CA2124936A1

CA2124936A1 - Steam sterilizable system for inactivating viral contaminants in body fluids

Info

Publication number: CA2124936A1
Application number: CA002124936A
Authority: CA
Inventors: Jack Debrauwere; Jean-Marie Mathias; Indrajit Patel
Original assignee: Individual
Current assignee: Baxter International Inc
Priority date: 1992-10-05
Filing date: 1993-10-04
Publication date: 1994-04-14
Also published as: JPH07503168A; DE69326147T2; EP0650345A4; EP0650345A1; DE69326147D1; WO1994007426A1; US6207107B1; EP0650345B1

Abstract

A steam sterilizable unit (10) for inactivating pathogens in a body fluid is provided comprising a plastic structure for housing a therapeutically effective amount of a methylene blue solution.
The plastic structure preferably includes at least an inner layer (128) constructed from a non-PVC plastic. Preferably, the methylene blue solution has a pH of less than 7.0 and preferably less than or equal to approximately 6.3.

Description

WO 94/074~6 Pcr/us~3/og3g6 2~ 24~6 ~ P C I F I C A T I O ~

STEAM STERILIZAB~E SYSTEM FOR
INAC~IV~TING VIRAL coN~AMINaNTs IN BODY FLUIDS
BACKG~D . OF THl~ INVEN~TION
The present in~ention relates generally to systems for col 1 ating and hou~;lng body fluid~. Mor~
specifically, the present ir~Yention relates to apparatus and mQthods for housing body fluids and ~;olutions for inactivating ~riral cont~minants that may be present in the body f luids .
In a variety of therapies, such as transfusions and tran~3plallts, body ~luid~;, esp@cially blood comlporlerlts such as red bl~od . ells, platel~ets, plasma, leu3~ocy. ~s, and bo~qe marrow, are infused from on~ or more individual~
into a patient. Althollgh such therapies provide treatments, some of which are life savingr and cannot otherwis~ be provided, due to the transmission of in~ectious di~eases there may be potential risks involved 2 0 with ~;u~h therapie~
By way o~ example, it i~ known that blood can car~
infectious agent~ sllch as hepatitis virus, human immuno-defi~::iency vinls (an etiological ag~nt for ATDS~, and herpes virus. ~lthough screening m~thod~ exi~t to identi~y blood that may include such viruses, blood contain~rlg viruses~ and other disease causing pathogens, such as bacteria, ::annot 3~e 10Q% eliminated ~ro~ the pool o~ possibl~ blood component supplies. Therefo:L ~, thera ~ 5 still a small risk that blood tran.sfusiorls can transmit viral or other infections.
Accordingly, a gl~l of rec~nt biomedical research has be~n to reduce the risk of transmitting an infectious agent by ~electively inactivating or depleting pathogens WO 94/07426 PCr/US9~/09396 'P
~ ~49~fi presen~ in such blood components. One approach has b~en to utilize photosensitive (photoactive~ agerlt~ that when activated by light of the appropriat~ wavel~ngth will d~stroy the ability o~ the pathogen to cause infe ::tion.
The us~ of photodynamic therapy has beell suggested as a way to eradicate iniEectious agents from collect~d blood and its componerlts prior to storag~ and/or transfusion.
A number of different photoactiYe agents have been prop;: sed as possibilities to be used to eradicate viral lo and other aontaminarlts in body fluidso Such pho~oacltive agent~ inc:lud~: psoralens; porphyrins; phthalocyanines:
and dyes such as methylene blue. See, for ~xampl~, U.S.
Pat~nt Nos.: 4,748,120; 4,878,891; 5,120,649; and German Pat~nt ~pplication No. DE 39 30 510 Al (Mohr).
~lthough much ~ffort has been foc:ussed on commercializing such methods using photoactive agents, the inventors believe that such methods are currently not commercial . Even though a commercial system f or utilizing a phol:oactive aqent to treat blood to eradicate 2 0 or remove viral and okher contaminants has not been developed, it is erlvisioned that such a system would entail combirling the blood wikh ~he photoas::tiv~ agent in a container and irradiating the resultant mixture with light of the appropriate wavelength.
It is known, of course, to use blood pack UIlit5 to collectplood. The blood pack units inalude a contairl~r typi~a~ly s::onstnlcted ~rom a plastic material , usually a polyvinyl chlorid~ mat~rial. The ~l~od pack unit:; are connected to tube~ ~hat allow blood to be infused into the container as w~ll a~ to be acce~sed therefrom.
of c:ourse, blood pa ::k units musk be sterilized.
qypically, steriliza!tioTI takes plac~ by steam W094/07426 ~T~US93/093g6 2~)36 sterilization at a temperature of above ~OOC for a predetermined period of time.
On~ phot~active agent that appears to be promising with respert to ~radicating ~iruses and bacteria ~rom S blood is methylene blue. ~ethylen~ blue, 3-7-bis(dime~hylamino)phenothiazine-5-ium chloride, (Cl~H18ClN3S) r in th~ pre~ence of light has been reported to damage DNA. Accordingly, it can be used to s~lectively, in a controll~d manner, modify the DNA and ~NA of bacterial and viral contaminants thereby inactivating the pathogens. See U~S. Patent No.

