BE1028814B1 - USE OF A EUTECT OR A LOW MELTING POINT MEDIUM FOR COOLING AND KEEPING BIOLOGICAL ACTIVE MATERIALS SUCH AS VACCINES AT VERY LOW TEMPERATURE, REFRIGERATOR FOR THE purpose, AND PROCEDURE FOR PRODUCING METALS CONTAINING EUTECTIDIUM MIXTURE - Google Patents

Abstract

The invention relates to the use of a eutectic medium or a low melting point medium for cooling biologically active materials such as vaccines to a required storage temperature of at most -70°C for at least 7 days, whereby the eutectic temperature of the eutectic medium or the melting point of the low melting point medium is less than or equal to the required storage temperature. The invention also relates to a cooling device for this purpose, and a method for producing containers comprising such eutectic medium or low melting point medium.

Description

USING AN EUTECTIC MEDIUM OR A LAYERED MEDIUM MELTING POINT FOR COOLING AND KEEPING COLD BIOLOGICAL ACTIVE MATERIALS SUCH AS VACCINES AT A VERY LOW TEMPERATURE, REFRIGERATION EQUIPMENT FOR THIS, AND PROCESS FOR PRODUCING HOLDERS CONTAINING SUCH EUTECTIC MEDIUM OR MEDIUM MET LOW MELTING POINT

TECHNICAL FIELD The invention relates to a use of a eutectic medium or a low melting point medium for cooling and cold keeping biologically active materials such as vaccines at a very low temperature, a cooling device therefor, and a method for producing containers comprising such eutectic medium or a low melting point medium.

BACKGROUND ART Many vaccines, or certain other biologically active materials including stem cells, proteins and enzymes, must be stored at a low temperature, e.g. -70°C or even lower, from manufacture through use to ensure their effectiveness. to keep. During transportation, as well as in resource-poor environments where the electricity and transportation infrastructure is underdeveloped, it is a problem to keep these biologically active materials within the desired temperature range.

For electrically powered stationary cold chain equipment, such as vaccine freezers, with an unreliable electrical supply, the challenge is to maintain cool temperatures in hot environments during sporadic to frequent intervals without power, thus relying on their ability to increase absorption. of heat in a cold room where vaccines are stored by slowing down a combination of insulation and cold thermal mass. It is problematic to be able to ensure a desired cooling in such a way. Non-electrically powered mobile cold chain equipment, such as cool boxes fitted with dry ice (a compressed solid form of CO: at a temperature of -78°C) for cooling biologically active materials such as vaccines, offer the advantages of not being depend on an electricity supply and are easy to transport. When, for example, vaccines are kept cold, the dry ice gradually sublimes. Dry ice is also released back into the environment upon sublimation, posing a serious health risk from very low concentrations.

Non-electrically powered mobile cold-chain equipment, such as vacuum insulated vessels supplied with liquid nitrogen (a deep-cooled form of Na at a temperature of -196 °C) for cooling biologically active materials such as vaccines, offer the advantages that they are not depend on an electricity supply and are easy to transport. When, for example, vaccines are kept cold, the nitrogen evaporates away, which poses a moderate risk to health from very low concentrations. But the temperature is always -196, which is too cold for many organic products and/or their packaging.

The present invention aims to find a solution to at least some of the above-mentioned problems.

SUMMARY OF THE INVENTION In a first aspect, the invention relates to a use of a eutectic medium or a low melting point medium for cooling and keeping biologically active materials such as vaccines cold at a required storage temperature of at most -70°C for at least 7 days, wherein the eutectic temperature of the eutectic medium or the melting point of the low melting medium is less than or equal to the required storage temperature, according to claim 1. Preferred forms of use are set forth in claims 2 to 15.

In a second aspect, the invention relates to a cooling device for cooling and keeping biologically active materials such as vaccines cold at a temperature of at most -70°C for at least 7 days, according to claim 16. Preferred forms of the cooling device are shown in claims 18 to and with 22.

In a third aspect, the invention relates to a method for producing containers comprising a eutectic medium or a low melting point medium, according to claim 23. Preferred forms of the method are set forth in claims 24 to 27.

