WO2017037491A1

WO2017037491A1 - Ethyleneoxide assisted expansion of tubing

Info

Publication number: WO2017037491A1
Application number: PCT/IB2015/001525
Authority: WO
Inventors: Melanie HUBBS; Masao Hitotsuyanagi; Andreas Becker
Original assignee: Terumo Europe N.V.
Priority date: 2015-09-04
Filing date: 2015-09-04
Publication date: 2017-03-09

Abstract

The invention relates to methods for permanently and reliably connecting smaller diameter non-standard size tubing (40) to larger diameter standard size tubing and components, and in particular to such method creating a system of connected tubing for use in medical applications or other applications where sterilization of the tubing is a concern and where reduction of priming volume in a system circulating priming fluids may be achieved by making use of the smaller non-standard size tubing. This is achieved by subjecting a first smaller diameter non-standard size tubing (40) to the combined impact of a radially outwardly exerted expansion force from a mechanical expansion member put into a lumen of the non-standard size tubing and an ethylene oxide gas sterilization treatment which softens the tubing material until the inner diameter of the non- standardized tubing has become equal to the inner diameter of tubings or other hollow fluid guiding components of standard size.

Description

ETHYLENEOXIDE ASSISTED EXPANSION OF TUBING

The invention relates to expansion of non-standard sized tubing (not commonly used) for connection with standard (commonly used) sized tubing and components, and in particular the invention relates to a method according to the preamble of claim 1.

The motivation for the present invention has arisen from consideration of the following practical problem:

In the field of extracorporeal blood circuits, such as they are used in the cardiopulmonary bypass circuit it is a general objective to reduce the so-called priming volume of the extracorporeal blood circuits. Fig. 1 shows a schematic diagram of a patient 1 being treated with an exemplary arrangement of a cardiopulmonary bypass circuit which is used to perform cardiopulmonary bypass (CPB). A CPB circuit must be primed with a suitable fluid and all air expunged before connection to the patient. Usually, the circuit is primed with a crystalloid solution and sometimes blood products are also added. The patient must be fully

anticoagulated with an anticoagulant such as heparin to prevent clotting of blood in the circuit. The volume of this priming liquid is generally referred to as "priming volume". While a large variety of biocompatible priming fluids have been developed that generally

satisfactorily fulfill the necessary requirements of not being physiologically harmful to the patient and which may generally be used without any safety concerns, it nevertheless obviously remains desirable to minimize the priming volume as far as possible for a variety of reasons, such as:

in rare cases even a generally biocompatible priming fluid may have unwanted side effects on some especially sensitive patients

- Any priming fluid inserted in the system, even if not harmful, is basically an unwanted

"dead load" in the process and may end up in the patient's body replacing the patient's original blood (hemodilution). Hemodilution of course occurs during CPB due to extracorporeal circuit priming and cardioplegia solution. It affects hemostatic factors and platelet count during CPB. If prime / blood volume ratio decreases platelet count or coagulation too much, a transfusion must be administered. Blood transfusions are directly and significantly negatively linked to patient outcome and additionally are costly.

Hence, it is generally highly desirable to reduce the priming volume in extracorporeal blood circuits.

In CPB, the patient's venous blood is pumped via venous tubing 2 to an oxygenator 3, where the blood is enriched with oxygen and then - possibly after having been directed through other components of the CPB circuit such as they are shown in Fig. 1 - returned via arterial tubing 4 to the patient's heart. Various other tubings and components constituting in their entirety an extracorporeal blood circuit are also shown in Fig. 1. Detailed descriptions of such CPB circuits may, for example, be found in cardiopulmonary bypass textbooks, such as "Cardiopulmonary Bypass: Principles and Techniques of Extracorporeal Circulation (Editor: Christina T. Mora). However, the focus of the following discussion will be on the relationship between the venous 2 and arterial 4 tubing in Fig. 1. Therefore, the remaining components shown in Fig. 1 need not be further discussed in detail, as they are generally well known to a person skilled in the field of CPB technology, and, furthermore, a detailed understanding thereof is presently not essential - neither for understanding the problem underlying the present invention nor for understanding its solution.

For understanding the present invention it suffices to realize that in the extracorporeal circuit shown in Fig. 1, when starting the CPB operation, an important contribution to the overall priming volume in the extracorporeal circuit arises from the priming volume of the venous tubing 2 and the arterial tubing 4.

The proposed invention aims at reducing unwanted priming volumes for extracorporeal blood circuits. It may also be beneficial for reducing any unwanted priming volumes in fluid circuits in other areas of application.

