch. The preferred suture is a braided suture made from a glycolide-lactide copolymer having a particular braid configuration and filled with a ~tablizing agent such as glycerol. In the preferred embodiment the stabilizing agent further includes a thickener, such as calcium lactate. Contrary to prior practice, the ~terile ~ynthetic absorbable ~uture~ prepared and packa~ed in acco~dance with the invention need not be packaged under the e~tremely dry condition~
required by prior packaged ~ynthetic absorbable sutures, and are preferabiy packaged having a moisturs level above about 0.2~ by weight of the fLlled, braided suture. It is further preferred that the moLsture level be above about 0.5% by weight of the suture. Indeed, the very dry packaging conditions of prior synthetic absorbable sutures would be deleterious to the packaged sutures of the present invention. The preferred package further includes a package stabilizing element for maintaining the moisture level within the package and suture within a very clo~e range of its initial, relatively high, level and for preventing migration of the suture filling to surrounding package materi~lsO Uniformity of the moisture level and ~uture filling contributes to con3i~tent force to withdraw the suture from the package, and to the highly de~irable out of package handling characteriatics of filled braided ~utures. By way of example only, the package stabilizing element may consist of a sheet of paper filled with the ~ame stabilizing agent used to fill the suture~.

The braided filled synthetic ab30rbable ~uture packaged in accordance with the invention ra~i~ts kinks and bends introduced by prior packaging conditions and mater~als ao a~ to provide a synthetic ab~orbable ~uture having remarkable handling characteri~tic~, ~.e. "hand~ and "feeln, upon removal of the suture from the package. Indeed, the pseferred braided filled synthetic absorbable suture~ packaged in accordance with the invention have favorable out of package vertical hanging length, bending length and Gurley stiffness charactexi3tics. That i3, upon removal from the package the ~utures have a straight vertical hanging length of about 80~ of their straightened lenyth, a bendlng length of ahout 3.0 and a Gurley stiffness le~s than about 5Ø In qualitative terms, the packaged synthetic absorbable ~utures in accordance with the pre~ent invention have remarkable out of package hand and feel comparable to commercially available braided silk suture~. Such handling characteristics for braided synthetic ab~orbable sutures are unheard of and simply amazing. ~ -In accordance with the method of the present invention, syntheticabsorbable sutures filled with a stabilizing agent, such as a mixture of glycerol and calcium lactate, are loaded into a retainer which is then placed in an open foil pouch, steril1zed, equilibrated and sealed. Preferably, the sutures are braided ~utures compo0ed primarily of glycolide, such as a copolymer of about 90~ glycollde and 10% lactide. The preferred r tainer is a molded retainer having at lea~t one convoluted pas~age, with the ~uture being drawn into the molded passaseway under vacuum 10av1ng one end of the suture, which may be needled or non-needled, protruding from the pas~ageway. The auture and retainer are placed into an open foil laminate envelope, which is preferably a peelable foil pouch. In a further embodiment of the invention, a package stabilizing element, which may consist of a paper sheet filled with the same stabiliz~ng agent used to fill the ~utures, L~ also inserted into the foil laminate envelope. The ~uture in the unsealed foil laminate envelope is ~terilized, ~uch as by treatment in an ethylene oxide ga~ sterilization cycle with subsequent aeration to remove re~idual ethylene oxide, all in a known manner. The sterile surgical elements are then equilibrated, such a~ in a dew ~ ~3 ~

point controlled environment, until the de~ired moisture level i~ attained.
The moisture level should be far above the very dry condition~ under which commercially available ~ynthetic ab30rbable ~uture0 have heretofore been packaged, since ~uch very dry condition3 are deleterious to the filled braided 3uture~. The moL~ture level ~hould exceed about 0.2~ by weight of the ~uture and i3 preferably above about .5~. ~he equilibrated ~uture package i3 then sealed and placsd Lnto inventory. The suture L~ ramoved from the paokage by opening the foil pouch, such aa by peeling open the preferred peelable pouch, gra~ping the end of the suture protruding from the passageway, and withdrawing the suture from the retainer. In the caae of the preferred molded retainer, withdrawing the ~uture by pulling the ~uture through the convoluted pa3sageway ha~ the desirable effect of flexing the suture, further improving the out of package characteristics of the ~uture.

The preferred braided filled suture packaged in accordance with the invention results in a packaged synthetic absorbable ~uture having amazing flexibility and ~ùppleness upon removal rom the package. As stated, the filled sutures advantageously are packaged at a relatively high moi~ture level, higher than could be tolerated by prior synthetic ab30rbable sutures.
The relatively high moisture level simplifie~ manufacturing proce~es and permits use of a molded retainer to a~ure that the suture i~ and remaina free from kinXs and bends introduced by prior packaging techniques. The high moi3ture level and molded retainer contribute to the ease with which the filled ~uture may be withdrawn from the ~uture package and the deairable out of package characteristic~ of~auch suture~. The package 3tabilizing element maintains the moi~ture level in the envelope wlthin a pre3et range and prevents undue change, whether increased or decrea~ed, thereby contributing to the stability of the filling compo~ition and consistant force to remove the 2 ~ ~ 6 ~ ~ ~

filled ~uture from the molded ~uture retainer. It haa al80 been found that the suture of the invention may be impregnated with one or more medico-surgically useful substances, such as therapeutic agents or Human Growth Factors. Advantageously, it has been found that the preferred filling compo3ition i~ an appropriate carrier for ~uman Growth Factor~ and that ~uman Growth Factor3 impregnated into the auture in the fi~lLng composition remain actlve even after sterili2ation.

The present invention provide~ a packaged synthetic abaorbable suture having improved handlinq characteristics which need not be packaged under extremely dry conditions and which may advantagously be packaged in a molded suture retainer. The braided, filled suture packaged in accordance with the invention consistently provides heretofore unknown convenience in removal of the suture from the package asd the suture, as removed from the package, exhibitY amazing flexibility and supplenes~ without undesirable bends, kink~
or memory effect3 commonly as30ciated with prior packaged synthetic absorbable sutures.

It will be under~tood that the foregoing general description and the following detailed de~cription as well are exemplary and explanatory of the invention but are not restrictive thereof.

The tPrm ~filled" a~ used herein refera to the assoclation of the polymeric articl0 with a storage stabilizing amount of atorage ~tabilizing agent, whether this as~ociation be one in which the 3torage stabilizing agent Ls ab30rbsd by the polymeric article, ia pre~ent on the surfaces thereof or i9 a combination of the two.

The term "~tabilizing agent~ as used herein refer~ to a material which, when associated, ~uch as by filling, with a polymeric article ~usceptible to hydrolysi~, improve~ the storage ~tability of the polymeric article and eliminates any need to store the article in an artificially-maintained very dry environment.

The term npackage stabilizing element" a~ u~ed herein refers to a material which maintalns the stabilizing ag2nt ~olvent level within a ~ealed package against any substantial increase or decrease, and ~pecifically include~ but is not limited to a mas0 of stabilizing agent within the package separate and apart from a filled polymeric article. ln the context of the preferred embodiment of the invention water ia the stabilizing agent ~olvent, and the pacXage stabilizing element will hereinafter be discussed in the context of water based sy0tema, but should not be con~trued to be limited thereto.

The term "braid" or "braided" as applied to the ~uture of thi~
invention refers to an arrangement of discrete units, or bundles, denominated "sheath yarns~, made up of individual filament~ with individual sheath yarns interlocking or interlacing each other in a regular cris~-cro~s pattern.
Although preferred braid structures are disclosed and di~cussed herein, the terms "braid" or "braided" as used herein should not be considered to be limited to such structuxes, and include~ other braid structure~, whether or not including a cors, and spiroid braids.

The term "pick count" refer~ to the number of cros~over~ of ~hea`h yarns per linear inch of suture and, together with the overall denier of the suture, the denier of the individual filamant~ constituting a sheath yarn and the number of ~heath yarn~ employed, define~ tha principal con~truction characteri~tics of the preferred braided auture herein.

The term "~tandard ~uture" i~ intended to deaignate any of the heretofore known braided ~uture~, e.g., those de3cribed in U.S. Patent No.

3,565,077, and in particular, braided ~uture product~ rnarketed by Ethicon, Inc. under it~ Vicryl brand and tho~e marketed by DaYi~ & Geck, Inc. (American Cyanamid Co.) under its Dexon brand.

BRIEF DESCRIPTION OF THE DRAWINGS

The aocompanying drawings, referred to herein and constituting a part hereof, illustrate the preferred embodiment~ of the product and method of the pre~ent invention, and together with the description ~erve to explain the principle~ of the invention, in which:

Fig. 1 is a plan v~ew of a flrst ~uture retainer embodiment;
., .

