FR2677556A1 - PROCESS FOR THE FILTRATION, LAYERED, OF PHARMACEUTICAL, BIOLOGICAL, CHEMICAL OR SIMILAR LIQUIDS. - Google Patents

Abstract

In the process according to the invention for the filtration, carried out in layers, of chemical or pharmaceutical liquids, in particular of solutions to be injected, such as blood plasma or other serums, or of photographic gelatin are used instead of the mineral components usual filtration activators, namely diatomaceous earth and perlites, as inert adjuvants which release practically no metal ions, highly dispersible fine granular polymer material and very pure cellulosic materials reduced to micrometric particles or mixtures of these materials, thus allowing the liquid to be filtered to be free of metal ions, in particular heavy metal ions such as those of iron or aluminum.

Description

i

  Process for the filtration, carried out in layers, of liqui-

  The present invention relates to a process for the production of pharmaceutical, biological, chemical or the like.

  filtration, carried out in layers, of pharmaceutical liquids

  biological, chemical or other, in particular solutions to be injected, for example blood plasma or other sera, or chemical liquids such as

  photographic gelatin, using filter layers

  made up of cellulosic materials, in particular

  bind cellulose fibers, having undergone fibrillation and preferably ground in refiners, and by filtration activating components introduced into these materials.

  It is universally known to use the wire-

  tration, carried out in layers, for the separation of mixture

  solid / liquid ges in order to obtain a filtrate Elle

  is particularly suitable for separating suspended matter

  very fine, for example colloids or particles

  compressible, such as mucous material as well as

  cro-organisms, and thus to clarify or sterilize the li-

  quide Layer filtration is also used to clarify natural drinks such as wine, beer, fruit juices, etc. but also in organic technology and for the manufacture of many

  pharmaceutical and chemical products.

  has just used, depending on the nature and quantity

  of suspended solids to be separated, fil-

  Trants of different filtration selectivities The li-

  which to filter (prefilt) is brought, during filtration

  in layers, to pass through filtering layers fa-

  industrially briquetted, which can also be called prefabricated filter cakes, of relatively thick

  weak The filter layers are made up of a

  three-dimensional labyrinthine bucket made of fine materials

  brittle and highly porous The basic structure of

  filter layers consists of bro- cellulose fibers

  yees; these are obtained by means of de-

  suitable integration from organic materials, for example hardwoods or softwoods Since

  filter layers consisting exclusively of cellu-

  lose offer only relatively low filter clarity, extremely filtration activating materials serving as filter aids, namely highly porous diatoms, ie diatomaceous earth, and if necessary, perlites are introduced. in the

  basic structure in cellulose fibers of the wire layers

  trantes It is also known, in order to increase the resistance

  humidity of the filter layers, adding

  so-called moisture resistance agents, namely

  impeccable synthetics in terms of food legislation, which condense during drying

  filter layers and give them a cohesive

  internal sion With regard to layered filtration

  a distinction is made, depending on the requirements relating to its

  finesse, coarse filtration, conventional filtration

  rifying, fine filtration and, as the finest filtration, that known as sterilizing Coarse filtration

  allows the separation of particles larger than 15 mm of li-

  which are slightly viscous by means of filtering layers formed accordingly Clarifying filtration is used to remove visible turbidities from the liquid to be filtered

  as well as reducing the population density of micro-organism

  nisms, in particular of yeasts By the use of

  filter layers for fine filtration we have

  kept clear filtrates even when joint troubles

  ideals were present in the product to be filtered

  fine filtration tanks further separate yeasts and

  are highly bacterioreductive For sterile filtration

  As sterile layers, so-called sterile layers are used, which also separate microorganisms from liquids. For the filtration phases mentioned, different types of filter layers are available. As a pre-layer support for trays and frames filters are generally used what is commonly known as infusory soil-bearing layers They support soil pre-layers with infusory filtration activators and do not fill

  themselves no filtration function.

