Method for freezing a liquid

Abstract

A method for freezing a liquid located in a container, in particular a liquid drug, includes exposing the container to a cooling element such as cold gas in order to freeze the liquid. The cold gas preferably flows around the container, and/or the liquid is cooled in another way in order to freeze the liquid. The container is insulated at a surface of at least one first volume portion of the container, and the container is cooled nearly immediately at a surface of a second volume portion of the container by the cold gas such that the liquid freezes through later in the at least one first volume portion than in the second volume portion.

Claims

1. A method of freezing a liquid drug disposed in a container, the method comprising: cooling the container for freezing the liquid drug; insulating the container at a surface of a first volume portion of the container by fitting an insulation body on the surface of the first volume portion in a lateral direction; and cooling the container by applying a cooling element at a surface of a second volume portion of the container, the second volume portion being located at a center of the container and the first volume portion extending from the center of the container to the edges of the container; wherein the container is cooled so that the liquid drug freezes therethrough in the first volume portion later than in the second volume portion.

2. The method according to claim 1, wherein the container has a cuboidal shape, and a height of the cuboidal container is less than a quarter of at least one of (i) a width and (ii) a length of the cuboidal container.

3. The method according to claim 1, wherein the insulation body has a U-shaped cross-section.

4. The method according to claim 1, wherein the container includes a flexible inner container holding the liquid drug and a rigid outer container.

5. The method according to claim 4, wherein the container includes a foam between the inner container and the outer container, the foam being configured to compensate for an expansion in the volume of the liquid drug upon freezing.

6. The method according to claim 5, wherein the foam has a decreasing elasticity with decreasing temperature below the freezing point.

7. The method according to claim 5, wherein the foam is configured to harden at a temperature between 0° C. to −30° C.

8. The method according to claim 7, wherein the foam is configured to harden at a temperature between −10° C. and −20° C.

9. The method according to claim 5, wherein the foam is configured to harden, and is configured so that a process of hardening is reversible.

10. The method according to claim 5, wherein the outer container is lined with the foam such that the inner container is completely surrounded by the foam when the inner container is arranged in the outer container.

11. The method according to claim 10, wherein the foam comprises a foam block in the outer container for receiving attachments.

12. The method according to claim 5, further comprising supplying an additional layer of foam in the outer container when the inner container is filled only partially to capacity.

13. The method according to claim 5, wherein the foam is an elastic foam to completely compensate for an expansion in the volume of the liquid drug upon freezing.

14. The method according to claim 1, wherein the container includes a top side and an underside formed of a metal plate.

15. A method of freezing liquid drugs in a plurality of containers, the method comprising freezing the liquid drugs in the containers at the same time in a mutually superposed relationship in a freezing apparatus, the freezing of the liquid drug in each of the containers being performed according to the method of claim 1.

16. An arrangement for carrying out the method according to claim 1, the arrangement comprising: the container filled with the liquid drug, and the insulation body arranged at the surface of the first volume portion of the container, wherein the surface of the second volume portion of the container is insulation-free.

17. A freezing apparatus comprising: one or more arrangements, each of the one or more arrangements being configured according to claim 16, the one or more arrangements being arranged within a freezing apparatus in mutually superposed relationship, the freezing apparatus being adapted to freeze the liquid drug within the container.

18. The method according to claim 1, wherein the cooling element is a cold gas, the container being exposed to the cold gas such that the cold gas flows around the liquid drug.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) Further details and advantages of the invention will be apparent from the Figures and the related specific description. In the Figures:

(2) FIGS. 1a to 1c show steps in a method of freezing a liquid according to the state of the art,

(3) FIGS. 2a to 2d show steps in a method according to the invention of freezing a liquid,

(4) FIGS. 3a and 3b show diagrammatic views of an arrangement according to the invention,

(5) FIG. 4 shows a diagrammatic view of an arrangement according to the invention with a plurality of containers,

(6) FIG. 5a shows a further but more detailed view of an arrangement according to the invention,

(7) FIGS. 5b and 5c show views of an arrangement comprising an inner container and an outer container using a foam,

(8) FIGS. 6a and 6b show views of an arrangement according to the invention with a plurality of mutually superposed containers, and

(9) FIGS. 7a and 7b show photographs of the arrangement according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

(10) FIGS. 1a to 1c show a method according to the state of the art of freezing a liquid, in particular a drug. At the beginning the liquid 3 is arranged in the container 2. Cooling from the exterior causes a partial volume 13 of the liquid 3 to freeze, more specifically in such a way that the partial volume 13 encloses the volume of the liquid 3 which is still liquid, as is shown in FIG. 1b (therefore from edge layers). As that process progresses, the expansion in volume upon freezing of the part of the liquid that is not yet frozen leads to relatively great stresses in the partial volume 13 which is already frozen. Those stresses are firstly transmitted to the container 2 and secondly can result in rupture of the frozen partial volume 13. The invention seeks to avoid that effect which is shown in FIG. 1c.