In the field of CPB, priming volume reductions have typically been accomplished through optimization of extracorporeal blood circuit components (oxygenators, arterial filters, etc.) attached to the CPB circuit tubing, as well as by minimizing the length of tubing in the CPB circuit.

The approach in the proposed invention will accomplish significant priming volume reductions through the use of smaller diameter, non-standard tubing for the venous tubing 2 and the arterial tubing 4. Applications to other tubing in the CPB circuit, such as but not limited to cardioplegia tubing (Fig. 1), may also accomplish significant priming volume reductions through the use of smaller diameter, non-standard tubing.

Fig. 2 shows PVC CPB tubing together with the main parameters characterizing the same, as based on Imperial Unit "standard" sizes with 1" = 1 inch equaling 2.54 cm.

Fig. 2 is an example of specifications for PVC standard sized tubing commonly used in CPB which are the most important components connecting to arterial and venous tubing, as previously shown in Fig. 1. Common sizes of ports connecting tubing to other components in the CPB circuit are ¼", 3/8" and ½". Examples or CPB circuit components having ports with such common sizes are oxygenator blood inlet and outlet ports, venous reservoir blood inlet and outlet ports and arterial and venous cannulae. A person skilled in the field of CPB technology implicitly understands that the standard sized connection sizes of these key elements dictate that tubing in the CPB circuit must be compatible with those standard sized connection sites. Therefore tubing most commonly used in the CPB circuit is comes in ¼", 3/8" and ½" inner diameter standard sizes.

Hence, in the current state of the art, tubing used in CPB circuits is generally based on pre- confectioned standardized tubing sizes based on the Imperial System of units with standard tubing inner diameters generally being based on multiples of 1/8" (with 1" = 1 inch = 2, 54 mm), whereas "non-standard tubing "in the state of the art in CPB treatment usually refers to tubing inner diameters being based on multiples of 1/16". Accordingly, in the following, whenever reference is made to "standard size" tubing or components, this generally implies tubing or other hollow connection components having lumens with inner diameters based on multiples of 1/8", such as ¼" (=2/8"), 3/8", 1/2 " ( = 4/8"), 5/8", etc., whereas "nonstandard tubing" refers to tubing or other hollow connection components having lumens with inner diameters based on (odd) multiples of 1/16", such as 3/16", 5/16", 7/16", etc.

Nevertheless, it is also evident for the skilled person that the terms "standard" and "nonstandard" tubing are arbitrarily chosen and merely denote the fact that certain sets of tubing ("standard") are commercially more readily available or more often used than others ("non- standard").

Fig. 3 shows a comparison of standard tubing sizes for commonly used adult and pediatric venous tubing 2 and arterial tubing sizes, based on multiples of 1/8", as they are currently often used in the CPB treatment, and possible smaller diameter non-standard tubing sizes, which are exemplarily based on increments of 1/16". In the following, the term "non-standard tubing" shall generally refer to tubing or other hollow connection components having lumens with inner diameters based on odd multiples of 1/16", such as 3/16", 5/16", 7/16" etc.

As may be seen from Fig. 3, for a given tube length of 150 cm, replacing a ½", 3/8" and ¼" (= 2/8") tube internal diameter, respectively, by a tube having a 7/16", 5/16" and 3/16" internal diameter lumen, respectively, would lead to significant savings in priming volume of 45 ml, 33 ml and 21 ml, respectively.

It is evident for the skilled person that two sets of larger inner diameter "standard sized tubings/components" and smaller inner diameter "non-standardized tubings/components" shown in Fig. 3 are arbitrarily chosen for illustrative purposes and that - as already explained in conjunction with Fig. 2 - they must be neither based exclusively on 1/8" increments nor on l/16"increments, respectively. The same principles apply for any situation where there is a first "non-standard" set of fluid guiding elements having inner diameters, with each inner diameter of a specific element in this first set being comparatively smaller than the inner diameter of a corresponding specific fluid guiding element in a second "standard" set of corresponding fluid guiding elements. At the same time it would be desirable to maintain for components of the CPB circuit shown in Fig. 1, such as the venous return catheter 5 or the arterial cannula 6 the larger inner diameter "standard components" in order not to unnecessarily reduce flow cross sections in critical regions close to the sensitive body parts of the patients, and thus avoid hampering flow of fluids into and out of the patient's body. Hence, it is desirable not to decrease the inner diameter of the venous return catheter 5 or the arterial cannula 6 to non-standard sizes. Similar considerations apply for the tubing connected to the oxygenator 3 or any other components in the extracorporeal blood circuit shown in Fig. 1. The CPB circuit has many different components, all based on standard sizes and often supplied by various

manufacturers. To adopt the many various components to non-standard tubing sizes is neither a technically nor financially logical proposal. Hence, it becomes a requirement that the nonstandard tubing sizes are compatible to the existing standard sized components of the CPB circuit.