4,950,66~.
It has recently been dete~ined, however, that if methylene blue is placed into a standard blood pa~k unit con~truated fr~m PVC under standard conditions and the unit i5 then sterilizedr that at least a certain amount o~ the methylene blue migrates into the PVC layer reducing the methylene blue present~ The spPcific amount of met~ylene blue ~hat migrates is variable dep~nding upon the conditions~ However, envisioned methods o~
using methylen~ blue to treat blood and oth~r body fluids require that precise amounts oî methylene blue be used.
This unfortunately requires that the blood p~c:k~
must be st~rilized prior to methylene blue being added thereto. This can create logistia problems as w~ll as increas~ the cost of areating the product.. Likewise, during'the methylene blue filling proc:ess, there is the risk o~ contaminating the sterilized c:on~ainer.
SU~ARY QF THE_INVENTION
3 O Appl icants have surprisingly discovered that methylene blue can bP- housed in -ertain containers, or under certain conditions, and st~rilized with the blood pack unit without the methylene blue migrating into the W094~07426 PCT/U~93/09396 Y
~1 24936 - 4 - :

pla~tic. It has been fou~d that two of the parameters that have a great effeGt on preventing methylene blue from migrating into the plastic are: the type of plastic; and the p~ of the methylene blue solution.
It has been surprisingly found that methylene blue does not migrate intQ non-PYC matexial ac well as into P~C material under sterilization conditions.
Accordinyly, in one embodiment of th~ in~ntion, the present invention provide~ a steam sterilizable housi~g that includes a therapeutically effective amount of methylene blue in a solution. The housing includes at least an inner surface, the ~urface that contact~ the m thylene blu~ solutinn, that i~; con~tructed from a non-~VC material.
In an embodiment/ the houF;ing is a container of a blood pack unit that is designed to receive blood or a blood compon~nt.
The housing can also be a steam sterilizable tube including a therapeutically effective amount of a viral ~:~
inactivating agent for use in blood therapy. The tube de~ines an interior having a first and a second end~
- These ends are lnitially ~losedO The int~rior is de~in~d by an inn~r ~urface construated from a non PVC material.
The interior includes ther~in a therapeutically effective amount of methyl~ne blue.
In an embodiment, the tube is constructed from a mono-l~yer material. In a furth~r 2mbodiment of the invention, the tube is constructed from a multi-layer materi~l. In a pref~rred embodiment o~ such a multi layer tub~, the outer layer of the tube is sealable to a P~C material~
In another ~m~odiment o~ th~ pre5ent invention, a therapeuti~ally effective methylene blue ~olution is .. : . ~ ... . ~

