Flat or capillary membrane manufactured from a mixture of polyvinylidene fluoride and a second by chemical reaction hydrophilable polymer.

The invention relates to a flat or capillary membrane based on a homogeneous mixture of polyvinylidene fluoride (PVDF) and a second, rendered hydrophilic by chemical reaction of polymers and to methods for their preparation and to further chemical modification.

Polyvinylidene fluoride, which in particular have an excellent heat resistance and resistance to chemicals, are known to be hydrophobic, and can be applied difficult for the separation of aqueous solutions. There are already in the prior art, numerous attempts have been made to hydrophilicize by modifications of various kinds such membranes.

Thus, DE-OS 27 35 887 describes a process in which impregnating the pores of a porous fluorocarbon polymers with at least one water-soluble polymers including polyvinyl alcohol and the polyvinyl alcohol by heat treatment or ionizing radiation makes insoluble in water.

However, impregnation methods have the disadvantage that the membrane structure can be blocked in part by the coating of the membrane pores, resulting in the flux values ​​of the membranes will be adversely affected. Furthermore, a coating of polyvinylidene fluoride with a hydrophilic polymer, especially in the case of the constellation of the incompatibility of the substrate and coating, not very resistant. It can therefore by certain media, in particular sulfuric acid or hypochlorite, which are required in the cleaning of membranes or in the semiconductor industry, are destroyed, resulting in disadvantages result as enhanced delivery of foreign substances or particles, and irrevocably lost the hydrophilicity of the membranes is ,

The compatibility of PVDF with hydrophilic polymers is unfortunately very limited. So can indeed be made of PVDF, and a few hydrophilic polymers such as polyvinylpyrrolidone, to produce hydrophilic membranes at a sufficiently high proportion by weight of the hydrophilic component. but they have a very low mechanical strength, and often the hydrophilic polymer is extracted at conditions of use of the membrane.

Also by graft PVDF membranes can be made hydrophilic. Thus, EP-A 0245000 a method is described, are first treated at the PVDF membranes with alkali metal hydroxide solution to produce by elimination of hydrogen fluoride on the surface of the PVDF membrane reactive sites. In this are then using a polymerization initiator polymerizable hydrophilic vinyl polymers, such as acrylic acid, methacrylic acid and itaconic acid, grafted. Apart from the risk of damage to the membrane by the caustic and blockage of the pores by the polymerized hydrophilic vinyl polymer is also disadvantageous in this procedure that the membrane still contains toxic acrylic monomers and oligomers after grafting that only with great effort completely from the membrane can be extracted.

To avoid the disadvantages of another way is known, which is made of a homogeneous mixture of PVDF and a second, hydrophilicizable by chemical reaction of polymers, so it must be compatible with PVDF in the applied weight range, a membrane, and then the second polymer by chemical reaction is converted into a hydrophilic. Thus, EP-A 0012557 a membrane made of a homogeneous mixture of PVDF and polyvinyl acetate, and the latter is then hydrolyzed, resulting in a hydrophilic membrane results which, because of the resulting polyvinyl alcohol hydroxyl groups. In this patent application, however, emphasized that the membranes must contain at least 35 weight percent polyvinyl acetate, if they are to have a sufficiently hydrophilic character after hydrolysis. Preferably, therefore, a polyvinyl alcohol content from 43 to 67 weight percent of the hydrophilic membrane, an originally present content by weight of polyvinyl acetate of 60 - corresponds to 80 percent by weight. At such high weight of polyvinyl alcohol or polyvinyl acetate but the favorable polymer properties of PVDF described above are deteriorated considerably naturally.

The present invention has as its object, a flat or capillary membrane based on a homogeneous mixture of PVDF and a second, hydrophilicizable by chemical reaction of polymers provide, which is characterized by a significantly lower proportion by weight of the second polymer, which is to ensure that one hand retaining the excellent chemical and physical properties of the total PVDF practical yet sufficient hydrophilic properties are obtained on the other hand by its chemical reaction.

Surprisingly, it was found that as the second polymer of very low weight, at least 2 percent by weight of a formed essentially from polymethyl and / or ethyl ester polymers to achieve the object is already sufficient. The term "a substantially from polymethyl and / or ethyl ester formed polymer" refers, in particular of pure polymethyl acrylate, polyethyl acrylate, the corresponding, mixtures of these two polyacrylates and all copolymers of the two monomers methyl acrylate and ethyl acrylate. Further herein, copolymers are included in the latter two substances that arise from that, the copolymerized Acrylsäuremethylester- and / or acrylate monomers, which have an excellent ability to copolymerization with small amounts known per se customary other monomers. For this purpose, suitable monomers that can be generally used only in amounts of up to 10 percent by weight, are, for example, acrylamide, acrylonitrile, maleic acid esters, vinyl acetate, vinyl propionate, methacrylates, styrene and butadiene. It is surprising in this context that besides the two above-mentioned basic types of acrylic ester polymers, the polymer of methyl methacrylate and / or ethyl acetate, or esters of acrylic acid or methacrylic acid with alcohols having more than two carbon atoms, are not suitable for producing membranes of the invention. Such monomers can at best, described as above, be used as a minor admixture with the monomers via the formation of a copolymer used in the invention.

The present invention therefore consists in that flat or capillary membranes of the kind specified above are provided which are characterized in that they consist of 70 to 98 percent by weight of polyvinylidene fluoride and from 2 to 30 weight percent of a formed essentially of polymethyl and / or ethyl polymers exist and have a maximum pore size in the range of 0.005 to 10 microns. Preferred ranges for the maximum pore size filters that are from 0.01 to 2 microns and from 0.05 to 0.8 .mu.m. The maximum pore diameter is determined by the bubble point method according to ASTM no. 128-61 and F 316-70.

Both the average molecular weight of the polyvinylidene fluoride, as well as the average molecular weight of the essentially from polymethyl and / or ethyl ester formed polymers may vary within wide limits. weight below the middle Molekularge herein is the weight average M_wAs measured by gel permeation chromatography after prior calibration with a corresponding standard polymer solution, understood. The method according to the invention for the two described below for the preparation of the flat or capillary membranes used polyvinylidene fluoride may generally have an average molecular weight from 30,000 to 500,000, an average molecular weight from 50,000 to 500,000 is preferred here. Likewise, the average molecular weight of essentially of polymethyl and / or ethyl polymer formed 5000-1000000 vary, although for the preparation of the flat or capillary membranes have an average molecular weight in the range 50,000 to 200,000 is preferred.

The flat or capillary membranes according to the invention can be prepared in such a way that, based on the total polymer weight, from 70 to 98 percent by weight of polyvinylidene fluoride and from 2 to 30 weight percent of a polymer formed essentially from polymethyl and / or ethyl acetate using one or more solvents and one or more non-solvents, a 10 to 40 wt .-% solution, based on their total weight, makes that in the liquid state having a range of full miscibility and a mixture gap above room temperature and above room temperature has a solidification range by the material components heats under intense homogeneous mixing to a temperature above the miscibility gap, the solution thus obtained from the temperature above the miscibility gap in a cooling liquid cools quickly while ausformt to a flat or capillary membrane and subsequently freeing the membrane by extraction of solvent -and- non-solvent residues.