Fig. 2 is a cros~-section view of the retair.er of Fig. 1 taken along lines 2-2;

Fig. 3 ia a plan view of a cover ~heet for the suture retainers of Fig~ 2 and 4-7;

Fig. 4 i~ a plan vie~w of a ~econd suture retainer embodiment;

~6~

Fig. 5 i~ a cross-3ection view of the retainer of Fig. 4 taken along line 5-5 of Fig. 4;

Fig. 6 i~ a plan vi8w of a third cuture retainer embodiment;

Fig. 7 is a cros~-section view of the retainer of Fig. 6 taken along lines 7-7 of Fig. 6;

Fig. 8 is an illustration of a tripled-over suture;

Figs. 9 and 10 are plan views of an alternative suture retainer in the fully unfolded and fully folded conditions, re~pectively;

Fig. 11 is a plan view of the pref~rred peelable pouch in a closed po~ition~

Fig. 12 is a plan view of a partially open peelable pouch;
, ~

Fig. 13 iY a perspsctive view of the preferred package stabilizing alement;

Fig. 14 is a plan view of a retainer and package stabilizing element;

..
FLg. lS is a cro~ ection view of the retainer of Fig. 14 taken along line~ 15-15 of Fig. 14;

Fig. 16 Ls a partial perapective section view of the retainer and package stabilizing element of Fig. 14;

Fig. 17 la a graph illustrating force to remove suture~ of various lengths from the preferred molded retainer; and Fig. 18 iB a diagram of a ~uture mounted for heart loop te~ting.

DETAILED DESC~IPTION OF THB PREFERRED FMBODI~ENTS

The preferred embodiment of the invention i~ directed to a package and method for braided synthetic ab~orbable auturea whlch results in a packaged synthetic ab~orbable suture having very desirable out of package handling characteri~tics. The preerred package i8 a peelable foil hou3ing a retainer, preEerably a molded retainer having at least one narrow convoluted pa~sageway, containing at least one braided ~ynthetic absorbable ~uture filled with an appropriate atabilizing agent. As described in greater detail below, the preferred ~tabilizing agent ls glycerol containing a thickener, 3uch a~
calcium lactate. The presence of the ~tabilizing agent permits the ~uture to be packaged at a relatively high moisture level, which eliminates any need for extreme mea~ures to enaure very dry conditions in the package. The combined effecta of the stabilizing agent and high moi~ture level advantageously permit the suture to b~ packaged ~n and removable from a molded ~uture retainer in order to preserve the desirable hand and feel of the filled suture. The preferred embodiment further includes a package stabilizLng element, such as a paper aheet fLlled with stabilizin~ agent, for maintaining the moisture level : .:.. i~ ,.. .. .

within the pac~age and preventing migration of the stabilizing agent from the ~uture to surrounding package materials. ~alntaining the moisture level within a close range also a~sures uniform force to withdraw the suture from the retainer. The braided, filled sutur2, a~ remov2d from the package, exhibita very desirable handling characteristics which may be expres~ed in terms of out of package hanging length, bending length and Gurley stiffness.

Referring now to Fig. 1, there is ~hown a plan view o~ a molded suture retainer lO in accordance with the invention. The molcled ~uture retainer illuatrated in Fig. l find particular application for holding full lPngth single suture~ up to about thirty inch~s in length. As shown, retainer 10 has a base 12 and an enlarged 0uture receiving section 14 leading to a convoluted narrow pas~ageway 16. The convoluted narrow passageway follows a spiral oval pattern through several turns and tarminates at a central vacuum receiving aection 18. Fig. 2 i~ a cross-aectlon view of the retainer ~hown in Fig. 1 taken along line3 2-2 of Fig. 1, illustrating base 12 with molded passageway 16 extending from the ba3e. Preferably, base 12 is approximately 3.355 inches ~85.217 milllmeters) by 1.375 inche~ (34.925 millimeters) in order to conform to commonly accepted overall dimenaion~ of conventional suture packages and display boxe Of courae, these dimensions require several convolutions of the narrow paasageway in order to accomodate any appreciable suture length.
It is believed that the number of curved sur~ace3 created by such convolutions may be a contributing cau~e to the prior inability to package synthetic absorbable suture~ in a molded su~uxe package having convoluted pas~agways.
That ia, the ~uture w~apped around the curved surfaces of the convolutions create3 a cap~tan effect which i8 exacerbated by the very dry package condition~ ~uch pr~or sutureq require. The retainer of Figs. 1 and 2 may be moldcd 80 that the convoluted pa~aageway ha~ a depth of approximately .070 ~' ' inche~ (1.778 millimeter~) and a width of approximately .047 inche~ ~1.194 ~illimeter~). Preferably, the molded ~uture retainer i8 made from polyethylen2 teraphthalate (PETG), such as Eastman Kodak 6763.

Referring now to Fig. 3, there is shown an appropriat~ cover sheet 20 for the retainer shown in Fig~. 1 and 2. Cover she~t 20 i~ configured and dimen~ioned to ovarlie the open top of the retainer, and i~ provided with a vacuum aperture 22 and a ~uture entrance aperture 2~. Cover sheet 20 i8 adheaively attached to the molded retainer and covers the convoluted pass~geway. Vacuum aperture 22 aligns and communicates with central vacuum receiving ~ection 18 of the molded retainer. Similarly, suture entrance aperture 24 aligns and communicates with enlarged ~uture receiving section 14. Preferably, cover sheet 20 i3 constructed of a material which L3 parvious to ethylene oxide sterilizing gas and which does not have a high affinity for ~utura filling material~ such aB glycerol. The preferred material is a ~pun bonded polyolefin, 3uch a3 Tyvek 1073B available from E.I.
DuPont de Nemour~ ~ Co. As stated, the cover sheet i~ adhesively attached to the molded retainer. In the preferred embodiment the cover sheet is adhered to the retainer with a hot melt adhesive, such as Oliver 18B adhesive coating available from Oliver Product~ of Minneapolis, Minne30ta. While not believed to be critical to the present invention, other combinations of cover 3heet and adhesive have been found ineffective for various rea~ons, such as failure of the adhe~ive to hold after sterilization. As ~hown, cover sheet 20 preferably includes ~ fold-over panal 26 joined to the main ~ection of the cover 0heet at a perforate acore llne 28 with openLng3 30. The cover ~heet al~o preferably ha~ a foam needle park 32 for holding a needle in place. In Fig. 3 convoluted passageway 16 is shown in phantom to lllustrate the relation~hip of the cover ~heet to the molded retainer.

- ..... ... .. . .

A~ a practical matter, it becomes difficult to fonm a pa3~ageway in excea~ of thirty inchea in the ~urface area permitted by commonly accepted ~uture package dimen~iona. Even if ~uch a retainer can reliably be fonmed, the inner ~piral develop~ a very tight radiu~ which increase~ the capstan effect, and, con3equently, the force to withdraw longer length suture~ from the retaLner. Therefore, it i~ contemplated that, ln order to provide optimum ~uture pull out force, it may be desirable to package in full length configuration only ~utureR having lengths les~ than thirty and preferably les~
than about twenty ~even inches. It i~ al~o contemplated that multiple lengths may be packaged in o~e retainer, and that longer length~ of ~uture~ may be packaged doubled or tripled over ~o a~ to obtain a ~horter overall eFfective suture length to be withdrawn from the retainer. In the ca~e of the latter mulkiply packed or doubled or tripled over ~uture~, modified retainers are contemplated.

Referring now to Fig~. 4 and 5, there i~ shown a first alternative retainer configured and dimen~ioned to receive and hold multiple full length suture~. Referring to Fig. 4, the retainer 110 ha~ a base 112 having an overall length of approximately 3.355 inche~ ~85.217 millimeters~ and a width of approximately 1.375 inche~ (34.925 millimeter~). Ba~e 112 has an enlarged suture receiving sectlon 114, a convoluted narrow pa~ageway 116, and a central vacuum receiving section 118. The cover ~heet 20 illuctrated in Fig.
3 may be adhered to retainer 110 in the ~ame manner a~ de~cribed with respect to rfftainer 10. Referring to Fig. 5, a cro~ ection viaw of retainer 110 along line~ 5-5 of Fig. 4, narrow passageway 116 preferably ia molded to have a depth o~ appro~imately .100 inche~ ~2.540 millimetar~) and a width of approximately .078 inche~ (1.984 millimeter~). The retainer of Fig~. 4 and 5 i8 particularly suited for receiving and holding as many a~ about five full langth quture 3trands up to about twenty seven or thirty lnches in length.
Preferably, the suture ~trand~ are simultaneou~ly loaded into the retainer.