Accordingly, one should maintain compatibility to the standard sized components of the CPB circuit, even when replacing the hitherto used standard size tubing for the venous tubing 2, the arterial tubing 4 or other tubing in the CPB circuit with non-standard size tubing.

Hence, in this situation there arises a practical problem at the main tube connection sites 7, namely how to practically accomplish the transition from the larger inner diameter standard size tubing or components to the smaller inner diameter non-standard size tubing. The issue is therefore how to reduce priming volume in cardiopulmonary bypass systems while using non-standard tubing and still be able to connect the non-standard tubing to standard sized components.

Furthermore it is desirable to avoid using additional connectors or adaptors (Fig. 8) within the CPB circuit, which can be associated with increased risk of blood trauma and present the inherent risk of creating additional sites at which the circuit could accidentally become disconnected. Preferably, any proposed solution should not only hold the potential to easily connect a tubing of a given smaller inner diameter to another element having a larger inner diameter, but it should preferably allow easily matching a tube with a given smaller inner diameter to a whole range of possible larger inner diameters components.

In the medical field, these considerations of connecting non-standard sized tubing at a main connection site to standard sized CPB circuit components must be made before the background of the additional requirement that the tubing must be sterilized by means of ethylene oxidation treatment wherein the product is sterilized in its final packaging by EO gas following a validated method assuring a sterility assurance level (SAL) of 10^"6 , according to the following applicable harmonized standards:

EN 556-1 : Sterilization of medical devices - Requirements for medical devices to be designated "STERILE" Parti: Requirements for terminally sterilized medical devices.

EN ISO 11135-1 : Sterilization of health care products - Ethylene oxide - Part 1 :

Requirements for the development, validation and routine control of a sterilization process for medical devices. EN ISO 10993-7: Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals.

The present invention was made taking into account the aforementioned problems. It is hence an object of the present invention to provide an efficient, reliable, easily applicable and cost-effective method of making hollow tubes with lumens of smaller diameter nonstandard sizes connectable to hollow fluid guiding components, in particular to tubes, having lumens with predefined larger inner diameters, and in particular for making such hollow tubes available for use in the medical field - or possibly other fields - where sterilized tubing systems are needed, in particular for reducing priming volume in CBP applications.

This object is accomplished by a method according to independent claim 1.

The co-dependent and the dependent claims relate to advantageous embodiments of the invention. Prior art known in the field:

US3068064 discloses that use of Ethylene Oxide (EO) gas sterilization was well-known for sterilization purposes.

US7291124 discloses a tubing set including quick disconnect couplings for the purpose of reducing blood circuit priming volume. Connectors for transitioning from small to large diameter tubing, such as they are shown in Fig. 8 are also known in the prior art.

Standard (1/2", 3/8", ¼") surgical tubing is commercially available from a wide variety of suppliers and non-standard (7/16", 5/16", 3/16", etc.) surgical tubing is commercially available from some suppliers.

It is essential for the present invention that a mechanical expansion component is attached to at least a region of non-standard tubing of appropriate material and then a radial expansion force is applied by the expansion component while undertaking an EO gas sterilization treatment. Appropriate materials include in particular PVC compositions.

The EO gas sterilization treatment applied to the non-standard tubing causes a thermal effect of the treated region and the mechanical expansion forces applied by the mechanical expansion component causes expansion of the non-standard tubings at said softened predetermined locations, in particular at the end regions of a non-standard tube. Non-standard tubes having end regions appropriately widened to standard tubing sizes are then easily connectable to other hollow fluid guiding elements having standard sized lumen diameters.

As the inner diameter of non-standard tubing is significantly less than that of standard tubing, use of non-standard tubing yields the desired result of the proposed invention, namely the dramatic reduction of blood circuit priming volume in CPB circuits, such as already discussed in conjunction with Fig. 3. The same effect may be achieved for areas other than CPB circuits where reduction of priming volume in sterilized tubing systems is also a consideration. The features and characteristics of the present invention may also be taken from the following detailed description of preferred embodiments of the invention in conjunction with the drawings. Fig. 1 shows a schematic representation of an extracorporeal circuit used in CPB

