Note: Descriptions are shown in the official language in which they were submitted.
8~3
Tile present invention relates to the packaging
of "dry type" articles, particularly artificial kidney
dialyzers u-tilizing hollow fiber membranes, in a package
: ~,
containin~ a controlled atmosphere or environment.
Articles such as dry -type artificial kidney
dialyzers utilizing permeable hollow fiher membranes are
typically sterilized with ethylene oxide and, after
sterilization/ the ethylene oxide gas in the dialyzer is
completely replaced with aseptic air during an outgassing
period. Prior to dialysis, the dialyzer must be cleared
of air and primed. In such procedures, the air is flushed
from the dialyzer and blood lines bypassing a saline -~
solution through the dialyzer. Typically, a dialyzer
undergoing priming requires a great deal of sharp rapping
~ ~ : .: ~ .: -
on the dialyzer itself, on the drip chambers and on tha
blood lines to effectively clear 1iny air bubbles there~
from. Often, the quantity of saline solution utilized
~.-
and the attention needed to prime a dialyzer requires a
substantial amount of time by skilled personnel and thus
substantially increases the time needed for dialyzation~
of each patient. Moreover, it is believed that the sharp
rappings required to clear any air bubbles from the
dialyzer may itself be the cause of damage to the mem~
branes, and the creation of leaks in the dialyzer thereby
destroying the useability of the dialyzer.
In another procedure attempted for priming a
::
dry, air-filled dialyzer, the arterial blood line con~
nected to the dialyzer is connected to a C02 cylinder and
the dialyzer flushed for 4-5 minutes with C02 to clear the
air from the dialyzer and blood lines. The dialyzer is
then primed in a procedure similar to the one set forth abo~e.
17,969-F
~I.il ~Z8~3 ~ :;
While i-t has been ~ound that a dialyzer flushed first
with CO2 generally can be primed more easily and in a shorter
period of time in comparison with an air-filled dialyzer, the ;
above CO2 flush procedure is disadvantageous in certain other;
respects. Thus, even though the priming time with a sallne rlnse
solution can be decreased, additional time and hence expense Is~
required for the individual or clinic technician to connect and~
flush the dialyzer with CO2. Extra space for cylinders of C0
must also be provided and an adequate supply of CO2 kept on hand~
Additionally, this priming procedure increases the risk of~
contamination of the dialyzer because of the extra connect~ons~
necessary to complete the priming of the dialyzer. These ~factors;;~
all clearly negate whatever advantage may have been gained in~
priming ease and time.
The present invention provides a package or comb~naeion~
comprising a dry sterilized artificial kidney dialyzer containing~
a plurality of semipermeable hollow fibers; and means for~main~
taining said kidney dialyzer in said dry sterilized cond~tion~and~
ready for immediate priming with a sterile saline solut~on~to~
render the kidney dialyzer suitable for immediate use in~dialys~is~
with a minimum of preparation and lapsed time and without recourse`~
to pre-flushing procedures to remove entrapped air compr~sing~a
first quantity of controlled atmosphere filling~said dialyze~r~ a~
second quantity of controlled atmosphere enveloping said~d~alyzer,~
and a gas impermeable enclosure containing said dialyzer and~
second quantity of controlled atmosphere, each said first;and~
second quantity of controlled atmosphere comprising a gas
compatible with said dialyzer and free of air and sterilant and~
amenable to said priming without pre-flushing.
The present invention also provides a method of
producing the above type of package which method comprises
- 2 -
,.",
;~
IL~L42~9~
(a) placing an ar~ificial kidney dialyzer having a pIurality o~
semi-permeable hollow fibers within an open enclosure comprising
a gas-impermeable material, (b) sterilizing said dialyzer~and~
said enclosure, (c~ evacuating the atmosphere from said~ ~dialyz~
and said enclosure, (d) passing an air-free controlled a ~ ~ 'r`e~
into said dialyzer and said enclosure, and (e) sealing~said
enclosure, thereby forming a gas-impermeable package~
In a preferred embodiment of the above processe~s `there~
is provided a method which comprises (a) sealing an ar~ ~f
kidney dialyzer having a plurality of semi-permeable hollow~
fibers in an enclosure comprising a gas-lmpermeable material~'
and having a gas-permeable zone, (b) :sterilizing said:dia~lyzer~
and said enclosure, (c) evacuating the atmosphere from~:sald~
dialyzer and said enclosure, (d) passing an air-free controLle
atmosphere into said dialyzer and said enclosure, and~(e~ seà~ingly~
dividing the package `:
- 2a - ' : ::::~
.
