GB2257053A

GB2257053A - Filtration of liquids

Info

Publication number: GB2257053A
Application number: GB9212425A
Authority: GB
Inventors: Dietmar Oechsle; Dieter Mohn; Bernhard Gopfert
Original assignee: Schenk Filterbau GmbH
Current assignee: Schenk Filterbau GmbH
Priority date: 1991-06-12
Filing date: 1992-06-11
Publication date: 1993-01-06
Anticipated expiration: 2012-06-11
Also published as: FR2677556B1; GB2257053B; DE4119288B4; CH686405A5; DE4119288A1; GB9212425D0; FR2677556A1

Description

4W METHOD FOR THE LAYER FILTRATION OF PHARMACEUTICAL BIOLOGICAL CHEMICAL

OR OTHER LIQUIDS The invention relates to a method for the layer filtration of pharmaceutical, biological, chemical or other liquids, in particular of injection solutions, for example blood plasma, serums, or of chemical liquids, such as photogelatines, using filter layers, which consist of fibrilated celluloses preferably ground in refiners, in filtrationactive particular cellulose f ibres and embedded components.

It is generally known to use layer filtration for the separation of solid/liquid mixtures to obtain a filtrate. It is particularly suitable for separating superfine turbidities, for example colloids or compressible particles, such as slimy substances and micro-organisms and thus for clarifying its use or sterilising the liquid. Apart from for clarifying natural drinks, such as wine, beer, fruit juices etc., layer filtration is also used in biotechnology and in the manufacture of many pharmaceutical and chemical products. Thus, depending on the nature and quantity of the turbidities to be separated, filter layers of different filtration capacities are used. In layer filtration, the liquid to be filtered (unfiltrate) is passed through industrially produced filter layers, which may also be referred to as prefabricated filter cakes, of relatively slight thickness. The filter layers consist of a labyrinth-like, three -dimensional network i 2 - of f ibrous and highly porous materials. The basic structure of the filter layers consists of ground cellulose f ibres; they are obtained by means of suitable decomposition methods from organic materials, for example leaf woods or pine woods. Since filter layers, which consist solely of cellulose, have a relatively low filtration capacity, extremely filtration-active materials as filter aids, namely highly porous - diatoms, thus diatomaceous earths, and if required additional perlite are embedded in the basic structure of the filter layers consisting of cellulose fibres. In order to increase the wet strength of the filter layers, it is also known to add agents increasing the so called wet strength, namely synthetic resins permitted according to foodstuffs legislation, which condense during the drying of the filter layers and give the latter inner cohesion. In layer filtration, as regards the degree of fineness of the filtration, one distinguishes according to requirements between coarse filtration, fine filtration and as the clarifying filtration, so called finest filtration, sterile filtration. In coarse filtration, particles greater than 15 pm are separated from liquids of low viscosity with filter layers of corresponding construction. Clarifying filtration serves for removing visible turbidity in the unfiltrate and for reducing the population density of micro-organisms, in particular yeasts. Due to the use of filter layers for fine filtration, one then obtains optically clear filtrates, if colloidal turbidity was present in the unfiltrate. Fine filtration layers furthermore separate yeasts and have a considerable bactericidal effect. In the case of sterile filtration, so called sterile layers are used as the filter layers, which also separate micro-organisms from liquids. Different types of filter layer are available for the aforementioned filtration stages. So called diatomaceous earth settling layers are generally used as the settling foundation for plate and frame filters. They serve as support material for filtration-active diatomaceous earth settling layers and have no filtration function themselves.