(CPB = cardiopulmonary bypass) comprising various extracorporeal circuit elements connected to a patient and comprises various tubes such as they are shown in Fig. 1 ; shows a schematic representation of tubing together with their characterizing parameters; shows an overview table presenting use scenarios for venous and arterial tubings for adults and pediatric for an exemplary tube of 150 cm length and the resulting priming volumes in the lumens of the tubings when using different types of standard or non-standard tubings in fluid guiding circuits;

Figs. 4a to 4c show different views and cross sections of a known flare cap such as it was previously used as a shrinkage prevention component (prevents shrinkage occurring during EO sterilization) when used with standard sized tubing. In a first embodiment of the present invention the known flare cap is used as an expansion component by applying it to a smaller diameter non-standard tubing, which due to mechanical effect and thermal effect during EO sterilization not only prevents shrinkage but also expands the tubing, allowing it to fit to larger diameter standard tubings or standard sized components;

Fig. 5a to 5 c show various situations in which smaller diameter, non-standard tubings are inserted into corresponding flare caps for expanding the inner diameter of end regions of the respective non-standard tubings to the sizes of the inner diameters of standard sized tubings or standard sized components; visualizes an alternative embodiment of a method for expanding non-standard tubing by using a stent-mechanism as another type of expansion member; which could also be used for expansion at the end of a tube or a length of

tubing not positioned at the end of a tube;

Fig. 7 shows a prior art (balloon) expandable stent which may be put on the distal end section of the stent-mechanism used in Fig. 6 for expanding a portion of a nonstandard sized tube when subjected to EO sterilization treatment;

Fig. 8 shows a prior art approach for providing (as)symmetric connectors for

connecting (non)-identically sized tubes.

Figs. 9a to 13b

show various examples of uses of systems composed of hollow non-standard tubes having been subjected to manufacturing steps of an inventive method creating an expanded region with its lumen being fluidly connected to the lumen of a hollow fluid guiding component, and in particular to hollow fluid guiding components in CPB systems for decreasing priming volume.

Description of preferred embodiments

1^st preferred embodiment

A first preferred embodiment of a method according the invention using a flare cap as an expansion member for expanding the smaller inner diameter in an end region of a nonstandard size tube to the larger inner diameter of a standard size fluid guiding element will be discussed in conjunction with Figs. 4 and 5.

Figs. 4a to 4c show different views of a flare cap. Such flare caps are known from the prior art for use in medical tubing and are available from TERUMO ® Corporation under the internal part numbers:

CB01X050, CB01X051, CB01X052, CB01X054, CB01X055, CB01X057) .

These flare caps are currently used during EO sterilization procedures as they will be further described below and they are suited for use with tubes of the following inner diameters.

Fig. 4a shows a partially cut away side view of a flare cap 10, Fig. 4b shows a cross section of a flare cap perpendicular to its longitudinal axis A along plane "IVb-IVb" shown in Fig, 4a (and 4c), Fig. 4c shows a cross section in plane IVc-IVc in Fig. 4b. In Fig. 4b, "IVa-IVa" indicates the view on the partially cut away region in Fig. 4a.

The flare cap 10 shown in Fig. 4a extends from a flat bottom side 11 (right hand side in Fig. 4a) to an arc-shaped top 12 (left hand side in Fig. 4a). In its interior there is a central lumen 13 extending from the bottom almost to the top. This central lumen 13 is surrounded by an inner cylindrical wall 14 extending from the bottom towards the inner side of top wall 15. The flare cap 10 in Figs. 4a to 4c shows rotational symmetry around its longitudinal axis A.

In the interior of the flare cap 10 there is an arrangement of spoke-like elements 16 in an equiangular arrangement in plane IVb - IVb, with said spoke-like elements 16 extending radially outwardly from the outer periphery of the inner cylindrical wall 14 towards the inner periphery of outer cylindrical wall 18.

Details of the spoke-like elements 16 may be best seen in Fig. 4a. Each spoke-like element 16 is comprised of three main sections:

Firstly, a radially inner segment 16a on the radially outer surface of the inner cylindrical wall 14, said radially inner segment 16a extending essentially along the outer side of the inner cylindrical wall 14 in its entire extension in the longitudinal direction and having a radially increasing thickness along the longitudinal direction from the bottom side 11 towards the arc-shaped top 12 of the flare cap 10. Secondly, a radially outward segment 16b extending essentially along the inner side of the outer cylindrical wall 18 in its entire extension in the longitudinal direction of the flare cap 10. Thirdly, a top segment 16c in the vicinity of the arc-shaped top 12 of the flare cap 10 connecting the top-most regions of the radially inward segment 16a and the radially outward segment 16b. The contours of the radially inward segment 16a and the radially outward segment 16b are chosen to leave a wedge-shaped tapered groove 19 between the two of them with the radial distance between the groove 19 and the longitudinal axis A increasing in the direction from the bottom side 11 towards the arc-shaped top 12 of the flare cap 10.

