WO2000006079A1

WO2000006079A1 - A bag or a bag system for collecting and storing blood and a method therefor

Info

Publication number: WO2000006079A1
Application number: PCT/DK1999/000422
Authority: WO
Inventors: Bjørn MEIER
Original assignee: Mesibo A/S
Priority date: 1998-07-29
Filing date: 1999-07-28
Publication date: 2000-02-10
Also published as: NO20010440L; TW477696B; CN1316895A; EP1100428A1; CA2338604A1; HUP0103416A3; PL345797A1; NO20010440D0; ID30222A; AU5027099A; JP2002521138A; BR9912546A; HUP0103416A2

Abstract

The present invention relates to a bag or a bag system for collecting and storing blood comprising at least two primary storage chambers and at least two secondary storage chambers, arranged in such a relation to each other so that each of the storage chambers can be sealed off from the others, and a method for collecting and storing blood.

Description

A bag or a bag system for collecting and storing blood and a method therefor

The present invention relates to a bag or a bag system for collecting and storing blood and a method for collecting and storing blood.

It is well known to extract blood from human beings and store this blood in a frozen or refrigerated condition for later use during operations, blood transfusions, and the like. For this purpose a number of different blood bags have been provided.

In the past few years it has become known that blood from the umbilical cord and the placenta at birth contains stem cells, cells that are only present in the blood at this specific time of a person's life. These cells have shown a considerable potential curative value, e.g. for use in bone marrow replacement procedures in cancer treatment and other immunodeficiency disorders.

In order to preserve these cells, blood from the umbilical cord and/or the placenta, which would otherwise just have been discarded, has been collected and stored at low temperatures. The containers used in this procedure are known to be conventional blood bags, as those mentioned above .

However, in order to take a sample from a bag with frozen blood, it is necessary to defrost the entire amount of blood, and once defrosted it must either be used shortly after or discarded, since it is not refreezable. The problem regarding the conventional bags and methods is therefore that the chance of using the stem cells to cure a patient is limited to only once. JP 10000224A discloses a bag system for isolating stem cells and precursor cells from umbilical cord blood by centrifugation. This system consisting of 6 bags equipped with connectors and tubes to lead the blood from bag to bag, comprises one bag wherein the obtained leucocyte component containing the above mentioned cells are fro^¬ zen. The problem relating to this bag is, however, the same, as it is not possible to defrost part of the cells without destroying the rest.

It is therefore the object of the present invention to provide a solution to the problem defined above, and in particular to provide a bag or a bag system for collecting and storing blood, in particular umbilical cord blood and/or blood from the placenta, designed to make it possible to defrost only a part of the stored blood.

The invention relates to a bag or a bag system for col^¬ lecting and storing blood as defined in claim 1, a bag or a bag system for collecting and storing blood in combination with a mixing bag as defined in claim 4, and a bag or a bag system for collecting, mixing, and storing blood as defined in claim 5.

A bag or a bag system according to the present invention may contain a system of storage chambers alone, equipped only with an opening for receiving blood, or the opening for receiving blood may comprise an inlet channel. This inlet channel can be a small tube suitable to be con- nected to a mixing chamber adapted with e.g. a snap lock, a clamp or a similar easy operational closing device.

Another aspect of the invention is a bag or a bag system for collecting and storing blood in combination with a mixing bag, where the mixing bag comprises at least one mixing chamber, an opening for receiving blood and an opening for discharging blood. Regarding the mixing bag, the opening for receiving blood and the opening for discharging blood may be the same. The opening for discharging blood is adapted to be connected to the opening for receiving blood in the bag or the bag system for collecting and storing blood, e.g. by use of suitable connectors .

A further aspect of the invention is a bag or a bag sys- tern for collecting and storing blood comprising a mixing chamber, where said mixing chamber can be sealed off from the storage chambers by closing e.g. a snap lock or by using a clamp or by welding. In order to minimise the amount of equipment to be stored, it is preferred that the mixing chamber is arranged in such a relation to the storage chambers so that it can be sealed off therefrom and removed before storage.