In a ssaond alternative embodiment illustrated in Fig~ 6 and 7, a much wider paasageway having fewer aonvolutlons is provided. The retainer 210 has a base 212 which is ~ubstantially the ~ame aize as the aforementLoned retainers, approximately 3.350 inches (85.09 millimeters) by 1.3~5 inches (34.925 millimeters). Passageway 216 i~ ~ubstantially wider than prior embodiment3, and preferably is about .060 inches (1.524 millimeter3) deep and .200 inche~ (5.080 millimeters) wide (~ee Fig. 7). Passageway 216 communicates with an enlarged suture receiving ~ection 214 and a central vacuum receiving section 218. As in the prior embQdiments, cover sheet 20 (see Fig. 3) is attached to retainer 210 by a hot melt adhe~ive such that vacuum aperture 22 aligns with vacuum receiving section 218 and suture entrance aperture 24 align~ with enlarged ~uturs receiving ~ection 214.
Retainer 210 is well auited for packaging doubled over sutures, such as double armed suture~, and is preferred for longer lengtha of ~uture, i.e. in exces~
of thirty inches, packaged in a tripled over configuration.

Referring to Fig. a, in order to load a tripled over suture into the retainer of Fig3~ 6 and 7, a 3uture 34, 3uch a3 a ~uture which exceed~ thirty or ev2n thirty six inche~ in length, i3 loopad to form a first curved portion or half loop 36 di~tal to tha needle 38 and a second aurved portion or half loop 40 ad~acant the n~edle. A suture tail end 42 extends beyond thf first half loop 36, preferably by at least about one inch. With vacuum applied to the retainer, 3uch as by placing a vacuum block over vacuum apertura 22 tsee Fig. 3), ~uture tail end 42 and then fir~t half loop 36 are sequentially inserted through ~uture entrance aperture 24 into pa~ageway 216, while holding the 3uture adjacent the needle and the second loop. The suture i~
drawn into the retainer by vacuum until the needle i~ disposed adjacent suture aperture 24 and may be mounted in needle parX 32. It i~ important that suture tail end 42 extend beyond the first half loop at all timea 80 that a Xnot i~
not inadvertently formed in the suture during Lnsertion or removal from the retainer.

As in the ca~e of the first molded retainer embodiment, the retainers ~hown in Figs. 4 through 7 may be molded of polyethylene teraphthalate, (PET
such as 3astman Rodak 6763. In all ca3es, the retainer~ should be about .010 inches ~.254 millimeters) thick.

Although not preferred, it is contemplated that other type3 of suture retainer3 could be u~sd in packaging the preferred braided filled ~utures to obtain improved out of package handling characteri3tic~, although not necessarily as remarkable as the results obtained with the molded retainer.
By way of example only, a suitable four panel suture retainer card is shown in Figs. 9-10. Fig. 9 illustrates a fully unfolded surgical suture retainer card member 300 which can also be u3ed in the package of thi~ invention and Fig. 10 illustrate~ retainer 300 in the fully folded condition which it assumes when loaded and ready to be in~erted within the pocket of the foil pouch.

Retainer member 300 i8 made up of four panels, namely, needle retainlng panel 302, front cover panel 304, ~uture winding panel 306 twhich al30 functions a~ the rear panel of the fully folded retainer) and fold-over panel 308. Retainer member 300 iB preferably formed from a ~ingle sheet of suitable material, e.g., stiff paper or paperboard such as 5 point to 12 point solid, bleached sulfate board, pla~tics, foila, laminates, and the like, which is die cut to provide the desired configuratlon. The panela are joined to each o~her along perforate, or score, linea 310, 312 and 314 which facilitate their folding and central gu~et aections 312a and 312b provide a ~pace or clearance between panel~ 304 and 306. Die cut 316 cooperates with die cut 318 to provide a anap-lock feature which maintaina the retainer in the fully folded condltion. Rounded indentations 320, 322 and 324 serve to prevant the suture from becoming caught between the panel~ when folded.

~ o load needle 326 with its attachsd suture (not visible) into retainer 300, the retainer is firat ~ecured in place by meana of loading pins (not ~hown) which project through openinga 328 in panel 306. The point of needle 326 is then inserted in die cut 330 wh$ch ia ahaped somewhat like a reveraed "S" by threading the point under the upper, and then over the lower, half of the reversed "S~ cut and then behind panel 302 ~o that the needle ahank and tip are on oppoaite aidea of panel 302. Slight tension i~
maintained on the suture from thia 0tage of the loading procedure to the con31usion of the procedure to ensure that needle 326 will maintain its placement in die cut 330 aa previoualy de~cribed. The ahank of needle 326 is then threaded through one of teardrop-ahaped cutouts 332 or 332', cutout 332 being used for smaller needles (as shown in Fig. 10) and cutout 332' being used for larger needle~. After panel 302 has ~0en folded over onto panel 304, the suture 1~ wound in a figure "8" pattern around the loading pins projecting through opening~ 328 in panel 306. Retainer 300, now loaded with needle 326 and the attached 0uture, i~ relea~ed from the loading pins, panel 308 18 folded over on panel 306 and the partly folded-over ~tructure i~ given a final folding along perforate line 312 and guaaets 312a and 312b. Finally, a slight counter-directional movement of the upper section of the retainer against its 2 ~ 3 ~ ~

lower section set~ the aforementioned snap-lock in place providing the fully aa~embled, loaded retainer of Fig. 10.

A11 of the retainers illu~trated in Fig~ 7, 9 and 10 are preferably packaged ln a pealable foil laminate pouch. The preferred peelable pouch i8 shown in Fig~. 11 and 12. Fig. 11 i~ a top plan vlew of the pre~erred peelable pouch in the clo~ed po~ition, and Fig. 12 illustrate~ the pouch partially peeled open. The peelable pouch 44 has a top layer comprised of fir3t and second top panel3 46, 48, respectively. The firat and second top panel3 are adhered to each other tran3ver~ely acro3~ the pouch, leaving a gripping tab 50. The top panels are adhered to a bottom panel 52 at a peripheral seal 54, i.e. at the tran~verse and longitudinal edge~ of the pouch or envelope, so as to defLne a pocket for receiving a suture retaLner. A3 ~hown in Fig. 12, first top panel 46 does not extend the full length of bottom panel 52, but terminate~ at a fir3t top panel tran3verse edge 56. Upon peeling the pouch open, needle 38 i~ seen protruding from ~uture aperture 14 in cover sheet 20 and i3 held in position by needle park 32. The needle is plainly vi3ible and acce3~ible for remova} of the auture from pas~ageway 16 (shown in phantom~ in the retainer. Preferably, fold over panel 26 is adhered to second top panel 48, ~o that upon opening the peelable pouch the needle i3 revealed and acce33ible. Top panels 46, 48 and bottom panel 52 may be con~tructed of a foil laminate material with a hot melt adhesive on the inner surface of each panel for forming peripheral seal 54 and the seal between the o~erlapping first and second top layer panel~. The foregoing peelable pouch ls preferred, but it will bo understood that othar type~ o~ envelopea, auch as conventional tearable foil lamlnate envelope~, can be u~ed. See, for example, United States Patent~ 3,939,969 and 4,014,433. It is contemplated that the 3uture could be ~terili~ed by ethylene oxide permeating through an opening in t~

the peelable pouch which i8 subsequently ~ealed, and that the peelable pouch itself ~hould be ~terilized and maintained ~terile in an outer breather pouch in a known manner. See, for example, United States Patents 3,815,315 and 4,603,538.

The suture can be monofilament or braided, and preferably i~ a braided suture made from a copolymer fabricated from any suitable bioab00rbable polymer. The polymer may be derived at least in part from glycolic acid, glycolide, lactic acid or lactide, and preferably ia a copolymer of about 90%
mol. weight glycolide and 10~ mol. weight lactide. The preferred braided suture is constructed in accordance with United ~tates Patent S,019,093.

In contrast to the methods described in U.S. patents 3,635,956;
3,728,839; 3,839,297; and 4,135,622 for achieving storage stability of packaged 3ynthetic ab~orbable sutures, i.e. heating the auture and package under vacuum, the preferred method for improving the storage stability of a polymeric article usceptible to hydrolysi~ comprises applying a 3torage ~tablIizing amount of at lea~t one water soluble hygroscopic polyhydroxy compound or ester thereof to the polymeric article a~ a ~torage ~tabilizing agent therefor. Such method does not require the article to be subjected to extreme drying steps prior to completion of the packaging operation, a~ must be done with prior synthetic absorbable sutures. In order to avoid migration of the hygro3copic polyhydroxy compound or e ter thereof from the polymeric surgical article to the surrounding packaging material a stor2ge stabilizing amount of a mixture of at leaat one water ~oluble hygroscopic polyhydroxy compound or ester thereof and a thickening compound is applied to the suture.
~any kinds of pharmaceutically acceptable non-aqueous thickeners can be utilized including water-~oluble polysaccharide~, e.g., hydroxypropyl methylcellulose (HPMC), and the other material~ of this type which are disclosed in European Patent Application 0 261 015, polysaccharide gum3 auch as guar, ~anthan, and the like, gelatin, collagen, etc. An especially preferred cla~ of thickeners are th~ ~aturated aliphatic hydroxycarboxylic acids of up to 6 carbon atoms and the alkali metal and alkaline earth metal salt~ and hydratea thereof. Within this preferred cla~s of compounds are tho~e of the general formula OH
R - C - (CH2)n-COOR' ~I) H

wherein ~ i~ hydrogen or methyl, R' i~ alkali metal or alkaline earth metal, and n i9 0 or 1 and hydrates thereof.