(11) FIGS. 2a to 2d show an embodiment according to the invention.

(12) The arrangement 1 which is shown in FIGS. 2a to 2d is expanded in relation to the state of the art by the two U-shaped insulation bodies 4, those insulation bodies 4 being fitted over edge regions of the cuboidal container 2. As can be seen from FIG. 2b the insulation bodies prevent that partial volume 13 of the liquid 3, which freezes first, from enclosing that partial volume of the liquid 3, which is not yet frozen. Rather, a cooling element such as cooling gas forms two “freezing fronts” which meet from the upper and lower central region. Admittedly, here too, the increase in volume upon freezing of the liquid 3 takes place. In this case, however, that is no problem as the additional volume can be pushed out to the side. In other words, there is no enclosed region of liquid 3 which has not yet frozen, which could exert greater stresses on the partial volume 13 which has already frozen.

(13) It can also be clearly seen from FIG. 2b that a relatively shallow cuboidal container can be advantageous because in that way the non-insulated region can freeze therethrough, before the further regions freeze to significant proportions.

(14) FIG. 2c shows further freezing of the liquid 3 after the “freezing fronts” of FIG. 2b have met and further freezing throughout the liquid slowly takes place to the sides. Here too there are no enclosed regions of unfrozen liquid 3.

(15) FIG. 2c also shows a foam 8 which has a compensation function for the normal expansion in volume of the liquid 3 upon freezing.

(16) The compensation function will be clear in comparison with FIG. 2d. FIG. 2d shows the state of the arrangement 1, in which the liquid has completely frozen through, that is to say the frozen-through partial volume 13 almost completely fills out the container 2. The foam 8 has reduced its volume for compensation and can only still be seen in the corners of the view in FIG. 2d.

(17) It will be clear from the comparison of FIGS. 1a to 1c on the one hand and FIGS. 2a to 2d on the other hand how an insulation, in particular insulation bodies 4, can prevent damage due to the expansion in volume of the liquid upon freezing.

(18) FIGS. 3a and 3b show diagrammatic views of the arrangement 1 according to the invention. That would again be FIG. 3a showing a side view. Besides the container 2 it is also possible to see the two U-shaped insulation bodies 4.

(19) FIG. 3b shows a plan view of the same structure.

(20) FIG. 4 shows an arrangement 10 comprising a plurality of mutually superposed containers 2 which are respectively provided with insulation bodies 4. In this case, each of the insulation bodies 4 has such a configuration that each insulation body 4 respectively accommodates a plurality of the containers 2. The containers 2 can thus, for example, also be really easily transported. Naturally, they can also be arranged completely as an arrangement 10 in a freezing apparatus 7 (see FIGS. 6a and 6b) and frozen in a single freezing process.

(21) FIG. 5a shows a more detailed sectional view of the arrangement 1, wherein the container 2 is made up of an inner container 5 and an outer container 6. That inner structure of the container 2 can also be used in the other illustrated embodiments. The flexible inner container 5 holds the liquid 3 and the outer container 6 is mechanically stable. In addition, there is a certain excess volume between the inner container 5 and the outer container 6 that can also be filled with a foam 8.

(22) FIGS. 5b and 5c show an example of an arrangement of a rigid outer container 6 and a flexible inner container 5 (single use bag) using a foam 8. The foam 8 compensates for the expansion in volume of the liquid 3 upon freezing. In addition, the foam 8 can be of such a nature that it also sets at low temperatures so that after freezing, the inner container 5 is enclosed in a close fit in the foam 8 and in the outer container 6.

(23) The foam 8 includes a foam block 9, by means of which attachments 12 like tubes and connecting elements can also be enclosed. The foam block 9 naturally also serves to compensate for the expansion in volume upon freezing of the liquid 3.

(24) The outer container 6 can comprise plastic and/or metal. In the present embodiment, the cover layers are respectively made from (relatively thin) stainless steel and the side walls from a polyethylene.

(25) For example, so-called visco-elastic foam 8 can be used as the foam 8, which hardens at certain negative temperatures.

(26) FIGS. 6a and 6b are a perspective and a sectional view of an arrangement 10 according to the invention with a plurality of containers 2 arranged in mutually superposed relationship within a freezing apparatus 7. FIG. 6b also indicates how the containers 2 also have an internal structure comprising an inner container 5 and an outer container 6. (Not all containers 2 are denoted by reference numerals in order not to make the views less clear).

(27) To illustrate the real aspects, FIG. 7a shows an arrangement according to the invention in a freezing apparatus 7 after it was cooled to −85° Celsius. It can be clearly seen that the container 2 has not experienced any outward buckling, and therefore it can be assumed that a desired freezing of the liquid 3 therethrough has occurred, that is to say the liquid 3 was frozen without damage (to the surrounding items of equipment).

(28) FIG. 7b shows how the inner container 5 looks after it has been removed from the outer container 6 in the frozen state. It can also be seen here that there are no major deformations.