Note: Descriptions are shown in the official language in which they were submitted.
WO 961058!i3 PCTISE95100795
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TITLE
Method and connection unit for sterile transfer of
solution via a connector.
TECHNICAL FIELD
The invention relates to a method and a connection unit for
l0 sterile transfer of solution via a connector.
BACKGROUND OF THE INVENTION
The invention is intended to be used in conjunction with
an on-line sterilizing arrangement as described in EP-A1
428 009. This document describes a continuous heat
sterilizing arrangement in which a solution is heated
during transport in a conduit to a high temperature, for
example about 130'C, and maintained at this temperature for
a predetermined period for sterilization. Thereafter, the
solution is cooled to the temperature at which it is to be
used. The sterilization takes place at high pressure which
is achieved with a pump and a throttle arrangement.
A heat exchanger is used to provide the heat energy. The
sterilization arrangement is used for sterilizing infusion
solutions such as Ringer's solution, other medical
solutions such as dialysis solutions, purified water to
obtain sterilized water or other similar solutions.
The sterilizing arrangement according to EP-A1-428 009 is
provided with a shunt conduit which in princigle connects
the inlet to the outlet so that the solution which is in
the system can be circulated in a closed circuit. In this
manner, the temperature of the circulating solution can be
raised to, for example, 120'C to sterilize the device
itself.
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The solution which has been sterilized with the above-
described sterilizing arrangement can be used directly, for
example in dialysis or infusion.
In certain circumstances it is also desirable to transfer
the sterilized solution to storage bags for later use, or
for delivery to other departments within the hospital. For
this purpose, disposable sets of tubes are available which
terminate with a bag.
Normally, such bags are filled with medical solution,
whereafter the set of tubes is sealed and the disposable
article sterilized in its entirety, i.e. with the medical
solution within the bag. Such sterilizing can be effected
with gamma-sterilization or via autoclaving.
Alternatively, the set of tubes can be provided with
medical solution after the set of tubes has been
sterilized.. In such cases, a sterile connector is normally
used which comprises a membrane which is broken when used.
Those parts which are connected together are sterile. With
such a ster 1e connector, there is always the risk that
bacteria which may reside on the outer side of the membrane
are introduced with the connector device and contaminate
the interior of the connector.
EP-A1-0 230 864 describes a sterile connection of two
containers whereby the connection takes place in a
sterilized chamber which is maintained aseptic by means of
a chemical disinfectant. Chemical disinfection does not
however guarantee sterility and instead the risk for
bacteria contamination is still present.
WU 9G!05883 ~ ~ ~ ~ ~ ~ ~ PCT/SE95f00795
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SUMMARY OF THE INVENTION
The object of the present invention is to propose a method
and a connection unit which permit sterile connection for
transfer of a sterilized solution to a previously
sterilized disposable set of tubes in such a manner that
bacteria,contamination is completely eliminated. The set of
tubes can be terminated with a connection bag or may lead
to an infusion device or dialysis machine or other medical
equipment.
A method and a connection unit which allow the achievement
of the above-mentioned object are presented in the
subsequent claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is described in greater detail in the
following with reference to the embodiments of the
invention shown in the drawings.
Fig. 1 is a schematic view of the sterilizing arrangement
according to EP-A1-0 428 009.
Fig. 2 is a view similar to Fig. 1 which shows the
connection of a connecting unit according to the
invention.
Fig. 3 is a cross sectional view through the connection
unit in stand-by position.
Fig. 4 is a cross sectional view through a connector
intended to be used in accordance with the
invention.
Fig. 5 is a plan view of the connector according to Fig.
4.
Fig. 6 is a view similar to Fig. 3 and shows the
connection unit in an open position for
introduction of the connector according to Fig. 4.
Fig. 7 is a view similar to Fig. 6 and shows the
connection unit with in situ connector in a
sterilizing position.
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Fig. 8 is a view similar to Fig. 6 and shows the
connection unit in a filling position.
Fig. 9 is a cross sectional view similar to Fig. 3 and
shows the connection unit in another adaptation.
Fig. 10 is an enlarged cross sectional viaw of a portion of ,
the connection unit according to an alternative
embodiment.
Fig. 11 is a cross sectional view similar to Fig. 3 and
shows a further adaptation of the connection unit.
DETAILED DESCRIPTION OF FURTHER EMBODIMENTS
A sterilizing arrangement according to EP-A1-0 428 009 is
shown in Fig. 1. A solution which is to be sterilized is
introduced via an inlet 5 and flows through a valve 12 to
a pump 8. The pump 8 increases the pressure of the solution
and pumps the solution to a first heat exchanger 2.