W~ 94/07426 ~ 9 3 6 P~ lS93/093 provided. The methylen~ blue solution is adjusted to a pH of le~ than 7 ~ o and preferably, approximately 6. 3 or less and is designed to be housed in a plastic contain2r that will be ~team sterilized.
5In another embodiment of the invention, a st~3arn steri~ izable unit ~or inactivating pathogens in a body ~luid i provided comprising a plastiG ~tructure housirlg a ther peutically effective amount s:~f a m~thylene blu~
~olution havi.ng a pH of less than 7.0 and preferably less 10than or e~ual to approximately 6 . 3 .
In an ~mbodimerlt, t:he pla~ ic structure is a container d~si~ned to house blood 3r a k)lood coml?orlent.
In an embodiment, the plastic structur~ is a tube that is coupled to a container designed to house blood 15or a blood c:omponent.
The pre~ent inYention also pro~ide~; methods for inactivating pathogens that may be present in a body ~luid., An advantage of th~ present invention is that a 20blood pack unit can be provided that includes a viral inactivating agent therein.
A further advantage o~ the present inv~ntion is that it provides a c::ontainer including a viral inacti~ating agent that can be steam sterilized.
25Furthermore" an advantage o~ the present inveIltiorl is that ,a sterilizable tubing~ that c:an be sealed to a p~lC con~ainer, c:an be provided that in~::ludes a therapeutic:ally effect~ve amount of methylene blue.
Still further, an advantage of th~ present invention 3 0is tc~ provide an improved method ~or inactivating pathogQns that may be contained in a }: ody ~luid.
Additiosnal f~atllr~s and advantag~s o~ th~ pre~ent inYention are desc:ribed ir~, and will be ~pparent from, WO 94/07~26 ~ 1 2 4 !~ 3 fi PC~/lJ~i93~g396 'J

the detail~d description of the presently preferred embodiments and f rom the drawings .

Figure 1 illustrates arl embodiment of a bloc~d pack unit constructed pursuan~ to the present invention.
Figure 2 illuætrate a further embodim~nt of a blood pack unit constructed pursuant to the pr~sent invention,.
Figure 3 illustrates a crc: s~;-sec:tio~ riew of the tube o~ Figure 2 taken along lines III III.
~igure 4 illustrates a ~urther embodiment of a blood pack unit constructed pursuant to the present imrention.
DETAILED I: E:SCRIPTION
Q, ~REr) :~MBODIM~N~$
~he pr~;ent imrention r~l.ates to apparatus and methods for containing body fluids and/or inactivating patho~ens that may be contained in the ~ody fluids. ~
used herein, body f luid not only includes blood and its components, but also includes other flui~s contained in the body or fluid containing structures such as , e . g O, 2 O bon~ marrow, semen ~ and internal organs .
As pr~sriously noted, althouqh body f luids ~ ~;uch as blood and its c:omponents, can be used in many therapeutic applicatiç3ns, there is th~ danger of the ~ransfer of infectious di~ease due to viral and bacterial 2 5 contaminants that may be c:ontained in such f luids ~
R~centl~ the use o~ photoactive agents has provided the hop~ of inactivating viral and bacterial contaminants that m~y be cantained in such fluids. Howe~rer, in order to commercialize such methods, certain obstacles must be o~rerc:ome. ~
It is known to house blood compon~nts in plas~is:
contain-3r~. ~ypically, ~he plastic container comprises a pol~rinyl chlorids structure that is plasticized with ... .. , ~ , ,.. ,. " . . .. , . ~ , , , WO 94/07426 ~ .1 2 ~ ~ 3 6 P~r/US93/093g6 di ~ 2 ethylhexyl ) phthalate ( DEHP ) and includes ~tabiliz~rs. It has be~n found that when a svlutit~n of methyl~ne blue, a pho~oinactive agerlt oP promise, is placed in such a container at a physiological pH of around 7, that upon steam ster lization~ the photoinEIctive ag~llt ~methyl~3ne blue) migr~tes into the pla~tic.
Methods o~ use of methylene blue to inactivate ~riral contaminants require rather precise amounts of mQthylene blue. See/ for example, Lam~srech~ et al;