  The cellulose filter layers, necessary for carrying out the various types of filtration and into which filter aids are introduced, namely diatomaceous earth and perlites, therefore separate, by filtration, solid constituents, turbidities, colloids, agglomerates and the like of the product to be filtered, but they have the disadvantage that during the filtration process metal ions, in particular ions

  iron and aluminum, are rinsed out and

  trent in the liquid to be filtered This is particularly annoying in the case of the filtration in layers of certain

  pharmaceutical or chemical liquids because metal ions

  that may, during the subsequent use of such li-

  that, for example solutions to be injected, during the filtration of blood plasma or during the filtration of photographic gelatin, produce undesirable side effects Metal ions, such as for example iron or aluminum ions, present in solutions to be injected, especially into the blood plasma, could

  according to recent research be at least one of the fac-

  the origin of the so-called Alz-

  heimer In addition, metal ions extracted from earth

  dippers and perlites and found in threads

  chemical trats, especially in the case of filtration

  photographic gelatin, may be harmful to

  as long as the gelatin promotes the extraction of metal ions

  that of the earth of diatomaceous earth and perlites (complex formation) and that this complex has an undesirable influence

  on the silver salts contained in gelatin photogra-

  As a result, the filtration and

  known filter media are detrimental or even total-

  ment unsuitable for the filtration of photographic gelatin or solutions to be injected, such as for example blood plasma, etc.

  The object of the present invention is to create a pro-

  yielded and filter layers which allow filtration

  tion, carried out in layers, of pharmaceutical liquids, in particular of solutions to be injected, and of sera, such as for example blood plasma, but also filtration

  chemical or biochemical liquids, in which the li-

  which to be filtered is poor or free of metal ions, in particular heavy metal ions, such as for example iron or aluminum ions, the content of these ions being

  at least below the detection threshold.

  This object is achieved, as regards a process

  for filtration, carried out in layers, of liquid liquids

  maceutical, biological, chemical or similar, in particular

  a collection of solutions to be injected, for example plasma

  guin or other serums, or photographic gelatin or the like, in which, as filter aids, cellulose, in particular fibers

  cellulose, very finely divided as well as

  active filtration activators introduced in this

  nière, according to the invention by the fact that instead of the

  sants mineral filtration activators usual, namely diatomaceous earth and perlites, are used, in

  as filter aids, filter aids

  inert, releasing practically no metal ions

  such as granular polymeric material

  highly dispersible or cellulosic material

  high purity sics reduced to micrometric particles

  or mixtures of these two kinds of matter.

  To filter, in a poor environment, in particular free, of metal ions, blood plasma or other sera it is advisable to use, as a fine granular polymer material highly capable of dispersing, in particular

  bind a urea-formaldehyde condensation product which pre-

  has a primary particle size of approximately 0.1 to 3.0 gm and a specific surface of 20 + 5 m 2 / g determined by the BET method. In this regard, the granular polymer can

  have a density of 1.30 to 1.50 g / cm 3 and a density of

  apparent sity of about 60 g / l It has been found that particularly satisfactory filtration results were obtained in particular for sterilizing filtration

  when primary particles from 0.1 to 0.20 pm of the pro-

  urea-formaldehyde condensation products were used.

  For less fine filtration, for example filtration

  clarifying, can be used agglomerates of par-

  primary particles of a size between 4 and 200 mm and more The fraction of filter aids free of metal ions, i.e. the fraction of the polymer material in fine granules highly capable of dispersing or

  cellulosic materials reduced to micrometre particles

  triques, or mixtures of these two kinds of material is advantageously between 5 and 60% of the total weight of

the filter layer.

  Thanks to the invention, it can now be made available to human blood banks for filtered blood plasma which does not have contents of iron ions or

  other metals increased by filtration since the compound

  health mineral filtration activator so far general

  actually used is replaced by a syn-

  cosmetic in granules or by cellulose materials

  micrometric particles by dry grinding The filtration, carried out in the absence of metal ions, of

  sera, in particular blood plasma or other liquids

  pharmaceutical, biochemical or chemical, can be

  achieved not only by the use of poly-

  granular mothers highly able to be dispersed but also by the use of reduced cellulosic materials

  into micrometric particles or mixtures of these two types

  Weighs of material Consequently, the invention is applicable not only particularly to filtration, in layers,

  blood plasma but also filtration of other li-

  pharmaceutical, biochemical or chemical matters, namely

  in particular to the filtration of photographic gelatin.

  For the filtration of photographic gelatin in

  the absence of metal ions it is however advisable to use

  ser, instead of a urea-formaldehyde condensation product

  as a filter aid, exclusively from cel-

  lulose reduced to micrometric particles since urea-formaldehyde condensation products contain small fractions of formaldehyde which, like the ions of

  iron, develop the silver salts contained in the gelatin

  photographic cellulose reduced to small particles

  and which is suitable both for filtering ge-

  photographic Latin than for other wire operations-

  such as filtration of pharmaceutical liquids

  ques consists of cellulosic materials, pre-

  ference from hardwoods such as beeches, etc., highly pure and very finely dry ground The fraction of cellulose, reduced to micrometric particles, in the filter material can also be understood substantially

  between 5 and 60% of the total weight of the filter layer.