:
:: : :: .:
~42893
nto a first section containing the gas-perm~able zone and a second sectl n~
containing the dialyzer, and where required ~f) separating said first section~
from said second section. :
A further embodiment of the present inventlon provldes~a:package~
comprising an outer gas-impermeable enclosure,~ an inner enclosure; compri:sing~
a gas-permeable material and enclosed within said outer enclosure, and an~
artificial kidney dialyzer having a plurality of semi-permeable hollow ibers~
and enclosed within said inner enclosure, each of said dialyz~er, said: mner
enclosure and said outer enclosure being free of sterilant and contain`m g~
an air-free controlled atmosphere therein.
The present invention also provides a method:for formlng the
above type of package which method comprises ~a) sealing an artiflclal~
kidney dialyzer having a plurality of semi-permeable hollow fibers~:in a:~f~
enclosure which is permeable to gas, ~b) sterilizing said~dlalyzer~and;~said
: first enclosure, ~c) enclosing said sealed dialyzer within a second~ènclo-~
sure which when sealed is impermeable to gas, (d) ;evacuat:ing~the ~t~osphëre~
rom said dialyzer, said first enclosure and said second~enclosure,~é);~
passing an air-free controlled atmosphere into sald second enclosurè,~ said:'~
first enclosure and said dialyzer, and ~f) sealing said second enclosure,~
thereby forming a gas-impermeable package.
In the above processes a number o operations may be:condu~cted~
concurrently.
In the first of the above noted methods steps (a) and~(b)~may~be~
conducted concurrently by placing a previously sterlllzed dialyier in:sai~d~
open enclosure. :~
In the third of the above noted processes steps ~a), ~b)~ and~:~c)~
may be conducted concurrently by placing a previously sterilized~dialyzer~
enclosed in a gas-permeable first enclosure in a second enclosure which:~when~
sealed is impermeable to gas.
-3- ~:
' . '
,
2~9;~
The present invention will be readily appreciated by reference
to the following detailed description and the accompanying drawings:in which~
Figure 1 is a plan view of a sealed, gas-impermeable dialyzer
package illustrating in phantom lines a dialyzer retained therein.
Figure 2 is a plan view of a sealed, gas-impermeable package~and~
in phantom lines a dialyzer contained therein.
:: ~: ~:
.
jl -3a- ~,-
893
. . .
i~`iyure 3 is a flow diagraM illus-trating the
me-thod steps in preparing a single package dialyzer as
illustrated in Figure l. ~ r
Figure 4 is a flow diagram illustrating the ;~
method steps in preparing a double package dialyzer.
:
In accordance with this invention there is
provided a dialyzer packaged in a material which is im~
perrneable to gas. The package and dialyzer are filled
with a controlled atmosphere or environment which enables
the priming of the dialyzer to be cornmenced without the~
need for pre-flushing procedures and which greatly in~
creases the ease of dialyzer priming. Packaged dialyzers
enclosed in a first gas-permeable enclosure or gas-imper~
meable enclosure bearing a zone of gas-permeability,
which in turn is enclosed in a second outer gas-impermeable
package, are also disclosed. Methods of preparing such;
packaged dialyzers are also part of the present invention.
In the embodiment illustrated in Figure 1,
there is provided a packaged and sealed dialyzer (1)
which comprises a hollow fiber kidney dialyzer (2) having
dialysate inlet and outlet ports (3) and (4) and blood
inlet and outlet ports (5) and (6) which is enclosed in;
a gas-impermeable enclosure (7). The package, i.e., the
enclosure and dialyzer, is sealed and contains a controlled
atmosphere therein. This particular package is also
referred to as a "single package" dialyzer.
; In a second embodiment, illustrated in Figure
2, there is provided a sealed packaged dialyzer (8) com- ~ ;
'
prising in combination an outer enclosure (9) of a gas~
-impermeable material and an inner sealed enclosure (7)
, ~ , .
17,969-F -4-
~' .
'': ~ ~: ' '
~L4~3~
having a dialyzer (2) emplaced therein. The inner~enclo~
sure is permeable to gas or, as illustrated, is made of
gas-irnpermeable material containing a gas-permeable zone~
(10). The packager i.e~, the outer and inner enclosures
and dialyzer~ contains a controlled atmosphere. Such
packaging is also referred to as a "double packaged"
dlalyzer.