The solution passes across the primary side of the heat
exchanger 2 and is fed to a heating arrangement 3. The
solution is transported from the heating arrangement 3 in
a delay conduit 15 of such length that the reside t'1me
permits sterilizing of the solution which has been heated
by the heating arrangement 3.
The solution is fed from the conduit 15 to the heat
exchanger 2 where the solution passes across the secondary
side of the heat exchanger and heats the incoming solution
on the primary side.
The solution is transported from the heat exchanger 2 to a
second heat exchanger 6 and passes across its primary side.
A heating medium is provided on the secondary side of the
heat exchanger 6, which heating medium can be cold water if
further cooling is required and which flows from an inlet
10 to an outlet 11. The solution flows from the heat
exchanger 6 via a throttle arrangement 7 and a valve 13 to
an outlet 9.
CA 02198087 2005-02-15
A shunt conduit 14 is connected between the inlet 5
downstream of the valve 12 and the outlet 9 upstream of the
valve 13. The function of the shunt conduit is to allow
recirculation of the solution in the system without any new
5 solution being introduced via the inlet 5 or removed by the
outlet 9. By shutting off the cooling means supply to the
second heat exchanger 6, the solution in the closed
circulating system can be heated to a high temperature, for
example 120'C, for sterilizing the system.
In addition, a bleed valve 4 is arranged downstream of the
throttle valve 7 and upstream of the outlet valve 13~.
The connection unit 20 according to the invention is
arranged in cooperation with the shunt conduit 14 and shown
in Fig. 2. The connection unit has an inlet 21 for incoming
solution from the throttle valve 7, an outlet 23 for
solution which is to be recirculated in the shunt conduit
14 and an outlet 22 for exiting sterile solution.
In Fig. 3, the connection unit 20 according to the present
invention is shown in a stand-by position. The connections
of the various conduits according to Fig. 2 are shown in
Fig. 3. Accordingly, there is'an inlet 21 (positioned
behind the unit 20 in Fig. 3j which is connected to the
throttle valve 7 and the bleed valve 4. In addition, there
is an outlet 23 to the shunt conduit 14. A piston 19 is
shown in a closed position and closes the opening 22 which
will be explained in greater detail below.
'
The inlet 21 opens into a space in the form of cylindrical bore 25 via
a tube 26 which is concentric with the bore 25 and which terminates
with a penetration element in the form of a point 27.
Solution from the throttle valve 7 can thus be fed via the
inlet conduit 24 to the inlet 21 and subsequently to the
tube 26 and, via the point 27, into the bore 25 and further
via the outlet 23 to the shunt conduit 14.
CA 02198087 2005-02-15
6
In Fig. 3, the bore 25 is sealed at its upper end by the
piston 19 which cooperates with an O-ring seal 28 arranged
in the side of the bore.
The operation in the stand-by position as shown in Fig_. 3
thus permits the sterilizing arrangement according to EP-
A1-O 428 009 to be used with recirculation according to
this document.
When the connection unit 20 is to be used for filling of a
disposable set of tubes, a connector 30 as shown in Figs.
4 and 5 is used. Fig. 4 is, a cross section through the
connector. The connector consists of a cylinder 3i of such
diameter that it fits in the bore 25 and seals against the
O-ring 28. At the lower region of the cylinder 31 there is
a reduced portion 32 on which a cover 33 is arranged. The
cover 33 can be of rubber. In addition, the connector 30
has a semi-cylindrical-shaped engagement portion 34 of such
dimension that the piston 19 fits therein. Finally, a
connection portion 35 is provided to which a tube is
connected. The tube leads to a container which is to be
filled or some other suitable device such as a dialysis
machine. In Fig. 5, the connector 30 is seen from above.
When the connection unit according to the invention is to
be used to fill a container connected to the connector 30,
this takes place in the following manner (see Figs. 6-8).
Firstly, it is assured that the connecting unit is
depressurized by means of opening the bleed valve 4.
Thereafter, the piston 19 is displaced by means of a
manoeuvre device 36 to the position shown in Fig. 6. By
means of this displacement of the manoeuvre device 36, an
opening 22 is revealed in the side of the connection unit
which leads to a cavity 37- The bore 35 opens into this
cavity. Accordingly, the opening to the bore 25 is exposed.
WO 96105883 PCT/BE95/00795
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The connector 30 is introduced through the opening 22 so
that the lower region 32 is located immediately above the
bore 25 and can be downwardly displaced into the bore 25 so
that the cylinder 31 cooperates with the O-ring 28. This
position is shown in Fig. 7.
