DIATOMACEOUS EARTH COMPOSITION WITH A LOW ENDOTOXIN CONTENT

Abstract

The present invention relates to a diatomaceous earth composition with a low endotoxin content, comprising an agglomerated mixture of calcined diatomaceous earth particles and water, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.0 to 1:2.0, and wherein the endotoxin content of the diatomaceous earth composition is equal to or less than 0.5 EU/mL. In a further aspect, the present invention relates to a method for producing the diatomaceous earth composition with a low endotoxin content. In another aspect, the present invention relates to the use of the diatomaceous earth composition with a low endotoxin content as a precoat agent for the precoat filtration in biopharmaceutical applications.

Claims

1. A diatomaceous earth composition with a low endotoxin content, comprising an agglomerated mixture of calcined diatomaceous earth particles and water, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.0 to 1:2.0, and wherein the endotoxin content of the diatomaceous earth composition is equal to or less than 0.5 EU/mL.

2. The diatomaceous earth composition according to claim 1, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.1 to 1:1.7.

3. The diatomaceous earth composition according to claim 2, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.2 to 1:1.4.

4. The diatomaceous earth composition according to claim 1, wherein the average particle size of the calcined diatomaceous earth particles is in the range of 0.5 m to 10 m.

5. The diatomaceous earth composition according to claim 1, further comprising a water-impermeable and -sterilizable packaging sealing the agglomerated mixture of calcined diatomaceous earth particles and water.

6. The diatomaceous earth composition according to claim 5, wherein the water-impermeable and -sterilizable packaging is composed of a four-layered laminate comprising the following layers (i) to (iv) from the inside to the outside of the packaging: (i) a layer of polyethylene or polypropylene having a thickness in the range of 30 m to 150 m; (ii) a layer of polyethylene terephthalate or oriented polyamide having a thickness in the range of 5 m to 20 m; (iii) a layer of aluminum having a thickness in the range of 5 m to 20 m; and (iv) a layer of polyethylene terephthalate having a thickness in the range of 5 m to 20 m.

7. A method for producing a diatomaceous earth composition with a low endotoxin content, comprising the following steps: (a) providing calcined diatomaceous earth particles; (b) mixing the calcined diatomaceous earth particles with water in a mass ratio of 1:1.0 to 1:2.0, thereby obtaining an agglomerated mixture of calcined diatomaceous earth particles and water; (c) sealing the agglomerated mixture of calcined diatomaceous earth particles and water obtained in step (b) in a water-impermeable and -sterilizable packaging, thereby obtaining a sealed agglomerated mixture of calcined diatomaceous earth particles and water; (d) sterilizing the sealed agglomerated mixture of calcined diatomaceous earth particles and water obtained in step (c) by exposure to -radiation, thereby obtaining a diatomaceous earth composition with an endotoxin content of equal to or less than 0.5 EU/mL; and (e) optionally removing the packaging from the diatomaceous earth composition obtained in step (d).

8. The method according to claim 7, wherein the mass ratio of the calcined diatomaceous earth particles and water provided in step (a) is in the range of 1:1.1 to 1:1.7.

9. The method according to claim 8, wherein the mass ratio of the calcined diatomaceous earth particles and water provided in step (a) is in the range of 1:1.2 to 1:1.4.

10. The method according to claim 7, wherein the average particle size of the calcined diatomaceous earth particles provided in step (a) is in the range of 0.5 m to 10 m.

11. The method according to claim 7, wherein the calcined diatomaceous earth particles and water are mixed in step (b) by spray-wetting.

12. The method according to claim 7, wherein the water-impermeable and -sterilizable packaging for sealing the agglomerated mixture of calcined diatomaceous earth particles and water in step (c) is composed of a four-layered laminate comprising the following layers (i) to (iv) from the inside to the outside of the packaging: (i) a layer of polyethylene or polypropylene having a thickness in the range of 30 to 150 m; (ii) a layer of polyethylene terephthalate or oriented polyamide having a thickness in the range of 5 m to 20 m; (iii) a layer of aluminum having a thickness in the range of 5 m to 20 m; and (iv) a layer of polyethylene terephthalate having a thickness in the range of 5 m to 20 m.