A method of preparing a packaged dialyzer is~
illustrated in the flow diagram of Figure 3, where a gas~
-impermeable package as shown in Figure 1 containing~a
dialyzer and a controlled atmosphere, is prepared by the~
following steps: (a) a package (11) is formed by~seallng
a dialyzer (2) in an enclosure (7) impermeable to gas.~
The enclosure is provided with a gas-permeable zone (10),
(b) sterilizing the package (11), (c) evacuating the
atmosphere from the package (11), (d) passing a controlled~
atmosphere into the package (11), and (e) sealingly dlvidin
the package along line 12-12 into a first sectlon (13)~con~
taining the gas permeable zone (10) and a second section
containing the dialyzer thereby forming a gas-impermeable
package (1) containing the dialyzer (2) and a controlled
atmosphere~
In a further embodiment (not illustrated),~
a packaged dialyzer is prepared by the steps of: (a)~
placing a sterilized dialyzer, having inlet and outlet~
ports which are capped with a permeable material to
constitute gas-permeable zones within an open gas-
-impermeable enclosure (7), (b) evacuating the atmos-
phere from the dialyzer and enclosure, (c) passing
17,969-F -5-
~ L2~393
a controlled atmosphere into the dialyzer and enclosure,
:
and (d) sealing the enclosure, thereby forming a gas~
-impermeable package containing the dialyzer and a
controlled atmosphere.
In still another embodiment as illustrated in
the diagram (4), a packaged dialyzer is prepared by thè~
steps of. (a) sealing the dialyzer (2) in a first ~enc~lo~
sure (7) which is permeable to gas, (b) sterilizing~ the~
dialyzer and enclosure, (c) enclosing said sealed~;~dialyzer~
(11) within a second sealable gas-impermeable enclosurè~
(14) thereby forming an outer, open enclosure~housing;thè~
sealed dialyzer, (d~ evacuating the atmosphere from the
permeable enclosure, dialyzer and from the outer enclosure,~
(e) passing a controlled atmosphere into the outer enclo-~
sure and into the housed sealed dialyzer, and (f) seallng
the outer enclosure (14), thereby forming a gas-impermeable~
package (15) containing the dialyzer and a control:led
atmosphere. :
In yet another embodiment (not illustrated):,~a~
packaged dialyzer is prepared by the steps of: (a) p~laaing
a previously sterilized packaged dialyzer, in which~the
enclosure is permeable to gas, in a second outer sealable~
enclosure which is gas-impermeable, (b) evacuating the~
atmosphere from the permeable enclosure, the dialyzer and~
from the outer enclosure, (c) passing a controlled atmos~
phere into the outer enclosure and into the permeable ~
enclosure, and (d) sealing the outer enclosure, thereby
forming a gas-impermeable package containing the dialyzer
and a controlled atmosphere.
17,969-F -6-
~28C1;3 ~ ~
,
Dialyzers which are packaged accordlng to the
present invention can be any one of the dry type units.
Multiple units can, of course, be contained within~a sin~le~
package, if desired. The invention is particularly suit~
able for packaging dialyzers wherein permeable, hollow
fiber membranes are employed. In a preferred embodlment,~
the packaged dialyzers of the present invention are~those
utilizing hollow fiber membranes. In another embodiment,~
the packaged dialyzers are used in blood dialysis~whereLn~
hollow fiber membranes are utllized.
As used herein, the term "dialyzer" ref~ers~to~
those devices useful for the dialyzation of fluids,~ par~
ticularly body fluids such as blood. The term "package"~
refers to a complete packaged dialyzer and the controlled~
atmosphere or environment contained wlthin the slngle~or
double enclosure and the dlalyzer.
The term "controlled atmosphere" or ~"environ~
ment" is used and is intended as a generic term to cover~
different gaseous substances which may be lntrod~ced lnto
the dialyzer to create an aseptic atmosphere and which;
are acceptable for use in priming procedures for dialyzers,~
especially artificial kidney dialyzers. The controlled~
atmosphere or environment contained in the dialyzer and~
package is preferably carbon dioxide.
The term "gas-impermeable" refers to materials
which are impermeable to the controlled atmosphere while
the term "gas-permeable" refers to enclosure materials~
which are permeable to the controlled atmosphere and~
sterilizing gas.
17,969-F ~7
' ' .
~28~3 ` :
The dry type dialyzers used herein are typically~
sterilized according to well-known procedures with a~
sterilizing agent such as ethylene oxide gas. The steril
zation can take place with the sin~le enclosure hàving~a~
permeable zone or, in the double enclosure package con~
cept, the inner packaged unit can be placed inside the
outer open enclosure and the unit then sterilized. After~
sterilization, the ethylene oxide gas in the dialyzer unit~
is completely replaced, usually with aseptic air, d~uring~
an "outgassing period". Typically, artificial kidney
dialyzers are outgassed for several days, e.g., as long as~
about 15-20 days, to insure that all ethylene oxlde res~
dues are rernoved. Hence, as used herein, the term
"sterilization" or "sterilizing" refers to the initial
act of sterilization as well as any following period
necessary to remove any toxic residues of sterilization;~
material before the units and package are subsequently
subjectad to the evacuation step herein. Additionally,
the atmosphere evacuated from the packaged unit in the~
methods claimed herein can be the sterilant gas and/or~
air. Radiation sterilization techniques which do not~
affect tlle dialyzer membranes may also be utillzed~and~
evacuation carried out without a waiting period or the
unit directly sealed with the controlled atmosphere.