A mixing chamber of a bag or a bag system according to the invention should have a volume which corresponds to or is bigger than the sum of the volumes of the primary and secondary storage chambers . In order to use the mixing chamber for mixing the blood with anticoagulation agent and/or preserving agent, the mixing bag should preferably have a volume at least twice as big as the sum of the volumes of the primary and secondary storage chambers. The mixing chamber may e.g. have a volume in the range of 100 to 500 ml, preferably 225 to 400 ml, more preferably 250 to 300 ml. In a preferred embodiment the mixing chamber may e.g. have a volume in the range of 100 to 500 ml, preferably 125 to 400 ml, more preferably 150 to 250 ml.

The mixing chamber may further comprise at least one port for injection of anticoagulation and/or preserving agents and/or at least one port for extracting blood in order to perform tests, e.g. to detect contamination by vira.

In all of the above mentioned bags the primary and secon- dary chambers are in liquid communication with each other. This liquid communication may preferably be provided by pipe connections with a length in the range of 10-20 mm, preferably 12-15 mm. In another embodiment the pipe connections has a length in the range of 10-300 mm, preferably about 100 mm.

The inner diameter of said pipe connections may be in the range of 2-10 mm, preferably 3-8 mm, more preferably 4-6 mm when the pipes are in a non collapsed condition.

During the process of sealing off each of the storage chambers, e.g. by welding (heat welding, impulse welding or other) or by closing a snap lock or a clamp, preferably shortly after the filling is completed, it is i por- tant to ensure that only a minimal amount of the obtained blood is destroyed. The bag or the bag system according to the invention, which is provided with the above mentioned pipe connections containing only a minimum of blood, ensures that only a very small percentage of the total amount of blood is damaged in connection with the closing of these channels by e.g. heat.

By using a bag or a bag system according to the present invention for storing umbilical cord blood it is possible to obtain at least two, preferably at least 5 primary storage chambers, more preferably at least 8 primary storage chambers, and most preferably at least 10 primary storage chambers, all containing blood. Of course the number of chambers filled with blood depends on how much blood it is possible to extract from the umbilical cord and the placenta as well as how the blood bag is de^¬ signed.

The volume of the primary storage chambers is usually in the range of 10 to 40 ml, preferably 25 to 35 ml, more preferably 25 to 30 ml. In a another embodiment the vol^¬ ume of the primary storage chambers is in the range of 10 to 80 ml, preferably 25 to 70 ml, more preferably 25 to 50 ml.

It is however preferred to obtain as many storage chambers as possible, since this provides the patient with the largest flexibility in using the stored blood. Since any number of chambers filled with blood can be removed from the bag, it is possible to defrost only the amount of blood needed for the intended treatment.

The system of chambers also comprises a number of secondary storage chambers, preferably equal to at least the number of primary storage chambers, all of which may be sealed off and removed individually as the primary cham^¬ bers. The object of these secondary chambers is to provide small amounts of blood for test purposes. Therefore the ratio between the volumes of the primary and secon- dary storage chambers is preferably between 40:1 and 60:1, more preferably about 50:1. In another embodiment the ratio between the volumes of the primary and secondary storage chamber is in between 40:1 and 150:1, preferably between 50:1 and 80:1.

Having secondary storage chambers with a volume in the range of 0,2 to 1,5 ml, preferably 0,3 to 0,7 ml, more preferably 0,4 to 0,6 ml, eliminates the need for defrosting more than one or two secondary storage chambers to obtain the necessary amount, e.g. 0,5 ml, of blood in order to test it and see if it is suitable for the in- tended use. This particular feature is of great importance, since it is essential to determine the quality of the blood in order to find out the right amount of blood needed for the treatment, to check for contamination of the blood (e.g. bacteria) or to perform a gene test.

In a preferred embodiment all the primary storage chambers are marked or adapted to be marked individually, each with at least one corresponding secondary storage chamber. Further, the bag or the bag system itself is preferably marked or adapted to be marked with a date and/or a number in order to be able to identify the bag.