The correct introduction of the connector into the bore 25
is 'facilitated by means of the engagement portion 34
cooperating with the piston 19 and snap fastening therewith
during the insertion of the connector 30 through the
opening 22. Thereafter, the manoeuvre device is displaced
downwardly to the position shown in Fig. 7.
As is evident from Fig. 7, the connector 30 is only
partially introduced into the bore 25. The connector 30 is
introduced into the bore 25 such a distance that the O-ring
28 cooperates with the cylindrical surface of the connector
so that sealing of the bore 25 is achieved. At the same
time, the connector 30 is so high up that the point 27 does
not reach the cover 33 on the connector 30.
The sterilizing arrangement'according to the Fig. 2 has a
particular sterilizing position in which the solution is
heated to a high temperature, for example 120'C. This is
achieved by means of cold water no longer being supplied to
the secondary side of the second heat exchanger 6 and that
the heating arrangement 3 is operated so that the
temperature in the recirculating system increases to 120'C.
In this manner, the pressure in the entire circulation
conduit rises to a pressure of about 2 atmospheres
(absolute pressure, i.e. an overpressure of one
atmosphere). This pressure arises automatically since the
' valves 12 and i3 are closed.
WO 9tf058R3 PCT/SE95l00793
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In the position shown in Fig. 7, the sterilizing
arrangement is activated so that solution with a ,
temperature of about 120'C circulates through the conduit
24, inlet 21, tube 26 and point 27 to the bore 25 and may
flow around the cover 33 of the connector 30 and further
via the outlet 23 to the shunt conduit 14 as described
above. This position is maintained for as long as it
requires for the bore 25 and the lower portion of the
connector 30 to become sterilized.
When a sufficiently long period of time has elapsed for the
sterilization to have been achieved, the drainage valve 4
is activated and the sterilizing arrangement is adjusted~so
that solution which is to be sterilized is introduced via
the inlet 5 and is allowed to flow through the system. For
this to occur, the shunt conduit 14 is closed by means of
the valve 29 (see Fig. 3). The bleed valve 4 is open until
normal operation is attained in the system.
When normal operation is attained, the manoeuvre device 36
is activated to press the connector 30 downwardly to its
lower position as shown in Fig. 8 at the same time that the
valve 4 is closed. In this position, the point 27
penetrates the cover 33 so that access is gained to the
interior of the connector. At the same time, the outer
peripheral portions of the cover 30 seal against the base
of the bore so that the outlet 23 is closed off. In this
manner, all solution which enters via the inlet 21 has to
flow into the connector 30 and to a connected storage bag
or dialysis machine or other medical equipment.
By means of this embodiment of the connecting unit, the
outer pot i:ion of the connector 25 and the point 27 are '
sterilized before these two parts cooperate with each
other. In this manner, the risk of bacteria entering the
connector 30 when the cover or membrane 33 is penetrated is
totally eliminated.
WQ~ 96f05883 fn J ,,i ~ ~~ ~ ~ PCT1SE95100795
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When filling of a storage bag is attained, the bag is
sealed in a suitable manner, for example via neat welding
in a known manner.
It is also possible to make the cover 33 of a rubber
material provided with slots which seal in a sterile manner
after removal of the point 27. Such a connector is
previously known from EP-B1-0 116 986.
As has been previously mentioned, the sterilizing solution
is heated to a high temperature, for example 121'C. The
pressure in the bore 25 thus becomes about 2 atmospheres.
In order to assure sterility, it is necessary that
circulation continues for 20 minutes.
It may be desirable to reduce this time and this can be
achieved by increasing the temperature to, for example,
130'C and a pressure of 2,7 atmospheres. In this manner,
the time can be reduced to about two minutes. It must be
ensured, however, that the hot sterilizing solution reaches
all the regions which are to be sterilized.
As is apparent from Fig. 3, the cover 33 is provided with
a depression in which the point 27 is positioned during the
sterilizing cycle. The region which must be sterilized is
this depression as well as the region of the cover which
forms the seal against the base of the bore 25. In
addition, the actual penetrating part 27 must be
sterilized. An effective sterilizing at high temperature
can be attained if the goirit 27 is shaped as a cone
provided with a plurality of small holes. The sterilizing
' solution will thus spray the inside of the depression of
the cover 33 which will thereby be intensely treated with
' sterilizing solution.