~ ~_ ~ , Vox Sang 1991; 60:207-213. Therefg:~:re, the migratio~l 9f the methylene blue solution into the pla~tic during th~
sterilization process provides ian unac eptable system.
.Tble inventors ha~re surprisingly found that the migration of methylene blue into the plastic i~ dependen~
orl a couple of controllable paramaters. Therefore, pur~;uant to the present invention, it is possible to provide apparatus and ~ystems wherein methylene blu~3 can be contained within a plastîc structure, the structure c:an be ~;team sterilized, and the methylene blue solution will be rec:oYer~d in suf f icient quantity to allow th~
solution to be used to inactivate vîral con~aminants in 2 5 a body *luid .
~or exa~nple, in an embodiment of the pr~sent - inve~ 'orl, the. in~Yentors have ~Eounc~ that by c:ontrolling the type of plastic from which the housing ~hat contaill~
the methylene blue is constructed, that th~ migral:ion of 3 0 methylene blue into th~ hou~ing can be controlled . In thi~; regard, it has been found that if at leask the layer o* the contain~r that contacts th2 methylene blu~ is construc:ted i~rom a non-PVC material; the methylene blue .

W0~4/0742~ P~T/US93/Og396 stored therein will not ~ubstantially migrate into the plastic.
Although it is ~nvision~d that with proper control8 of other parame~ers, any non-PVC plastic material can be used, of mo~t interest ar~ the more inert plas~ics, uch as polyolefins and polyurethane~. In a preferred embodimen~, polypropylene, styrene-ethylene-butylen~-styrene ~SEBS~, ethylenevinyl acetate, and polyester~ are u~ed.
By way of example, referring now to Figure 1, a blood pack unit 10 is i~lus~rated. The blood pack unit includes a container 12 having ports 14 and 16 extending ther~from to provide aaces~ to an interior 18 o~ the container. Additionally, a tub.ing 20 ~xtends from the containerO The ~ubing 20 can b~ used to in~u~e a body fluid such as whole blood or a blood component into the container 12~
In the blood pack unit 10 illustrated, the tubing 20 extends from the contain~r 12 and provides means for infu~ing blood or blood compon~nts into the blood pack.
An example of a system that can be u6ed ls the Optipak~
sy~tem that is disclosed in U.S. Patent No. 4,6~8,178.
In thi~ ~y~tem, plasma or red blood cells, for example, can be infused into the container 12 through the tubing 2~ 20 after having been separa ed ~rom whole blood.
The container ~2 can have ~ structure that is substantially ~imilar to the container for h~using blood and blood components available ~rom the Fenwal Di~ision of Baxter International Inc. However, pre~erably, the container 12 i~ constructed so that at lea t an interior layer that def~nes the interior surface of the contain~r is cons~ruc~ed ~r~m a non-PVC material. ~ost preferably, at least the inner curfac~ of the containe~ 12 is WO 94/07426 2 1 2 ~ 9 3 6 P~ US93/û9396 corlstructed from SEBS, polypropylene, polyester, polyurethane, or ethylene~inyl acetate, or blends th~reof. O~ course, if deslred, the entire c:ontainer 12 can be c:onstructed f rom a non-PVC material .
Pursuanlt to the present invention/ the container 12 in ::~ ud~s a quantity of methylene blue. In a preferred ~mbodiment that has been found t:o ~unction . satis~actorily, the container c:ontains 10 ml of a methylene blue solution. As set forth in the experiments disc:losed below, it has been fourld that the pH o~ the sc~lution can effect the migratiorl OI the solution into the plastic: ma~erial during stexilizatlon. Pre~erably, the methyl~n~3 3blue solution ha~; been adjustPd to a pH of less than 7 . O and most pre~erably approximately 6. 3 or les~. ~
Pursuant to the present invention, the methyléne blue solu~ion i5 in~used into the container 12 of the blood pack unit 10, The blood park unit 1 O including container 12 and methylene blue solution can then be 2û steam sterilized, e.g., at 115C for 65 minutes. Due to th~ use of a methylene blue solution having a pH of less than 7. 0 and the fact that the container 12 includes at least an inner surface that is constructed from a non-PVC
mat~rial, the methylene blue solution, during steam steril ization, will not substantially migrate into the pla~tic;
.A~body fluid~ such as a blood component t can then be infu~ed into the container 12 through tubing 20. To contro~ fluid flow ~hrough the tubing 20, a breakable 3 n c:annula 21 or ot}ler m~eans can b~ used .
In the c:ontainer 12, the blosd component wil~ mix with the meth~ene blue solution. The container ~ is then irradiated by light of the appropriate wavelengtn : ~ .
.

