CA1049970A - Storage stable package for absorbable polyglycolic acid sutures, and process for preparing same - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
This invention relates to a method of dry packaging polyglycolic acid sutures for storage stability And the pro-ducts produced thereby.

Description

iO ~ 70 At the present time, virtually all absorbable fiutures used in animal and human surgery are prepared from mammalian in-testines, such sutures being commonly called catgut sutures. Re-cently, however, research efforts to provide a synthetic absor-bable suture have borne fruit. U.S. Patent 3,297,033 i~sued to Schmitt et al. on January 10, 1967 describes an absorbable sur-gical suture made from polyglycolic acid. These sutures are made from synthetically prepared high molecular weight polyglycolic acid. Although a variety of methods are known for preparing polyglycolic acid, it is established that i~ high molecular weight polymer is required) a preferred route is to polymerize substan-tially pure glycolide in the presence of an appropriate catalyst, such as described, for example in U.S. Patent 2,668,162 issued to Lowe on February 2, 1954.
Polyglycolic sutures possess a number of advantages over catgut. For example, they exhibit greater uniformity of composition and hopefully will be easier to manufacture. They are capable of exhibiting stronger package strength, i.e., straight pull and knot pull, as well as greater in-vivo strength retention. Polyglycolic sutures are also absorbed by living tissue within 90 days after implantation therein.
Despite the aforementioned advantages of polyglyco-lic acid as a suture, it has been found that the desirable package properties and in-vivo properties of the sutures dete-riorate rapidly when the sutures are exposed to moisture.
More surprising, the exposure of dry polyglycolic acid sutures to small amounts of moisture for very short periods of time - is sufficient to cause serious deterioration in the package and in-vivo strength of the sutures on long term standing as will be discussed in greater detail hereinbelow.
Although the reason for the aforementioned affect of moisture on the properties of polyglycolic acid sutures is not known with certainty, it is believed that several mechanisms may be involved. First, the water may be hydrolytically '~'\'1 1-iO49970 attacking the polymer structure to thereby degrade and weaken the polymer. It is also poEsible that the water may be react-ing with the unreacte~ glycoli~e monomer whic~l can be present in the polymer in an amounc up to about 8~ to cleave the gly-colide ring structure into the linear dimer ~f glycolic acidwhich is represented by the following formula:
O O

The linear dimer in turn can react with the polymer to break up the high molecular weight polymer into lower molecular weight chains thereby degrading the polymer and causing a re-duction in strength. It is also possible that glycolide or the linear dimer of glycolic acid are formed in the polymer as a result of thermal degradation of the polymer which can occur during processing such as, for example, in a high tem-perature extrusion step.
As often occurs during actual practice, a suture is not used for months or sometimes years after it is prepared and packaged. In the meevntime, the suture is stored under a variety of environmental conditions. Most of these storage environments will contain some moisture. In view of the afore-mentioned adverse effect of water upon the properties of a polyglycolic acid suture, it is mandatory that such sutures be packaged in a material which will prevent permeation of water vapor from the environment surrounding the package through the package and into contact with the suture contained therein. On the other hand, a package material which pre-vents the entry of water vapor will ordinarily also prevent the exit of water vapor; therefore, any water vapor which is present within the package when it is sealed will remaln in the package in intimate contact with the suture. Applicant has further discovered ~hat the exposure of a dry suture to moisture ~or even extremely brief times (i.e. 20 minutes or iO4S~97V
less) prior to packaging the suture can have disastrous effects upon tlle suture Wl~cll it is pclckaged in a water impermeable package, es-pecially if the package should happen to be stored at elevated temper-atures.
It is an object of this invention, in view of the afore-mentioned difficulties with regard to stably packaging polyglycolic acid sutures, to provide a package for these sutures which insures acceptable retention of package andin vivo strength for prolonged periods of time even under the most undesirable conditions of temper-ature and humidity. It is another object of this invention to provide a method of preparing such a package.
This invention provides a storage stable, packaged poly-glycolic acid suture comprising an air-tight sealed water vapor-imper-vious container and a desiccated sterile polyglycolic acid suture, the suture being located in said container ln vacuo or in a desiccated gas-eous atmosphere non-reactive with polyglycolic acid, the suture and the interior of the container being essentially free of all absorbed moisture.
A variety of different packaging materials were evaluated in an attempt to find a storage stable package for polyglycolic acid sutures. For exampleJ when the suture was packaged in saran (a vinyl chloride-vinylidene chloride copolymer) the suture had totally disin-tegrated after only 42 days storage at 100F. and 100% relative humidity.
A similar result was observed with Scotch Pak~ film. Scotch Pak~ is a laminate of polyethylene and the polymeric ester of ethylene glycol and terephthalic acid. Other package materials also failed to protect the suture from similar adverse affects. However, an aluminum foil package has been found to protect the suture satisfactorily, particularly a package in which the foil is laminated to a plastics film such as a polyethylene film. Such a laminate may, for instance, be structured as follows:

(a) a heat sealable thermoplastic layer, said layer forming at least a portion of the inner surface of the container, said inner surface being that surface adjacent to the suture, (b) an aluminum foil layer adjacent to the polyethylene layer of (a), said layer being from about 0.35 to 1.0 mils thick, (c) an adhesive layer suitable for bonding aluminum foil to paper adjacent the aluminum foil layer of (b), said aluminum foil layer being sandwiched between the layers described in ~a) and (c), and (d) a paper outer layer adjacent the adhesive layer described in (c), said outer layer being that layer exposed to the environment surround-ing said package.
Prior to sealing the suture within the package of this invention, it is essential that the suture be desiccated or bone dry. The suture can be desiccated by heating for a sufficient period of time to remove the water therefrom. However, it must be noted that once this water is removed, the suture cannot be allowed to contact an environment containing moisture for even a very brief period of time, since even such a brief contact can cause severe deterioration of suture package and in-vivo strength after the suture is sealed in a water impervious container and stored for a prolonged period of time. It therefore becomes necessary when a processing gap be-tween when the suture is dried and when it is packaged is anticipated, to provide for interim storage in a dry area where the possibility of contact with moisture is eliminated.
This invention also provides a method for preparing a storage stable, packaged polyglycolic acid suture characterized by the steps of (a) inserting a polyglycolic acid suture in a container fabricated from a material which is impervious to air and water vapor, (b) sterilizing the suture and container, (c) removing essentially all of the water from said suture and container, (d) maintaining the suture and container in a desiccated, sterile ~ _ 4 _ 1049~
environment, and (e) evacuating the gaseous contents of said container or flushing substantially all of the gaseous cOntentS out of said container, replacing them with a gas which is non-reactive with polyglycolic acid and which is essentially free from water, and then sealing saicl container with an air- and moisture-tight seal.
There has also been discovered a method for sterilizing an ab-sorbable polyglycolic acid with ethylene oxide vapor without adverse effect upon the package or in-vivo strength of the suture. In accordance with this embodiment, a (non-sterile) polyglycolic acid suture is contacted with a gas having as its active component ethylene o~ide. The ~as is :

- 4a -104~70 maintained ~t a temperature of from about 70 to 90F. The molsture content of the gas is the ambient moisture content and no ad~itional water is added to the ~as to e6tabllsh any required relative humidity therein. When a no~-sterile poly-glycolic acid suture i6 contacted with the gas describedabove, sterility o~ the suture can be achieved with a contact time of about 4 hours or more. Suitable sterilization i~
achieved when the pressure of the sterilizing gas is mainta~n-ed at about 5 to 15 lbs. psig.
Previous gaseous ethylene oxide sterilization pro-cedures have called for sterilizing gas maintained at a re-latively high pressure (25 psig) and high temperature (120-130F.). Ordinarily, a prescribed relative humidity (i.e. 50~) is achieved by adding to the gas that amount of water which is required to establish the desired relative humidity at the temperat~lre of sterilization. Contact times of 20 hours or more are ordinarily used. In view o~ the aforementioned adverse effect of water, and especially of the effect of water coupled with high temperature, upon polygly-colic acid, it becomes apparent that sterilizing polyglycolicacid sutures by such extreme conditions of pressure, tempera-ture, relative hl~midity as previously used for prolonged periods of time would be most undesirable. It is known that when polyglycolic acid is contacted with water, and particu-larly at high temperatures, that degradation of the polymerwill occur quite rapidly. The sterilization process of this invention permits poly~lycolic acid s~tures to be sterilized at significantly lower temperatures and pressures and shorter time cycles. Additionally, since no moisture is deliberately added to the sterilized gas and since the compounds of the sterilized gas are anhydro~ls, the amount of moisture present in the sterilized chamber is significantly less than would be available using prior ethylene oxide sterilization tech-iO4~5~7~
niques. Applicant has found that polyglycolic acld suture6 can be sterllized using the process of this inyention without adverse effects upon the package Or in-vivo properties Or the suture.
Figure 1 is a frontal view of a preferred embodi-ment of the suture package of this invention.
Figure 2 is a sectional view taken along the line