This procedure is closely modeled on that described in DE-OS 33 29 578 and derived from patent applicants process for preparing voided polyvinylidene moldings on, is expressly made to the content here. To prepare the solution, the polymers are at elevated temperature, preferably dissolved at 200 to 230 ° C, in a mixture of at least one solvent and at least one non-solvent. Among solvents are also to understand liquids in the framework of the invention at room temperature, the polymers do not dissolve or only very poorly, but which exhibit good dissolution properties at elevated temperature. Suitable solvents for the polymers are glycerol triacetate, glycerol diacetate, 2- (2-Butoxyäthoxy-) ethyl acetate, ε-caprolactam, and mixtures of the aforementioned compounds. The use of glycerol triacetate as the solvent or a mixture of glyceryl triacetate and ε-caprolactam is preferred. As non-solvent di-n-octyl adipate or castor oil or a mixture thereof are suitable. The solution at elevated temperature produced homogeneous 10 to 40 wt .-% strength, preferably 20 to 30 wt .-% strength, based on the total weight thereof contains, based on the total polymer weight, preferably 80 to 95 percent by weight polyvinylidene fluoride and 5 to 20 weight percent polymethyl - and / or ethyl. The average molecular weight of the PVDF should preferably 50,000 to 500,000 and the amount of polymethyl and / or ethyl, preferably 50,000 to 200,000.

Said homogeneous solutions are formed into a capillary membrane or a flat membrane and cooled rapidly, first passing through a portion of the phase separation. One of the two liquid phases formed after the separation provides a depleted polymer liquid phase of solvent (s) and non-solvent (s) represents the other one of solvent (s) and non-solvent (s) depleted and the polymer liquid phase , The latter leads on further cooling to solidify the polymer. For cooling, it is advantageous, as cooling liquid is water, optionally to use with the addition of surfactant.

but it is also possible to use as a solvent a liquid or a liquid mixture arising at room temperature or only slightly elevated temperature, ie, generally in a temperature range of 15 to 50 ° C, a clear solution. the aprotic solvent particularly suitable solvents in question. In this case, preferably made of one or more compounds from the group of N-methylpyrrolidone, dimethyl sulfoxide, dioxane, dimethylformamide and dimethylacetamide at a temperature of 0 to 80 ° C, especially 20 to 40 ° C and a 10 to 40 wt .-% solution, based on their total weight, prepared, and the solution after molding precipitated as capillary membrane or a flat membrane by immersion in a non-solvent, wherein the temperature of the non-solvent bath from 0 to 80 ° C, particularly 20 to 40 ° C. When all non-solvent liquids are that do not dissolve the polymer at room temperature and are miscible with the solvent of the polymer solution at least to a limited extent. For coagulation of the membrane as a non-solvent alcohols having 1 to 12 C-atoms, in particular having 1 to 3 carbon atoms, water or mixtures of the said substances are preferred.

It is low in some cases, the solution prior to its contact with the liquid non-solvent for a period of time that can range from a few seconds to a few minutes, in contact with gaseous non-solvent, such as moist air, steam or vapors of the aforementioned alcohols to bring. It may also be advantageous for the polymer solution used for the membrane preparation to add certain additives. In question, for example, are thickeners for increasing the viscosity of the polymer solution or nucleating agents for influencing the membrane formation process or dyes or pigments.

The membrane produced by a method described is extracted in order to remove residues of solvents and other substances which would interfere with any subsequent application of the membrane. As extractant all fluids can be used, the resolve to be extracted substances but not the membrane polymer PVDF, polymethyl acrylate and / or polyethyl acrylate. Preferred are lower alcohols having 1 to 3 C-atoms, in particular isopropanol. The extraction agent is removed by drying out of the membrane.

The polymethyl used in the invention for the preparation of the flat or capillary membrane substantially and / or ethyl esters of an average molecular weight of 5000-1000 000 are well known, are not commercially available. They can, however, according to known methods even in a solvent such as triacetin (= glycerol triacetate), N-methylpyrrolidone or dimethyl sulfoxide, which is also used as solvent in the membrane preparation, be synthesized by reacting this at room temperature a quantity of 1 to 30 weight percent methyl acrylate and / or ethyl ester and 0.02 to 5 weight percent, based on the monomers, of a radical initiator such as benzoyl peroxide, azobisisobutyronitrile or acetovaleronitrile, are added. According to the methyl acrylate and / or ethyl ester monomers will proceed with small amounts of the above-exemplified monomers in the copolymerization. The solution is then heated to 80 ° C, to initiate polymerization. After the polymerization, unreacted monomers at elevated temperature and with the aid of an entraining agent, such as water, lower alcohols or ethyl acetate, expelled. The solution should not contain more monomers, so as not to jeopardize during membrane production staff through the toxic monomers and to residual contents of monomers in the fertien membrane reliably avoid.

The polymethyl thus obtained and / or ethyl ester solution 33 29 578 added for the above-described membrane preparation according to DE-OS only with the corresponding amounts of non-solvents, and polyvinylidene fluoride and heated to obtain a homogeneous solution while stirring.

The inventive hydrophobic membrane according to claim 1 is mechanically and thermally stable and has a high chemical resistance to attack by oxidizing agents and acids. Surprisingly, it was found that they compared to sodium hydroxide solution significantly better chemical resistance than has the hydrophobic PVDF membranes of the prior art. So the first discoloration of customary PVDF membranes in 10% already occurs sodium hydroxide solution at 40 ° C after 5 minutes, whereas the inventively modified membranes show until between 40 and 60 minutes first discoloration phenomena. The resistance of the membranes to alkalis is in practice during filtration of basic media or in the cleaning of the membrane with sodium hydroxide solution is of great importance.

The inventive hydrophobic membrane according to claim 1 is characterized spanked on PVDF membranes with the same pore size by a higher porosity of the outer surface. Porosity of the outer surface, the surface is understood to open pores on the outer surface of the membrane in relation to the outer surface. The porosity of the outer surface is of decisive importance for clogging of a membrane. The greater this porosity of a membrane, the slower it will be blocked, if used properly.

The new hydrophobic membrane is therefore eminently suitable for the filtration of gases or for applications in which a hydrophilic liquid may not pass through the membrane. Examples are the gassing of liquids (blood, bioreactors, effluent) or the transmembrane distillation.

The inventive hydrophobic membrane of claim 1 can be subjected to the whole surface of a chemical modification for the purpose of obtaining a hydrophilic membrane in particular by the ester groups on the total surface of the membrane at least partial hydrolysis and / or an at least partial trans-esterification with a polyhydric alcohol and / or an at least partial aminolysis with an amino compound having 2 - 8 carbon atoms subjected werden.Unter total surface area is not only understood to mean herein the outer surface, but also the internal surfaces, that the surfaces of the micropores of the membrane which during its use by fluids be contacted. The hydrophilized flat or capillary membranes are then characterized in that on their entire surface from 0.001 to 10 mVal / g membrane, preferably from 0.01 to 5 mVal / g membrane -OH, -NH₂ or -COOH groups or mixtures of these hydrophilic functional groups.

The permanent Hyrophilierung the membrane of the invention is, as already mentioned above, so surprising, because the membranes, in addition to PVDF up to 30 wt .-% esters of acrylic acid with monohydric alcohols having a higher number of carbon atoms than 2 or esters of methacrylic acid with monohydric alcohols included, can not be described by the procedure hydrophilicize.

