DE2265243A1 - Artificial kidney has porous membrane parallel to flow - giving effective filtration of particles smaller than pore size - Google Patents

Abstract

An artificial kidney comprises a membrane filter having pores of diameter 0.01-0.10 mu and arranged parallel to the flow direction of the blood stream. A pressure difference sufficient to cause filtration is applied across the membrane. The membrane may be arranged flat or cylindrical. Its outlet side may be connected to a buffer soln. circuit. It may be prepd. from cellulose acetate. Particles having mol. wts. in the range 40,000-50,000 although they would pass through a filter of the above pore size if it were arranged transversely to the flow direction, are effectively retained by the filter when it lies parallel to the direction of flow. The vortex radius only needs to be 1/10 of the pore size to prevent practically all the particles from passing through the filter.

Description

The invention relates to an artificial mere with a the inlet side for the blood and the outlet side for the filtrate separating filter.

Human blood contains about 60-80% by weight water, and the Kidney patients almost always have to be treated periodically so that the excess water content of their blood is removed will. In this case, protein and similar valuable blood components must not be removed, while urea, Uric acid, creatinine and the like waste materials must be removed.

Bas molecular weight of the water-soluble albumin of the im

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The white molecules contained in blood are of the order of 65,000; the size of the molecule in aqueous solution can be compared to a sphere with a diameter of about 100 Å. The membrane filter used for the artificial kidney should therefore have pores of less than 100 Å (or less than 0.01 / u). The use of a flat filter with a porous filter membrane, which corresponds to the membrane according to the invention, has so far been described by the technology as inadequate for the removal of the excess water content from human blood by filtration at a relatively low pressure (100-200 mmHg) compared to regular blood pressure been. In addition, it has been believed that filtering blood through such a porous membrane filter would lead to rapid clogging of the fine pores with blood cells. It was further assumed that the selection by the permeability of the porous membrane relates only to the molecular size. Based on these previous considerations, it was considered impossible to use, as a filter medium for artificial kidneys, a membrane filter whose pore size was larger than 0.01 Ai .

See also US Pat. No. 3,579,441 for an example. It describes an artificial kidney working with a filter, in the particle sizes, the molecular weights from 40 * 000 to 50 * 000, are not treated well

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could. Therefore, the "previously known membrane could pore sizes in the maximum order of about 0.01 / o have;. That is, that it almost is an osmosis membrane, which is generally used for the separation of molecules in a solution ₀ A blood pressure filtration with Such a known membrane in an artificial kidney leads to a very extensive device that would be extremely inconvenient as a portable device.

In connection with the invention, the relationship between the forum size and the filter performance is that of the invention porous membrane has been investigated. It was found that if a membrane with the mean forum size of more than 0.01 / U across into a blood fluid flow to be filtered is set, even particles with molecular weights of 4-0,000 to 50,000 pass well while in the blood contained serum substances cannot be filtered to a satisfactory extent.

it has surprisingly been found that if a membrane is placed in the liquid flow so that it lies parallel to the direction of flow, almost all particles whose vortex or rotation radius is about 1/10 of the pore size cannot pass through the membrane filter. The invention therefore creates an artificial kidney, in which a membrane filter with pores in diameter

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from 0.01 to 0.10 , η is arranged in a blood stream parallel to its flow direction, so that the surrounding space is thereby separated from the blood and the filtration can be brought about by the pressure difference between the surrounding space and the blood.

"Filter" in this specification refers to a mesh filter using a permeable membrane, which is described in US Pat its ideal shape has an infinitely large number of fine holes passing through the membrane, wherein each opening on the front and back of the membrane should be substantially circular. In a The preferred embodiment of the invention is the artificial kidney with a porous cellulose acetate symmetry membrane filter which has been prepared by dissolving cellulose acetate having a degree of acetylation from 20 - 65.5% in an organic solvent with a weight ratio of 5 - 4-0% to the solvent and Addition of a diluting solvent with a boiling point higher than that of the aforementioned organic solvent, and further a metal salt whose metal component has an ionic radius of less than 1.33A and is a member of Group I - III of the periodic table and which has a ratio of 20 - 200% by weight to the acetate, to the solution, so that a homogeneous solution is created which is applied to a polished flat surface to form a thin film,

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from which the solvent contained therein is removed by evaporation and that by micro-phase separation in its gel state is transferred, whereupon the metal salt contained therein is finally dissolved out to form the porous membrane will.