2-2 of Figure 1 and serves to illustrate the laminate struc-ture of a preferred water impermeable container for the poly-glycolic sllture.
Figure 3 is a schematic flow sheet depicting a pro-cess for preparing the storage stable polyglycolic acid suture package of this invention.
Figure 4a shows the effect of the interim conditions which exist between drying the suture and packaging the suture in the package of this invention upon package straight pull of the suture after storage at 132F.
Figure 4b shows the effect of the interim conditions which exist between drying the suture and packaging the suture in the package of this invention upon 15 day in-vivo straight pull after storage at 132F.
Figure 5a compares the storage capabilities of the package of this invention with those of an acceptable catgut suture package under storage :-onditions of 100F. and 100 relative humidity.
Figure 5b compares the storage capabilities of the package of this invention with those of an acceptable catgut suture package under storage conditions of 132F. and 10 relative humidity.
Figures 1 and 2 present a preferred embodiment of the package of this invention. Referring to these figures, the package comprises sealed envelope 11 containing therein sterile needled polyglycolic acid suture braid 12 wrapped ~049~70 clrourld papel mounti~g 13. 'I'he package is sealed by peri-pheral heat seal 14. rhe material from which envelope 11 is fabricated is a four layered wa-ter impervious laminate .lS l~es~- seell h~v refererlce to ~i,yure 2. 'I~he laminate comprises a Eirst layer 15 of heat sealable polyethylene, a second layer 16 of aluminum foil, a third layer 17 of polyethylene and a fourth layer 18 of printable paper.
Envelope 11 is conveniently formed by p~acing two pieces of the aforementioned laminate on top of e~ch other with heat sealable polyethylene layers 15 contacting each other. Three of the four edges are then sealed together using a standard heated dye to form an envelope into which mounted suture 12 is inserted. After evacuating the contents of the envelope or replacing them with an anhydrous inert gas, the fourth edge of the envelope is sealed to produce a completely sealed pacakage.
Polyethylene layer 15 is preferably comprised of 15 lb. low density polyethylene having a thickness of about 1.5 mils. The function of this layer is to provide a vehicle for heat sealing the package; of course, any other suitable heat sealable thermoplastic which will achieve this goal is also suitable. Examples of such other mater~als are Saran , mediaum and high density poly olefines, tetrafluoroethylenes, and such.
Aluminum foil layer 16 should have a thickness of at least about .35 mils in order to insure suitable water barrier propterties with preferred thicknesses of about 0.35 to 1.0 mils and a highly preferred thickness of about 0.5 mils.
Polyethylene layer 17 preferably has a thickness of about 0.5 mils. Its function is to serve as an adhesive vehicle for joining together aluminum layer 16 and paper layer 18. Of course, any other suitable adhesive would be operable.

~049970 Paper layer 18 is preferably Z5 lb. super-~ale~dered ~leached I~OUCI1 I'aper (Virgin Sulpha-te Pulp) having a thickness ;~