An only partial hydrolysis or partial transesterification or partial aminolysis of the membrane of the invention as defined in claim 1 can in particular be considered when the membrane contains relatively large amounts of polymethyl and / or ethyl acetate, for example, 10 or 20 wt .-%. Partial reactions of the type according to the invention can be considered, but even if the membrane does contain hydrophilic groups, but should remain hydrophobic, or if the hydrophilized membrane to contain mixtures of the abovementioned hydrophilic functional groups. For this purpose, the sequence of the chemical reactions can be chosen arbitrarily.

With respect to the feasibility of the chemical reactions is believed that the polyacrylate macromolecules are randomly distributed in the PVDF. Thereby, on the entire surface inside the pores of the membrane occasionally encountered parts of macromolecules of polymethyl and / or ethyl ester. The ester groups in these macromolecule parts can be converted by the chemical reactions at least partially in -OH, -NH₂ or -COOH groups, while the corresponding parts of the polyacrylate macromolecules in the interior of the membrane may suffer no chemical reaction. Thus, these remain anchored in the membrane structure and can not be washed. The hydrophilic functional groups in the macromolecule parts of the present on the outer and inner surfaces of the membrane acrylic acid polymer contrast hydrophilicize the membrane permanently.

The hydrolysis of the membrane of the invention according to claim 1 can be carried out in such a way that treating the ester groups on the total surface of the membrane with concentrated sulfuric acid at a temperature of 40 to 80 ° C for 1 to 20 hours. The rate of hydrolysis increases with increasing temperature in this case. When other strong acids may be used for the hydrolysis, such as hydrochloric acid, methanesulfonic acid and perchloric acid, as a treatment of the membrane with concentrated sulfuric acid is preferred in the context of the invention. To be able to wet the membrane in this treatment and to maintain the temperature increase by the heat of dilution of sulfuric acid is sufficiently small, it may be advantageous, for example, to dip the membrane successively in the following solutions: C₁-alcohol - water - 50% H₂SO₄ - 70% H₂SO₄ - 98% H₂SO₄ - 70% H₂SO₄ - 50% H₂SO₄ - water.

The hydrolysis can be carried out in this case also under basic conditions. However, it should be noted that the p_Hshould be value of the reaction medium <11, otherwise the polyvinylidene fluoride is attacked. For this purpose it is convenient to work in the presence of a buffer solution as a saturated aqueous solution of borax at room temperature was found to be particularly suitable. Since the basic hydrolysis is relatively lengthy, the process is advantageously carried out in a pressure vessel at a temperature of 80 to 140 ° C and a pH of 9 to 11

The membrane of the invention according to claim 1 can also be made hydrophilic by providing them over their entire surface with alcoholic OH groups by means of a transesterification (alcoholysis =). To this end, the ester groups on the total surface of the membrane with an at least trihydric alcohol with addition of 0.1 to 10 wt .-%, based on the polyhydric alcohol, of a strong acid at a temperature of 100 to 150 ° C from 1 to 30 hours subject to an at least partial transesterification. As strong acids in this case, for example, sulfuric acid, hydrochloric acid, methane sulfonic acid and perchloric acid may be used.

Suitable polyhydric alcohols are alcohols having three or more OH groups, such as glycerol, diglycerol, triglycerol, Polyglyceringemische, trimethylolethane, trimethylolpropane, pentaerythritol, dipentaerythritol, Tripentaerythit, Butantriol- suitable (1.2.4), hexanetriol, sugar alcohols such as sorbitol and mannitol, and monosaccharides, such as fructose and mannose. Of course, mixtures of polyhydric alcohols can be used. are preferred as the polyhydric alcohol, one or more compounds from the group of glycerol, diglycerol, triglycerol, a polyglycerol mixture, pentaerythritol and sorbitol used.

Noteworthy, an analogous treatment of the membrane in ethylene glycol or low molecular weight polyethylene glycols not in hydrophilization of the membrane surface. Ethylene glycol can also be advantageously used as the reaction medium for the alcoholysis, the eligible solids, such as pentaerythritol and the monosaccharides to solve and bring to the membrane in response.

Another method for hydrophilizing the membrane of the invention as claimed in claim 1 represents the aminolysis. Since primary and secondary amines attack at elevated temperature because of their basicity polyvinylidene fluoride, the reaction conditions, such as p_HValue, to adjust temperature and reaction time of this fact. It has proved to be advantageous in that the ester groups on the total surface of the membrane with at least one amino compound having 2 to 8 C atoms, using appropriate buffer mixtures at a p_HValue <11 and a temperature of 50 to 150 ° C a to 24 hours at least partial aminolysis subjects. In the simplest case, the solution of the corresponding amino compound can hereby be buffered until it is saturated with ammonium chloride.

Among the amino compound in the sense of the invention herein are organic compounds having 2 to 8 carbon atoms understood with one or more primary amino groups, with the proviso that in the presence of only one primary amino group of at least two more hydrophilic funktionielle groups in the form of hydroxyl and / or carboxyl groups are present. Examples are 1,2-diaminoethane, 1,2-diaminopropane, 1,3-diaminopropane, 1,4-diaminobutane, 1,3-diaminobutane, 1,5-diaminopentane, 1,8-diaminooctane, aspartic acid, glutamic acid and homo serine.

Included herein are in particular primary and secondary polyamines with two primary amino groups, and amines having three primary amino groups, specific urea derivatives and heterocyclic hydrazines with more hydrazine residues. As in the case of alcoholysis, as described above then the conversion according to the invention the hydrophobic membrane requires a hydrophilic membrane because of the higher number of hydrophilic groups per molecule, the presence of only relatively low amounts by weight of polymethyl and / or ethyl in the flat or capillary membrane according to claim 1, which the usage properties of the hydrophilic membrane benefit. Examples are diethylenetriamine, triethylene tetramine, tetraethylenepentamine, dipropylenetriamine, 1,2,3-triaminopropane, 2,4,6-triamino-1,3,5-triazine, 2,4,6-trihydrazino-1,3,5- triazine, isobutylidene, biuret and triuret. Of course, mixtures of useful amino compounds can be used. It is preferred that one or more compounds from the group consisting of diethylenetriamine, triethylenetetramine and tetraethylenepentamine are used as amino compound.

Surprisingly, it was found that the hydrophilized in the manner described above, flat or capillary membranes with respect to sodium hydroxide solution significantly better chemical resistance than that possess hydrophobic PVDF membranes of the prior art. During the first discoloration of customary PVDF membranes in 10% sodium hydroxide solution occurs after 5 minutes at 40 ° C, only 45 minutes to show the invention hydrophilicized membranes first discoloration phenomena. This surprising property therefore allows extreme application conditions of use of the hydrophilic flat or capillary membrane according to the invention for immobilizing biochemically active compounds which are excluded in the hydrophilic membranes of the prior art. Under biochemically active compounds herein substrates, inhibitors and coenzymes of enzymes and their analogs, enzymes themselves, other proteins, other cell components, whole cells or produced by cells compounds, and compounds in the substance groups listed, including whole cells, can somehow interact understood.

The hydrophilic membranes described in claims 7-8 having OH-, NH₂- or COOH end groups or mixtures of these hydrophilic functional end groups. Such membranes can be implemented in an advantageous manner with biochemically active compounds. Such reactions can reactions of NH₂ groups with aldehydes, reactive carboxylic acid derivatives, and alkyl or aryl halides, of OH groups with reactive carboxylic acid derivatives, and alkyl or aryl halides as well as of (activated) COOH groups with amines, alcohols, and alkyl or aryl halides include as an initial step. A number of such reactions will be described for example in DE 28 28 194 for the derivatization of a polysaccharide-based matrix. However, due to the complexity of this field, the reactions listed here and in DE 28 28 194 may not be comprehensive. A suitable chemical reaction is always matched to the individual case to be processed, since the nature of the processed biologically active compounds can vary to a considerable extent and the nature of the matrix can have influence on the result. If such reactions are carried out on the hydrophilic membrane according to the invention, as an activated membrane is obtained, which in turn can react easily with having other functional groups molecules. For contrast, a membrane to which a biochemically active molecule, a cellular component or a cell is attached, is referred to herein as the derivatized membrane.