WO 94/07426 2 ~ 2 4 9 3 6 P~USg3/093g6 ` ~

-- 10 -- ~

(approximately 520-~70 nm) to activate the m~thylene blue withirl the container 12. This will cause the methyl~ne blu~ to inactivate any pathogen~, e~ g. viruses and bacteria, that are contained within the blood component, thus insuring a blood c:omponent that does not contain pathogens .
In a further embodiment o~ the present invention illustrated in Figure 2, the methylene blue is contained within a coaxtr-aded tubing 12 0 that is connected to the container ~12. The tubing 120 is closed at each of a first and second end l~ and :~2~, respec~ively. The tubing 120 can be closed using b~salcable cannulas 1~3 and 125 that allow fluid flow after being manipulated, or other means.
Pre:Eerably, the tube 12 0 is constructed ~rom a material ha~ing at least an inner layer, that dç2fin~s ~he interior 127, that is ~-onstructed from a non-PVC
material . In ~ this r~gard, the tubing ï20 can be construrted ~rom a monolayer or a multi-layer material.
If a monol~yer materials is used, pre~ra}:)ly1 it i~
a non-PVC material ~ ~qost preferably f the monolayer material is solvent ~;ealable to PVC allowing the t~e 120 to be sealed to a standard PVC container. Polyur~tharle will function satisfactorily for this application. It can be sealed to PVC with cyclohexanone. Additiorlally, it is seal~ble using radio ~requency (a H0mat~0n~
allowi~qg the tube to be sealed after being used to allow blood to be infused into the container.
~eferring to Figure 3, an embodiment of the pr~sent invention is illustrated wherein a multi-layer material i5 used. In the preferred embodiment illustrated, the inner layer 1~8 is con~truc:ted from a non-PVC material.
In an embodiment that has been found to iEunction ... . . - ., . . . . . . . , . . , i . .

~! ~ 94/07426 Pcr/US93tO9396 2~2~936 satisfactorily, the inner layer 128 i5 ccsnstruc::ted fxom a blend of approximately: 60% SEBS; 20% polypropylene;
and 20% ethylenevinyl acetate.
The middle layer 130 is constructed-from a blend of approximately 50% SEE~S; 3~6 polyester; 10% EVA; and 2~;
polyp~opylene. ~he middle layer 130 func:tions as a tie layer. The outer layer 13~ is constructed frorn a PVC
material to allow the tube 120 to be s~aled to a standard PVC contailler 112. In an embodimen~, the outer layer is constructed from PVC, DEHP, and stabili~ers. Due to the middle layer 130~ the inner layer 128 and outer layer ï32 are serured t~getner.
In an embodiment, the t~be 120 can be a two layer coextruded tube. The interior :layer is non-PVC and ~ àe Quter layer is sPalable to P~C, for example, PVC. An exaraple of a structure th~t ha~; been found to ~unction sati~fackorily is an inn~ r layer of a blend of: SEBS;
polye~ter; polyvinyl acetate; and polypropylen~, and an outer layer of: PVC; DEHP; and stabilizers. Pr~ferably, the outside to inside layer thickness ratio : is approximately 9 :1.
As in the pr~3vious embodiment illustrated in Figure 1, preferably, 10 ml of methylene blue solution is contain~d with the tube 120. Likewise, preferably the solution has a pH of approximately 6. 3 or less.
I~uring manu~act Lare, the ~ube 12 0 containing the hylene blue solution is steam sterilized at 115C for 65 minut~s along with the blood pack 110~ The ~lood pack unit 110 carl then be utilized to inactivate any pathogens contairl~d in a body ~luid. To this end, t~ in~use blood into the container, the breakable cannulas 123 and 125 are broJcen allowing blood to flow through the tubing 120.
A$ the blood ~lows through the -tubing 120 it flows WO 94/07426 ~cr/US9~/09396 ~12~93fi through the methylene blue solutiorl mixing therewith.
This mixture flows into the container 112.
Once in the container 112, the methylene blue ~olution and blood are completely mixed and then irradi~ted with light of tne appropriate waveleIlgth to activat~ the photoactive ag2nt. Th~ activated methyl~ e blue will thereby inactiYate any pathogerls that may be contain~3d within the blood.
Figure 4 illustrates a further embodiment of a blood lV pac)c unit; 210. As i~ lustrated, the unit 210 includes a container 21~. A tubing 220 prov~des fluid coIIummication ~rom a body ~luid source to the container 210.
A further t~abe 230 includes a solution of methylene blue. The tu~?e 230 can be constructed in accordarlc:e with th principles disrussed with respect to the embodiment of the tubing 120 set fo.rth aboveO In us~, aft~r, during, or before a body fluid is infused into the contain~r 212, the methylene bllle solution i~
s::ommunicated into th~ container by stripping the tube 2 0 ~ 3 0 . The container 212 and body f luid/methylene blue solution ~re then irradiated.
By way of ~xampl~ and not limitation, examples of the pre~nt invention will now be given.
~AllPI,læ NO. 1 Three c:ontainers constructed fro~n different PYC
materia1s wer~ tested to determine recovery of the methy1~ne blue.
To this end, a sc)1ution of methy1ene blue was made by disso1ving 50 mg o~ methy1ene blue into a 1iter of citrat~ bu~fer solution, pH 4 ~ O. A 50 ppm resultant ~;o1ution was created. Thi~ so1ution was th~n di1uted 5 times with the same citrate buffer solution, pH 4 . O, to obtain a s~lution o~ 10 ppm.