  It has further been found that layers f il-

  trantes according to the invention could also be used.

  with the same advantage as yarn additives

  tration for pre-layer filtration For this purpose the

  finished filter layers are, after the fact, still fragmented

  tees, for example in a toothed crown crusher, and are then particularly suitable for forming the pre-layer which for its part serves as a basis for finer filter aids, subsequently added in a metered manner, and allows a thorough rinsing of fine particles. and cleaning without

  problem of the cake after filtration It is con-

  depending on the filtration operation, the layers

  filter media crushed according to the invention are further

  other additives such as cellulose flour or

  other fibrous materials for precoat, such as

  full of polyethylene-based fibrids, to optimize a

  first preliminary pre-coat or to make pre-

  stable, homogeneous layers uniformly distributed over

the entire filtering surface.

  In order to increase the adsorption forces intended

  born from the separation of the finest particles and dissolved matter, in particular in the case of solutions

  neutral to slightly acidic with a superficial charge

  negative sky it is recommended to give the material

  filtering a positive potential which depends on p H, adding

  as long as, preferably, to the aqueous suspension of the celluloses used, an epichlorohydrin resin. This binds to the cellulose, then condenses during the subsequent drying process, carried out between 130 and 1500 ° C., and thus becomes insoluble. This so-called zeta potential is the electrical charge that builds up around solid particles in

  a liquid containing an electrolyte.

  In addition, the process can be further optimized by allowing the filter material, after its preparation and

  its priming, to be dried and, during this drying, conso-

  the idea by the addition of moisture-resistant agents, for example by the addition of an aqueous solution of a resin

  epichlorohydrin or a melamine formaldehyde resin

  The use of other moisture-resistant agents

  tee is conceivable; these condense during the drying of the filtering layer and give it an internal cohesion. As for the moisture-resistant agents mentioned, these are synthetic resins which are impeccable in terms of food legislation. The aforementioned additives intended to vary the electrical charge of the filter material does not pose any health risk either.

  As an example of realization for the filter-

  tion according to the invention there is mentioned cellulosi-

  that, reduced to micrometric particles, obtained from a pure alphacellulose and representing approximately 90%, with a calcination residue of 0.3% at most as regards

  concerns the mineral component, namely calcium-magnesium

  um, as a building block of cellulosi-

  that fragmented, that is to say vegetable or analogous frag-

  mented, a cellulose purity (whiteness) of 86% being

  advantageous The alpha-cellulose used can have a long

  fiber scent from 10 to 300 µm, preferably from 18 to 200

  gm, an average fiber thickness of 5 to 30 µm being advanced

  Such a cellulose reduced to micrometer particles

  triques is suitable for both plasma filtration and

  guin than that of photographic gelatin Given

  that this cellulose lacks a surface potential for

  When added to the aqueous suspension, that is to say to the suspension of micrometric cellulose, for example polyamido-aminoepichlorohydrin resin, after which the strip of prefabricated filter paper on an endless cloth is dried in an installation. drying at temperatures

  between 130 and 1500 C During this drying the

  said additive condenses and deposits in long chains on the surface of the cellulose. Then, also during the drying of the filter material, suitable moisture-resistant agents can be added, for example modified melamine-formaldehyde resins or a solution

  aqueous of an epichlorohydrin resin, these materials are

  also denser during the drying process.

  For clarifying filtration of phar-

  maceuticals, in particular blood plasma or other sera, it is worth mentioning, by way of example, the mode

following operation.

  % of mixture of cellulose material crushed in the wet state, that is to say a normal cellulose, are prepared, as for usual filtering layers, with a Schopper-Riegler apparatus between 30 and 400 C, that is to say say a mixture of cellulosic materials formed from highly bleached celluloses obtained by the sulphite and sulphate processes To this mixture are added approximately 10% of polyethylene-based fibride (PE fibride) as it is marketed for example under designation ESS 21 by the company Schwarzwâlder Textilwerke With 50% mixture of cellulosic material crushed in the wet state and added

  10% PE fibrid is added about 40% pro-

  urea-formaldehyde condensation product, agglomerates of

  6 to 60 pm, as a medium size, which can be pre-

  feel in this example the increase in resistance to

  humidity is achieved by adding about 0.3% of

  sine polyamino-epichlorohydrin Then the filter material is dried in the dryer between 130 and 1500 C and this until a residual humidity of less than 1% is obtained This is done by adjusting the speed of passage through the dryer accordingly The result obtained is a filter material

  extremely dry and sufficiently consolidated.