%V The filter layers of cellulose with embedded filter aids, namely diatomaceous earth and perlite, which f ilter layers are necessary for the various filtration tasks, thus filter out solid components, turbidity, colloids, agglomerates and the like from the unfiltrate, but have the drawback that during the filtration process, metallic ions, in particular iron and aluminium ions, are washed out of the latter and enter the liquid to be filtered. This has a particularly disadvantageous effect layer filtration of certain pharmaceutical or liquids, since the metallic ions may have undesirable in the chemical secondary effects at the time of reuse of such liquids, for example of injection solutions, in blood plasma filtration or in the filtration of photogelatines. According to recent research, metallic ions, such as for example iron or aluminium ions, in injection solutions, in particular in blood plasma, are at least a secondary cause of so called Alzheimer's disease. Likewise, the metallic ions dissolved out of diatomaceous earth and perlites, in chemical filtrates, in particular in the filtration of photogelatines, may be harmful, especially since gelatine promotes the release of metallic ions from diatomaceous earth and perlites (complexing) and the latter influences the silver salts contained in the photogelatines, in an undesirable manner. The known filtration methods or filter layers are therefore prejudicially or completely unsuitable for the filtration of photogelatines or of injection solutions, such as blood plasma etc..

It is the object of the invention to provide a method or filter layers, with which a layer filtration of pharmaceutical liquids, in particular of injection solutions, serums, such as blood plasma, but also the filtration 41p of chemical or biochemical liquids is facilitated, in which the liquid to be f iltered is low in or free - namely below the detection limit from metallic ions, in particular from heavy metallic ions, such as iron or aluminium ions.

This object is achieved in a method according to the generic notion of Claim 1 due to the f act that in place of the customary f iltrationactive, mineral components, namely diatomaceous earth and perlite, f ilter aids which are low in metallic ions, preferably free from metallic ions, such as f ine, highly dispersed granulated polymer material, micronised celluloses or mixtures of these substances are used as the filtration-active components.

Particularly suitable for the filtration of blood plasma or other serums, which filtration is low in metallic ions, in particular for a filtration ions, as the fine highly dispersed granulated polymer material, is a urea formaldehyde condensation product, which has a primary particle size of approximately 0.1 to 3.0 lim and a specific surface area of 20 5M2 /g according to the BET method. The granulated free from metallic nolvmer material mav in this case have a specific weight of 1.30 to 1.50 g/cm' and a bulk weight of approximately 60 g/l. It has been shown that particularly good filtration results are achieved, in particular for a sterile filtration, if primary particles of 0.1 to 0.20 pm. of the urea formaldehyde condensation product are used. For less fine filtrations, for example for clarifying filtration, agglomerates of primary particles of the size between 4 to 200 pm or more can be used. The proportion of filter aid free from metallic ions, thus the proportion of the fine, highly dispersed granulated polymer material or of the micronised celluloses or mixtures thereof, should advantageously amount to between 5 and 60% of the total weight of the filter layer.

With the invention, human blood banks may now receive - 5 filtered blood plasma, which does not have contents of iron or other metallic ions increased by filtration, since the hitherto generally conventional mineral, filtrationactive component is replaced by a synthetic granulated polymer material or micronised celluloses which are ground dry. The filtration of serums free from metallic ions, in particular blood plasma or other pharmaceutical or biochemical or chemical liquids, apart from due to the use of highly dispersed granulated polymer materials, can also be achieved by micronised celluloses or by mixtures of both substances. Accordingly, the invention is suitable not solely particularly for the layer filtration of blood plasma, but also for the filtration of other pharmaceutical, biochemical or chemical liquids and indeed in particular for the filtration of photogelatines.

In the filtration of photogelatines free from metallic ions, in place of a urea formaldehyde condensation product as the filter aid, above all exclusively micronised cellulose can be used, because urea formaldehyde condensation products have low formaldehyde constituents, which like iron ions develop the silver salts contained in the photogelatines. The micronised cellulose, which is suitable both for the filtration of photogelatines as well as for other filtration tasks, such as the filtration of pharmaceutical liquids, consists of highly pure celluloses which are ground dry and very fine, preferably of leaf woods, such as beech etc.. The proportion of micronised cellulose in the filter material may likewise amount to approximately 5 to 60% of the total weight of the filter layer.