W094/07426 2 1 2 4 9 3 ~i P~T/US93/093~6 Another solution of methylene blue was made by dissolving 50 mg of methylene blue into~ a liter of phoæphate ~uffer solution, pH 7.5. A 50 ppm resultant solution was created. This solution was then diluted 5 times with the same phosphate buffer solution, pH 7.5, to obtain a solution of 10 ppm~ To each type of PVC
plastic con~ainer were added either 10 ml of the pH 4~0 methylene blue solution or 10 ml of the pH 7.5 methylene blue solution.
Each ccr,~ainer was then steam sterilized at 115C
for 65 minute~. The methylene blue present in each container was then measured to det~rmine the percent of recovery after sterilization.
It was found that the highest methylene blue recov~ry was o~tained wi~h the type 1 PVC plastic container (81%) filled with lO ml o~ methylene ~lue solution buffered at pH 4Ø It was also found that virtually all the methylene blue had migrated inside any of the PVC plastic container when the solution was bu~fered at pH 7.5.
TA~LE_1 Effect of pH of the MB Solution Container 2~ ~ :
4.0 ~1 80 6~
7.5 1.5 0 0 ~ of MB Recovery After Sterilization.
Container Material:
3~ l - PVC; DEHP; and Stabilizers.
2 - ~C; TEHTM; and Stabilizers.
3 PVC; N-butyl, Tri-N-hexyl, Citrate; and Stabilizers~

WO 94/074~6 PCr/US~3/~19396 .. ;`~
~l2~36 ` i . ' ,`

E~AMPL~3 ~O . 2 It has been found that just a Ph adjustmerlt (no u~e of any buf~er) of the methylene blue can have an ~3ffect on the pexcent recovery oî the methylene blue after sterilization of a PVC plastic: containerO In this re~ard, the follc)wing experiments were conduc:ted.
The e:ffect o~ the pH OI the methylene blue ~olution of Example 1 ~et forth above wa~ considered.
The 10 ppm me~hylene blue solution was prepared in ;
two steps - by dissolving 50 mg of methylene blue into a liter of distilled water followed by dilution 5 times of this 50 ppm solution witlh distilled water to obtain ~-.
a solution of 10 ppm.
The pH was adjusted at various ~evels utilizing 0.1: ::
N hydrochloric acid.
To a pla~tic blood bag container corlstructed ~rom poly~inyl ~hloride, di ( 2-ethylhexyl ) phthalate ~ DEHP - a pla~;ticizer~, and stabilizers was added 10 ml of the m~thylene blue solutlon adjusted at 4 different leYels of pH. ~:ach container was then steam sterilized at 115C
for 65 mi nutes ~, Th~ p~rcent o~ methylene blue recoYery was measllred a~ter sterilization. .