Preferably, the component~ which make up the stabilizing ~gent of the present invention have no appreciable toxicity for the body at the level~
preYent. With these requirements Ln mind, those ~killed in the art are readily capable of identifying any number of compounds whiah may be useful in the practice of thi~ invention. Among the specific water-soluble hygroscopic polyhydroxy compounds or estera thereof which can be used herein with generally good results are glycerol and its mona- and diesters dexived from low molecular weight carboxylic acids, e.g., monoacetin and diacetin (respectively, glyceryl monoacetate and glyceryl diacetate), ethylene glycol, di~thylene glycol, triethylene glycol, 1,3-propanediol, trimethylolethane, trimethylolpropane, pentaerythritol, sorbitol, and the like. Glycerol i~
especLally preferred. ~L~ture~ of the afore-discussed polyhydroxy compounds or e~ters, e.g., ~or~itol dis~olved in glycerol, glycerol combined wLth ~ !~

monoacetin and/or diacetin, etc., are also u~eful. Compound0 within the general formula (I), above, u~eful in form~lating the ~tabilizing agent mixture of the preEent lnvention include, for example, salts of lactic acid such as calcium lactate, pota~sLum lactate, sodLum lactate, salta of glycolic acid, such as calcium glycolate, potassium glycolate, ~odium glycolate, ~alts of 3~hydroxy propanoic acid, such as the calcium, pota~sium and sodium ~alt~
thereof, salt~ of 3-hydroxybutanoic acid, such a~ the calcium, potassium and aodium Ealt~ thereof and the like. ~ ~tated hereinbefore, hydratea of the compound~ within the scope of the general formula (I) hereinabove are also within the scope of the pre~ent invention. Calcium lactate, e~pecially calcium lactate pentahydrate, is a particularly preferred thickener. Where a thickener i8 utilized, it will be incorporated in the filling composition in at least that amount required to increa~e the overall visco~ity of the compo~ition to the point where the composition no longer readily drains away from the Euture in a relatively short period.

If neces~ary or desirable, the stabilizing agent can be dissolved in any 3uitable non-aqueous ~olvent or combination of solvents prior to use. To be suitable, the ~olvent must (1) be miscible with the storage ~tabilizins agent at the concentration of the latter, (2) have a sufficiently high vapor pres~ure to be readily removed by evaporation, (3) not appreciably affect the integrity of the polymeric article and (4) be capable, in combination with the storage Etabilizing agent, of wetting the ~urface of the surgical article.
Applying these criteria to a preferred storage stabilizing agent, glycerol and calcium lactata, lower alcohol~ ~uch as methanol and ethanol are entirely suitable ~olvent carrier~.

6 ~ ~ ~

Prsparing the storage ~t~bilizing agent of the pra~ent invention ia a relatively simple procedure. For example, in the CaHe of glycerol and calcium lactate, ths de~ired amount of glycerol ia first introduced to a container, followed by the addition thereto of the desired amount of calcium lactate. If no solvent L~ to be uaed, the mixture i8 then thoroughly mixed. In the event a aolvent i~ de~ired, the ~olvent ~uch aa methanol is added to the mixture of glycerol and calcium lactate and the aolution is then thoroughly mixed to dissolve the compounds.

Generally, the stabilizing agent of the present invention ia compri~ed of a mixture of a compound within formula ~I) hereinabove, auch as calcium lactate, and a water ~oluble hygroscopic polyhydroxy compound, such as glycerol, in a weight ratio of between about 1:1 to about 1:10, mo3t preferably 1:7, reapectively. When a solvent, ~uch aa methanol, i8 utili~ed in the preparation of the stabillzing agent, the solvent i~ employed in amounta to provide a solution concentratlon of from about 20~ to about 50~, preferably about 30% to about 45~, ba~ed on the total weight of the aolution.

Application of the storage ~tabilizing agent to the polymeric article can be carried out in any number of waya. Thus, for example, the article can be aubmerged in the atorage stabilizing agent or ~olution thereo~ until at least a torage stabilizing amount of the ~tabilizing agent i8 acquired or otherwiae retained by the article, even after the optional removal of any exce~s agent andtor accompanying ~olvent (i~ preaent) auch as by drainage, wiping, evaporation, etc. In many cases, contact time~ on the order of from just a few aecond~, e.g., about 10 ~econds or ~o, to ~everal hours, a.g., about 2 hour~ and even longer, are suPPicient to impart a aubatantial improvement in the storage ~tability of the treated article compared to the ~ame type of article which has not been treated with a storage stabilizing agent. In the case of a braided ~ynthetic ab~orbable suture, it has been found that calendering tha auture prior to filling, ~uch a~ by pa6sing the ~uture through at least two pair~ of transversely mounted calender rolls, improve~ receptivity of the suture to filling and improves the supplenes~ of the resulting filled ~uture. It i~ believed that calendering the suture ~eparate0 the individual suture filaments to open up ~pace therebetween which are conducive to ensuring that the filling composition penetrates within and fills the interstice~ of the braided suture.

The foregoing submer~ion mathod of contacting the polymeric article with storage stabilizing agent can be conducted continuously or in batch.
Thus, in the ca~e of an absorbable suture, a running length of the ~uture can be continuously passed through a guantity of the stabilizing agent at a velocity whLch has been prevLously determined to provide the neceasary degree of exposure, or contact time, of the suture with the ~torage stabilizing agent. As the ~uture emerge~ from the storage stabilLzLng agent, it can be pa~sed through a wLper or sLmLlar devLce to remove exce~s agent prLor to the packagLng operatLon. Preferably, the suturs L~ passed through a coatLng head ~upplLed by a metering pump with a constant supply of fillLng ~olution, with the suture emergLng from the coatLng head and passLng through an evaporatLon oven to remove the filling ~olution solvent prior to any further ~urface contact, L. wLth roller~, etc. In a batch operation, a quantity of ~uture Ls merely submerged within the ~torage stabLlLzLng agent for the requi~Lte perLod of time wLth any excess agent being removed from the ~uture if desired.

2 ~

Alternatively, the storage stabilizing agent and ~olutions thereof canbe applied by ~prayin~, bru~hinq, wiping, etc., on the surfaces of the polymeric articlea such that the latter receive and retain at least a storage stabilizing amount of the agent. Yet another procedure which can be used to apply the storage stabili~ing agent involves inserting the polymeric article in a package containing an effective amount of the agent such that intimate contact between the polymeric article and the agent will be achieved.

Whatever the contacting procedure employed, it is necsssary that the article being treated acquire a storage stabilizing amount of the storage stabilizing agent. In general, amounts of from about ~ to about 25, and preferable from about 5 to about 15 weight percent, of storage stabilizing agent ~exclusive of any solvent) by weight of the polymeric article contacted therewith is ~ufficient to provide significantly improved storage stability compared to that of the untreated article.

As previously pointed out, braided, filled sutures in accordancs with the invention need not be packaged and maintained under the very dry condition~ required for prior synthetic absorbable sutures. Instead, it is preferred that the filled sutures bè equilibrated so that the level of moisture or other stabilizing agent solvent is sufficient to result in an appropriate viscosity level for the ~tabilizing agent and thickener in order to keep the stabili~ing agent on the ~uture. In the preferred embodiment of a braided sutura filled with a mixture of glycerol and calcium lactate, the moisture level may be equilibrated to as low a~ about 0.2% by welght of the suture, and is preferably above 0.3% or, even mora preferably, above 0.5~ by weight of the suture.

2 ~

Indeed, it ha~ been found that the preferred 3utures filled with glycerol calcium lactate undergo undesirable changea Lf exposed to a very dry environment. More particularly, if the sutures are expoaed to a very dry environment, the 3urface of the suture accumulates a flaked or powdered sub~tance on the surface thereof. It is believed such accumulation could interfere with removal of the auture or, at the very least, increase the force re~uired to withdraw the suture from the retainer. Equilibrating the auture, 3uch a~ in a dew point controlled environment, 30 that the ~uture containa a relatively high moi~ture level in æxces~ of .2~, and preferably in exce3s of .5~ by weight of the urgical auture, prevent3 the unde3irable effect3 which would otherwise reault if the suture~ were to be exposed to an extremely dry environment. Conversely, the presence of too much moisture can also have deleterioua effect3, such a3 cauaing the glycerol filling to run. Therefore, it is preferable to control the moi3ture level within a range, ~uch as 0.5 to 0.7~ by weight of the suture.