The biochemically active compound may sometimes directly to the membrane or if, for example steric hindrance does not permit this, several spacers also be immobilized by the interposition of one or. Under a spacer is herein understood a molecule comprising at least two functional groups, for example in the form of an aldehyde group, amino group, carboxyl group or hydroxyl group, and includes functions as a constant "spacers".

The inventive use of hydrophilic flat or capillary membrane for immobilizing biochemically active compounds leads to a derivatized membrane which may, among other things, see as a medium for a combination of filtration and affinity chromatography using. For this purpose, for example, substrate (s), coenzyme (s), inhibitor (s), antibodies and / or their analogues are used as a covalently bound ligand. Furthermore, is the chemically activated membrane for immobilizing enzymes, other proteins, cell constituents and / or whole cells. This combines the advantage of a filtration unit with those known from the literature immobilizations.

The derivatized membranes in question have the particularly advantageous property of having a chemically and physically extremely stable, generally hydrophilic base structure. This is especially for the chemical activation under severe conditions (extreme p_HValues, higher temperature, aggressive solvent) a decisive advantage. When cleaning used derivatized membrane is also committed to the following surprising effect a. Thus, as will be set forth in Example 24, are cleaned with the use of chemically-resistant ligands much more quickly and effectively not only with strong acids, but also with strong bases as for example in the known substrates of cellulosic nature, without any degradation of the membrane or of the ligand occurs. With the known membranes based on cellulose such a procedure would be unthinkable, because they would be very badly damaged or destroyed under these conditions.

Further, even a less-resistant bond between the membrane and the ligand under correspondingly drastic conditions, such as are the cited in Examples 10, 16 and 23, split and thus the diaphragm is restored to its original state hydrophilic. The membrane is therefore times for immobilizing biochemically active compounds can be used, which has not yet been described for a derivatizable membrane. This is particularly for the immobilization of enzymes with a low lifetime of advantage.

The present invention is further illustrated by the following examples:

A.

Preparation of polyacrylate

A₁: Preparation of polymethyl acrylate (PMA =), M_w = 7400

In a heatable 4 l glass envelope 1 800 g triacetin at 70 ° C are presented. The liquid is about 0.5 h flows through with nitrogen to remove oxygen. In 200 g of methyl acrylate (MA) 4 weight percent acetovaleronitrile are dissolved at room temperature. This solution is dropped within an hour in the glass bulb with the triacetin. Half an hour after the addition is the reaction mixture heated for half an hour at 160 ° C, substantial reaction of residual monomers. Then remove of monomers from the solution by distillation of about 100 g of triacetin the last remnants. A viscous solution of Poly (PMA) in triacetin. The average molecular weight was 7 400th

A₂ Preparation of PMA, M

w

= 35,000

In a heatable 4 l glass envelope 1 400 g triacetin (= glycerol triacetate) are placed at 70 ° C. The liquid is about 0.5 h flows through with nitrogen to remove oxygen. In 600 g of methyl acrylate (MA) 5 percent by weight benzoyl peroxide are dissolved at room temperature. This solution is sep into the flask with the triacetin within an hour OPFT. Half an hour after the addition is the reaction mixture heated for half an hour at 160 ° C, substantial reaction of residual monomers. Then remove of monomers from the solution by distillation of about 100 g of triacetin the last remnants. A viscous solution of Poly (PMA) in triacetin. The average molecular weight M_w (Weight average) was 35 000th

A₃ Preparation of PMA, M

w

= 235 000

In a heatable 4 l glass envelope 1 400 g triacetin at 70 ° C are presented. The liquid is about 0.5 h flows through with nitrogen to remove oxygen. In 600 g of methyl acrylate (MA) 3 percent by weight benzoyl peroxide are dissolved at room temperature. This solution is dropped within an hour in the glass bulb with the triacetin. Half an hour after the addition is the reaction mixture heated for half an hour at 160 ° C, substantial reaction of residual monomers. Then remove of monomers from the solution by distillation of about 100 g of triacetin the last remnants. A viscous solution of Poly (PMA) in triacetin. The average molecular weight was 230 000th

A₄ Preparation of PMA, M

w

= 688 000

In 20 g of methyl acrylate (MA) 0.5 weight percent acetovaleronitrile are dissolved at room temperature. This solution is heated within one hour in a glass flask at 80 ° C. After another half hour, the reaction mixture is heated for half an hour at 160 ° C, substantial reaction of residual monomers. After cooling, a rubbery clear polymer. The average molecular weight was 688,000.

A₅ Preparation of polyethyl acrylate (= PEA), M

w

= 114 000

In a heatable 4 l glass flask, 1600 g triacetin at 70 ° C are presented. The liquid is about 0.5 h flows through with nitrogen to remove oxygen. In 400 g of ethyl acrylate (EA) 0.2 percent by weight benzoyl peroxide are dissolved at room temperature. This solution is dropped within an hour in the glass bulb with the triacetin. Half an hour after the addition is the reaction mixture heated for half an hour at 160 ° C, substantial reaction of residual monomers. Then remove of monomers from the solution by distillation of about 100 g of triacetin the last remnants. A viscous solution of polyethyl (PEA) in triacetin. The average molecular weight M_w was 114 000th

A₆: Preparation of PMA / PEA, M

w

= 160 000

In a heatable 2 liter glass flask 800 g triacetin at 70 ° C are presented. The liquid is about 0.5 h flows through with nitrogen to remove oxygen. In 150 g of methyl acrylate (MA) and 150 g of ethyl acrylate (EA) are dissolved at room temperature, 0.2 percent by weight benzoyl peroxide. This solution is dropped within an hour in the glass bulb with the triacetin. Half an hour after the addition is the reaction mixture heated for half an hour at 160 ° C, substantial reaction of residual monomers. Then remove of monomers from the solution by distillation of about 100 g of triacetin the last remnants. A viscous solution of a copolymer of methyl acrylate (MA) and ethyl acrylate (EA) in triacetin. The average molecular weight Mw was 160 000th

B. Preparation of the flat or capillary membranes according to the invention.

Example 1:

Preparation of a PVDF / PMA-flat membrane.

In a glass flask with a stirrer 27 parts (always parts by weight) PVDF of the type Kynar 460 (Pennwalt), 3 parts of polymethyl combined (A₁), 18.2 parts of triacetin, 4.55 parts ε-caprolactam and 47.25 parts dioctyl. The in this and further experiments, with the exception of Example 2, PVDF employed will have, unless otherwise stated, by gel permeation chromatography, a weight average molecular weight of 361 000. While stirring the mixture at 240 ° C was heated to obtain a homogeneous solution , Thereafter, the solution was cooled to 190 ° C. This solution was formed on a casting roll that was temperature controlled to 20 ° C with aid of a casting into a sheet and wound onto a roll. Samples of the films were extracted 3 times for 0.5 h in isopropanol at 60 ° C in order to wash the largely solvent from the membrane. After drying, a white flat membrane.