13. The method of claim 7, wherein the -radiation for sterilizing the sealed agglomerated mixture of calcined diatomaceous earth particles and water in step (d) has a dose in the range of 25 kGy to 100 kGy.

14. (canceled)

15. (canceled)

16. A precoat agent for a precoat filtration in a biopharmaceutical application comprising: a diatomaceous earth composition with a low endotoxin content, comprising an agglomerated mixture of calcined diatomaceous earth particles and water, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.0 to 1:2.0, and wherein the endotoxin content of the diatomaceous earth composition is equal to or less than 0.5 EU/mL

17. The precoat agent of claim 16, wherein the biopharmaceutical application is precoat filtration of and/or prokaryotic cells in an aqueous medium.

18. The precoat agent of claim 16, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.1 to 1:1.7.

19. The precoat agent of claim 16, wherein the mass ratio of calcined diatomaceous earth particles and water is in the range of 1:1.2 to 1:1.4.

20. The precoat agent of claim 16, wherein the average particle size of the calcined diatomaceous earth particles is in the range of 0.5 m to 10 m.

21. The precoat agent of claim 16, further comprising a water-impermeable and -sterilizable packaging sealing the agglomerated mixture of calcined diatomaceous earth particles and water.

22. The diatomaceous earth composition according to claim 21, wherein the water-impermeable and -sterilizable packaging is composed of a four-layered laminate comprising the following layers (i) to (iv) from the inside to the outside of the packaging: (i) a layer of polyethylene or polypropylene having a thickness in the range of 30 m to 150 m; (ii) a layer of polyethylene terephthalate or oriented polyamide having a thickness in the range of 5 m to 20 m; (iii) a layer of aluminum having a thickness in the range of 5 m to 20 m; and (iv) a layer of polyethylene terephthalate having a thickness in the range of 5 m to 20 m.

Description

[0071] The Figures show:

[0072] FIG. 1 shows the particle count rate (number of particles/min) as measured for different mass ratios of calcined diatomaceous earth particles and water.

[0073] FIG. 2 shows photographic images of dry diatomaceous earth (FIG. 2A) and of a diatomaceous earth composition according to the present invention, having a mass ratio of calcined diatomaceous earth particles and water of 1:1.25, i.e. which contains the calcined diatomaceous earth particles in an amount of 44.4 mass %, and which contains water in an amount of 55.6 mass % (FIG. 2B).

EXAMPLES

[0074] The present invention will be further illustrated by the way of Examples. However, the present invention is not to be construed as being limited to the following Examples.

[0075] Diatomaceous earth compositions comprising agglomerated mixtures of calcined diatomaceous earth particles (Celpuree C300, Advanced Minerals) and water in different mass ratios, sealed with a packaging, were unpacked and poured into a beaker. Then, the release of dust particles was determined over a period of one minute by means of a dust particle measurement instrument (MET ONE 3400, Hach).

[0076] Herein, the calcined diatomaceous earth particles had particles sizes of 10, 5, 3, 2, 1, and 0.5 m, and the water had an endotoxin content of less than 0.05 EU/mL. The packaging used herein was a four-layered laminate comprising layers of PE (75 m), OPA (12 m), ALU (12 m), and PET (12 m).

[0077] Unexpectedly, mixing one part of calcined diatomaceous earth particles and 1.25 parts of water led to a diatomaceous earth composition, wherein the release of dust particles is reduced by more than 85% compared to dry diatomaceous earth, as can be deduced from the respective particle count rates (number of particles/min) in FIG. 1. Surprisingly, as can be taken from FIG. 2, when comparing the diatomaceous earth composition having a mass ratio of calcined diatomaceous earth particles and water of 1:1.25 with the dry diatomaceous earth, no visible difference could be observed.

[0078] The diatomaceous earth composition according to the present invention, having a low endotoxin content, shows a reduced release of dust particles, while still exhibiting excellent free-flowing characteristics. As such, it is particularly suitable as a precoat agent for the precoat filtration in biopharmaceutical applications, in particular for the precoat filtration of eukaryotic and prokaryotic cells in an aqueous medium. Advantageously, the diatomaceous earth composition according to the present invention allows for an easy handling and minimizes the risk of inhaling dust particles.