The primary storage chambers can have various shapes, preferred embodiments, however, are those where the shape is substantially rectangular or substantially round when the bag or the bag system is in a collapsed condition.

Since long term storage of blood typically includes sub- jecting the bag or the bag system to temperatures below - 170 °C, it is very important that the bag or the bag sys^¬ tem is made of a suitable material, e.g. a material of medical or pharmaceutical grade. Examples of suitable materials are e.g. a polyethylen, an ethylene vinyl acetate copolymer, a fluorine resin, a polyimide, silicone, an ABS polymer (acrylonitrile/butadien/styrene polymer) or a polycarbonate .

The bag or the bag system may consist of one or more fo- lio layers, e.g. joined by welding, and in cases regarding more than one folio layer, the material of the layers may be selected among the above-mentioned materials and may be identical or different.

In a preferred embodiment according to the invention, the bag system comprises primary and secondary storage chain- bers made of one of the above mentioned materials, said bag system being arranged or being able to be arranged in a second bag e.g. surrounding the bag system by the sec^¬ ond bag made of a suitable material. The second bag may be divided into a number of compartments.

The invention also relates to a method for collecting and storing umbilical cord blood and/or blood from a pla^¬ centa, comprising the steps of:

a) extracting blood from the umbilical cord and/or the placenta,

b) leading it into a mixing chamber, e.g. by injection,

c) mixing the blood with a preserving agent and/or an anticoagulation agent,

d) optionally storing it for no longer than 24 hours,

e) optionally adding further chemicals to prepare the blood for cryo-preservation,

f) providing a liquid communication between the mixing chamber and a number of storage chambers, allowing the blood mixture to flow into said storage chambers,

g) closing the bag or the bag system with a clamp and optionally removing the mixing chamber,

h) closing the channels between the various chambers e.g. by welding or by closing a snap lock or a clamp, thereby providing a number of primary and secondary storage chambers sealed off from each other, and i) immediately placing the bag or the bag system in a freezer bringing the temperature below about -70 °C,

wherein said primary and said secondary storage chambers are arranged in a bag or a bag system wherein the channels are linked to each other with intermediate seals, and the volume of the primary storage chambers is larger than the volume of the secondary storage chambers.

It should be observed that step e)-i) may be carried out after storing the blood for no longer than 24 hours under conditions with no bacteria growth, e.g. in a refrigera^¬ tor.

The extracting of blood from an umbilical cord and leading it into a mixing chamber may be done in any conventional way. Preferably the extracting should be done in a way accepted by those skilled in the art.

The anticoagulation agent and/or the preserving agent may be added after the blood has been led into the mixing chamber, however, it is preferred that they are already present in the chamber at the time the blood is led, which simplifies the method, since the mixing chambers can be prepared for use in advance.

However, in special cases where the amount of extracted blood is small it may be preferred to add the anticoagulation agent and/or the preserving agent after the col- lecting of the blood, in order to ensure that the ratio between the blood and the above mentioned agents is in the best possible range. Therefore, in a preferred embodiment, the mixing chamber is provided with at least one extra port to facilitate the addition of anticoagula- tion agent and/or preserving agent. After mixing the blood with the above mentioned agents, the mixing chamber is brought into liquid communication with the storage chambers of the bag or the bag system according to the invention. Depending on which type of bag is being used, the connection can be made by use of tubes and connectors, or in a preferred embodiment of the invention simply by opening a snap lock between the mixing chamber and the storage chambers.

This allows the blood to flow into the primary and secon^¬ dary storage chambers, and after filling of as many cham^¬ bers as possible with blood, the opening for receiving blood is closed, e.g. by use of a clamp or a snap lock.

Since there is no need to store the attached empty mixing chamber, it is preferred to remove the mixing chamber, e.g. by cutting it of or removing the tubes and connec^¬ tors that have been used.

In order to obtain a number of chambers that can be re^¬ moved individually, the liquid communication between the chambers has to be sealed off. This may preferably be done by use of heat.