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It is preferred that the cover 33 be made from a material
which tolerates high temperatures up to at least about
150'C. The remaining part of the connector 33 can be mare
or less effectively insulated from the warm sterilizing
solution, for example by means of the cover 33, which
extends a certain amount upwardly along the cylindrical
outer surface of the connector.
The connection unit according to the invention can of
course be used independently of the sterilizing arrangement
as is apparent. from EP-A1-0 428 009. Thus an arrangement
can be used as shown in Fig. 9. The sterile solution which
is to be transferred to a container via the connector 30 is
fed via a conduit 41 and a non-return valve 42. A pump 43
feeds the sterile solution in the conduit 41 to the inlet
21. When the connection unit is in the sterilizing position
shown in Fiq. 9, the solution which is introduced via the
conduit 21 has to flow out through the outlet 23 to the
shunt conduit 44. The shunt conduit extends via a heating
arrangement~45 back to the inlet of the pump 43.
When the pump 43 is actuated, the solution circulates in a
closed circuit via the inlet 21 through the bore 25 to the
outlet 23 via the shunt conduit 44 and the heating
arrangement 45 back to the pump 43. No further solution can
be introduced via the inlet 41.
When the cover 33 of the connector 30 and the bore 25, as
well as the penetrating element 27, are to be sterilized,
the heating arrangement 45 is activated and heats the
solution which circulates in the circuit to a temperature ,
of about 120'C. The pressure in the circulating s~lution
rises but because of the non-return valve 42 the solution s
does not boil. When the solution has circulated at 120'C
for a sufficiently long time, for example about 20 minutes,
the heating arrangement 45 is disconnected and the still
circulating solution is allowed to cool. When a
W C6 96105883
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sufficiently low temperature has been attained, which is
measured by a temperature sensor 46, the manoeuvre device
36 is activated to press the connector 30 to the position
shown in Fig. 8. The temperature at which this activation
occurs is dependent on the material of the connector 30. If
PVC-material is used, it is preferred that the temperature
has decreased to at least 80'C. Measurements can
alternatively be carried out using a pressure sensor 48,
possibly in combination with the temperature sensor 46.
When the connector 30 is pushed down to its bottom
position, the cover 33 seals the outlet 23 so that the
circulation in the conduit 44 ceases. The pump 43 continues
to operate and thereby draws solution from the conduit 41
via the non-return valve 42 and feeds the solution via the
inlet 21 and the connector 30 to a storage bag or similar
connected to the connector 30.
The sterilizing of the penetrating member 27 and the
connector 30 can take place using the sterile solution
which is introduced via the conduit 41 and which is heated
with the heating arrangement 45.
Alternatively, pure water can be circulated in the
circulation circuit 44. When the sterilizing is completed,
a valve 47 is adjusted which is shown with dashed lines in
Fig. 9 and the content in the pump 43, the inlet 21, the
bore 25 and the outlet 23 can pass to an outlet at the same
time as the sterile solution which is to be fed in passes
through the conduit 41, the pump 43, the inlet 21 and to
the bore 25 and further via the outlet 23. At the same
time, the pressure drops to about atmospheric pressure.
When a sufficiently long time has expired for all the water
to have been replaced, the manoeuvre device 36 is activated
so that filling is initiated.
WO 96105$$3 PCTlSE95I00795
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An alternative embodiment of the bore 25 is shown in Fig.
10. Thus, the bore is provided with a lower expansion 51.
In this manner, the sterilizing solution will circulate
around the ehtire lower portion of the connector 30 so that
it becomes sterilized. This embodiment is suitable if the
connector 30 is made from a material which tolerates
temperatures in the order of 120'C without deformation,
such as polycarbonate.
Furthermore, the penetrating element 52 is provided with a
conical region 53 which, when activation of the manoeuvre
device and downward displacement of the connector 30 take
place, cooperates with the cover or seal 33 of the
connector at the same time that cooperation occurs with the
base of the bore. in this manner, the region which has to
be sterile to allow sterile transfer to be able to take
place is further restricted.
In order to facilitate the recirculation, the conical
region 52 is provided with a plurality of holes 54 so that
the sterilizing solution can flow through the tip 55 of the
penetrating element as well as through the opening 54. In
this manner, a larger circulation flow is maintained during
the sterilizing phase.
Two outlets 56 and 57 corresponding to the outlet 23 are
shown in Fig. 10. These outlets can be tangentially
arranged to ensure the bast flow properties in the bare 25.
It is also possible to use the conduit 56 as an inlet as
well as the inlet 52 in order to further increase the flow.
Further'variations will be apparent to a skilled person. A
further variant of the present invention is shown in Fig.