As may be best seen in Fig. 4b, there results an annular regular (equiangular) arrangement of grooves 19, each of which shows a wedge-shaped tapered contour in the direction

perpendicular to the plane of Fig. 4b, which together with the empty spaces between adjacent spoke-like elements yield an annular shaped cavity for accommodating the annular end region of a hollow tube inserted into the interior of the flare cap as will be shown and discussed in more detail in conjunction with Figs. 5a) to 5c) below. The outer cylindrical wall 18 of the flare cap 10 may be totally or partially covered with corrugated sections 17 in order to improve grip for a user when manually manipulating the flare cap 10.

Fig. 5a) to 5c) shows three different sets of non-standard tubes and corresponding flare caps corresponding to sizes of 7/16", 5/16" and 3/16" (11.1, 7.9 and 4.76 mm, respectively).

As may be seen in the cross sectional part in the central section (right side of Fig. 5b) a sufficiently flexible tube 40 may be forcibly pushed into the annular arrangement of tapered grooves 19 (Fig. 4) contained in the interior of each flare cap 10. As the radial distance of the wedge-shaped groove from the longitudinal axis A of a flare cap 10 increases when moving from bottom to top of a flare cap, the end region of the tube pushed into the grooves is radially expanded when following the (from left to right in Fig. 5b) "upward" slope of the tapered grooves 19 (Fig. 4). Thereby, the inner diameter of the end region of the tube is widened. At this stage, when subjecting the tube inserted into a flare cap such as shown in the central portion of Fig. 5b, to an ethylene oxide (EO) sterilization treatment, it is found that when the material of the tube has been appropriately chosen, the tube material may soften. The end region of the softened tube shown in the central portion of Fig. 5b will thus easily adapt to the wedge shaped contours of the annularly arranged tapered grooves 19. Accordingly, if the shape of the tapered groove 19 is appropriately chosen, the diameter in the end region of a non-standard tube 40, e.g. a 7/16" tube, may be readily widened to a desired diameter of a standard tube, e.g. a ½" (8/16") tube.

When finishing the EO gas sterilization treatment while the widened end region of the nonstandard size tube is still held in the arrangements of tapered grooves 19 of a flare cap 10 it is found that the deformation of the widened end region of tube 40 is permanent. In other words: in the end region of the non-standard tube 40, the inner diameter has been permanently widened to a standard tube size.

Accordingly, the widened end region of the non-standard size tube (e.g. 7/16") may now be readily connected to a corresponding standard size tube (via connector as shown in Fig. 8) or standard sized fluid guiding component (e.g. ½" = 8/16").

According to the invention, the process of widening the inner diameter of the end region of a non-standard size tube to the inner diameter of a standard size tube relies on the use of an ethylene oxide gas treatment step. Ethylene oxide (EO), properly called oxirane by IUPAC, is an organic compound with the formula C₂H₄0. It is a cyclic ether. EO is a flammable, colorless gas at temperatures above 51.3 degrees F (10.7 °C) that smells like ether at toxic levels. EO is used for sterilizing certain types of equipment that are considered to be too fragile for sterilization with steam. EO has a micro biocidal potential which makes it particularly useful in the sterilization of medical devices but also in the sterilization needed in equipment used in the food and beverages industry. EO gas sterilization is done in order to kill any microorganisms that are left during production or packaging processes. During an EO gas sterilization process, an EO gas sterilization chamber (not shown) is equipped with heat and humidity and pressure controls. An assembled and packaged tubing set containing non-standard size tubing 40, a free end of which has been put on a flare cap 10, such as shown in Fig. 5b, or non-standard tubing such as it is shown in Fig. 6 with an expandable stent member being placed in an interior region thereof, is placed within the EO gas sterilization chamber.

The EO gas chamber process causes the tubing material to soften and become malleable. The malleable tubing expands while within the EO gas sterilization chamber due to physical contact with the inner part of the flare cap during EO gas sterilization.

The widening of the end region of the tube during EO treatment is subject to a thermal effect caused by the heat applied during EO gas sterilization.

Following are the preferred parameters for EO treatment when applying the present invention: Tube material: PVC

Tube diameter and length: Various (not critical for flare cap application)

EO treatment of a PVC tube may be conducted in a container with EO partial pressure between 150 to 1 800 mbar, in particular 605 mbar.

The (partial) pressure of other gases present in the container where EO treatment takes place may be 145mbar,

The temperature during EO treatment in the container is 45-55 °C.