Finally the bag or the bag system is frozen to a temperature below about -70 °C to make sure that the blood can be stored until the need for use thereof arises.

Various embodiments of the invention will be described below with reference to the drawings.

Fig. 1 illustrates a preferred embodiment of a bag according to the invention comprising a mixing chamber.

Fig. 2 illustrates a bag according to the invention adapted to be connected with a mixing bag. Fig. 3 illustrates a bag in combination with a mixing bag according to the invention.

Fig. 4 illustrates a bag system according to the inven^¬ tion comprising a mixing chamber.

Fig. 5 illustrates another embodiment of storage chambers as a part of a bag system according to the invention.

Fig. 1 illustrates a bag according to the invention comprising a mixing chamber (1) with a double welding (5), and an inlet (11) equipped with a tube (3), which tube (3) at one end is equipped with a connector (4) to be connected with a needle for harvesting blood. Two snap locks (2) and (6) are placed at the inlet (11) and at the outlet (12) of the mixing chamber (1). The storage bag (13), which is connected with the mixing chamber (1) through a tube (14) equipped with a clamp (7), comprises ten primary storage chambers (8) and ten secondary storage chambers (9) in liquid communication with each other via pipe connections (10). The dotted lines show where the bag or the bag system is welded in order to seal off each chamber after the bag has been filled with blood.

When using a bag according to Fig. 1 the blood is led into the mixing chamber (1), where the above mentioned necessary agents are preferably already present, then the snap lock (2) is closed, and the bag is turned upside down or shaken in order to mix the ingredients properly. Then the snap lock (6) is opened and the blood mixture flows into the storage bag (13) filling up as many primary (8) and secondary (9) storage chambers as possible. To make sure that the blood mixture flows properly into the chambers, the person handling the bag can preferably squeeze or shake the bag a little to ease the flow of the blood mixture.

When all of the blood mixture contained in the mixing chamber (1) has flown into the storage bag (13), the clamp (7) is closed and the mixing chamber (1) is cut off. Then the pipe connections (10) are closed e.g. by welding, either shortly after the bag has been filled or at the latest just before the bag is frozen. The welding can be performed at the site, if the proper welding equipment is available or the bag can be placed at a temperature where substantially no bacteria can grow for up to 24 hours, and during that time be transported to a facility at which the welding can be performed.

Fig. 1 illustrates a preferred embodiment of a bag according to the invention wherein the mixing chamber constitutes part of the bag. In such a bag according to the invention, where the mixing chamber is included as a part of the bag, the risk of infection has been minimised, since there are no unnecessary contact with the surroundings, such as transferring the blood from one bag to another, once the blood has been led into the bag. This bag also ensures that only a minimum of the blood is lost or destroyed during the process of collecting and storing the blood. In cases where the amount of blood obtained from the umbilical cord and the placenta is very small, this is particularly important.

As shown in Fig. 1 the primary storage chambers and the pipe connections form a certain pattern. However, this is merely one example of a pattern and many others may be appropriate, as e.g. shown in Figs. 2 and 3. The important aspect is that the pattern is designed to make it possible to fill as many storage chambers as possible, even with only a small amount of blood available. Fig. 2 shows a storage bag according to the invention with an opening for receiving blood (21) equipped with a snap lock (22) and a clamp (23) . The bag comprises 12 primary storage chambers (24) and 12 secondary storage chambers (25) in liquid communication with each other via pipe connections (26) . The dotted lines show where the bag is welded in order to seal off each chamber after the bag has been filled with blood.

This bag is adapted to be connected with a mixing bag, wherein the extracted blood is mixed with agents mentioned above.

Fig. 3 shows a mixing bag (31) and a storage bag (35) according to the invention. The mixing bag (31) consists of a mixing chamber (32) surrounded by a double welding (33) and is equipped with a connector (34) adapted to be connected with the storage bag (35) . The storage bag (35) , which is provided with an opening for receiving blood (36) equipped with a snap lock (37) and a clamp (28), comprises ten primary storage chambers (39) and ten secondary storage chambers (40) in liquid communication with each other via pipe connections (41). The dotted lines show where the bag is welded in order to seal off each chamber after the bag has been filled with blood.