The membrane thickness is 120 microns, the maximum pore size of the membrane 0.55 microns. The isopropanol flow of the membrane is 7.4 ml / (cm min bar).

At a transmembrane pressure of 0.5 bar, no water flow takes place through the membrane.

The surfaces of the flat membrane are very porous (see. Photomicrography, image 1).

example 2

:

Preparation of a PVDF / PMA flat membrane with a low M

w

of PVDF.

In a glass flask with stirrer, 56 g of PVDF of the type Kynar were 740 (Pennwalt) (M_w = 180 000), the 132 g dioctyl, 12 g of triacetin and 75 g of a 20 percent solution of polyethyl (A₅) combined in triacetin. While stirring the mixture at 240 ° C was heated to obtain a homogeneous solution. This solution was coated onto a glass plate to give a film of 200 microns thickness. the film was solidified by immersion in water. The film was extracted 3 times at 60 ° C to wash out the solvent largely from the membrane for 0.5 h in isopropanol. After drying, a white flat membrane.

The maximum pore size of the membrane was 1.3 microns.

example 3

:

Preparation of PVDF / PMA capillary membranes with very small pores.

An analogously prepared to Example 1 solution of 32.5 parts of PVDF of the type Kynar 460, 2.5 parts of PMA (A₂), 22.75 parts of triacetin and 42.25 parts dioctyl was at a temperature of 205 ° C through an annular die to a capillary spun. To keep the capillary was supported by a hollow needle inside the annular die glycerin.

The membrane was extracted 3 half an hour in isopropanol at 60 ° C.

The capillary had an inner diameter of 0.2 mm and an outer diameter of 0.29 mm.

The maximum pore size of the membrane was less than about 0.2 microns and thus can not be determined by the bubble point method. The flow of isopropanol was 0.15 ml / (cm min bar).

The separation properties of the membrane were measured by determination of sieving coefficients for different macromolecules. The sieving coefficient is defined as the quotient of the concentration of the macromolecules in the original test solution by the concentration of the macromolecules in the solution passing through the membrane.

This gave the following values ​​for the sieving coefficient: <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">macromolecule</entry><entry namest="col2" nameend="col2" align="center">molecular weight</entry><entry namest="col3" nameend="col3" align="center">sieving coefficient</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Vitamin B12</entry><entry namest="col2" nameend="col2" align="right">1300</entry><entry namest="col3" nameend="col3" align="char" char=",">0.87</entry></row><row><entry namest="col1" nameend="col1" align="left">inulin</entry><entry namest="col2" nameend="col2" align="right">5500</entry><entry namest="col3" nameend="col3" align="char" char=",">0.79</entry></row><row><entry namest="col1" nameend="col1" align="left">cytochrome C</entry><entry namest="col2" nameend="col2" align="right">12,000</entry><entry namest="col3" nameend="col3" align="char" char=",">12:54</entry></row><row><entry namest="col1" nameend="col1" align="left">a-amylase</entry><entry namest="col2" nameend="col2" align="right">45,000</entry><entry namest="col3" nameend="col3" align="char" char=",">0.24</entry></row><row><entry namest="col1" nameend="col1" align="left">Bovin Serum Albumin</entry><entry namest="col2" nameend="col2" align="right">60,000</entry><entry namest="col3" nameend="col3" align="char" char=",">0.16</entry></row></tbody></tgroup></table></tables>

This means that molecules having a molecular weight of 45000, which corresponds to a molecular diameter of 0.03 micron, are almost completely retained by the membrane.

Example 4:

Comparative Example: Preparation of a PVDF flat membrane.

In a glass flask with a stirrer 27.5 parts were PVDF of the type Kynar 460 (Pennwalt), 18.85 parts of triacetin, 4.71 parts ε-caprolactam and 48.94 parts dioctyl combined. While stirring the mixture at 240 ° C was heated to obtain a homogeneous solution. Thereafter, the solution was cooled to 190 ° C. This solution was formed on a casting roll that was temperature controlled to 20 ° C with aid of a casting into a sheet and wound onto a roll.

Samples of the films were extracted 3 times for 0.5 h in isopropanol at 60 ° C in order to wash the largely solvent from the membrane. After drying, a white flat membrane.

The membrane thickness is 140 microns, the maximum pore size of the membrane 0.59 microns. The isopropanol flow of the membrane is 9.4 ml / (cm min bar).

At a transmembrane pressure of 0.5 bar, no water flow takes place through the membrane.

The surfaces of the membrane are less porous than in Example 1 (see FIG. Photomicrography, image 2).

Example 5:

Preparation of a PVDF / PEA flat membrane.

In a glass flask with stirrer, 56 g of PVDF of the type Kynar 460 (Pennwalt), 132 g dioctyl, 12 g of triacetin and 75 g of a 20 weight percent solution of polyethyl (A₅) were combined in triacetin. While stirring the mixture at 240 ° C was heated to obtain a homogeneous solution. This solution was coated onto a glass plate to give a film of 200 microns thickness. the film was solidified by immersion in water. The film was extracted 3 times at 60 ° C to wash out the solvent largely from the membrane for 0.5 h in isopropanol. After drying, a white flat membrane. The maximum pore diameter of 0.82 microns the flow of isopropanol 9.1 ml / (cm^, min ^, bear).

Example 6:

Preparation of a PVDF / PMA / PEA flat membrane

In a glass flask with a stirrer, 135 g of PVDF type Kynar 460 (Pennwalt), 303.8 g dioctyl, 29.2 g ε-caprolactam, 117 g of triacetin and 10 g polymethyl / ethyl acrylate (A₆) combined. While stirring the mixture at 240 ° C was heated to obtain a homogeneous solution. This solution was cooled to 195 ° C and coated onto a glass plate to a film of 200 microns thickness. the film was solidified by immersion in water. The film was extracted 3 times at 60 ° C to wash out the solvent largely from the membrane for 0.5 h in isopropanol. After drying, a white flat membrane. The maximum pore diameter was 0.86 microns the flow of isopropanol 9.4 ml / (cm^, min ^, bear).

Example 7:

Preparation of a PVDF / PMA flat membrane with DMSO as a solvent.

In a glass flask with stirrer, 54 g of PVDF of the type Kynar were 460 (Pennwalt) and a solution of 6 g polymethyl (A₃) into 340 g of dimethyl sulfoxide (DMSO) combined. While stirring the mixture at 80 ° C was heated to obtain a homogeneous solution. The solution, 100 g of propylene carbonate. This solution was cooled to room temperature without phase separation took place. On a glass plate, the solution was knife-coated to a film of 200 microns thickness. The film was first held a minute of air and then solidified by immersion in water.

The film was extracted 3 times at 60 ° C to wash out the solvent largely from the membrane for 0.5 h in isopropanol. After drying, a white flat membrane.

The maximum pore size of the membrane is 2.46 .mu.m, the isopropanol flow of the membrane 11.2 ml / (cm min bar).

The membrane was treated similarly to Example 16 with 2% sulfuric acid and diglycerol. The penetration time (see Example 10) the thus treated membrane was 12 seconds.

Example 8:

Preparation of PVDF / PMA capillary membranes

A prepared as in Example 1 solution of 31.1 parts of PVDF, 2.9 parts of PMA (A₄), 22.44 parts of triacetin, 4.29 parts ε-caprolactam and 44.55 parts dioctyl was at a temperature of 210 ° C spun through an annular die at a capillary membrane. To keep the capillary was supported by a hollow needle inside the annular die a mixture of equal parts of castor oil and dioctyl.