.
In order to ensure consistent force to remove the 3uture from the retainer and pr~vent undesirable changes in the aurgical article due to moisture level variations, it is de~ired to maintain the moisture of ths suture within a close range of the original packaged value, and to prevent any significant variation of the moisture level, up or down, during storag2 after the package ha~ been ~ealed. Notwith~tanding the foil laminate construction of the preferred peelable pouch, moisture may permeate the peelable adhe3ive line of the peelable pouch to enter or leave the pouch after it has been sealsd. For example, it 1B contemplated that suture~ shipped to a de~ert environmsnt might undesirably lose moisture through the seal line and, conversely, moiature may enter the pouch ln a very humid environment. In either case, undesirable variation of the moisture level in the pouch and force to remove the suture may result.

To prevent such variationa, a package ~tabllizing element ia packaged in the pouch with the ~urgical article, i.e. the sutur~ in the retalner. ~he package stabili~ing element 58 i~ illu~trated in Fig. 13, and may conatitute a pad impregnated with th~ aame stabllizing agent composltion uaed to fill the suture. The package ~tabilizing element preferably i~ inaerted into the peelable pouch prior to sterilization, and i~ ~terilixed, aerated and equilibrated with the ~illed auture and aealed within the pouch.

~ eferring now to Figs. 14-16, package ~tabilizing element 58 preferably i~ centrally located on the ~uture retainer surrounded by spiral passageway 16, although any location within the envelope or peelable pouch i5 acceptabla. Package stabilizLng element 58 may comprise a 3heet of medical grade cardboard, paper or other ceIlulosic material filled with ~tabilizing agent. As in the case of the stabilizing agent for filling ~uture~, the stabilizing agent used to ill the pad preferably is a mixture of glycerol and calcium lactate, ~uch as in a ratio of between about 1:1 to about lO:1, most preferably 7:1, re~pectLvely. The ataoilizing agent may be applied to the pad in any acceptable manner, such as by spraying, soaking, dipping, etc. By way of example only, for ~uture packaging the package atabilizing ~lement may be a sheet of modical grade cardboard meaauring about 0.4 inche~ by 1.5 inche~
containing about 70 milllgrams of atabilizing agent, 0uch as 60 milligram~
glycerol a~d 8.6 milllgram~ calcium lactate distributed 80 aa to provide about 107 milligram~ per ~guare inch glycerol and 15 milligram~ per ~quare inch calcium lactata. For non-0uturc polymeric articlas of greater mass a larger O ~ ~

package ~tabilizing element containing a larger amount of stabilizing agent may be required.

It also can be advantageoua to apply one or more coating compo~ition~
to the storage ~tabLlized article of this iDven~ion to improve unctional propertie~ ~uch a~ ~urface lubricity and knot tie-down behavior. A variety of suture coating compoaitions propoaed for either or both purpo~e~ are known in the art, e.g. those diaclosed in United State~ Patenta 3,867,190t 3,942,532;
4,047,533; 4,452,973; 4,624,2S6; 4,649,920; 4,716,203; and 4,826,945. It is contemplated that the coating could be applied to the suture either before or after filling. Suitable resulta have been obtained by coating the auture prior to filling, and thereafter calendering the suture to enaure optimum filling of the coated ~uture.

It is al~o within the acope of thia invention to impregnate the braided suture with, or otherwiae apply thereto, one or more medico-surgically useful ~ubstances, e.gO, tho~e which accelerate or beneficially modify the healiny proce~ when the suture is applied to a wound or aurgical site. So, for example, the ~uture herein can be provided with a therapeutic agent which will be depo~ited at the sutured aite. Tha therapeutic agent can be chosen for it~ antimicrobial propertiea, capability for promoting wound repair and/or tisaue growth or for ~pecific indicationa such aa thrombosis. Antimicrobial agenta auch aa broad spectrum antibiotica (gentamicin aulphate, erythromycin or deriYatized glycop~ptidea) which are alowly released into the ti~sue can be applied in this manner to aid in combating clinical and aub-cllnLcal infections in a surgical or trauma wound aite.

: .~

J ~3 -To promote wound repair and/or tis~ue growth, one or more biologlcally active material~ known to achieve either or both of ~he6e objective~ can be applied to the suture. Such matarials include any of 3everal Human Growth Factora (HGF~), maqainLn, ti88ue or kidney plasminogen acti~ator to cauae thrombo~i~, superoxida di~muta~e to ~ca~anga ti~u~ damaging free radical~, tumor necro~ia factor for cancer therapy, colony ~t~mulating factor, interferon, Lnterleukin-2 or other lympho~ine to enhance the immune ny~tsm, and ~o forth.

The term "Human Growth Factor" or "RGF~ embraces tho~e material3, known in the lilterature, which are referred to a~ ~uch and include~ their biologically actlve clo~ely related d~rivative~. The HGFn can be derived from naturally occurring sources including human and non-human ~ource~, e.g., bovine 30urce~, and are preferably produced by r~combinant DNA techniques.
Specifically, any of the HGFs which are mitogenically active and a~ ~uch are effectlve in stimulating, accelerating, potentiating or otherwi~e Pnhancing the wound healing procecs can be usefully applied to the suture herein, e.g., hEGF (uroga~trone)~ TGF-beta, IGF, PDGD, FGF, atc. The~e and other u3eful HGFs and clo~ely related HGF deri~ativea, method~ by which they can be obtained and methodc and compositiona featurinq the u0e of HGF~ to enhance wound healLng are variou~ly di~clo~ed, inter ~1~, in U.S. Patent No~.
3,883,497; 3,917,824; 3,948,875; 4,338,397; 4,41B,691; 4,528,186; 4,621,052;
4,743,679; 4,717,717; 4,961,757 and 4,874,746 European Patent ApplLcation~ 0 046 039, 0 128 733, 0 131 868, 0 136 490, 0 147 178, 0 150 572, 0 177 915 and 0 267 015, PCT International Application~ WO 83/04030, W0 85/003698, W0 85/01284 and W0 86/02271 and Ug Patent Application~ GB 2 092 155 A, 2 162 851 A and GB 2 172 890 A, and "Growth Factor~ in Wound H~aling", Lynch, et. al. J.

Clin. Invest. Vol. 84, pageu 640-646 tAugust 1989). Of the known HGF~, hEGF, TGF-beta, IGF, PDGF and FGF are preferred, either singly or in combination.

A filling compo~ition compri~ing a surgical wound healing enhancing amount of at least one HGF and as carrier therefor at least one water soluble, liquid polyhydroxy compound and/or ester thereof such a~ any of tho~e previously mentioned may be applied to the suture. The carrier protects the ~GF component of the filling composition from exces~ive degradation or 10~8 of biopotency during storage and, when the suture i8 fabricated from an absorbable resin which is su~ceptible to hydrolysi~, the carrier also con~titute~ the stabilizing agent for improving the 3torage ~tability of the suture. In addition to aarrier, the EIGF can contain a thickener such as any of those previou~ly mentioned in order to reduce or limit the tendency of carrier run-off.

~ he filling composition can contain one or more additional components which promote or enhance the wound healing effectiveness of the HGF
component. Thu~, e.g., ~ite-specific hybrid proteins can be incorporated in the filling composition to maximi~e the availabLlity of the HGF at the wound ~ite and/or to potentiate wound healing. See, e.g., Tomlin~on (Ciba-Geigy Pharmaceuticals, West Sus~ex, U.X.), "Selective Delivery and Targeting of Therapeutic Proteinun, a paper presented at a symposium held June 12-14, 198g in Bo~ton, ~A. The HGF~ can also be associated with carrier protein~ ~CPs), e.g., in the form of CP~bound HGF(~), to further enhance availability of the ~GF~s) at a wound ~ite a~ di~closed in "Carrie~ Protein-Ba#ed Delivery of Protein Pharmaceutical~n, a paper of BioGro~th, Inc., Richmond, CA presented 2 ~

at the aforementioned aymposium. The HGFs can also be incorporated in liposomes to provide for their release over an extended period. Lactate ion can be present to augment the wound healing activity of the ~GF. Protectant~
for the ~GF can also be utilized, e.g., polyethylene glycol~, acetoxyphenoxy polyethoxy ethanols, polyoxyethylene sorbitans, dextrans, albumin, poly-D-alanyl peptide~ and N-(2-hydroxypropyl)-mathacrylamide ~HPMA).

The types and amounts of HGF, carrier and optional component(s) such as thickener, site-specific hybrid protein, carrier protein, etc., identified above can vary widely and in general will be at least that amount of a particular component which is required to perform it~ respective function in an effective way. Those akilled in the art employing known or conventional procedures can readily determine optimum amounts of each component for a particular filling composition and particular braided suture filled therewith.