Fig. 4 shows a bag system according to the invention comprising a mixing chamber (41) provided with means (51) for hanging the mixing chamber on a suitable stand or similar means, an opening for receiving and discharging blood (42) and a further port (43) for injection of additives and/or extraction of blood for tests. The bag system further comprises 4 primary storage chambers (48) in liquid communication with each other and the mixing chamber via pipe connections (46) and connectors (45,49) and for each primary storage chamber two secondary storage chambers (50) . Each primary storage chamber may be sealed off from each other and from the mixing bag by using clamps (47) .

When using a bag according to Figs. 2, 3 and 4 the blood is led into a mixing bag and treated as described above, the difference being that the mixing chamber does not constitute part of the storage bag, but is provided as a separate bag. After the separate mixing bag has been connected to the storage bag, the blood flows into the primary and secondary storage chambers as already described. After the storage chambers have been filled the mixing bag is disconnected from the storage bag, and the storage bag is handled as explained above.

When using a bag system according to fig. 4 the primary and secondary storage chambers are preferably placed in a separate bag after being disconnected from the mixing chamber and optionally disconnected from the pipe connection by simply cutting them off. This bag may consist of one or more compartments each suitable for containing one ore more primary storage chambers and secondary storage chambers connected thereto. The compartments may be sepa- rated by weldings.

In all four figures the secondary storage chambers have a substantial rectangular shape. However, this is only one example, and other shapes may be just as appropriate.

Even though it appears from the figures that the primary and secondary storage chambers of a bag, respectively, have equal sizes and shapes, it should be understood that the sizes and shapes of the primary and secondary storage chambers of a bag, respectively, can differ from each other . As shown in figs. 1 and 3 the mixing chamber is preferably provided with a double welding, but other embodiments may be just as appropriate, e.g. a triple welding, or a double folio and a single welding.

An alternative embodiment of the storage chambers is shown in fig. 5, where the primary storage chamber (61) via a connector (63) is connected to the secondary stor- age chambers (65) which are sealed off from each other and the primary storage chamber by talurites (62) after being filled with blood. The clamp (64) is for sealing off the storage chamber from the pipe connection.

Claims

1. A bag or a bag system for collecting and storing blood comprising an opening for receiving blood and at least two primary storage chambers and at least two secondary storage chambers, said primary storage chambers and said secondary storage chambers being in liquid communication with each other and arranged in such a relation to each other so that each of the storage chambers can be sealed off from the others, wherein the volume of the primary storage chambers is larger than the volume of the secondary storage chambers .

2. A bag or a bag system according to claim 1, wherein the opening for receiving blood comprises an inlet channel .

3. A bag or a bag system according to claim 2, wherein the inlet channel is provided in a form suitable for con- necting with an opening in a mixing bag.

4. A bag or a bag system for collecting and storing blood in combination with a mixing bag, said bag for collecting and storing blood being defined in claim 1, and wherein said mixing bag comprises at least one mixing chamber, an opening for receiving blood, and an opening for discharging blood, wherein said opening for discharging blood is adapted to be connected to the opening for receiving blood in the bag or the bag system for collecting and storing blood.

5. A bag or a bag system for collecting, mixing, and storing blood comprising an opening for receiving blood, and a mixing chamber, said mixing chamber being in liquid communication with at least two primary storage chambers and at least two secondary storage chambers, said primary storage chambers and said secondary storage chambers be^┬¼ ing in liquid communication with each other, and arranged in such a relation to each other so that each of the storage chambers and the mixing chamber can be sealed off from the others.

6. A bag or a bag system according to claims 1-5, wherein said liquid communication is provided by pipe connections .

7. A bag or a bag system according to claim 6, wherein the pipe connections have a length in the range of 10-20 mm, preferably 12-15 mm.

8. A bag or a bag system according to claims 6-7, wherein the pipe connections have a length in the range of 10-300 mm, preferably about 100 mm.