The membrane was 3 times extracted half an hour in isopropanol at 60 ° C extrahiert.Die membrane has a maximum pore size of 0.63 microns and an isopropanol of 9.24 ml / (cm min bar). The capillary has an inner diameter of 1.0 mm and an outer diameter of 1.5 mm.

The membrane can not be wetted with water.

Example 9:

Preparation of a PVDF capillary membrane

According to Example 8 a PVDF solution consisting of 29.9 parts of PVDF, 18.2 parts of triacetin, 4.6 parts of ε-caprolactam and 47.3 parts dioctyl was without the addition of a polyacrylate spun into a capillary.

The membrane was 3 times extracted half an hour in isopropanol at 60 ° C extrahiert.Die membrane has a maximum pore size of 0.54 microns and an isopropanol of 6.55 ml / (cm min bar). The membrane can not be wetted with water. The capillary has an inner diameter of 1.0 mm and an outer diameter of 1.5 mm.

Example 10:

Reaction of PVDF / PEA with H₂SO₄

the membrane according to Example 5, samples were reacted with sulfuric acid.

For this, the membranes were only wetted with ethanol. The membranes were then placed (98%) in contact without incorporation of gas bubbles in the membrane structure with the concentrated sulfuric acid by replacing the alcohol with demineralized water, then against 70 percent sulfuric acid and then to concentrated sulfuric acid. The membranes left for 1.5 h at 60 ° C in the sulfuric acid.

Thereafter, the membranes were washed first with 70 percent sulfuric acid and then with demineralized water and then dried. The dry samples were hydrophilic.

The penetration time was about 30 seconds.

Under penetration is understood in this and in the following examples, the time after which a water drop of 2 .mu.l, which is given with a precision pipette on the membrane, has completely disappeared. serves as a comparative time of more than about 300 seconds for the water droplets to disappear completely on a glass rod by evaporation. When a hydrophilic membrane, it takes naturally less, until the water droplets is gone, because it is absorbed by the membrane structure. Due to the not always the same diaphragm structure, which also affects the penetration times, provides the determination of the penetration time only a semi-quantitative, but sufficient, and especially practical measure of the hydrophilicity of a membrane because it with in the practical application of the membrane to complete wetting of the membrane water arrives within a certain time.

Example 11:

Reaction of PVDF / PMA with borax solution

A sample of the flat membrane of Example 5 was wetted with isopropanol and then treated in 5 weight percent sodium hydroxide solution, which was saturated with borax in the pressure vessel for 8 hours at 120 ° C. Subsequently, the membrane was rinsed with demineralized water and dried. The membrane was slightly brown and hydrophilic. The penetration time was about 40 seconds.

Example 12:

Reaction with glycerol and diglycerol

Capillary membranes, which were prepared analogously to Examples 8 and 9, and a different content of PMA, based on the polymer had been treated with glycerol or diglycerol as a hydrophilizing solution. The treatment time was 6 hours each at 140 ° C. The hydrophilizing was 1 wt .-% perchloric acid was added.

The membrane samples were thereby first wetted with ethanol and then immersed in the respective rendering them hydrophilic. After treatment, the membranes were washed with demineralized water and dried. On the dry membrane samples the penetration times were determined.<tables id="tabl0002" num="0002"><table frame="topbot"><tgroup cols="4" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">Membrane: PVDF and</entry><entry namest="col2" nameend="col2" align="center">glycerin</entry><entry namest="col3" nameend="col3" align="center">diglycerol</entry><entry namest="col4" nameend="col4" align="center">Diglycerol + 10% water</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col4" align="center">Penetration times in seconds</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">0% PMA</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry><entry namest="col3" nameend="col3" align="right">&gt; 300</entry><entry namest="col4" nameend="col4" align="right">&gt; 300</entry></row><row><entry namest="col1" nameend="col1" align="left">13.5% PMA</entry><entry namest="col2" nameend="col2" align="right">1-2</entry><entry namest="col3" nameend="col3" align="right">1</entry><entry namest="col4" nameend="col4" align="right">1</entry></row><row><entry namest="col1" nameend="col1" align="left">8.5% PMA</entry><entry namest="col2" nameend="col2" align="right">2 - 3</entry><entry namest="col3" nameend="col3" align="right">2 - 3</entry><entry namest="col4" nameend="col4" align="right">1-2</entry></row></tbody></tgroup></table></tables>

Example 13:

Transesterification of PVDF / PMA / PEA with diglycerin

A membrane according to Example 6 was added to prewetting with ethanol in a solution of diglycerol and 6 wt .-% concentrated sulfuric acid (98%). The solution was kept for 8 hours at 140 ° C. The membranes were then taken out and extracted several times with demineralized water and dried.

The penetration of the dry membrane was 2 - 3 seconds.

Example 14:

Transesterification of PVDF with 2% PMA

A flat membrane, which had been prepared analogously to Example 5 from 2% PVDF and PMA was treated as in Example 13 with diglycerol and 2 wt .-% of concentrated sulfuric acid for 20 hours at 140 ° C. After washing and drying the membrane, the penetration time was 70 seconds.

Example 15:

Transesterification of PVDF / PMA with various alcohols

Membrane samples that had been prepared according to example 8 were wetted with methanol, and reacted with various alcohols at 140 ° C for 6 hours with addition of 1 wt .-% perchloric acid. <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">Alcohol:</entry><entry namest="col2" nameend="col2" align="center">Penetration time (s)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">glycerin</entry><entry namest="col2" nameend="col2" align="right">3</entry></row><row><entry namest="col1" nameend="col1" align="left">diglycerol</entry><entry namest="col2" nameend="col2" align="right">1</entry></row><row><entry namest="col1" nameend="col1" align="left">polyglycerol</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="left">ethylene glycol</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row><row><entry namest="col1" nameend="col1" align="left">polyethylene glycol 300</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row></tbody></tgroup><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="left">10 wt .-% alcohol in ethylene glycol:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">sorbitol</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="left">sucrose</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="left">Strength</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row><row><entry namest="col1" nameend="col1" align="left">pentaerythritol</entry><entry namest="col2" nameend="col2" align="right">3</entry></row><row><entry namest="col1" nameend="col1" align="left">TRIS</entry><entry namest="col2" nameend="col2" align="right">60</entry></row><row><entry namest="col1" nameend="col2" align="justify">(TRIS = Tris (hydroxymethyl) aminomethane)</entry></row></tbody></tgroup></table></tables>

Example 16:

Transesterification of PVDF / PMA flat membranes with diglycerol and various acids

Membrane samples of Example 1 were reacted with a solution of diglycerol and 4 different concentrations of acids. The treatment lasted for 8 hours at 140 ° C. There are given the penetration times of the rinsed and dried membranes.<tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">acid</entry><entry namest="col2" nameend="col2" align="center">Penetration time (s)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Hydrochloric acid (35%)</entry><entry namest="col2" nameend="col2" align="right">8th</entry></row><row><entry namest="col1" nameend="col1" align="left">Perchloric acid (70%)</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="left">Sulfuric acid (98% strength)</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="left">Phosphoric acid (85% strength)</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row></tbody></tgroup></table></tables>

In contrast to the membranes from Examples 1 and 4, the hydrophilic membrane samples according to Example 16, a water flow of about 7.4 ml / (min cm bar) at 0.5 bar trans-membrane pressure.