In general, the HGF~s) can be present in the total composition at a level ranging from about 0.1 to about 25,000 micrograms per gram of ~uch composition, preferably from about 0.5 to about 10000 miCrograms per gram of composition and mo t preferably from about 1 to about 500 micrograms per gram of compo~ition.

Application of the ~GF-containing composition to the suture can be carried out by any ~uitable technique, e.g., by any of the procedurea described above for applying a storage stabilizing agent to the suture.

The following examples are illu~trative of the storage ~tabilizing method and storage stabilized polymeric article of thi~ in~ention.

EXAMPL~ 1 Glycerol filled and glycerol/calcium lactate filled braided ~uture~
were centrifuged u~Lng a Clay Adams bench top lab centrlfuge in order to compare retention as a percentage of ba~eline fill. Fvur ~amples were apun after collecting ba~eline data on the uncentrifuged ~ample~ The centrifuge was run for 15 minute~ at top ~peed, centrlfugal force 3,000 Gs. The re~ultq are ~hown in Table I.

T~BLE I

Uncentrifuged Centrifuged ~ Retention _ Sam~le wt%G wt~CaL wt~ G wt~CaL G _ CaL

A: Size 3/0 Synthetic Absorbable Suture 21.7 --- 10.5+3 --- 48~14 B: Size l/0 Synthetic Absorbable Suture; 3.4 2.7 3.3 2.8 about lO0 about 100 C: Size 3/0 Synthetic Ab~orbable Suture 14.9 ~.2 12.9 1.7 87 78 D: Size 3/0 Synthetic Absorbable Suture 15.4 3.8 9.9 2.7 64 71 G = glycexol CaL = calcium lactate 5 H20 absorbabl~ ~uture~ - flber from glycolide/lactide copolymer~

~ i3 /~

The foreqoing data indicate that adding calcium lactate to glycerol givea an increa~e in glycerol retention.

~XAMPLE 2 Samples of calcium lactate/glycerol - filled braided sutures ~how equally improved ~tability to storage compared to glycerol filled braid without calciu~ lactate as shown in Table II (Compare C and D to A and E). In both case~, the 3tability i~ excellent compared to braid without glycerol and equilibrated at about the iame moisture level.

TABLE II

Sample C D A L F

Glycerin 14.9 15.4 21.7 10 -O-% Ca lactate 2.2 3.8 -O- -O- -O-% Water 0.55 0.55 0.450.45 Q.45 Storage T~me Ln ~ Strength Retained After 2 Week~ In Vitro at 37C
week~ at 56C After Accelerated Storaqe at 56C

3 49 50 45 32 2~

The following exa~ples demonstrate th~ propertie~, characteristics and advantages of filled braided synthetic ab~orbable suture~ packaged in accordance with the invention. All moisture analyses were performed on a Mitsubishi Moisture ~eter Model CA-05 with a water vaporizer Model VA-05 attachment and a transfer time of no more than five ~sconds.

EXI~PLE 3 Braided Si~e 0 sutures composed of 90 percent mol weight glycolide and 10 percent mol weight lactide were prepared in thirty inch length~ and attached to needle0 by swaging. One set of suturea were filled with 10~
glycerol and 1.2% calcium lactate by weight of the suture, and coated with the copolymerlzation product of polyalkylene glycol and a copolymer of 18%
glycolide, 32~ lactideO A ~econd set of utures were not filled or coated.
All sutures were inserted by vacuum draw into the preferred molded retainers shown in Figs. 1-3 constructed as de~cribed above of molded PETG with a TYVEK
cover ~heet adhered thereto with Oliver 188 hot melt adhesive. One half of each set of suture~ wa~ ~terilized in an ethylene ga3 sterilization cycle and aerated to remove ethylene oxide re~iduals. The qterilized filled ~amples were equilibrated in an environment having a dew point of about -10 C.
Each retainer wao mounted in the vise of an Instron tester. Using a crosshead ~peed o 10 inche~ per minute and a full scale load of one pound, the maximum, peak load to withdraw both the sterilized and un#terilized ~uture~ from the package was recorded. The reqults are ~et out in Table III.

~J~69~

Table III
FORCE TO ~EMOVE ST~TURE FROM MOLDED I~ETAIN~ (POUNDS) Unfilled Suturea Filled Suture~
Pre-steril. Po~t-steril. Pre-~teril. Post-~teril./equil.

0.63 * 0.30 0.68 0.69 * 0.25 0.90 1.03 * 0.36 0.64 0.88 * 0.16 0.55 0.31 * 0.18 0.53 1.09 ~ 0.46 0.66 0.94 * 0.20 0.72 0.91 * 0.26 0.84 1.06 * 0.34 0.68 0.53 * 0.20 0.61 0.84 * 0.22 0.80 0.47 1.44 0.25 0.94 Average 0.78 - 0.27 0.71 *Needle pulled off or ~uture broke.

The results ~hown in Table III show that unfilled uncoated braided 3ize 0 sutures, packaged ln the preferred retainer, could not be removed from the retainer after ~terilization and equilibration. Thu3, the preaence of a filling composition, ~uch a~ the preferred glycerol calcium lactate filling, appear~ to be neces~ary to obtain sati3factory withdrawal of the suture from the retainer.

, .

_AMPBE 4 Thirty inch length~ of ~ize 3/0 braided ~utures were prepared. One ~et of autures wa~ fllled with 11.3~ glycarol and coated with 2.9~ of the coating de~cribed in Example 3, both by weight of the Huture. A ~econd set of sutures was filled with 1.9~ calcium lactate and 11.2~ glycerol and coated with 2.8~ coating, all by weight of the auture. Equal number~ of samples were inserted into the retainer~ of Example 3 and equilibrated under different moisture conditions and ~ealed in foil laminate envelope~. The Group A
~amples were equilibrated to about 10C dew point. The Group B sample3 were equilibrated in the range of about -10 to -8C dew point, and the Group C ~amples were equilibrated to a range of about -14 to -12C dew point.
The Group B sampl2s filled with glycerol had a measured moi~ture content of about .58~ by weight of the suture. Ths Group C ~amples filled with glycerol and calcium lactate had a moi~ture content of about .55~. The force in pounds to remove the equilibrated sutures from the package are set out in Table IV.

, .

:

Table IV
AVERAGE FORCE TO RE~OVE SUTURE ( POUNDS L

~ G-CaL 'Filled 0.31 0.32 0.28 0.34 0.44 0.46 The~e result~ ~how ~hat aa the equilibration conditiona become drier, the glycerol calcium lactate filled auturea become more difficult to remove from the molded retainer. While not iDtending to be bound by theory, it is believed that, as condition~ become drier, calcium lactate accumulatea in a powdery or flaked form at or near the surface of the ~uture, and inhibit~
removal of the ~uture from tha ratainer. Thu~, in addition to other factors, a balance mu~t be atruck between the amount of calcium lactate and moisture level.

' ~ ~3 ~

Size 0 braided aynthetic absorbable auture0 of variou~ l~ngtha filled with 9.0% glycerol and 1.3~ calcium lactate and coated with 2.8% of the preferred coating were inaerted into the retainer lllustrated in Figs. 1-3 described above. The ~utures were aterilized, aerated, equilibrated in an environment controlled at about -10C dew point until the suturea contained approximately 0.46~ by weight moisture, and aealed in bulk in a foil laminate envelope container. The force to withdraw the varioua suturea length~ from the retainer wa~ mea~ured and i~ r~ported, in pound~, in Table V.

Table V

Averaqe Suture Removal Force (Pounds) vs. Lenqth 15"18" 21n 24n 27 30 0.020.04 0.08 0.20 0.29 0.56 ' The a~erage force to remove each suture from the retainer i~ plotted in Fig. 17. From this data it may be concluded that relatively long lengths o~
~uture may be packaged in the preferred retainer with acceptable ~uture withdrawal force~. For consistent, easy removal, it has been found the optimum force to remoYe the ~uture from the retainer should in all ca~es be below about 0.20 kilogram~. In order to accomodate sl~aller ~ize suture~, particularly those of the variety having relea~able needle~, it is favorable to further limit the sutura withdrawal force. Thu~, the optimum force to withdraw the suture ~hould not exceed about .02 kilograms for a si7e 8/0 ~uture, .04 kilogram~ for a ~ize 7/0 suture, .08 Xilograms for a si~e 6/0 ~uture, and .12 kilograms for a ~i~e 5/0 suture.

Braided filled ~uture~ were prepared in thirty inch lengths. Single ~uture~ were loaded full length into the retainer of Fig~ 3, doubled and tripled o~er into the retainer of Fig~. 3 and 6-7. The ~utures were sterili~ed aerated and equilibrated. All suture~ were then ~ealed in foil pouches. The force to withdraw the sterile ~utures from the retainers was measured and the re~ultc are reported in Table VI.