9. A bag or a bag system according to claims 6-8, wherein the pipe connections in a non collapsed condition have an inner diameter in the range of 2-10 mm, preferably 3-8 mm, more preferably 4-6 mm.

10. A bag or a bag system according to claim 4-9, wherein the mixing chamber is arranged in such a relation to the storage chambers so that it can be sealed off therefrom and removed before storage.

11. A bag or a bag system according to claims 1-10, wherein the primary storage chambers are marked or adapted to be marked individually, each primary storage chamber corresponding to at least one secondary storage chamber.

12. A bag or a bag system according to any of the preceding claims, wherein the bag or the bag system comprises at least 5 primary storage chambers, preferably at least 8 primary storage chambers, and more preferably at least 10 primary storage chambers.

13. A bag or a bag system according to any of the preceding claims, wherein the ratio between the volumes of the primary and secondary storage chambers is between 40:1 and 60:1, preferably 50:1.

14. A bag or a bag system according to any of the preceding claims, wherein the ratio between the volumes of the primary and secondary storage chamber is in between 40:1 and 150:1, preferably between 50:1 and 80:1.

15. A bag or a bag system according to claims 4-14, wherein the volume of the mixing chamber is in the range of 100 to 500 ml, preferably 225 to 400 ml, more preferably 250 to 300 ml.

16. A bag or a bag system according to claims 4-15, wherein the volume of the mixing chamber is in the range of 100 to 500 ml, preferably 125 to 400 ml, more preferably 150 to 250 ml.

17. A bag or a bag system according to any of the preceding claims, wherein the volume of the primary storage chambers is in the range of 10 to 40 ml, preferably 25 to 35 ml, more preferably 25 to 30 ml.

18. A bag or a bag system according to claims 1-16, wherein the volume of the primary storage chambers is in the range of 10 to 80 ml, preferably 25 to 70 ml, more preferably 25 to 50 ml.

19. A bag or a bag system according to any of the preceding claims, wherein the volume of the secondary storage chambers is in the range of 0,2 to 1,5 ml, preferably 0,3 to 0,7 ml, more preferably 0,4 to 0,6 ml.

20. A bag or a bag system according to any of the preced- ing claims, wherein the shape of the primary storage chambers, when the bag or the bag system is in a collapsed condition, is substantially rectangular.

21. A bag or a bag system according to claims 1-19, wherein the shape of the primary storage chambers, when the bag or the bag system is in a collapsed condition, is substantially round.

22. A bag or a bag system according to claims 4-21, wherein the mixing chamber further comprises at least one port for injection of anticoagulation and/or preserving agents and/or for extracting blood for tests.

23. A bag or a bag system according to any of the preced- ing claims, wherein the bag or the bag system is made of a material of medical or pharmaceutical grade.

24. A bag or a bag system according to claim 23, wherein the material may be selected from a group comprising polyethylene, ethylene vinyl acetate copolymer, fluorine resin, polyimide silicone, an ABS polymer (acrylonitrile/butadien/styrene polymer or a polycarbon^┬¼ ate .

25. A method for collecting and storing umbilical cord blood and/or blood from a placenta, comprising the steps of:

a) extracting blood from the umbilical cord and/or the placenta, b) leading it into a mixing chamber, e.g. by injection,

c) mixing the blood with a preserving agent and/or an anticoagulation agent,

d) optionally storing it for no longer than 24 hours,

e) optionally adding further chemical to prepare the blood for cryo-preservation,

h) closing the channels between the various chambers e.g. by welding or by closing a snap lock or a clamp, thereby providing a number of primary and secondary storage chambers sealed off from each other, and

i) immediately placing the bag or the bag system in a freezer bringing the temperature below about -70 ┬░C,

wherein said primary and said secondary storage chambers are arranged in a storage bag or a bag system wherein the channels are linked to each other with intermediate seals, and the volume of the primary storage chambers is larger than the volume of the secondary storage chambers.

26. Method according to claim 25, wherein the bag or the bag system is according to any of the claims 1-24.