DESCRIPTION OF THE FIGURES FIG. 1 shows a longitudinal section of a container during various steps of producing a container comprising a eutectic medium, according to preferred embodiments of the invention.

fig. 2-3 show longitudinal cross-sections of various cooling devices within which an inner container is provided containing biologically active materials such as vaccines, according to preferred embodiments of the invention.

fig. 4 shows perspective views of various steps in which a cooling device is prepared to keep biologically active materials cool, according to preferred embodiments of the invention.

DETAILED DESCRIPTION The term "eutectic medium" is to be understood as a mixture of two or more elements with a melting point lower than the melting point of each of the components making up the mixture, but may also include a pure eutectic liquid such as be paraffin. The term "eutectic temperature", which term is also known as "eutectic point", refers to the lowest possible melting temperature for all mixing ratios of the constituent components of a eutectic medium, or in the case of a pure eutectic liquid to its melting temperature.

The term “COVID-19”, as used in this text, refers to coronavirus disease 2019, which is an infectious disease caused by the virus SARS-CoV.

2. Infectious diseases caused by mutations of the Corona virus are also included here.

The term wt.%, here and throughout, refers to the relative weight of a respective component to the total weight of a composition.

Phase transition materials are materials that undergo a phase change when heated or cooled. The phase change can be a physical transition (solid-solid, solid-liquid, liquid gas, solid gas) or a reversible chemical reaction such as a hydration-dehydration reaction. During the phase change, a phase transition material will absorb or release heat while maintaining a nearly constant temperature until all the material has reached the new phase. The amount of heat absorbed or released per unit mass during a phase change (latent heat) is usually much greater than the amount of heat absorbed or released per unit mass when a material changes temperature without undergoing a phase change (specific heat ). Incorporation of a phase change material into the design of a cold chain device can therefore significantly increase the amount of heat that can be absorbed or released while maintaining the desired temperature.

In a first aspect, the invention relates to a use of a eutectic medium or a low melting point medium for cooling and keeping biologically active materials such as vaccines cold at a required storage temperature of at most -70°C for at least 7 days, wherein the eutectic temperature of the eutectic medium or the melting point of the low melting medium is less than or equal to the required storage temperature, according to claim 1.

This has the advantage of allowing long transport or storage of the biologically active materials at very low temperatures, without requiring electrically powered refrigerants such as freezers or gases such as CO 2 and N 2 .

Moreover, such transport or storage can always be guaranteed, in contrast to dry ice, which quickly loses its cooling capacity or electrically driven refrigerants, which may no longer be able to provide the desired cooling in the event of a power failure or battery exhaustion.

Preferred uses are set forth in claims 2 to

15.

Alcohols, and preferably ethanol, which are the subject of claims 3-5, because of their low melting point or the eutectic mediums with low eutectic temperatures which they can form with a non-alcohol such as water, glycol, silver powder or oil, are very suitable for the application according to the invention.

With said amounts of ethanol and one or more other liquids according to claim 1, eutectic mediums having a melting point of -90°C or lower can be obtained. Cooling may first be carried out to a temperature below -91°C, preferably below -100°C, even more preferably below -110 °C and most preferably to -120 °C. During storage, the temperature of the medium will then gradually rise to its melting point, after which the temperature can remain at such a level for a reasonable time until the total phase transition from frozen state to liquid state, after which the heating will take place more quickly. These conditions are well suited to store biologically active materials such as vaccines at a temperature of up to -70°C for at least 7 days, so that the efficacy of such materials can be maintained. More preferably, the eutectic medium comprises from 92 to 97 wt.% ethanol and from 3 to 8 wt.% other liquids. Such a composition of the eutectic medium is optimal to arrive at a eutectic medium that has a eutectic temperature of -120 °C and can thus reach such a low temperature in the cooled state, and is therefore very suitable for more temperature-sensitive biologically active materials, such as more temperature-sensitive vaccines, or packaging materials at a temperature of at most -80°C, and preferably at most -85°C and more preferably at most -86°C, refrigerated and kept cold for at least 7 days. The embodiment according to claim 7 offers the advantage that it is thus avoided that the temperature would fall below -90 °C during the first 7 days and that, as a result, a cooling to at most -70 °C, preferably at most -80 °C, is even more preferably at most -85 °C and even more preferably at most -86 °C, would be compromised. The fact that the one or more containers according to claim 9 can be removed offers the advantage that the containers, comprising the eutectic medium or the medium with a low melting point, can be cooled in advance at another location. In a second aspect, the invention relates to a cooling device for cooling and keeping biologically active materials such as vaccines cold at a temperature of at most -70°C for at least 7 days, according to claim 16.