It was also found that filter layers according to the invention can also be used with the same advantage as filter aids for settling filtration. For this purpose, the finished filter layers are reduced further by dry grinding subsequently, for example in a pinned disc mill and are thus particularly suitable even for preliminary settling, which in turn forms the basis for subsequently added, finer filter aids and facilitates flushing through of fine particles and troublefree cleaning of the filter cake after the filtration is terminated. It is conceivable that depending on the filter application, the crushed filter layers according to the invention may be supplemented by further additives, such as cellular powders or other fibrous settling materials, such as for example PE-Fibrids, for optimizing a first preliminary settling or for producing stable and homogeneous settling material distributed uniformly over the entire filter surface.

In order to increase the adsorptive forces for separating the finest particles and dissolved substances, in particular in the case of neutral to slightly acid solutions with a negative surface charge, it is recommended to give the filter material a positive potential, which is dependent on the pH-value, in that an epichlorohydrin resin is preferably added to the aqueous suspension of the celluloses used. The latter becomes attached to the cellulose, condenses during the subsequent drying process at 130' to 1500C and thus becomes insoluble. This so called Zeta potential is the electrical charge, which is formed around solid particles in a liquid containing electrolyte.

Furthermore, the method may be further optimized by the fact that after preparation and treatment, the filter material is dried and in this case strengthened by the addition of agents increasing the wet strength, for example by the addition of an aqueous solution of an epichlorohydrin resin or of a modified melamine formaldehyde resin. The use of other agents increasing the wet strength is conceivable; the latter condense during the drying of the filter layer and give the latter inner cohesion. The given agents increasing the wet strength are synthetic resins permitted according to foodstuffs legislation. The addition of the aforesaid additives for changing the electrical charge of the f ilter medium is also not permitted as regards health.

0 As one embodiment for the filtration according to the invention, micronised cellulose from approximately 90% pure 4)r- -cellulose is mentioned, with a residue on ignition of approximately 0.3% as regards the mineral components, namely calciummagnesium, as a component of the crushed cellulose, thus of crushed plants or the like, a purity of the cellulose (white) of 86% being advantageous. The riC, -cellulose used may have a fibre length of 10 to 300 pm, preferably of 18 to 200 pm, an thickness of 5 to 30 pm being appropriate.

average fibre A micronised cellulose of this type is suitable both for the filtration of blood plasma as well as for that of photogelatines. Since this cellulose lacks a positive surface potential, for example polyamido-aminoepichlorohydrin resin is added to the aqueous suspension, thus the suspension of micronised cellulose, whereupon the filter paper web prefabricated on an endless wire is dried in a drying plant at temperatures of between 130' and 150'. At the time of this drying, the additive added condenses and is deposited in long chains on the surface of the cellulose. Then, even during the drying of the filter material, suitable agents increasing the wet strength, for example modified melamine formaldehyde resins or an aqueous solution of an epichlorohydrin resin can be added, these substances likewise condensing during the drying process.

For the clarifying filtration of pharmaceutical products, in particular for blood plasma or other serums, the following recipe is given as an example:

50% of a wet ground cellulose mixture, thus a normal cellulose, as in conventional filter layers, is used with 30 to 400 degree of freeness, thus a cellulose mixture 8 - of highly bleached Approximately 10% also added to this sulphide and sulphate celluloses. polyethylene fibrid (PEFibrid) are as is sold commercially for example under the name ESS 21 by the company Schwarzw51der Textilwerke. Approximately 40% urea formaldehyde condensate is added to the 50% wet ground cellulose mixture with 10% PE-Fibrid, in this example agglomerates of between 6 and 60 pm being present as the average size. The increase in the wet strength takes place due to the addition of approximately 0.3% polyamine-epichlorohydrin resin. The filter material is then dried in the drier at a temperature of 130 to 1500 and indeed up to a residual moisture of less than 1 %. This takes place due to a corresponding control of the speed of travel in the drier. The result is an extraordinarily dry, adequately strengthened f ilter material.