TABLE VI

Average Force to Remove Coiled, Doubled-over and Tripled-over Suture~ (Pounds~
~ Tri~led-over Doub:Led-over 1.05 .12 .56 Thus, the average force to remove doubled-ove:e thirty inch suture is approximately one-half the force required to pull-out a ~ull length coiled suture. The average ~orce to remove the tripled-over auture wa3 roughly one-tenth the force to remove the full-length ~uture.

~$~

Ten samples of ~ize 3t0 suture3 filled with a glycerol calcium lactate mixture were ~terilized, aerated, equilibrated and sealed in peelable pouches with a package ~tabilizing element con~isting of a pape.r ~heet impregnated with approximately 60 milligrams of a glycerol/calcium lactate ~tabilizing agent having a weight ratio of 6.5:1 glycerin to calcium lactate. $en sample3 of ~ize 3/0 autures packaged without the stabilizing element were selected for comparative testing. Ab~orbable sutur2s fabricated from a copolymer of glycolide and lactide were u~ed. The~z sutures had an average weight of 0.06g per suture. All aample~ were equilibrat d at -10 to -8C dew point before sealing. Water was added to the packages of each group through a vent hole in the package using a mic~oliter syringe and the vent hole immediately sealed.
The samples were labeled with the amount of water added and allowed to stand for 72 hour~ to allow for equilibration in the paaket. At this tlme, the ~utures and the ~tabilizing element were teated for moisture and compared to the control which was ~ealed without the addition of water. The data shown in Table VII illustrate the percent weight in moisture of the sutures packaged with the package atabilizing element as compared with ~uture~ packaged without the stabilizing element when vasiou~ increments of water were added.

TABLE VII
ADDED ~Initial moisture content: auture with atabilizing element = .53 stabilizing element = 1.62 auture without atabilizing element = 0.59 Wt. ~
Water Added No Stabilizing Suture with Stabilizing Element Element (ug) Suture Suture Stabilizing Element 0~57 0.59 1.67 200 0.64 0.61 1.74 500 0.6~ 0.59 1.85 lO00 0.78 0.64 l.9O
2000 0.96 0.64 2.30 3000 0.97 0.74 2.59 4000 1.52 0.80 3.06 5000 1.87 1.12 3.80 7000 2.49 1.09 4.22 Slope 2.7x10'4/ug 8.1xl0-5~/ug 3.8xlO~4%~ug .....

,.

The data show that, for a aize 3tO suture, the moiature content will increase by 0.00027% for each microgram (ug) of water added while the qame ~uture, when packaged with the package stabilizing element will increase by only 0.000081~. These numbers are for ~ize 3/0 auture and will vary accordingly to the size of the suture.

The amount o~ water contained in the auture and the stabilizing agent wa~ calculated from the data presented above in Example 7. Total moisture in the suture wa~ directly read from the raw data, total moisture in the ~tabilizing agent wa~ calculated based on an average dry weight of 0.167 g per ~tabilizing element. The added water content of each component at each increment wa~ determined by subtracting the initial total water from the total water found after water addition. It wa~ assumed that the packaging absorbed all water not found in ths suture or the ~tabilizing element.

:

O O g ~D

c u~
~ ~ ,P ~ ~ ,p ~ ' C ~

~n a~ ' ~ co o 1~ ~ ~ a -- W O a~ ~ 3 ~ C ~

0~ n dP 3 ~t ~ g ~ I' ~ 1-' ~ tD O U~ tD ~ rt ~ t:1 ~ E ~ o =' ~ 3 W o~ ~ ~O O cr tt a~ 3 ~-- N

~ ~ W ~ ,P ~ C
~ ~ ~ ~ ~ ~ ~ ~ ~ 8 ~
I rt ~a Ul ~ ~ ~ ~ ~ O~ O

~al O N=
\~ Y 1~ Y 1~ 1 U~ Ul n 2 ~

Example3 7 and 8 demonstrate that the package 3tabilizing element aubstantially reduces the range o~ varia~ion in moiature content in the ~uture which might otherwiae result due to moi~ture entering the pouch. Similar results are expected in relation to moisture leavLng the foil pouch, but would be more difficult and time consuMing to te~t. Thus, the moisture content of the suture ia maintained very close to the relatively high level present at the time the pouch is ~ealed, and varie~ only very slightly a~ moi~ture enters or leavea the pouch. In the context of the preferred molded retainer having a convoluted paasageway, the filled suture is protected against the effects of moisture entering or leaving the pouch, and the force to remove the suture from the retainer remains aubatantially conatant. It is also contemplated that the package atabilizing element may havP aimilar advantages in the packaging of other types of hydrolyzable surgical articles containing or a~sociated with a atabilizing agent. Types of article~ include va~cular graft~, bone ~crew~, ~taples, clips, splint~, ligament~, drug delivery syRtem~, etc.

The package stabilizing element also ha~ other significant advantagea. For exa~ple, a glycerol baqed ~tabili~ing agent haE a tendency to migrate and coat the entire urface of a closed container, such a~ the peelable pouch. The pre~ence of the package stabilizing element including a relatively large quantity of ~tabilizing agent provides an alternative ~ource of glycerol for migration. It ha~ been found that inclu~ion of the package stabilizing element in the closed package reducea losa due to migration of a glycerol based ~tabLli~ing agent matsrial from the ~urgical article, i.e. the filled ~uture. This desirable reault also contributes to the consi~tent force required to remove the ~uture fro~ the package by ensuring a subatantially con~tant amount of glycerol ln the filled auture.

As ~tated, prior #ynthetic absorbable sutures packaged in the conventional "figur~ 8" configuration in a cardboard retainer under very dry conditiona unde~irably retain kinka and bends when removed Erom the retainer and do not exhibit good hand and feel characteriatic~ which ar~ ao important to the end user. The preferred braided, fillad synthetic absorbable suturea pacXaged in accordance with the invention aynergi~tically provide a remarkably supple, flexible suture which is readily removed from the package and has desirable hand and feel as removed from the package. Advantageously, the convolutions of the preferred molded retainer alao enhance the flexibility and aupplene~a of the sutures prepared in accordance with the invention by flexing the suture a~ it is withdrawn from the retainer. Although it is dif~icult to quantify the characterLatics of good hand and feel, ~everal testY have been developed in an attempt to do 80.

In the first test, a vertical hanglng test, the auture iB removed from the package and ~imply allowed to hang under gravity. The hanging length of the suture is mea~ured and compared to the full, ~traLghtened length of the suture. The result is expres~ed a~ percent of straightened length.

The ~econd te~t ia a hanging ~heart loop~ test based on ASTM D 1388.
In this test, the suture is removed from the package and one end of the suture i~ taped to a bar. Holding the ~uture taut, the other end of the ~uture ia taped to a second bar. The bara are mounted in a test fixture in the configuration shown in FLg. 18 Yo that the suture 60 as~umes the heart ~haped loop configuration supported by the bars 62. The suture ia allowed to hang vertically for one minute, and the diatance "1~ from the top of the mounting bars to the bottom of the auture loop is rPcorded. The bending length of the $

~uture i~ calculated, con~i~tent with ASTM D 1388, acco~ding to the following formula:

C = lo F(O) where:
' l = loop length in centimetexs lo = 0.1337L

L = ~uture ~trip length, i.e. the di~tance between the bars when the auture i~ mounted, in centimeter~.
f(O) = (COB O/tan o)l/3 O = 32.85 d/lo, in degre~, and d = l - lo :: ~

~ 47 -The third te~t use~ a G~lrley Stiffne~ Tester, Model 4171, in a test method ~imilar to that descrLbed Ln United State~ Patent 3,630,205. Multiple two inch suture segments are prepared with minimal handling and are in3erted into a holding fixture and clamped ~o that one and one-half inches of each ~trand protrudles ~rom the bottom of the fixture. The fixture is mounted in the Gurley instrument so that the bottom of the gage lie~ one-half inch above the edge of the ~winging pendulum. rhe apparatu~ i~ operated through one or two cycles ~a left swing plus a right swing) to adju~t the weight distance so that the average Gurley unit i8 between 2.0 and 7Ø The apparatus is then operated for 5 cycles without recording results. The readLngs of cycles 6 through 10 are recorded and averaged. The stiffness of the suture iB calculated as follows:

Stiffne88, gram~ = weight u~ed x scsle re~dinq x arm diBtanc The preferred number of ~trands and te~t weight and di~tance are set out for each suture ~ize in Table IX.