Preferred forms of the cooling device are set forth in claims 17 to 22. In a third aspect, the invention relates to a method for producing containers comprising a eutectic medium or a low melting point medium, according to claim 23.

Preferred forms of the method are presented in claims 24 to 24 inclusive

27. In what follows, the invention is described with reference to non-limiting examples and figures which illustrate the invention, and which are not intended or should be interpreted to limit the scope of the invention.

EXAMPLES Example 1: Composition of Eutectic Medium An example of a eutectic medium according to the invention comprises 94-96 wt.% ethanol and 4-6 wt.% water. Example 2: Cooling of eutectic medium in container A container 1 is filled with a eutectic medium 4 comprising 94-96 wt.% ethanol and 4-6 wt.% water, the medium being initially in a liquid or gel state. The result of this is shown in the longitudinal section according to FIG. 1A. In particular, the medium is filled in such a way that a headspace 5 is still left at the top of the container. The container 1, its wall 2 is provided at the top on the inside with a negative 3 of a screw thread, which negative is adapted to receive a screw cap 6. After filling, the container 1 is closed via the screw cap 6, the result of which is shown in FIG. 1B. Subsequently, the eutectic medium 4 is cooled to a temperature of at most -90°C, preferably to a temperature of at most -100°C, even more preferably to a temperature of at most -110 °C and even more preferably to a temperature of at most -120 °C. A container 1 containing the resulting cooled eutectic medium 4 is shown in FIG. 1C. The difference between the liquid and cooled (actually frozen) state of the medium in Figs. 1A-1B and FIG. 1C is schematically indicated by a different orientation of applied hatching. It is clear here that the headspace 5 is reduced by expansion of water or ethanol in the medium during the cooling. If no use was made of a headspace 5, there would be a risk that the container 1 would burst during cooling. Example 3: Cube-shaped refrigerated container containing containers filled with eutectic medium for transport of vaccines

A cubic refrigerated container 7 according to this example is shown in the longitudinal section according to FIG. 2 The cubic refrigerated container 7 includes an inner container 10 in which vaccines (not shown in Fig. 2) are stored.

The outer dimensions of the inner container 10 are 20 cm x 20 cm x 20 cm.

The inner container 10 is surrounded by one or more containers 1 formed therefor and filled with a cooled eutectic medium 4 as described above in Example 2. The two containers 1 are in turn enclosed by an outer container formed by expanded polystyrene (EPS). walls 8, 9, the latter being formed in such a way that the outer container can be closed and opened in a simple manner.

Said outer container has outer dimensions of 70 cm x 70 cm x 70 cm.

The outer container isolates the containers 1 and the inner container 10 from an environment, so that the cooled eutectic medium 4 in the containers 1 can optimally cool the vaccines in the inner container 10 and keep them cold during storage and transportation.

Due to the long time during which the eutectic medium 4 can remain at a low temperature of at most -90 °C, the vaccines can be kept at a desired temperature of at most -70 °C, preferably at most -80 °C, for a long time of at least 7 days. C, more preferably at most -85°C and more preferably at most -86°C.

This allows transport of the vaccines while maintaining their effectiveness.

Example 4: Mainly cylindrical cooling container comprising containers filled with eutectic medium for transport of vaccines. A mainly cylindrical cooling container 11 according to this example is shown in the longitudinal section according to Figs. 3. The cooling container 11 comprises three stacked inner containers 10 in which vaccines (not shown in Fig. 3) are stored.

The inner containers 10 are surrounded by a specially formed container 1 filled with a cooled eutectic medium 4 as described above in Example 2. The container 1 is in turn enclosed by an outer container formed by a double vacuum wall 12 and a closing cap 13 Inside the double vacuum wall 12 is vacuum drawn air, so that a good insulation is obtained.