- 7a -of about 1.1 mils + 20~. The function of paper layer 18 is to permit direct printing of l~bel6 and such on the external surface of the package and hence any printable paper would ~e suitable.
A particularly suitable laminate of polyethylene-aluminum foil-polyethylene-paper i8 available from the Riegal Paper Corp., New York, New York, under the trade designatlon of Pouchpak ~.
A convenient method for preparing the package of this invention is shown schematically in Figure 3. Referring to Figure 3, surgical needle 19 is affixed to braided poly-glycolic acid suture 20 to produce needled polyglycolic acid suture braid 12 Braid 12 is then wrapped around suture mount-ing 13. The ~ounted sl~ture is placed in envelope 11, said envelope being prepared as described above.
Envelope 11 containing mounted suture 12 iB then placed within a sealed container which is permeable to steril-izing gas but not to bacteria. This container is then placed in a suitable ethylene oxide sterilizing oven. The oven is evacuated after which a mixture of 12~ by volume ethylene oxide and 88~ by volume dichlorodifluoromethane (Freon ~ 12) is admitted to the oven. The oven pressure is raised to about 10 psig by admitting more of the gas mixture. The temperature of the gas mlxture is maintained at 70-90F. The ethylene oxide-Freon~mixture is non-flammable and explosion proof and is safe in all proportions when mixed with air. The Freon is essentially a diluent and, of course, other suitable diluents such as carbon dioxide or other members of the Freon family and their mixtures are also quite suitable. The im-~o portant aspect about the sterilization process is that thepolyglycolic acid suture can, surprisingly, be sterilized in a relatively dry environment at low temperatures, moderate pressures, and with very brief sterilization time cycles.

104~70 After the suture has been in contact with the steril-izing mixture for at least 4 hours and preferably 8 hours, the sealed container containing suture 12 is removed from the ethylene oxide oven and placed in a drying oven whereupon it is heated at 180 to 188F. for one hour under a 26 inch vacuum. Sterility of the suture is malntained during this drying step since bacteria cannot permeate the container sur-rounding suture 12. The container having suture 12 therein is then stored in a dry area 21, i.e., an environment substan-tially free from moisture, until the final sealing of envelope 11. At this point the bacteria proof container containing envelope 11 and suture 12 is removed from the dry area 21 and transferred into sterile area 22 whereupon envelope 11 containing suture _ is removed from its bacteria-proof con-tainer. The gaseous contents of envelope 11 are evacuated -~
in sterile area 22 and envelope 12 is heat sealed to produce an air-tight vacuum packaged polyglycolic acid suture.
Alternatively in sterile area 22, the gaseous contents of envelope 11 can be replaced by an anhydrous gas which is inert towards polyglycolic acid such as nitrogen, argon, xenon, helium, hydrogen, carbon dioxide, or the like after which en-velope 11 is heat sealed to produce a non-vacuum packaged polyglycolic acid suture. Sealed envelope 11 is then removed from sterile area _ and inserted into folded plastic sheet - . Sheet 23 is heat sealed around envelope 11 by means of_ cathedral seal 24 to form outer strippable envelope 25 contain-ing therein eealed, suture containing, inner envelope 11. A
variety of materials is suitable for use as outer strippable envelope 25. For example various plastic, paper, and metallic

3 foil materials can be used for this purpose. A particularly suitable material for use as outer envelope 25 is described in U.S. Patent 2,949,181, issued to Buccino on August 16, 1960.
The dual envelope suture package is then placed f, _ g_ 1045~7V
in an ethylene oxlde oven ln order to sterilize the outer surface6 of envelope 11, the inner surface of envelope 25 arld t~e void volullle defined by sald surface~. The ethylene oxide vapor permeates outer envelope 25 to achieve this sterilization. The mechanics of this sterilization step are well known and are o~tlined in greater detail in U.S. Patent 2,917,878, said patents being herein incorporated by reference.
When sterilization is complete a storage stable polyglycolic acid suture package is provided which is entirely sterile except for the outer surface of envelope 25. Such package is particularly suitable for serving a sterile suture to a sur-geon for use.
In reference to the above process, it is apparent that the sequence and nature of the process steps can be changed somewhat without effecting the nature of the finished packaged product. For example, suture 12 and envelope 11 may be separately sterilized and then assembled in sterile area 22. Alternatively, suture 12 contained in envelope 11 can be vacuum dried prior to sterilization except that, in . . .
that event, a subsequent drying step would be required if any moisture was picked up by the suture in the sterilization process. Also, suture 12 can be dried prior to inserting it into envelope 11. Of course, a variety of sterilization tech-niques can be used such as heat sterilization, X-rays, beta or gamma radiation and such. However, the preferred method of sterilization is by gaseous ethylene oxide. Such variations in the sequence and nature of the process steps are apparent to those skilled in the art and are deemed to fall within the scope of the claims appended hereto.
~0 The polyglycolic acid suture itself may be in any form whatsoever such as a multifilament braid or a monofila-ment. It may further be needled, dyed, coated, or otherwise treated in accordance with standard suture techniques.