The duration of the treatment in the container is 190 +/- 15 minutes.

EO profiles may vary and the above parameters are an example which has been found to have the desired effect to PVC tubing when used with an expansion component.

The preferred material for the tubing shown in Fig. 5b is PVC (polyvinylchloride).

PVC tubing for medical use comes in variants with different types of plasticizers

such as for example TOTM or DEHP, with TERUMO ® X-coating or heparin coating, or uncoated, and in various shore hardness/durometer. TOTM (Tri-Octyl-Trimellilate is a primary branched monomeric plasticizer for vinyl homopolymer and copolymer resins. Due to its suitable properties and the low cost, DEHP (Diethylhexyl phthalate,) is widely used as a plasticizer in manufacturing of articles made of PVC.

PVC is the standard material of perfusion circuit tubing used in CPB applications.

Other tubing bearing the same malleability properties as PVC under EO gas sterilization should respond to flare cap/EO treatment in the same manner as PVC.

The tubing considered in the present invention is preferably made of PVC, preferably of the following types of PVC :

For medical surgical tubing

As practical examples but by no means limited to the following types of tubing:

Renolit Solmed, PVC Tubing - Compound 3270

PVC compound 3270 is manufactured from materials that meet USP <88> Class VI and ISO 10993-1. Also the tubing has a durometer of 74A, a tensile strength of 20 MPa (2900psi), a break at cold temperature of -35°C (-95°F) and the elongation at break is 360%.

HMC DEHP Free PVC Tubing - Compound type AM 770/T

PVC compound type AM 770/T is manufactured from materials that meet USP <88> Class VI. Also the tubing has a durometer of 70A, a tensile strength of 16.5 N/mm² (2393psi) and the elongation at break is 340%.

Hence, the invention lies in the realization that the EO sterilization treatment has the beneficial side effect of softening the PVC which is then expanded by the radial forces exerted by an appropriate mechanical expansion member.

2^nd preferred embodiment

Fig. 6 shows a set-up for employing a second embodiment of the method according to the invention wherein the expansion member is not a flare cap but a stent (positioning and expanding) mechanism 20 insertable into a central region 41 of a non-standard type tubing 40. Fig. 7 shows a conventional (balloon) expandable stent, such as it is for example known from US 7,540,930, which are hereby incorporated in its entirety, and which may be put on the stent mechanism 20 shown in Figs, 6a and 6b. Fig. 6a shows a non-standard sized tubing 40 into which the distal end 21 of a stent

(positioning and expanding) mechanism 20 has been inserted. On its distal end 21 the stent mechanism 20 comprises an expandable portion 22 which in a first non-expanded state has a radial extension smaller than the inner diameter of the non-standard size tubing 40.

Additionally, the stent mechanism 20 has an elongated central portion 23 which extends in a longitudinal direction and which has also radial expansion smaller than the inner diameter of the non-standard sized tubing 40. Finally, the stent mechanism 20 has a proximal end 24. The proximal end 24 may comprise a mechanical manipulating aid 25 which can be operated by a user. In Fig. 6 this manipulating aid 25 is hook-shaped to allow a user easy handling thereof.

In the stent mechanism 20, the expandable portion 22 carries a stent 41 such as it is shown in Fig. 7. Said stent may be radially expanded by a suitable mechanical expansion

mechanism. For example the stent mechanism 20 could be a telescopic pole with the expandable portion 22 comprising a section with a male screw thread interacting with a female screw thread rotatably connected to the manipulating aid 25 on the proximal end via the central portion of the stent mechanism 20. Rotating the manipulating aid 25 in either the clockwise or counter-clockwise direction would thus rotate the female screw thread which would thus advance into the male screw thread of the distal end of the stent mechanism or retract therefrom. This may be used for precise advancement of the distal end of the stent 41 along the longitudinal axis of the tube 40.

The stent 41 shown in Fig, 7 may also be a balloon expandable stent which is expanded by pumping air or another appropriate gas through an air conduit (not shown) in the stent mechanism to an inflatable balloon at the distal tip of the stent mechanism which will expand the balloon and force the stent 41 in Fig. 7 radially apart to widen the surrounding wall of the tube 40 while it is softened by an EO sterilization treatment. Balloon inflatable stents as well as means for positioning the same in the lumen of a long extended tube and means for inflating and expanding such a balloon inflatable stent are well- known to the skilled person. Hence, once again, when the material of the tube was appropriately chosen to be sensitive to ethylene oxide sterilization treatment, the inner radius of the tube will be radially expanded when inflation of the balloon inflates the balloon expandable stent.