In the following example for filtering photogelatines, a very fine filter layer is formed,- which consists of approximately 60% wet ground, fibrilated cellulose mixture, having a 35 to 450 degree of freeness. The filter layer is thus ground finer than that in the preceding example and likewise consists of a mixture of highly bleached sulphidesulphatecelluloses plus approximately 40% dry ground, micronised, highly pure leaf wood cellulose, for example of beech wood. Particularly good results are achieved if this leaf wood cellulose has a fibre length and a fibre thickness of approximately 15 pm. For cationisation, thus for the formation of a desired Zeta-potential, approximately 0.5% cationic polyamido-amino-epichlorohydrinresin and for increasing the wet strength approximately 0.3% polyamine-epichlorohydrin resin are added.

The invention also relates to filter layers, which are particularly suitable for the filtration of pharmaceutical, biochemical or chemical liquids according to the method described and consist of a basic structure 9 - 0 of cellulose fibres and in which highly dispersed granulated polymer material is embedded in the cellulose fibres. As a particularly suitable granulated polymer material, these filter layers comprise ureaformaldehyde condensation products with a primary particle size of approximately 0. 1 to 3. 0 pm and a specif ic surf ace area of 20 5 M2/g according to the BET-method. A polymer with primary particles of the size between 0.5 to 0.20 pm is particularly suitable for fine filtration, thus for sterile filtration. For less fine filtrations, for example for clarifying filtration, the filter layer may comprise agglomerates of the urea-formaldehyde condensation product, which consists of primary particles in the size of 4 to 200 pm or above. Furthermore, the granulated polymer material used in the filter layer may have a specific weight of 1.30 to 1.50 g/cm' and a loose weight of approximately 60 g/l. Advantageously, the proportion of filtration-active substances giving off no metallic ions, thus the proportion of micronised cellulose, or the proportion of the fine, highly dispersed granulated polymer material amounts to between 5 and 60% of the total weight of the filter layer.

According to a further feature, the micronised cellulose for the filter layer is characterised by the fact that it consists of dry ground cellulose materials, in particular of leaf wood cellulose. Filter aids for settling filtration may be produced from these filter layers, if the finished filter layers are crushed finely by dry grinding. Such finely separated or finely crushed filter layers according to the invention may advantageously be used for the preliminary filtration of products with very high requirements as regards purity.

Finally, according to a further feature of the invention, in order to achieve a desired electrical charge of the filter material, the filter layer may be provided with a Zeta potential. For strengthening the f ilter layer, the latter may also be treated with suitable agents f or increasing the wet strength, in particular with a melamineformaldehyde resin or an epichlorohydrin resin.

0 With the method according to the invention and the f ilter layers according to the invention, it is possible for the first time to produce pharmaceutical liquids, such as blood plasma or other serums, f ree f rom metallic ions, thus below the detection level -, in particular f ree f rom aluminium and iron ions, due to which blood plasma can be made available which no longer contains metallic ions which are detrimental to health. Likewise, filtrates can be produced without the absorption of metallic ions from the filter agent, which filtrates are desirable in the chemical industry or in other areas and indeed in particular in the filtration of photogelatines, which can now be filtered without complicated washing or other necessary additional measures.