Example 17:

Determination of hydroxyl

At the hydrophilized with diglycerol / sulfuric acid membrane of Example 16, the hydroxyl value was determined as a measure of the amount of free OH groups on the membrane surface.

The membrane was reacted to with an acetylation. The consumed amount is determined by back-titration of the solution.

Manufacture of acetylation:

3.5 ml of perchloric acid (70%) are added together with 150 ml of ethyl acetate and 5 ml of acetic anhydride. To 4 parts of the solution part of hexane is added.

Measurement:

A weighed piece of membrane was placed in an Erlenmeyer flask, to 5 ml of acetylation and 2 ml of water were added. After 5 minutes, 25 ml of a mixture of 3 parts of pyridine, and 1 part water was added. After another 5 minutes, with 50 ml of isopropanol diluted and titrated with phenolphthalein as an indicator with 1 N sodium hydroxide.

The content of OH groups was determined to be 0.3 meq / g.

Example 18:

Producing a hydrophilic membrane as compared to DE-OS 27 35 887

Analogously to Example 29 of the patent DE 27 35 887 was (according to Example 9) dipped a hydrophobic capillary membrane of PVDF in an aqueous solution containing 6 wt .-% polyvinyl alcohol. The membrane was dried and then treated at 90 ° C and 15 minutes at 140 ° C for 20 minutes. The membrane was rinsed 2 times 10 minutes with water at 90 ° C. The dried membrane was immersed at room temperature for two minutes in a Acetalisierungsbad of 20 parts of sulfuric acid (96%), 2 parts of sodium sulfate and 100 parts of a 40 weight percent solution of formaldehyde in water. The membranes were then rinsed with water and dried.

On the dried membrane has a penetration time of 59 seconds were measured.

Example 19:

Treatment of hydrophilic membranes with hypochlorite solution

A capillary membrane according to Example 12 with 8.5 wt.% Glycerol and PMA treatment, and the comparison membrane according to Example 16 were stored in an aqueous solution with 5000 ppm of sodium hypochlorite, then rinsed with water and dried for 16 hours. The membrane of the invention was still good hydrophilic properties, while the comparative membrane was no longer wetted by water, as can be seen from the comparison of the penetration.<tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">membrane</entry><entry namest="col2" nameend="col2" align="center">Penetration time (s)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Example 10</entry><entry namest="col2" nameend="col2" align="right">15</entry></row><row><entry namest="col1" nameend="col1" align="left">Example 16</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row></tbody></tgroup></table></tables>

Example 20:

Comparison with a hydrophilic PVDF membrane from Millipore

A commercially available hydrophilic flat membrane of PVDF from Millipore and an inventive PVDF flat membrane that has been rendered hydrophilic according to Example 16 by treatment with sulfuric acid and diglycerol were kept 16 hours in concentrated sulfuric acid. The membranes were then rinsed with water and dried.

The membrane of the invention was still good hydrophilic properties, while the comparative membrane was no longer wetted by water, as can be seen from the comparison of the penetration. <tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">membrane</entry><entry namest="col2" nameend="col2" align="center">Penetration time (s)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">According to Example 16</entry><entry namest="col2" nameend="col2" align="right">12</entry></row><row><entry namest="col1" nameend="col1" align="left">Millipore</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row></tbody></tgroup></table></tables>

example 21

Treating a PVDF / PMA capillary membrane according to Example 8 with tetraethylenepentamine

It is a reaction solution was prepared by an aqueous solution containing 40 wt .-% tetraethylenepentamine at 80 ° C was saturated with ammonium chloride. A capillary membrane according to Example 8 was wetted with ethanol, and then dipped at 80 ° C in the solution. After evaporation of ethanol, the solution was heated with the membrane in a pressure vessel at 140 ° C. After various times, the membrane samples were removed from the solution, washed with water and dried. The membranes were only slightly discolored and easily wettable after a reaction time of more than 3 hours with water.<tables id="tabl0007" num="0007"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">Reaction time (h)</entry><entry namest="col2" nameend="col2" align="center">Penetration time (s)</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="right">1</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row><row><entry namest="col1" nameend="col1" align="right">3</entry><entry namest="col2" nameend="col2" align="right">&gt; 300</entry></row><row><entry namest="col1" nameend="col1" align="right">5</entry><entry namest="col2" nameend="col2" align="right">26</entry></row><row><entry namest="col1" nameend="col1" align="right">7</entry><entry namest="col2" nameend="col2" align="right">2</entry></row><row><entry namest="col1" nameend="col1" align="right">16</entry><entry namest="col2" nameend="col2" align="right">2</entry></row></tbody></tgroup></table></tables>

A treated in the same way comparison membrane according to Example 9 without the addition of polyacrylate showed after 16 hours of reaction time no hydrophilicity.

Example 22:

Treating a PVDF / PMA capillary membrane according to Example 8 with glutamic acid

It is a reaction solution was prepared by an aqueous solution of 40 wt .-% glutamic acid was buffered with ammonia to pH 10th A capillary membrane according to Example 8 was wetted with ethanol, and then dipped at 80 ° C in the solution. After evaporation of ethanol, the solution was heated with the membrane in a pressure vessel at 140 ° C. After 16 hours the membrane from the solution was taken out, washed with water and dried.

The membrane had a penetration time of 18 seconds. A membrane according to Comparative Example 9, which was treated in the same manner, was not water wettable and thus showed a penetration time of&gt; 300 seconds.

Example 23:

Resistance to caustic soda

Depending on a flat membrane according to Example 1 and Example 4, as well as a hydrophilic transesterified with diglycerol flat membrane according to Example 15 were wetted with methanol and placed in 10 weight percent sodium hydroxide solution at 40 ° C. It was the time until the first discoloration of the membrane samples.

Discoloration of the membrane indicates a chemical change of the membrane by the attack of sodium hydroxide. <tables id="tabl0008" num="0008"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">membrane</entry><entry namest="col2" nameend="col2" align="center">Time to first discoloration</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">example 1</entry><entry namest="col2" nameend="col2" align="right">50 minutes</entry></row><row><entry namest="col1" nameend="col1" align="left">example 4</entry><entry namest="col2" nameend="col2" align="right">5 minutes</entry></row><row><entry namest="col1" nameend="col1" align="left">The hydrophilic membrane of Example 15</entry><entry namest="col2" nameend="col2" align="right">45 minutes</entry></row></tbody></tgroup></table></tables>

example 24

Affinity with a chemically stable ligands

a) Membrane Cibacron Blue

Hollow fiber membrane data: Inside diameter: 960 - 1120 microns; Wall: 230 microns; PVDF: 90.5 wt .-%; PMA: 9.5 wt .-% Content of OH groups: 0.012 m Val / g membrane obtained in Example 12 by reacting a 8.5% PMA containing capillary membrane with glycerol Maximum pore diameter: 0.79 .mu.m; Transmembrane flux of isopropanol: 19.4 ml / min^,cm²^,bear. Module data: effective length 155 mm; 62 fibers (5.6 g; 314 cm² inner wall surface) pretreatment: The activation of the membrane is carried out by pumping the respective solutions through the membrane. The membrane is treated with 300 mg Cibacron Blue 3GA in 60 ml of water for 45 minutes. Thereafter, up to saturation solid NaCl is added and treated a further 30 minutes. Subsequently, 600 mg NaCO₃ is heated to 80 ° C, is added and left at this temperature for a further 2 hours. After cooling, is washed with 2 liters of water in single-pass.