The closing cap 13 is preferably made of a material with a high insulation value or also provided with a double vacuum wall.

Thus, the outer container optimally isolates the containers 1 and the inner containers 10 from an environment, so that the cooled eutectic medium 4 in the container 1 can optimally cool the vaccines in the inner containers 10 and keep them cold during storage and transport. .

Again, the long time during which the eutectic medium 4 can remain at a low temperature of at most -90 °C, the vaccines can be kept for a long time of at least 7 days at a desired temperature of at most -70 °C, preferably at most - 80°C, more preferably at most -85°C and more preferably at most -86°C. This allows transport of the vaccines while maintaining their effectiveness. Example 5: Cooling and cold keeping of vaccines for 7 days at a desired temperature in a cube-shaped cooling container comprising containers filled with cooled eutectic medium. This example indicates a possible embodiment in which vaccines are kept at a desired temperature of -86°C for a period of 7 days. can be kept. In this example, vaccines are stored in a cube-shaped cooling container 7 as described in Example 3. During the 7 days, about 34 W of heat loss occurs in such an arrangement. To cool at the desired temperature of -86°C for 7 days, only 26 to 50 kg of the cooled eutectic medium 4, comprising 94-96 wt.% ethanol and 4-6 wt.% water, are needed.

Example 6: Cooling and cold keeping of vaccines for 7 days at a desired temperature in a substantially cylindrical refrigerated container comprising a container filled with cooled eutectic medium. °C can be kept. In this example, vaccines are stored in a substantially cylindrical refrigerated container 11 as described in Example 4. During the 7 days, a lower heat loss occurs in such an arrangement than described in Example 5, because of less surface through which heat can be lost and a better insulation value of the outer container. To cool for 7 days at the desired temperature of -86°C there is only 10 kg (which corresponds to about 13 liters in liquid state) of the cooled eutectic medium 4 comprising 94-96 wt.% ethanol and 4-6 wt .% water, needed.

Example 7: Step-by-step preparation for refrigerating vaccines with a cube-shaped refrigerated container comprising a hollow cylindrical container filled with cooled eutectic medium. A cube-shaped refrigerated container 14 according to this example is shown in FIG. 4. In FIG. 4A, the cubic refrigerated container 14 is shown in its outer container which is formed from a hinged lid 15 suspended from a cubic body 16 with an upper central circular opening 17. The outer container is preferably formed by a double vacuum wall 12 or is preferably made of an insulating material such as expanded polystyrene.

In fig. 4B shows a hollow cylindrical container 18 having a closed end face 19 and an opposite opening 20. The container 18 has its wall filled with a cooled eutectic medium (not visible in FIG. 4B) obtained in a similar manner as above. explained for the container 1 according to Example 2. The hollow cylindrical container 18 additionally comprises a closing cap 21 formed for this purpose in order to be able to close the opening 20 of the container 18 .

The closing cap 21 is preferably made of a material with a high insulation value or provided with a double vacuum wall.

In fig. 4C shows an inner container 10 in which vaccines (not visible in Fig. 4C) are stored.

This inner container 10 fits inside the hollow cylindrical container 18 and in particular, several inner containers 10 can be arranged inside the hollow cylindrical container 18 according to Example 7 .

In fig. 4D shows a detail of this.

fig. 4E, a sealed container 18 comprising a plurality of inner containers (not visible in FIG. 4E) is shown.

fig. 4F finally shows a cube-shaped cooling container 12 ready for transport of the vaccines for a certain period of time at a desired temperature.

Claims (27)