104~970 Data are presented in Table I which indicate the effect of various storage conditions upon the p~ckage and in-vivo strengtll Or poiyglycollc acid s~lture~ stored in the package of this invention.

3o 104'~5~70 ~1 ~ le ~
3 1~1 ~ 8~8~og 8~ g~ 8æ~} oo ~o~ ~u~ ~ooo ~i .n ~1 N _~ N N ~ ~ N ~ N N ~1 ~1~ ~ 1~ .~ ~, j~ ~ _I N ~ O U;
~ ~ _ 9 ..
l ~ ~ ~ .
I ~ ~3 ~
l '~; ~ ~E~ ~00 ~ Og ~ l Jo~00~n Ito~g l~oD 1~0 lo~0Do O~ E ~
o~ _ . ._ ~E~ E~m oo ooo ooo oooo 80 oo o oo L-~P~ oo8 ou~o ooo oooo o oo8 oo8 oo8 r.l ~i ~ ~ N rJ~ rJ~ N a~ :~ N 0~ N N E~ ~1 0 N E~ N N t~ ~ N ~I t~ 1~ ~
~ gQ L4 UO ;~ UO ~D r,~ O ~ O O 1~ ~ ~ N ~ ~ N r~J ~ ~1~ , ~ ~ N
E ~ _ _ Q
~, r ~

H~ I O~U~ I O J~ I O r7~ I ro ~ 0 J~ O I IJ~G~ I 0 ~ I O rJ~0 E~ ~ In o ~ ~ ooo ooo 8 oooo ooo o o ooo oooo r,~ .~1 l r ~ EO~ 8 ,~ ~o ~ ~o~0 o ~o~ ,o~ ~o ,~ K~0 2 ~r~ æ ,~ 2 a~ o a; ~ r~r~ ~ r~ r o ~ ~ a~a; r~ o r~ ~I N 11~
_ n ~ r~ r0~ 0 rD r51 0 rO a~ .D 0 rD 0 ~ r~ C~ r:~ , ~ ~D ~D C~ ~ ~ r~ 0 ~ ~, 77 7, 7 777 7, 7, , , 7 777 o~ ol .~ 770, o ~ ~n ~ ~ ~ ~ ~ ~ ~ 1~ ~ 1~ 1 l l lO E-l O 1<~ 0 O r~ ~D O 1~ ~ O N 1.~ :t O 1<~ ~D O 1-~ ~9 O K~ ~D O N 1.~ ~
I~ rn ,t ~1 a ~. r~
~ ~1 ~ ~i ~ ~ ~

~0'~9 97 0 Value5 are pre8ented a~ the percent of the original stren~th ret~lned. In reference to pnckage propertles, this termlnolo~y meane that on day zero of the storage perlod, the pACkaee ~trength of a control (packaged) suture was measured.
As storage time progre5sed, package strength (i.e., knot pull and straight pull) was measured at prescribed intervals and compared to the value of the control package strength on day zero to give a "percent of strength retained". In reference to ln-vivo strength, this terminology means that a control suture (no storage time) was impl~nted on day zero of the storage period in a rabbit for periods of 7 or 15 days after which the rabbit was sacrificed and the suture removed. The tensile strength of the removed suture was then measured and used as a standard control. As storage progressed, suturcs, at prescribed storage intervals were implanted in rabbits as described above and their strength measured after 7 or 15 days.
This strength was then compared to the strength observed with the control suture from day zero to give a "percent of strength retained".
The data of Table I show the effect of various stor-age conditions upon the package and in-vivo straight pull of a size 3-0 and 1-0 suture. The strength retention both in the case of package and in-vivo properties is generally satis-factory over all the conditions studied except at 132F. and ~5 10~ relative humidity. The data clearly indicate the extreme-ly rapid deterioration in suture strength to be expected even with the preferred package of this invention when the relative humidity on the outside of the package is lo~ while the tem-perature on both the inside and outside of the package is high. The data also indicate that where temperatures are low but the external relative hlmidity is high, satisfactory storage can be achieved. An analysis of these data show t~lat the package of this invention adeq~ately prevents the moisture 10~970 existine ln either a high or low moi~ture environment sur-roundlng the package from contacting the suture therein. How-ever, as stora~e temperatures are ralsed, rapid deterioration Or the suture ~trength, and in particular the in-vivo strength of the suture, occurs despite the ability of the package to prevent the entry of moisture into the contents of the package.
Dataare presented in Table II which lndicate why æuch rapid deterioration of suture properties occurs after storage at 132F. Certain of these data are presented in Figure 4a (package straight pull) and Figure 4b (15 day in-vivo straight pull) and clearly indicate the importance of keepin~ the suture dry up to the point of packaging it in the package of this invention if suture strength is to be re-tained during prolonged storage at elevated temperatures such as 132F.