Dry type dialyzers sterilized by ethylene oxide, radiation~
or other means and having the inlet and outlet ports
covered with a gas-permeable material, e.g., insert, cap~
etc., can be placed in an open, gas-impermeable enclosure~
and the kidney unit and enclosure evacuated (or first
sterilized if desired), filled with a controlled atmosphere
and then sealed.
17,969-F -8-
''
Z~3
~ith respect to the gas-impermeable packaglng
materials from which the enclosures herein are prepared,~
sealable flexible or rigid materials, also yenerally
impermeable to moisture, are utilized. Suitable gas~
-impermeable materials include, for example, synthetic
plastic laminates, metal foils, or laminates or films ~
having barrier layers of metal, e.g., foils. MYLA ~ is
a well-known polyester film which can be conventlon~ally
coated with a metal foil barrier~ Other materials,~ such~
as, for example, laminations of polyesters and polyethy~
lene and a co-extrusion of nylon and SURLY ~ are al~so
available. Enclosures comprising a laminated polyethylene~
and SURLY~ material constitute a preferred embodiment.
Also, other materials such as polyethylene, could~be~
employed as gas-impermeable materials provided sufficient~
thicknesses thereof are utilizecl. However, these generally~
are disadvantageous from a cost viewpoint and relatively
inexpensive, thin laminates are available. A laminate
material of MYLA ~, low density polyethylene and SURLY
containing a metal foil barrier is particularly preferred.
Gas-impermeable enclosures can also be prepared~
with some of the above mentioned materials which are~
thermo-formable and other materials such as, for example,~
polypropylene or styrene. The thermo-formed enclosure~
can typically have a suitable barrier coating which is;
impermeable to the controlled atmosphere, if necessary.
These and various other materials which can be used as
the gas-impermeable enclosure, as well as techniques for
varying enclosure thicknesses or barrier coatings to
, :
control permeability, will be readily apparent to those
skilled in the art.
@~ = Registered Trademark
17,969-F _g_
~ ~ '
~2~93 ;:
The inner enclosure of the double-packaged
dialyzer and the gas-permeable material coverinc3 the ports
of the dialyzer can be preparecl from the same materia~ls~as~
the gas-perrneable zone. Such materials should be permeable~
to sterilizing gases and controlled atmosphere, and can~be~
formed of materials such as permeable papers or plastics.;
:: : ~ - ~: :
The inner enclosure can also be prepared from the same
gas-impermeable material as the outer enclosure as long
as a yas-permeable zone is provided on the inner enclo~
sure. Preferably, a gas-impermeable enclosure provided
with a gas-permeable zone is utilized as the inner enclo~
sure.
The gas-permeable materials, e.g., gas-perrneable
zones, are typically prepared from papers or synthetic
plastic materials having a controlled porosity and~belng~
permeable to the sterilization gases and controlled~atmos~
:: ;::
phere. Such papers or plastic materials also serve as
microbial barriers to maintain the sterility or aseptic
condition of the dialyzer. ~laterials of this type~are
available and include spun-bound polyolefins such as TYVE
and various controlled porosity papers. Those skilled in~
the art will recognize these and other materials which
can be utilized for the purpose.
The gas-irnpermeable enclosure having a gas~
-permeable zone which is employed in preparing a single ;~
enclosure packaged dialyzer has the permeable zones located
in an area where it can be readilv sealed off and subse~
quently removed, if desired.