Claims

Claims h# 1. Method for the layer filtration of pharmaceutical,

biological, chemical or such liquids, in particular of injection solutions, for example blood plasma or other serums or photogelatines or the like, in which superfine crushed cellulose, in particular cellulose fibres, as well as embedded filtrationactive components are used as a f ilter aid, characterised in that in place of the customary f iltration-active, mineral components, diatomaceous earth and perlite as f ilter aids, inert f ilter aids emitting virtually no metallic ions, such as f ine, highly dispersed granulated polymer material, micronised, highly pure celluloses or mixtures of these substances are used.
2. Method according to Claim 1, characterised in that for the filtration low in metallic ions or free from metallic ions of serums, in particular blood plasma, a urea f ormaldehyde condensation product with a primary particle size of approximately 0.1 to 3.0 pm and a specific surface area of 20 5 m2/g (BET-method) is used as a f ine, highly dispersed granulated polymer material.
3. Method according to one of Claims 1 or 2, characterised in that for sterile filtration, primary particles of 0.1 to 0.20 pm of the ureaformaldehyde condensation product and for less fine filtrations, for example for clarifying filtration, agglomerates of primary particles in the size between 4 to 200 pm are used.
4. Method according to one of Claims 1 to 3, characterised in that the granulated polymer material has a specific weight of 1. 30 to 1. 50 g/cm' and a loose weight of approximately 60 g/1.
5. Method according to one of Claims 1 to 4, characterised in that the proportion of inert filter aid giving off to between 5% and 60% k 0 virtually no metallic ions amounts of the total weight of the filter layer
6. Method according to Claim 1, characterised in that for the filtration free from metallic ions of formaldehydesensitive products, such as for example photogelatines, micronised cellulose is used as a filter aid instead of granulated polymer material.
7. Method according to one of Claims 1 or 6, characterised in that the micronised cellulose consists of dry ground celluloses, in particular of leaf wood cellulose of high purity.
8. Method according to one of Claims 1 to 7, characterised in that for preliminary filtration, finished filter layers with a basic structure of cellulose and embedded granulated polymer material and/or micronised celluloses are ground and used for settling.
9. Method according to one of Claims 1 to 8, characterised in that with a negative charge of the particles or colloids to be filtered off, located in the unfiltrate, a positive surface potential (Zeta-potential) is imparted to the cellulose fibres of the filter layer, preferably in such a way that an epichlorohydrin resin is added to the aqueous suspension of micronised cellulose, the latter attaches itself to the cellulose and condenses during the subsequent drying process at 130' to 1500C.
10. Method according to one of Claims 1 to 9, characterised in that after preparation and treatment, the filter material is dried and strengthened by the addition of agents increasing the wet strength, for example of a modified melamine- formaldehyde resin or an aqueous solution of an epichlorohydrin resin.
11. Filter layer, in particular for the filtration of pharmaceutical, biological or chemical liquids, which have a basic structure of fibrilated cellulose fibres, in particular for carrying out the method according to Claims 1 to 10, characterised by fine, highly dispersed granulated polymer material embedded in the cellulose fibres.
12. Filter layer according to Claim 11, characterised in that the granulated polymer material is a urea-formaldehyde condensation product with a primary particle size of 0. 1 to 3.0 pm and a specific surface of 20 5 M2/g (BET-method).
13. Filter layer according to Claim 11 or 12, characterised in that for fine filtration, in particular for sterile filtration, it consists of primary particles of 0.1 to 0.20 pm of the urea-formaldehyde condensation product.
14. Filter layer according to one of Claims 11 to 13, characterised in that for less fine filtrations, for example for clarifying filtration, it comprises agglomerates of primary particles in the size between 4 to 200 pm.
15. Filter layer according to one of the preceding Claims 11 to 14, characterised in that it consists of mixtures of primary particles of between 0.1 to 0.20 pm of the urea-formaldehyde condensation product and its agglomerates.
16. Filter layer according to one of Claims 11 to 15, characterised in that the granulated polymer material has a specific weight of 1.30 or 1. 50 g/CM 3 and a loose weight of approximately 60 g/1.
17. Filter layer according to one of Claims 11 to 16, characterised in that the proportion of f ilter aid which is low in metallic ions or f ree from metallic ions amounts to between 5% and 60% of the total weight of the filter layer.
18. Filter layer with a basic structure of fibrilated cellulose, in particular cellulose fibres, for the filtration free from metallic ions of photogelatines, in particular according to Claims 1, 6 and 7, characterised by embedded, micronised cellulose, preferably of leaf wood.
19. Filter layer according to one of Claims 11 to 18, characterised in that the finished filter layer of cellulose and embedded granulated polymer material and/or micronised cellulose is crushed so that it is very fine by grinding, for use in settling filtrations.
20. Filter layer according to one of Claims 11 to 19, characterised in that the cellulose fibres are provided with a Zeta potential.
21. Filter layer according to one of Claims 11 to 20, characterised in that the filter layer is strengthened with an agent increasing the wet strength, in particular an aqueous solution of a melamine-formaldehyde resin or an epichlorohydrin resin.

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