' .i ,i c -14- .
' ` , .

O r _ ~ ~ ~ O ~ O ~ ~ ~ 0 ~ ~
~ ~; ~ ~.
_ C-~ ~ V~
~ ~ _ .
~ E~
~P~ O O O O O O O O O O O O O $ O O O O
Z ~ ~ O O O O O O O O O O O O O ~ O O O O
w ~ ~ ~ ~ ~ ~ ~ co O ~ ~ ~ ~ O O ^ ~ ~ CO c~
~ ~ U~ 0~ ~ co~ O~

~ _ a ¢Z
~o ~ ~ ~`D ~ I~ O ~ C~ O ~ Ul U~
W ~CO ~ I CO I ~ I o~ I I ~

~ æO æ~ ~
Zo E~ _ ~ 4 H a u~
Z ~ tn ~8gg8 8$ g88g 888 888g g888 E~ L~l ~~ ~O O 1~ ~ ~ ~ ~ ~O ~ ~ ~ ~ ~ ~ co ~ D 0 `D
W ~ H E-l~~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ^ ~ ^~
~; O E-l O ~co 1` ~ O 0 _I 0 1~ u-) ~ 0 ~ ~') CO 0 ~J ~ co u~ ~
Q~ Z~ 11 `;t ~ -;t `;t ~ ~ _1 ~ ~ `;t ~ ~t ~ `;t ~ O
C~. - C~ ' w HW C ~æ
~3 ~ W H ~ CO ~0 1~ ~ 0 ~ ~1 U~ 1 O
:Z ~: ~ ~ 0 1'` ! I ~ Ico~ Icr~ u ~ Z ~ ~ ZW
~ ~7 ~; _~
o ~ .
H E-~ ,_ . ~
~ u~ ~ oooo oo ' oooo ooo oooo oooo ~
W ~ H ~, O O O O O O O O O O O O O O O O O O O O O QJ al w ~ o o o ;t ~o ~ ~o ~ o 1` ~o o 0 ~o o In ~O ~O ~O ~ ~O ~ U
~ E~ P~ ~ ^ ^ ^~ ~ . U u z ~ ~ ~ _I co co ~ _ ~ ~ a~ CJ~ ~ _I O r~ ~ 0 u~ tO
C~ ¢ ~ 0 `D ~ la ,r- ~o ~o ~0 - r~ ~o _I 1~ ~0 `D ~0 1` ~0 ~0 ~0 P~
¢, u~ ~ w o~ ~
~; ~ :~ N O O O O O O O O O O O O O O O O O O O O O O O O U
¢ 3 E~ H I I I I I I I I I I I I I I I I ~ O U
P~ ~ :~c~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~~ ~ ~ ~ ~ ~ ~ cY~ ~ ~ ~ ~ ~ o~
~ ~n tn ul ~ ~ . .~ u ~
I ~ ~ I ~ ro_ X v~ ~ ~ ~ ~ ~ ~ u~
O ~Z e '~ ~ ~ o o a~ ~ ~
w :~ 0~o C ~ " e ~ o ~ 0 ~ JJ c ~ ~ CO ~ J ~ O ~ 0 ~ CO ~ ~ ~ 00 1~ 0¢ ~ ~ I oo ~h ~ ~ a Z J J C 1~ O~ ~0 ~ C C ~ o ~ _I .,.~ k ~
oo ~ o C U~ ~ ~ Y; t~1 ~O U Ul ta u . H E~ ~ ~ ~ ~ ~ a~ 00 ~ ~ ~ ~ CL. ~ 10 H H ~ ~ C~ g ~ O ~ O ~ ~-c~o u ~ ~ t U ~ U ~ U~
r .l Z H ~ e ~ ~ ~, ,, c ~ . ~ u ~1 0 ~ O ~ O O ~ O~ O ~ O ~ O rO e ~ c ~ c ~ _, U~ ~ ~ L .C ~ ~ o U~
cr~ . c ~
~o o _l ~ ~ o ~ o o ~ o o ~ o o ~ ~ ~o o _l 3 U~ _ . . ~ .
:1 _ O ~ o~ o o~ ~ o~ o o~ ~ o~ o~ o~ ~o Z u~ o o c~l o o o ~1 o o o C~l o ~ Du~ O Z O _~ ~ ~ O ~ O ~ ~ _~
C~ O ~ _l ~ ~ _~
. _ 9 ~ 70 The data of Table II detail a Btudy of the eff~ct Or the lnterlm conditions to which the suture i8 exposed be-tween when it ls dried and when it is sealed in the package Or this invention. In one casel the dried suture was exposed to an environment maintained at room temperature but havlng 50% relative humidity for 24 hours. The envelope containing the ~uture was then sealed, packaged in any outer strlppable envelope, and stored at 1~2~F. and 10% relative humidity;
after only one week storage at these conditions, the suture had retained virtually no in-vivo strength while simultaneously its packaged strength had severely deteriorated.
In another case a dried suture was stored in a con-tainer at room temperature in an environment having 20 to 30 relative humidity. The suture was then packaged as above.
The same rapid deterioration in suture strength which was noted with interim storage under conditions of 50~ relatlve humidity was also observ~d in ti,is case.
In a final case, the dried suture was removed from the drying oven and immediately placed in a dessicator where it remained until sealed in its package. As can be seen from Figures 4a and 4b, after 6 weeks storage at 1~2F., the pack-age and in-vivo strength retention of the sutures were at satisfactory levels. Storage for one week at 132~F. and 10%
relative humidity is equivalent to storage for one year at 72qF. and ambient humidity.
The above results are provided to clearly indicate the lmportance of preserving the suture ln a dry state once it has been dried until it is sealed within its water-imper-vious package. In some cases, even very brief exposure of dried sutures to moist environmental conditions has, surpris-ingly, produced extremely rapid deterioration of suture ~trength when the sutures are subsequently packaged and stored, particularly when storage occurs under conditions of high 1045~70 temperature which accelerate the undeslrable effect upon the polyglycolic acid suture.
Table III present6 data which compares the storage capabilities of the package of this invention with those of a typical package which is in widespread use for catgut sutures under various storage conditions. The catgut p.ackage referred to is that described in U.S. Patent 2,917,878.