CONCLUSIONS 1. Use of a eutectic medium or a low melting point medium for cooling and keeping biologically active materials such as vaccines cold at a required storage temperature not exceeding -70°C for at least 7 days, whereby the eutectic temperature of the eutectic medium or melting point of the low melting medium is less than or equal to the required storage temperature, wherein a eutectic medium (4) comprising from 87 to 99 wt.% ethanol and from 1 to 13 wt.% one or more other liquids such as, for example, water, is selected is for cooling and keeping the biologically active materials such as vaccines cold. Use according to claim 1, wherein the required storage temperature is at most -80°C. Use according to claim 1 or 2, wherein the medium is an alcohol optionally supplemented with a non-alcohol such as water, glycol, silver powder or oil. Use according to any one of claims 1 to 3, wherein the alcohol is selected from the group consisting of ethanol, isopropanol, methanol, 1-propanol, 1-butanol and 1-pentanol, or any mixtures thereof. Use according to claim 4, wherein ethanol is selected as alcohol. Use according to any one of claims 1 to 5, wherein the medium is a synthesized coolant with a low freezing point, such as for example Paratherm™ CR low-temperature heat transfer fluid or 3M™ Novec™ Engineered Fluids, which synthesized coolant is optionally supplemented with another component such as water, glycol, silver powder or oil. Use according to any one of claims 1 to 6, wherein the eutectic or low melting medium has a temperature of at most -90°C during said at least 7 days. Use according to any one of claims 1 to 7, wherein the biologically active materials such as vaccines are placed in an inner container (10), said inner container (10) being at least partially externally enclosed by one or more containers (1) comprising the eutectic medium or the low melting point medium, which containers (1) are in turn at least partly enclosed by an outer container. Use according to claim 8, wherein the one or more containers (1) are removable from the outer container. Use according to claim 8 or 9, wherein the outer container is formed by a double vacuum wall 12 within which evacuated air is provided. Use according to any one of claims 8 to 10, wherein the outer container is made of a vacuum insulation material or of expanded polystyrene (EPS). Use according to any one of claims 1 to 11, wherein 2 to 70 kg of the eutectic medium or the low melting point medium is used. Use according to any one of claims 8 to 12, wherein the one or more containers (1) are made of plastic or metal. Use according to any one of claims 1 to 13, wherein one or more vaccines are selected as biologically active materials. Use according to claim 14, wherein a vaccine effective against COVID-19 is selected as the vaccine. Cooling device (7, 11) for cooling and keeping biologically active materials such as vaccines cold at a required storage temperature of at most -70 °C for at least 7 days, characterized in that the cooling device (7, 11) contains one or more containers (1) comprising a eutectic medium or a low melting point medium, wherein the eutectic temperature of the eutectic medium or the melting point of the low melting point medium is less than or equal to the required storage temperature, and an outer container constructed comprising one or more insulating wall parts (8, 9, 12, 13), the outer container defining an inner space which, in use, allows one or more of said containers (1) to be placed inside the inner space in such a way to be placed so that another inner container (10) suitable for packaging biologically active materials such as vaccines together can still be placed inside said containers (1) on a man In that said containers (1) enclose the inner container (10) at least partly. A cooling device (7, 11) according to claim 16, wherein the one or more containers (1) can be removed from the outer container. A cooling device (7, 11) according to claim 16 or 17, wherein the one or more containers (1) are filled with the eutectic medium or the medium with a low melting point such that there is still a headspace (5 above the obtained level of the medium). ) is present inside each container (1). A cooling device according to any one of claims 16 to 18, wherein the eutectic medium or a low melting point medium (4) has been cooled to below the required storage temperature. A cooling device according to any one of claims 16 to 19, wherein the outer container is formed by a double vacuum wall 12 within which evacuated air is provided. A cooling device according to any one of claims 16 to 20, wherein the one or more insulating wall parts (8, 9, 12, 13) are made of expanded polystyrene (EPS) or of vacuum insulating material. A cooling device according to any one of claims 16 to 21, wherein the one or more containers (1) are made of plastic or metal. A method for producing containers (1) comprising a strongly cooled eutectic medium or low melting point medium, characterized in that the eutectic medium or low melting point medium is filled into one or more containers (1) in a manner that there is a further headspace (5) within each of the containers (1), followed by cooling the eutectic or low melting medium to a temperature of -90°C at most. A method according to claim 23, wherein the containers (1) are filled with a eutectic medium (4) comprising from 87 to 99 wt.% ethanol and from 1 to 13 wt.% one or more other liquids such as, for example, water. A method according to claim 23 or 24, wherein the one or more containers (1) are sealed before cooling the eutectic medium or low melting point medium. A method according to claim 25, wherein the sealing takes place by placing a closing cap (6) or by gluing, melting and/or welding. A method according to any one of claims 23 to 26, wherein the one or more containers (1) are made of plastic or metal.