It is also beneficial in CPB application to have a length of standard sized tubing within the non-standard sized tubing which can be used to connect certain CPB circuit components, such as a flow sensor or bubble detector, which measure by "hugging" a segment of standard sized tubing.

Examples for practical use

Figs. 9a 13b show various examples of uses of systems composed of hollow

non-standard tubes having been subjected to manufacturing steps of an inventive method creating an expanded region with its lumen being fluidly connected to the lumen of a hollow fluid guiding component, and in particular to hollow fluid guiding components in CPB systems for decreasing priming volume.

Figs. 9a to 10b show use of a nominally non-standard PVC 3/16" (or PVC 5/16") tube after EO treatment according to the invention which has led to widening of the inner diameters at the ends of said non-standard tube so that said tube can now be readily

connected to a standard ¼" (or 3/8") component for use in an arterial line.

Figs. 11a and lib show use of nominally non-standard PVC 5/16" (or PVC 7/16") tubes after EO treatment according to the invention which has led to widening of the inner diameters of said non-standard tubes so that said tubes can now be readily connected to a standard 3/8" (or ½") component for use in a venous line.

Figs. 12a and 12b show use of two segments of nominally non-standard PVC 5/16" (or PVC 7/16") tubes after EO treatment according to the invention which has led to widening of the inner diameters at the ends of said non-standard tube so that said tube segments can now be readily connected to a standard 3/8" (or 1/2") venous reservoir inlet port or a component for use in a venous line.

Figs. 13a and 13b show use of a nominally non-standard PVC 5/16" (or PVC 7/16") tube after EO treatment according to the invention which has led to widening of the inner diameters at the ends of said non-standard tube so that said tube can now be readily connected to a standard 3/8" (or 1/2") component for use in a venous line.

Other fields of application

Although originally being motivated by the application of the inventive method solely in the medical field of CPB, the inventors have realized that the inventive method can also be advantageously employed in other fields, where end portions or middle segments of sterilized non-standard tubings need to be connected to end portions of sterilized standard tubings or standard components; or benefit from a mid-segment expanded to be compatible with standard sized tubing or components. For example, considerations similar to the problem of minimizing priming volume in CPB circuits may apply in the food and beverage processing industries where liquid food or beverages processed and contained in a first container must naturally flow (by gravitational force) or be pumped through tubings to other containers (where further processing steps such as purification or enrichment of the liquid food or beverage take place) and where at the beginning of the process exposure of the liquid food or beverage to air contained in the tubings between the containers - and hence unwanted oxidation - must be avoided.

Again, such unwanted contact to air contained in the tubings may be avoided by preloading the tubing with a priming fluid which will not be harmful for the processed liquid food or beverage. The similarities to the operation of a CPB as discussed above are quite obvious in that in this case it would nevertheless eventually also be desirable to minimize use of any priming fluid in the food or beverage processing equipment. This may again be done by replacing, wherever possible, standard sized tubing of larger inner diameter with nonstandard sized tubing of smaller inner diameter and employing the method of the invention for manufacturing systems of non-standard sized reliably and easily connectable to any remaining standard sized tubings.

In many cases the hollow fluid guiding component may contain an appropriately designed port inlet or outlet, which allows for the connection of the hollow tube directly to the hollow fluid guiding component. In this case no there is no need for an additional connector bringing the widened region of the hollow tube into fluid connection with the lumen of said hollow fluid guiding component.

For practical use, in particular in CBP applications, it is particularly advantageous to make available a packaged set of sterilized components comprising - at least one hollow tube (generally having a lumen of a predefined smaller inner

diameter and additionally comprising a radially expanded region, said radially expanded region having been expanded to a larger inner diameter by a method of EO sterilization treatment and mechanical expansion of certain regions by a mechanical expansion member, and

- a hollow fluid guiding component having a lumen with said predefined larger inner diameter, and

- a connector for bringing the widened region of the hollow tube into fluid connection with the lumen of said hollow fluid guiding component.