3o 10~71~

. . .

K I ~ rl 0~ ~ ~ O` ~ ~ O ~ I
O :Z; ~_ O ~ ~ D ~ In ~ ~ u~ ~
D: ~
~0 ~ U~ , Z ~ , _ .
'C ~ ~ g g ul o~g 1O~ O ~D ~D 1` U~ o 00 0~ ~ 00 ~0 ~: ~ ~ ~ ~ U'l C~ ~ t'~ ~ I` ~ ~o .~
~ a ~ ~ ~ o~ .. .~ ~ o ~
o ~ ~ ~ 0 ~ ~ ~ ~ _, _, ~ ~ U~ ~ ~ ~ O
K I ~ ~ t ~ I I

~ ~ ~ ~ ~ ~ ~ ~ ~o~
E-1 H Z ~ C~` CO ~ I ~ a~ ~ ~ ~ 0 1~ I 0 k~
0~ R E~
~n E~ ~ ~ ~ . . .
E~ ~Ç r: ~n O o o O O o o o o o O O o o o O o o O o ::~ ~ :~ ~ o o o o ~ O o O O O O Q O O ~9 O O O O O
1--I 14 C:~ ~ ~ O O ~ 1~ 0~ N ~ 1~ 1~ ~) ~t 1~ a` 1~ `D `:t ~-1 o ~C 'G ~ ~ a` ~ ô o~ r) O~ o^o^~ a~
n F4 u~ r~ r~ v~ ~ r~
~i ~ 3 v.~ .. _ _ . .
,~
:~ e ~ O~ O 1~ 1~ ~ J O~ ~
~n C~ ~ 3 ~ ~ ~ ~ ~ o o o o o ~ ~ ~ ~ ~ o o o o o W ~ ~
~ ~ ~ . . .
~ ~ ~3 JJ ~ ~ _i ~ ~, ~ ~ CO ~ ~ P~
K u O O U 0 0 ~
n ~j . _ . _ _ _ _ _ . o Q
~n ~n ~n o r~ ~ ~ ~ o r~ ~ ~ ~ O ~ ~ o 1~ ~ ~ ~