The size and shape of the inner or outer enclo~
sures is not critical. They can take the shape of flexible
~; '
17,969-F -10-
:
~ 42~
bags, wraps~ pouches, or rigid or semi-ric~id canisters,~
or tubs. Flexible bags are preferably employe~d for~,ease~
in assembly and savings in cost. Relatlvely rlg~ld~ th`ermo~
-formed enclosures having a gas-permeable llddlng may~bè~
desirable for protective purposes or for forming con~
venient, readily storable rigid containers. Where,thermo~
-formed enclosures having a permeable zone aré employ,ed,~
flexible or thermo-formed, gas-impermeable materials'
can also be placed over the permeable zone in a seallnq~
relationship with the gas-impermeable enclosure~to;,the
form a sealed, gas-impermeable package contalning~the~rein~
a dialyæer and a controlled atmosphere. All~of the èn~
closures are readily sealable and typically have means~
provided in the package for ease in opening~the sealed~
package. The enclosures are preferably of sufficiènt~
strength to resist abrasive ripping, puncturi~ng or thé~
like. Typlcally, an artificlal kidney dlalyz~er utl-lzlng
hollow fiber membranes is packaged~in~an lnner enc;~losure~
comprising a bag (prepared from a lamlnate~material~of;~
low density polyethylene and SURLY ~) being about 36 cm.;~ ''",
long and about 17 cm. wide. The bag contains a~ga~s~- ~ eab~le,~
zone of spun polyolefin material (TYVE ~) of about~7~.60~cm.
in dlameter. The oùter gas-lmpermeable enclosure is o'f~
the same material and ls sllghtly larger (about~40 ~cm`.~by~
about 19.5 cm.) to accommodate the dialyzer wlthin the innèr~
package.
Where the dialyzer is to be enclosed within a
single enclosure, a bag about 48 cm. long and having a 7.60
cm, diameter gas-permeable zone (TYVE ~) so located that~
17,969-F
. .,
~4Z~39~
it can be sealed off from the rest of the package containing~
the dialyzer, can be utilize(l. The gas-l)errrleable area is
preferably located at one elld of the enclosure, an excess
enclosure area of about 12.70 cm. is provided for the
permeable zone. Once the bag lS sealed, the steps of
sterilization, evacuation and filling of the bag with the
controlled atmosphere are carried out through the permeab]e~
zone. Once the controlled atmosphere is introduced into the~
package, a second seal dividing the package into two sections;~
is made across the bag between the dialyzer and the area~ m~
containing the permeable zone so that the permeable zone
is cornpletely sealed off from the rest of the package
containing the dialyzer, which is thus isolated withi.n a
gas-impermeable bag. The section containing the permeable
zone can be removed from the packaged dialyzer if desired `~
but this is not necessary.
Those skilled in the art will recognize that many
variations in the bags or enclosures and location, type~ànd~
size of the permeable zone on the bag or enclosure~can~be~
made in providing the various embodiments of dialyzers
containing a controlled atmosphere disclosed herein. The
steps of initially sealing, sterilizing, evacuating, f~ nq~
with controlled atrnosphere and subsequent sealing for either~
- : ~ , - ,,
the single or double enclosed dialyzers and variatlons
thereof will also be readily apparent and can be carried
out by those skilled in the art of packaying. ;;
While these steps can be manually carried out
with each unit, semi-automated procedures can also be
utilized. For example, multiple packaged units (e.g.;,
single or double packaged sterilized dialyzers) can readily
17,969-F -12-
~12~3
be evacuated, filled with a controlled atmosphere and
,
sealed to form a gas-impermeable package by use of a vacuum;~
and gas backfill packaging machine. In typical operations
three sterilized dialyzers individually ~ackaged in an
inner gas irnperrneable bag bearing a gas-permeable zone
and an outer open gas-impermeable bag are placed within the~
vacuum chamber of the machine and the bags and dialyzers
are evacuated under a reduced pressure of about 29~lnches~
of mercury~ The evacuation period is usually about~6~0
seconds but shorter or longer periods may be necessà~ry;~
depending upon conditions such as dialyzer sizes~and~con~
figurations. Carbon dioxide gas is then injected into the~
chamber, completely fIooding the dialyzers and inner and~
outer bags. The pressure of the C02 is maintained~at
about atmospheric. Once the chamber is completely~flooded~
with C02, the outer open bags are sealed with an i~mpulsè~
sealing machanism contained in the chamber. The chamber~
is then vented to remove excess C02 before the sealed,
gas-impermeable packaged dialyzers containing the Co2~are~
removed therefrom.
From the foregoing description, lt will be~ppàrent `~
that this invention provides a new package for packaging~
articles where sterility is required. It will be understood~
that any article requiring sterility may be pack~aged~in~the
manner described such as medical devices.
~50re particularly, the present invention provides
a new, packaged kidney dialyzer containing a controlled
atmosphere which will enable the priming of the dialyzer~
e.g., with a saline solution rinse, to be instituted and
completed in a quick, convenient manner without increaslng~
the risks of contamination.
17,969-F -13-
' ~
:
~42893
The above described embodiments and methods are~
exemplary only, and it will be understood that modification
in form, detail or procedure can be made without departing~
from the spirit and scope of the inventlon. Accordlngly,~
the invention is not to be considered as l1mited save'as~
is consonant with the scope of the following claims.
17,969-F -14-