Reference numerals

1 patient

2 venous tubing

3 oxygenator

4 arterial tubing

5 venous return catheter

6 arterial cannula

7 main tube connection sites

I st embodiment

10 flare cap

A longitudinal axis A

I I flat bottom side of flare cap

12 arc-shaped top of flare cap

13 central lumen

14 inner cylindrical wall

15 top wall

16 spoke-like elements

16a radially inward segment

16b radially outward segment

16c top segment

17 corrugated sections

18 outer cylindrical wall

19 tapered groove

40 flexible hollow tube with predetermined smaller diameter lumen 2nd embodiment

20 stent (positioning and expanding) mechanism 20

21 distal end 21

22 expandable portion

23 elongated central portion 23 proximal end 24 manipulating aid 25 non-standard sized tubing (balloon inflatable) stent

Claims

1. A method for expanding at least a region of a lumen of a hollow tube (40) having a smaller inner diameter lumen to a larger inner diameter of a lumen of a hollow fluid guiding component, said lumen in the hollow tube defining a longitudinal direction along its central axis (A) and a radial direction perpendicular thereto, wherein said region of said hollow tube (40) is widened by inserting an expansion component (10, 20) which fits into said first smaller inner diameter lumen,

characterized by,

said hollow tube (40) being made of a material that softens when being subjected to a sterilization treatment with ethylene oxide gas,

said method comprising the following steps:

placing the expansion component (10, 20) at a predetermined region of the lumen of the hollow tube (40) ,

subjecting the hollow tube to thermal effect during ethylene oxide gas sterilization in at least said predetermined region of the lumen of the hollow tube (40),

exerting a radially outwardly directed force on the inner wall of the lumen by said expansion component (10, 20) until said predetermined region of the lumen of the hollow tube has sufficiently widened to acquire the larger inner diameter.

2. A method according to claim 1 , wherein the hollow fluid guiding component having a larger inner diameter is a second hollow tube.

3. A method according to claims 1 or 2, wherein said expansion component is a flare cap (10) having a base (11) and a top (12) with a tapered inner wall surface (14) expanding from the base (11) into the vicinity of the top (12) , and an outer wall surface (18) defining an annular cavity between the inner wall surface and the outer wall surface, with the base end of the inner wall surface being adapted to allow inserting the first hollow tube (40) into said annular cavity between the inner wall surface and the outer wall surface, and thereby allowing radially expanding the inner diameter of the first tube by adapting to the tapered inner wall surface of said flare cap (10).

4. A method according to claims 1 or 2, wherein said expansion component consists of an elongated shaft member (20) that has an outer diameter smaller than the first

predetermined diameter of the hollow tube (40) and which is inserted into the hollow tube (40) in its axial direction until it reaches a region to be expanded inside the lumen of the hollow tube (40) , wherein said elongated shaft member (20) comprises an extension element 22) which is axially moveable relative to the elongated shaft member (20) in order to be pushed outside the shaft in a distal direction and which is connected to a manipulating aid (25) to be kept at the proximal end outside of the first hollow tube (40) , wherein

manipulation of said manipulating aid (25) forces the extension element (22) to expand in the radial direction in said region in the lumen in the first hollow tube (40) thereby radially expanding the first predefined smaller inner diameter lumen to the predetermined, larger inner diameter lumen of said hollow fluid guiding component.

5. A method according to any one of claims 1 to 4, wherein the following parameters are used:

inner diameter of hollow tube is 7/16", 5/16", 3/16" etc. inches

Wall thickness of hollow tube is 1/16", 3/32", etc. inches

predefined larger inner diameter of the lumen of said hollow fluid guiding component is ½," 3/8", ¼", materials of which hollow tube is composed is PVC.

6. A method according to claim 5, wherein the partial pressure of EO in a container where the EO sterilization treatment takes place is in the range from 150 to 1 800 mbar, in particular 605 mbar,

wherein, the (partial) pressure of other gases present in a container where EO treatment takes place is 145mbar,

wherein the temperature during EO treatment in the container is 45-55°C,

wherein the duration of treatment in the container is 190 +/- 15 minutes.

7. A system composed of a hollow tube (40) having been subjected to manufacturing steps of any of the methods according to claims 1 to 6 for creating an expanded region with its lumen being fluidly connected to the lumen of a hollow fluid guiding component.

8. Use of a system according to claim 7 in an extracorporeal blood circuit in a CPB system for decreasing priming volume in those segments of the extracorporeal circuit where tubing of the larger diameter is replaced by tubing of a smaller diameter subjected to treatment according to any of methods 1 to 6 with the widened portions of the EO treated tubing of smaller diameter being connected to the tubing or the component of the larger diameter.

9. Use of a system according to claim 5 in a circuit in which liquid foods and/or beverages are moved.

10. A packaged set of sterilized components comprising at least one hollow tube (40) generally having a lumen of a predefined smaller inner diameter and additionally comprising a radially expanded region, said radially expanded region having been expanded to a larger inner diameter by a method according to any of claims 1 to 5,

a hollow fluid guiding component having a lumen with said predefined larger inner diameter,

a connecting piece for bringing the widened region of the hollow tube into fluid connection with the lumen of said hollow fluid guiding component.