O . . : ~R _ _ Z m o ~ o l ~9 ~o ~ ~ O o o ~ ~ ~Y o .
. _ .- _ ,.` ., Z~ O ~0 ., ~ ~ ~ ~ l O U~ rl ~ ~ .~;0 ~ V ~
~n~ ~t~ ~ ~ ~o 10'~17V
The data of Table III are presented in F1gures 5a and 5b. Referrin~ to these Figures, it is noted that at both stora~e conditions studied (l.e. 100~ 100% r~lative humidity and 132F.-10~ relative hvmidity), the storage capabilities of polyglycolic acid sutures with respect to both package and in-vivo strength were at least equal to that of catgut sutures and, in ~act, appear to be somewhat better.
The data shown in Figures 5a and 5b serve to clearly indlcate the ability of th~e package of this invention to pro-vide prolonged stable storage of absorbable polyglycolic acidsurgical s~tures.

3o

Claims (10)

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

1. A method for preparing a storage stable, packaged polyglycolic acid suture characterized by the steps of (a) inserting a polyglycolic acid suture in a container fabricated from a material which is impervious to air and water vapor, (b) sterilizing the suture and container, (c) removing essentially all of the water from said suture and con-tainer, (d) maintaining the suture and container in a desiccated, sterile environment, and (e) evacuating the gaseous contents of said container or flushing substantially all of the gaseous contents out of said container, replacing them with a gas which is non-reactive with polyglycolic acid and which is es-sentially free from water, and then sealing said container with an air- and moisture-tight seal.

2. A method according to claim 1, wherein step (e) consists in evacu-ating said container with an air- and moisture-tight seal.

3. A method according to claim 1, wherein step (e) consists in flushing substantially all of the gaseous contents out of said container and replacing them with a gas which is non-reactive with polyglycolic acid and which is es-sentially free from water and then sealing said container with an air- or moisture-tight seal.

4. A method according to claim 1, 2 or 3, characterized by the use of ethylene oxide vapor to sterilize the suture and container wherein the suture is contacted with a gas having as its active component ethylene oxide, said gas having an ambient moisture content and being maintained at a temperature of from about 70°F to 90°F and a pressure of about 5 to 15 pounds per square inch for a period of at least about four hours.

5. A storage stable,packaged polyglycolic acid suture comprising an air-tight sealed water vapor-impervious container and a desiccated sterile poly-glycolic acid suture, the suture being located in said container in vacuo or in a desiccated gaseous atmosphere non-reactive with polyglycolic acid, the suture and the interior of the container being essentially free of all absorbed moisture.

6. A storage stable,packaged polyglycolic acid suture according to claim 5 wherein said container is rendered moisture vapor impervious through the use of aluminum foil.

7. A storage stable, packaged polyglycolic acid suture according to claim 5 wherein said container is a laminate structured as follows:
(a) a heat sealable thermoplastic layer, said layer forming at least a portion of the inner surface of the container, said inner surface be-ing that surface adjacent to the suture, (b) an aluminum foil layer adjacent to the polyethylene layer of (a), said layer being from about 0.35 to 1.0 mils thick, (c) an adhesive layer suitable for bonding aluminum foil to paper adjacent the aluminum foil layer of (b), said aluminum foil layer being sand-wiched between the layers described in (a) and (c), and (d) a paper outer layer adjacent the adhesive layer described in (c), said outer layer being that layer exposed to the environment surrounding said package.

8. A storage stable, packaged polyglycolic acid suture according to claim 7, wherein the compositions and thicknesses of said layers are as follows:
polyethylene layer (a): about 1.5 mils aluminum foil layer (b): about 0.5 mils polyethylene layer (c): about 0.5 mils paper layer (d): about 1.1 mils ? 20 %.

9. A storage stable, vacuum-packaged polyglycolic acid suture accord-ing to claim 8.

10. A storage stable, packaged polyglycolic acid suture according to claim 8, further characterized in that said package is further enclosed in a sterile enclosure having a strippable seal thereon.