  In the following example for filtering ge-

  photographic latin there is formed a very fine filtering layer consisting of about 60% mixture of cellulosic materials which, having undergone fibrillation and ground to

  the wet state, is obtained by means of a Schopper-

  s & Riegler between 35 and 45 C The filter layer is therefore more finely ground than in the previous example and

  also consists of a mixture of sulphate celluloses

  fite and highly bleached sulphate, with added

  40% highly pure hardwood cellulose, e.g.

  full of beech wood, reduced by dry grinding in particular

  micrometrics Particularly satisfactory results

  are obtained when this broadleaf cellulose has a fiber length and a fiber thickness of approximately 15 μm. For cationization purposes, that is to say to obtain a desired zeta potential, is added approximately 0.5% of cationic polyamido-amino-epichlorohydrin resin and for increasing resistance to

  humidity is added about 0.3% of polyamino resin

epichlorohydrin.

  Furthermore, the subject of the present invention are filter layers which lend themselves in particular to the filtration of pharmaceutical, biochemical or chemical liquids by the process described and consist of a

  basic structure formed from cellulose fibers in the

  what is a fine granular polymer material introduced

  very able to disperse These filter layers include

  as a particularly suitable granulated polymeric material, urea-formaldehyde condensation products having a particle size of approximately 0.1 to 3.0 Am and a specific surface of 20 + 5 m 2 / g determined by the

  BET method A polymer with primary particles of a large-

  sor between 0.5 and 0.20 mm is particularly suitable-

  for fine filtration, i.e. for filtration

  sterilizing tion For less fine filtration, for example clarifying filtration, the filtering layer can

  present agglomerates of the urea condensation product

  formaldehyde which is made up of primary particles

  with a size of 4 to 200 µm or more The granular polymer

  The material used in the filtering layer may also have 1 1 a density of 1.30 to 1.50 g / cm 3 and an apparent density of approximately 60 g / l Advantageously, the proportion of filtration activating material does not release ion

  metallic, i.e. the proportion of cellulose reduced

  te in micrometric particles, or the proportion of poly-

  mother in fine granule highly able to disperse is com-

  taken between 5 and 60% of the total weight of the filter layer

  you. According to another characteristic of the invention, the micrometric cellulose constituting the filtering layer

  is distinguished by the fact that it is made up of ma-

  dry milled cellulosic materials, particularly hardwood cellulose From these filter layers can be made adjuvants for pre-layer filtration if the finished filter layers are reduced to fine particles by dry grinding Filter layers thus finely shredded or reduced to fine particles according to the invention can be advantageously used for the preliminary filtration of products which have to meet

  very stringent purity requirements.

  Finally, according to another characteristic of the

  vention, in order to impart a desired electrical charge to the filtering material, a zeta potential can be applied to the filtering layer To reinforce the filtering layer

  it can also be treated by agents

  both at appropriate humidity, in particular by a resin

  melamine-formaldehyde or an epichlorohydrin resin.

  The process according to the invention and the wire layers

  trantes according to the invention allow for the first time to obtain pharmaceutical liquids, such as for example

  blood plasma or other sera, free from metal ions-

  lics, in particular of aluminum and iron ions, the concentration of these ions being at least below the detection limit, so that it can be supplied from

  blood plasma no longer containing prejudiced metal ions

  similar to health Similarly, filtrates can be made which, not collecting metal ions from the

  filter material, are sought after in the chemical industry

  that or in other fields and this in particular for the filtration of photographic gelatin which can now

  be filtered without costly washing or other additional measures

nelle.

Claims (18)