11 which can be used to connect a bag containing sterile
solution to a machine in which the sterile solution is to
be used, far example a dialysis machine or an infusion
tube.
WO 9(i/05883 ~ i..~ ~ ~ j.~ ~ ? PC1'/SE95/00795
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The sterile solution is ~.n a storage bag or a device which
is connected via a connector 30 on the left in Fig. 11. The
connector 30 is connected to a connector 35 of a user who
is to use the sterile solution. The two connectors 30 and
30' are each inserted in respective bores 25, 25' with
respective points 27, 27'. The bores 25, 25' are connected
to each other via a communication passage 61. During the
sterilizing phase, a solution which can be water is
circulated by the pump 8 to the tip 27', around the cover
33', into the bore 25' and via the communication passage 61
to the other bore 25, further around the cover 33, to the
point 27 and via the heating arrangement 3 back to the pump
8. By activating the heating arrangement 3, the circulating
solution is heated to about 121'C. In this manner, an inner
pressure of about 2 atmospheres is reached. When the thus
initiated sterilizing has gone on for about 20 minutes, a
valve 62 is switched before the pump 8 to its second
position so that the heating arrangement 3 is by-passed by
the conduit 63. The circulation continues until the
temperature which is sensed by a temperature sensor 64 has
fallen to a safe temperature, for example about 60'C.
The second bore 25' is connected to a valve 66 and a
flexible storage bag 67 via a conduit 65.
When the temperature has dropped to a suitable level, the
manoeuvre device 36 is activated on the left-side connector
and presses the connector 30 down to its lower position.
This causes the point 27 to penetrate the cover 33 and the
30 cover 33 seals the gassage 6l and the bore 25. ~. sterile
connection between the connector 30 with the point 27 has
been attained.
W096lUSfl83 ~ I . ' PCTISE95I00795
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The sterile solution which is supplied via the connector 30
flows through the point 27, the conduit 63, the valve 62
and the pump 8 to the point 27'. The solution flows from
the point 27' further to the bore 25'. Since the conduit 61
is closed at its left end by means of the cover 33, the
solution cannot pass through the conduit 61. Instead the
solution flows through the conduit 65 via the now open
valve 66 to the storage hag 67.
YThen a sufficient quantity of sterile solution has flowed
along this path and has displaced all solution which has
been used for sterilizing, which occurs after say one
minute, the manoeuvre device 36' is activated and connects
the connector 30' with the point 27' which penetrates the
cover 33' which simultaneously seals against the base of
the bore 25'. In this manner, the conduit 25 is sealed off
whereby the valve 66 can be closed. & sterile connection
between the connector 30 and the connector 30' has now been
attained.
In the embodiment of the connection unit which is shown in
Figs. 3-9, the bore 25 is preferably arranged in a heat-
insulating material such as polycarbonate. In this manner,
the regions of the connector 30 above the cover 33 are
prevented from being heated to a great degree during the
sterilizing phase. This implies that cheap material for the
connector 30, such as PVC, can be used without the risk of
deformation during the sterilizing phase.
The sterile solution can be infusion solutions, dialysis
solutions or other medical solutions such as physiological
sodium chloride solution, a t c.
Wm 9GIOSRR3 PCTISE95/00795
The sterile solution can also be water which is filled in
bags via the connector. The bags contain a salt in powder
form and are sterilized by suitable means so that the
5 interior of the connector, the bags and their contents are
sterile. When the bags are to be used, they are connected
to the sterilizing arrangement 1 according to Fig. 2 and
water is added to the bags. In this manner, the salt is
dissolved and a medical solution is attained ready for use.
10 The salt can contain several substances, such as a
concentrate which is used in haemodialysis. The salt can
also contain further substances such as medically active
substances in connection with infusion.
15 Suitably, the sterile solution itself is also used for the
sterilizing phase. That portion of the sterile solution
which has been used for sterilizing can be disposed of and
new sterile solution used for filling the connector.
As has been mentioned above, a particular solution such as
physiological sodium chloride solution or water can be used
for the heat-sterilizing phase of the connector's outer
gortion, whereafter the solution is disposed of and
replaced by the sterile solution which is to be added to
the connector, such as dialysis solution, peritoneal
dialysis solution (containing i.e. glucose) infusion
solution, a t c.
The invention is not restricted to the above-described
embodiment but can be modified within the scope of the
invention in a manner obvious for the skilled person. The
various described components can be combined in other ways
than those which have been shown in the drawings. The
invention is limited only by the claims.