TABLE IX
Gurlev Te~t Parameter3 Weight Weight Suture Si7el Number of Strands (arams! Dist:ance (Inches) 3/0 ~ 5 ~/0 8 . 5 2 5/015 . 5 2 :: 6/024 . 5 2 7/045 . 5 2 `' :' 2 ~

Yarious sizea of braided filled ~uture~ w0re made, packaged in the retainer of Flg~ 3 and the preferred mid-peel pouch, equilibrated and sealed in accordance with ths invention. Upon removal from the package the suture~ were teated uaing the vertical hanging te3t, the heart loop te~t and Gurley stiffnes~ teat. The result~ are set out in T~ble~ X through XII.

TABLE X
Braided Filled Suturea Vertical Hanqinq Te~t Average Average Average Length a~ Length % Straight ,Si~e i~ Lcm~ Straiqhtened Lcm) Lenqth 2 62.7 68.9 91.0 1 65.3 70.1 93.1 1 64.3 68.8 93.5 0 66.3 71.8 92.3 0 61.2 76.2 80.3 2/0 70.7 '75.6 93.5 (No Stabill~ng element in pckg.) 3/0 72.3 75.7 95.6 5/0 60.6 68.7 88.2 5/0 67.6 75.1 90.0 - 50 ~

.
, ABLE XI
BraLded Filled Sutures Heart Loo~ Teat Average Average Size Loo~ lenath Ben_ n~ len~th 2 7.44 3.26 1 7.1 3.56 1 7.2 3.47 ~ 7.2 3.41 0 9.5 2.17 2/0 8.8 ~.54 (No atabilizing element in package) 3/0 9.1 2.~0 5/0 7.2 3.34 5/0 7~2 3.37 ~;
~, s~ 3 TABLE XII
Braided Filled Sutures Gurley Stiffness Size (weight, grams) A~erage ~distance, inches1 Scale Readina Stiffne~s 2 4.45 4.45 (5) (2) l 4.34 2.17 (5) (1) l 4.3 2.15 (5) (1) 0 , 3.27 1.64 (5) (1) 0 5.23 2.62 (5) (1) . 2/0 3.76 1.88 (5) (No stabilizing . element in ~:- package) 3/0 3.16 .28 (.45) (2) 5/0 4.5 .68 (1.50) (1) 5/0 4.28 .64 (1.5) (1) .~

For purposes of comprarison, Ethicon Vicryl ~i3e 0 braided absorbable sutures were tested for out of package v~rtical hang and Gurley atiffne3s.
Because the Vicryl suture~ exhibited too many kinks or ~ets~, they could not be teated using the heart loop test.

TABI,E XIII

Vlcryl Size 0 Vertlcal Hanainq Test Length% Straight Sample No. Lenqth as,is Strai~htened Lenqth 1 39.7 70.1 57 2 37.5 70.2 53 3 37.4 69.9 54 4 42.2 69.7 61 46.5 70.1 66 Ave.: 58 ~ .

TABLE XIV

Vicryl Size 0 Gurley Stiffne~s (5 qram weiqht - 2 inch di~tance) Scale reading Te~t (Averaae 5 measurements) ~ 1 4.52 : 2 5.38 3 5.10 4 5.48 6.26 Ave.: 5.35 Stiffne~: 5.35 Vicryl Size 3-0 braided ab~orbable 3uture~ ~ere te~ted. The ~utures had 63~ vertical hang. Gurley tiffne ~ et out in Table XV.

~' : - 54 -TABLE XV
Vlcryl Size 3-0 Gurley Stiffne~s ~1.5 ram wei~ht - l lnch distance~

Scale Reading Test (Ave. of 5 mea~urements) 1 5.6 2 4.7 Ave.: 5.15 Stiffness:5.15 The braided filled ~utures in accordance with the invention display remarkable ~uppleness and flexibility comparable to the feel and hand of braided sllk ~utures. For comparison, commercially available braided silk sutures from Davi~ & Geck, American CyanamLd Co. were teated for Gurley stiffne~s. The result~ ~et out in Table XVI, as compared to Table XII, ~how that the ~ynthetic absorbable suture~ in accordance with the invention display flexibility and ~upplona~a comparable to ~ilk ~uturaa.

' TABLE ~VI

B~AIDED SILK
GURLEY STIFFNESS

Suture Size Gurley Stiffness ~Ave.

2 3.4 1 2.5 0 3.13 2-0 2.5 3-0 1.09 4_0 0.30 5-0 .44 6-0 .18 7-0 .07 In 3ummary, braided filled synthetic absorbable ~utures packaged in accordance with the inventio~ display an out of packaye hanging length greater than about 80~ of actual length, a bending length of about 3.00, and Gurley stiffnes~ le~s than 5.00. Indeed, suture~ ~f the invention have a Gurley ~tiffness comparable to braided silk ~uture~.

' A size 2/0 braided ~uture po~e~sing ~tructural characteristicA a~

described in U.S. Patent 5,019,093 coated with the preferred coating desoribed in Example 3 was filled with a mixture of glycerin calcium lactate and packaged in a retainer substantially as ~hown $n Pigs. 1-3 within the peelable pouch of Figs. 11-12. The suture wa~ ~terilized, moisture eq~ilibrated and sealed. Post-~terility testing howed that the auture contained 10.1%
glycerin, l.7% calcium lactate and 3.4~ coating. The suture wa~ removed ~rom ~ ~ f~

the package and was compared with a size 2/0 braided silk suture of Davis &
Geck, Inc. ("D ~ G Silk~) and a Vicryl ~ize 2/0 braided absorbable suture for tissue drag. The braided filled suture conatructed in accordance with the principles of thia inventLon exhlbited a dramatically reduced level of tissue drag compared to eith2r of the other two standard suture~.

The foregoing examples demonstrate ~h2 superiority of the braided, filled sutures packaged in accordance with the invention in comparison to commercially available packaged synthetic absorbable ~utures, and that the pacXaged suturs0 in accordance with the present in~ention display superior handling and tissue drag characteristics.

Claims (21)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A method of packaging synthetic absorbable sutures comprising the steps of:

a) inserting a synthetic absorbable suture filled with a stabilizing agent into a retainer;
b) inserting said retainer containing said filled suture into a substantially moisture impervious pouch having at least one opening therein;
c) sterilizing said filled suture;
d) equilibrating said filled suture within said pouch; and e) sealing said pouch.

2. The method of claim 1 characterized in that said step of equilibrating said suture comprises equilibrating the moisture level within said suture in an environment having a controlled dew point.

3. The method of claim 1 characterized in that said step of equilibrating said suture comprises equilibrating the moisture level of said suture unit the moisture level is above about 0.2% by weight of the suture.

4. The method of claim 1 characterized in that said step of equilibrating said suture comprises equilibrating the moisture level of said suture until the moisture level is above about 0.5% by weight of the suture.

5. The method of claim 1 further characterized by the step of:

inserting a package stabilizing element into said pouch prior to equilibrating said suture.

6. A surgical package characterized by:

i) a subsantaially moisture impervious pouch; and ii) a sterile synthetic absorbable surgical element filled with stabilizing agent disposed in said pouch.

7. The package of claim 6 further characterized in that said synthetic absorbable surgical element is a suture, and a suture retainer containing said suture is disposed in said pouch.

8. The package according to claim 7 characterized in that said suture retainer includes a convoluted passageway.

9. The package according to claim 7 characterized in that said sterile synthetic absorbalbe suture is fabricated from a bioabsorbable polymer derived at least in part from one or more monomers selected from the group consisting of glycolic acid, glycolide, lactic acid and lactide.

10. The package according to claim 7 characterized in that said stabilizing agent comprises a polyhydroxy compound or ester thereof and a thickener.

11. The package according to claim 10 characterized in that said stabilizing agent comprises a polyhydroxy compound or ester thereof and at least one thickener compound having the general formula wherein R is hydrogen or methyl, R' is a metal selected from the group consisting of alkali metal and alkaline earth metal, and n is 0 or 1, and hydrates thereof.

12. The package according to claim 11 characterized in that said stabilizing agent comprises a mixture of glycerol and calcium lactate.

13. The package according to claim 7 characterized in that said suture contains at least about 0.2% moisture by weight of the suture.

14. The package according to claim 7 characterized in that said retainer comprises a molded retainer having at least one spiral oval suture passageway and a cover sheet.

15. The package according to claim 7 characterized in that said pouch is a peelable pouch.

16. The package according to claim 7 further characterized by a package stabilizing element disposed within said pouch.

17. The package according to claim 16 characterized in that said package stabilizing element is a pad filled with said stabilizing agent.

18. The package according to claim 17 characterized in that said stabilizing agent comprises a polyhdroxy compound or ester thereof and at least one thickener compound having the general formula wherein r is hydrogen or methyl, R' is a metal selected from the group consisting of alkali metal and alkaline earth metal, and n is 0 or 1, and hydrates thereof.

19. The package of claim 17 characterized in that said stabilizing agent includes glycerol.

20. The package of claim 7 characterized in that said suture is doubled-over in said retainer.

21. The package of claim 7 characterized in that said suture is tripled-over in said retainer.