In this tabïe, the e~fect of pH range of methylene blue solution for a ~iven P~C container made from PVC, ;~
DEHP, and stabilizers was con~idered. The methylene blue ~ .
ss: lutlorl was made as set: forth in :E:xample 1 except the pH was adjusted~sing .1 n HCl as indicated. ~ ::
96 oiE MB Recovery ~ ~ :

3.0 95 :
4.0 88 .0 78 6.3 81 WO 94/0742~ PCr/U593/09396 -- 15 ~

The ~ffect of plastic material (P~C and non-PVC
container) for a given pH of the methylene blue solution (pH = 4 ., o) was considered. As set forth in the Table below, two container~; were compared:
a plastic blood bag container constructed from polyvinyl chloride, tri(2-ethylhexyl~trimel1itate (TEHTM
- a pla~;ticizer), and stabilizers ; and a blood l~ag container constru ::ted from a bl nd of approximately 6096 5EBS, 20% polypropylelle, and 20%
ethylenevinyl aceta~e (the non--P~C container).
Each container was fîlled with 10 ml of the methylene blue solution, pH 4 ~ 0 o:E Example No~ 2 . The contain~rs wer~3 then ste2lm sterilized at 115C for 65 minut~ The percent s~ recov~ry c~f methylene blue was th2n mea~;ured.
It was found that in the PVC container, only 81% of the methylene blue was r~covered after sterilization.
In con~rast~ h~w~ver, in the non-PVC c:ont~iner, 9~% of the methylene blue was recovered a~ter sterilization.
96~ recov~ry o~ t~e methylene blue is su~ficiently high to provide a ~iab.~ ~.ys~em.
% o ~B R~covery ~ zation A - PVC; TEHT~; and Stabilizers.
B ~ A blend o~ approximately 60% SEBS, 20% PP, and 20% EVA.
In view of the experiments set ~orth in the above example~, in an embodiment of the pr~sent invention, the pH of the methylene blue solution is adjust~d to insure WO 9~1/07426 P~/US93/0~396 , ?~124~36 ~,~

that it is less than 7 . 0 and preferably equal to or les~
than approximately 6. 3 .
l~X~IPL O. 4 Additionally, the ef fect of aging has been S considered using methylene blue and a non-P~C container.
Ac:celerated stability studies have shown ~hat a lO ml methylene blue solution, made in acc:ordance with ~:xample No. 2, in ~ container made from a blend of approximately 60% SEBS, 20g~ PP, 2~% E~IA and overwrapped ~ n an alumirlum foil ~prs~tection from daylight exposure) did not degrade after 6 month storag~ at 45C.
It should be understood that various c:hang~s and ms:dification~; to the pre;ently pref~rred embodiments described her~in will be apparent to those skilled in the art., Such changes and modi~ications can be mad~ without ~eparting f rom the spiri~ andL scope of the present imrention and without dimini~hing ltS attendant advantag~s . It is th~ref ore intended that suc:h changes and modif ications be covered by the appended claims .

Claims

WE CLAIM:

1. A steam sterilizable structure that can be used in a system for inactivating viruses comprising:
a structure including a therapeutically effective amount of a viral inactivating agent, the structure having at least an inner surface, the surface that contacts the viral inactivating agent, that is constructed from a non-PVC plastic material.

2. The steam sterilizable structure of Claim 1 wherein the structure is entirely constructed from non-PVC plastic material.

3. The steam sterilizable structure of Claim 1 wherein the non-PVC plastic is at least one plastic chosen from the group consisting of: polypropylene, styrene-ethylene-butylene-styrene, ethylenevinyl acetate, polyester, and polyurethane.

4. The steam sterilizable structure of Claim l wherein the structure is a container for storing a body fluid.

5. The steam sterilizable structure of Claim 1 wherein the structure is a tube secured to a container for storing a body fluid.