b) chromatography

I. Purification of hexokinase

A crude preparation of hexokinase (From Yeast, Sigma Cat. No. H 5125) in 50 ml of 5 mM (millimolar) TRIS-HCl buffer p_H 6.4 and filtered through the membrane. To wash 2 x used 50 ml of the same buffer. eluting with 50 ml of 20 mM Tris-HCl buffer p_H 8.6. The results are shown in Table 1 below.<tables id="tabl0009" num="0009"><table frame="all"><title>Table 1</title><tgroup cols="4" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="left">hexokinase:</entry><entry namest="col2" nameend="col2" align="center">activity</entry><entry namest="col3" nameend="col3" align="center">protein</entry><entry namest="col4" nameend="col4" align="center">specific activity</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">[IU] *</entry><entry namest="col3" nameend="col3" align="center">[Mg]</entry><entry namest="col4" nameend="col4" align="center">[IU / mg]</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Starting solution:</entry><entry namest="col2" nameend="col2" align="right">528</entry><entry namest="col3" nameend="col3" align="char" char=".">22:55</entry><entry namest="col4" nameend="col4" align="char" char=".">23:41</entry></row><row><entry namest="col1" nameend="col1" align="left">Radical solution:</entry><entry namest="col2" nameend="col2" align="right">394</entry><entry namest="col3" nameend="col3" align="char" char=".">17:14</entry><entry namest="col4" nameend="col4" align="char" char=".">22.99</entry></row><row><entry namest="col1" nameend="col1" align="left">rinse:</entry><entry namest="col2" nameend="col2" align="right">9</entry><entry namest="col3" nameend="col3" align="char" char=".">12:39</entry><entry namest="col4" nameend="col4" align="char" char=".">23:08</entry></row><row><entry namest="col1" nameend="col1" align="left">bound</entry><entry namest="col2" nameend="col2" align="right">125 (100%)</entry><entry namest="col3" nameend="col3" align="char" char=".">5:02</entry><entry namest="col4" nameend="col4" /></row><row><entry namest="col1" nameend="col1" align="left">eluted:</entry><entry namest="col2" nameend="col2" align="right">122 (97.6%)</entry><entry namest="col3" nameend="col3" align="char" char=".">2.77</entry><entry namest="col4" nameend="col4" align="char" char=".">44.04</entry></row></tbody></tgroup><tgroup cols="4" colsep="0" rowsep="0"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><tbody valign="top"><row><entry namest="col1" nameend="col4" align="justify">*) International Units (1 micromolar Umsatz.min under standard conditions)</entry></row></tbody></tgroup></table></tables>

As is apparent from Table 1, almost all adsorbed hexokinase activity was also eluted again, whereby the specific activity of hexokinase was almost doubled. The hexokinase is not cleaned naturally homogeneity in this purification step.

II. Adsorption of Albumin

Human albumin (Serva, Order No. 11870) is, in 50 ml of 100 mM KCl in 50 mM TRIS-HCl buffer p_H 7.0 dissolved, adsorbed by pumping to the membrane. After washing of the module with the same buffer (2 x 50 ml) with 50 ml of 1.5 M KCl solution in 50 mM phosphate buffer p_H 7.0 desorbed. The results are summarized in Table 2 below.<tables id="tabl0010" num="0010"><table frame="all"><title>Table 2</title><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col1" align="center">Albumin from human serum</entry><entry namest="col2" nameend="col2" align="center">protein</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" align="center">[Mg]</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Initial solution (50 ml)</entry><entry namest="col2" nameend="col2" align="char" char=".">22:10</entry></row><row><entry namest="col1" nameend="col1" align="left">Radical solution (50 ml)</entry><entry namest="col2" nameend="col2" align="char" char=".">4:45</entry></row><row><entry namest="col1" nameend="col1" align="left">Rinse solution 1 (50 ml)</entry><entry namest="col2" nameend="col2" align="char" char=".">6:06</entry></row><row><entry namest="col1" nameend="col1" align="left">Rinse solution 2 (50 ml)</entry><entry namest="col2" nameend="col2" align="char" char=".">1:11</entry></row><row><entry namest="col1" nameend="col1" align="left">bound</entry><entry namest="col2" nameend="col2" align="char" char=".">10:48</entry></row><row><entry namest="col1" nameend="col1" align="left">eluted</entry><entry namest="col2" nameend="col2" align="char" char=".">10:43</entry></row></tbody></tgroup></table></tables>

As is apparent from Table 2, all the adsorbed albumin is also desorbed.

c) regeneration of the module

Although the cleaning may analog Blue Sepharose (for example, by the company Pharmacia) with 0.1 M TRIS buffer p_H 9.3 and acetate buffer to 3.2 performed at reduced efficiency and a longer period of time. However, much more effective is the cleaning with 0.1 N NaOH or 1 N HCl, which is endured surprisingly of the derivatized membrane without injury (p_H = 1 and 13). When cleaning with acid, a reversible color change from blue to red, which is due to protonation of the aromatic system of Cibacron. Due to the very stable bond of matrix and dye no measurable amount of dye is cleaved under these conditions. The thus purified module corresponds to the new state.

General remarks:

The protein contents are tested according to biuret. The hexokinase activity is to: HU Berg Meyer, Methods of Enzymatic Analysis, 3rd Edition (1974), Verlag Chemie, Weinheim, pages 502-503, determined.

example 25

Reloading with covalently immobilized enzyme

The hydrophilization of the flat membrane is carried out analogously as described in Example 21st Subsequently, the reaction of the membrane is carried out (effective area of ​​32 cm², effective weight, 0.31 g, 0.014 meq NH₂ groups / g membrane) with 10% glutaraldehyde solution in 10 mM phosphate buffer pH 7.0 for 1 hour at room temperature. The invertase solution (EC3.2.1.26; from yeast, Boehringer Mannheim, Cat 104922, spec activity 330 U / mg..) In 10 mM acetate buffer pH 4.6 is in excess overnight in circulation through the activated membrane filtered. Under these conditions, the catalytic activity of the immobilized invertase remains almost completely intact.

To load the membrane, for example after a protein denaturation again with protein, the membrane is again subjected to the aminolysis of Example 21st The second loading of the membrane with invertase is carried out under the same conditions as above.<tables id="tabl0011" num="0011"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="left">Determination of immobilized invertase:</entry></row><row><entry namest="col1" nameend="col2" align="center">1.Immobilisierung:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Starting solution:</entry><entry namest="col2" nameend="col2" align="right">3060 IU</entry></row><row><entry namest="col1" nameend="col1" align="left">Radical solution, not immobilized:</entry><entry namest="col2" nameend="col2" align="right">1680 IU</entry></row><row><entry namest="col1" nameend="col1" align="left">Immobilized Invertase:</entry><entry namest="col2" nameend="col2" align="right">1380 IU</entry></row></tbody></tgroup><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="center">2.Immobilisierung:</entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Starting solution:</entry><entry namest="col2" nameend="col2" align="right">2510 IU</entry></row><row><entry namest="col1" nameend="col1" align="left">Radical solution, not immobilized:</entry><entry namest="col2" nameend="col2" align="right">1180 IU</entry></row><row><entry namest="col1" nameend="col1" align="left">Immobilized Invertase:</entry><entry namest="col2" nameend="col2" align="right">1330 IU</entry></row></tbody></tgroup></table></tables>