  1 Filtration process, carried out in   pharmaceutical, biological, chemical or similar liquids, in particular solutions to be injected, for example blood plasma or other sera, or   photographic Latin or similar, in which are used   as filter aids, the material   lulosic, especially cellulose fibers, reduced   in very fine particles, as well as activating components   filtration agents introduced into this cellulosic material   sic, characterized in that instead of the usual mineral components activating filtration, namely earth   diatomaceous earth and perlites are used as an ad-   filter aids, inert additives that do not release practically any metal ions, such as   the fine granular polymer material highly capable of being   perser or highly pure cellulosic material reduced to micrometric particles, or mixtures of these two kinds of matter.   2 Method according to claim l, characterized in that to filter sera, in particular blood plasma, in a poor environment or free of metal ions it is used, as a fine granular polymer material highly capable of dispersing, a urea-formaldehyde condensation product having a primary particle size of approximately 0.1 to 3.0 µm and a specific surface   20 + 5 m 2 / g (determined by the BET method).   3 Method according to claim 1 or 2, charac-   terized in that for sterilizing filtration are used   primary particles from 0.1 to 0.20 μm of the urea-formaldehyde condensation product and for filtrations   less fine, for example clarifying filtration, ag-   glomerates of primary particles of a size included t> between 4 and 200 pm.   4 Process according to any one of the claims   above, characterized in that the polymeric material   re granulated has a density of 1.30 to 1.50 g / cm 3 and an apparent density of approximately 60 g / l. Process according to any one of the preceding claims, characterized in that the proportion of inert filter aids which release practically no metal ions is between 5 and 60% of the total weight of the filter layer.   6 Method according to claim 1, characterized   in that for the filtration of products sensitive to   maldehyde, such as for example photographic gelatin, carried out in the absence of metal ions is used, replacing a granular polymeric material, as   as a filter aid, cellulose reduced in part micrometric sheets.   7 Method according to any one of the claims   above, characterized in that the cellulose re-   micrometric particle is made up of cellulosic materials, in particular cellulose of   high purity hardwood, dry ground.   8 Method according to any one of the claims   tions, characterized in that, for the filtration   preliminary tion, finished filter layers having a basic structure composed of cellulosic material and of granular polymer material deposited therein   and / or cellulosic materials reduced to mid-particles   are ground and used for wire- pre-layer tration. b.   9 Process according to any one of the claims   above, characterized in that in the case where the particles or colloids, to be separated by filtration, which are in the prefilt have a negative charge, it is communicated to the cellulosic fibers of the filtering layer a positive surface potential (zeta potential ) and preferably by introducing into the aqueous suspension   of cellulose reduced to micrometric particles a resistance   epichlorohydrin which binds to cellulose and is   dense during the subsequent drying process carried out be 130 and 1500 C.   A method according to any of the claims.   previous cations, characterized in that the material fil-   trante, after having been prepared and primed, is dried and consolidated by the addition of moisture-resistant agents, for example a modified melamine-formaldehyde resin or   an aqueous solution of an epichlorohydrin resin.   11 Filter layer which, in particular   bind to filtration of pharmaceutical, biological fluids   ques or chemical, has a basic structure of fibros cellulose having undergone fibrillation, in particular for the implementation of the method according to any one   of the preceding claims, characterized by a material   re polymer in fine granules and highly capable of dispersing   deposited in cellulosic fibers.   12 Filter layer according to claim 11, characterized in that the granular polymeric material is a ureaformaldehyde condensation product having a size of primary particles of 0.1 to 3.0 mm and a   specific surface of 20 + 5 m 2 / g (BET method).   13 filter layer according to claim il   or 12, characterized in that that intended for the filtration   fine tion, in particular in sterilizing filtration, consists of primary particles, of a size of   0.1 to 0.20 Ai, of the urea condensation product   formaldehyde. 14 Filter layer according to any one of the   claims 11 to 13, characterized in that that intended   born from less fine filtration, for example the filtration   clarifying, has agglomerates of particles   primers with a size between 4 and 200 µm.   15 Filter layer according to any one of   claims 11 to 14, characterized in that it is   formed by mixtures of primary particles of a   size between 0.1 to 0.20 µm, of the con-   urea-formaldehyde densities and agglomerates thereof eras.   16 Filter layer according to any one of   claims il to 15, characterized in that the material   granular polymer has a density of 1.30 to   1.50 g / cm 3 and an apparent density of approximately 60 g / l.   17 Filter layer according to any one of   claims 11 to 16, characterized in that the proportion   poor or ion-free filtration aid   sizes is between 5 and 60% of the total weight of the filter layer.   18 Filter layer having a basic structure of cellulosic material having undergone fibrillation, in particular cellulose fibers, for the filtration of photographic gelatin in the absence of metal ions,   in particular according to any one of claims 1,   6 and 7, characterized by cellulose, preferably   from hardwood, reduced to micro-particles 1 01   triques and deposited in said fibril cellulosic material   lée. 19 Filter layer according to any one of   Claims 11 to 18, characterized in that the layer   filtering finished, composed of cellulosic material and   polymer granular material deposited in cellulosic material   sic and / or cellulose reduced to micrometric particles   ques, is fragmented as finely as possible by crushing   ge for use in pre-cut filtration che.   Filter layer according to any one of   claims II to 19, characterized in that the fibers   cellulosics are treated to present a potential tiel zeta.   21 Filter layer according to any one of   claims II to 20, characterized in that the material   filter material is consolidated with a resistant agent   moisture, especially an aqueous solution of a   sine melamine-formaldehyde or an epichlorohydrin resin.