6. A steam sterilizable tube designed to be part of a system for housing a body fluid including a therapeutically effective amount of a viral inactivating agent for use in inactivating pathogens in the body fluid comprising:
a tube defining an interior and having a first and a second and which are initially closed, the interior defining an inner surface constructed from a non-PVC
material and including therein a therapeutically effective amount of methylene blue.

7. The steam sterilizable tube of Claim 6 wherein the tube is constructed from a mono-layer material.

8. The steam sterilizable tube of Claim 6 wherein the tube is constructed from a multi-layer material.

9. The steam sterilizable tube of Claim 6 wherein the tube is sealable to a PVC material.

10. The steam sterilizable tube of Claim 8 wherein an outer layer of the multi-layer material is sealable to a PVC material.

11. A steam sterilizable container for housing a body fluid including a therapeutically effective amount of a viral inactivating agent for use in inactivating pathogens in the body fluid comprising:
a container defining an interior, the interior defining an inner surface constructed from, a non-PVC
material and including therein a therapeutically effective amount of methylene blue.

12. A steam sterilizable blood pack unit for containing blood or blood components comprising:
a container defining an interior for housing blood or blood components, the interior including inner walls that are constructed from a non-PVC plastic material; and a sufficient amount of a methylene blue solution to inactivate viral contaminants that may be present in blood or blood components housed within the container upon the application of light of a sufficient wavelength.

13. The steam sterilizable structure of Claim 12 wherein the structure is entirely constructed from non-PVC plastic material.

14. The steam sterilizable blood pack unit of Claim 12 wherein the non-PVC plastic is at least one plastic chosen from the group consisting of: polypropylene, styrene-ethylene-butylene-styrene, ethylenevinyl acetate, polyester, and polyurethane.

15. The steam sterilizable blood pack unit of Claim 12 wherein the pH of the methylene blue solution is less than 7Ø

16. A steam sterilizable system for housing a body fluid and inactivating a pathogen that may be contained within the system comprising:
a container having a therapeutically effective amount of a methylene blue solution that has a pH of less than or equal to 6.3.

17. The system of Claim 16 wherein the container includes an interior that contacts the solution constructed from a non-PVC material.

18. A steam sterilizable system for housing a body fluid and inactivating a pathogen that may be contained in the body fluid comprising:
a container;
a tube connected to the container; and a therapeutically effective amount of a methylene blue solution having a pH of 6.3 or less.

19. The system of Claim 18 wherein the methylene blue solution is housed in the tube.

20. The system of Claim 19 wherein the tube has at least an inner surface constructed from a non-PVC
material.

21. The system of Claim 18 wherein the methylene blue solution is housed within the container.

22. The system of Claim 18 including at least two tube, a first tubing allowing a body fluid to flow into the container and the second tube housing the methylene blue solution.

23. A method for storing a body fluid and inactivating pathogens contained therein comprising the steps of:
providing a container for receiving a body fluid;
providing the container with an interior having inner walls constructed from non-PVC material;
placing a therapeutically effective amount of a methylene blue in the interior of the container;
steam sterilizing the container;
transferring the body fluid into the interior of the container; and irradiating the container with light of a sufficient wavelength to activate the methylene blue solution,

24. The method of Claim 23 wherein the methylene blue solution has a pH of less than 7Ø

25. A method for inactivating pathogens that may be present in a body fluid comprising the steps of:
providing a system including a container for receiving a body fluid and a tube connecting the container with a source of body fluid;
locating within the system a therapeutically effective amount of a methylene blue solution having a pH of less than 7.0;
steam sterilizing the system;
transferring a body fluid into the container through the tube and causing the body fluid to mix with the methylene blue solution; and irradiating a resultant body fluid/methylene blue solution with light of a sufficient wavelength to inactivate pathogens contained therein.

26. The method of Claim 25 including the step of:
initially locating the methylene blue in the tube of the system.

27. The method of Claim 25 including the step of:
initially locating the methylene blue in the container of the system.

28. The method of Claim 25 including the step of:
providing the tube with an inner surface constructed from a non-PVC material.

29. The method of Claim 25 including the step of:
providing the container with an interior constructed from a non-PVC material.

30. The method of Claim 25 including the step of providing the system with a second tube that initially houses the methylene blue solution.