The use of such a membrane filter is particularly advantageous, since it is between the filter performance of a membrane and the specific shape of the end openings of the pores on both sides of this membrane and the pore diameter ratio There are special relationships to which a membrane filter of the type mentioned above in particular Wise enough.

After the experiments on which the invention is based, it has been found that there is a considerable difference in the filter performance with one and the same membrane filter, there is either one or the other surface as the filter side is used. On the other hand, in recent years, the application technology is increasingly becoming a sieve-like one Membrane filter requires that is easily washable by backwashing.

In connection with the invention, extensive practical tests have been made to the actual and to clarify reliable filter performance of a sieve-like membrane filter and to create a filter that

essentially easy to wash in the reverse direction. Here, it has been determined that the Porendurchmesservertellung together play an important role on both sides of the membrane, which appears on these membrane surfaces pores opening shape and the pore diameter ratio every single pore between the front and back of the membrane _e therefore have been used for the desired assess filtration performance photographs made on the scanning electron microscope from the membrane surfaces, instead of the commonly used method of penetration of pressurized mercury.

In the case of a conventional sieve membrane filter, the structure is such that for each of the fine pores the shapes of the openings appearing on the two sides of the membrane are essentially different from one another are different. Often one finds pores that are essentially circular on the front surface of the membrane show an opening, while on the back the same pores have an extremely irregular shape, such as a natural swan, to have. The particles to be filtered out by using such a filter membrane are on its front side collected, and it is generally observed on such a membrane that the pore density and the pore occupancy ratio per unit area on the front of the membrane are significantly lower than on the rear. That means na-

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of course, a considerable disadvantage. The filtering performance of a sieve membrane is determined by the filter area on which the smaller pore opening is located _o This type of sieve membrane therefore has a rather limited filtering capacity. In addition, this type of membrane shows rather poor strength

ο no more than about 30 kg / cm.

Sieve membrane filters are also known which have pore openings of the same size and shape on both surfaces of the membrane. Membrane filters of this type show improved strength, but at the expense of lower pore density and a considerable amount Filter resistance.

The membrane filter to be used according to the invention is distinguished by pores, the diameter of which is only small Borders fluctuates and their opening xand is smooth circular or is substantially circular, the opening ratio between the front and back of the membrane being for each pore is at least about 3 »0. If the filtering capacity is good, these membrane filters have a proportionate effect high filtration speed, high mechanical strength and can be very easily backwashed clean. The membrane used for the filter is a type of symmetry filter and has at least 40% porosity a thickness of 50 - 500 / U and a pore opening diameter of 0.01 τ 10 / U, observed on both sides of the membrane.

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Other advantages and features of the invention will become apparent from the claims and from the following description and drawings, in which embodiments of the invention are explained and illustrated _o In the drawings:

Fig. 1 is a simplified and enlarged view of a representative pore opening shape, which on both'-the Areas of a filter to be used for the artificial kidney according to the invention appear,

FIG. 2 shows a simplified comparison illustration of sections through a membrane filter according to the prior art Technique (Fig. 2A) and a filter to be used for the invention (Fig. 2B),

3 shows a triangular coordinate representation of a three-component system, namely a CaCIp. 2H ₂ 0 / CH, 0H / acetate solution to illustrate the phase separation properties, the dotted lines showing the separation,

Fig. 4- a diagram to illustrate the effect of a Additional amount of CaCIp. 2HpO on the porosity of the Membrane made from a cellulose acetate solution containing an acetate / acetone / methanol / Cyclohexanol mixture in a weight ratio of 12.5 / 100/25 / 62.5,

Fig. 5 is a diagram to illustrate the effect of a

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'■ Amount of CaCl ₂ · 2H ₂ O added to the pore size of the

Membrane made from a cellulose acetate solution with the same composition as mentioned for Pig 4 • is,

. 6 a three-axis coordinate diagram to illustrate the effect of an additional amount of CaCl ₂ · 2H ₂ O on the pore size in a membrane that is made from a cellulose • acetate solution that contains an acetate /

Acetone / methanol / cyclohexanol mixture is. 7 is a triangular coordinate diagram to illustrate an additional amount of CaCl ₂ · 2H ₂ O on the porosity of the membrane, which is made from a cellulose acetate solution, which is an acetate / acetone / methanol / cyclohexanol mixture,

Piss. 8 is a diagrammatic view of an ^{artificial tie working with a flat filter v} , which is equipped with a porous membrane according to the invention as a filter element.

Pig. 9 shows an axial section along the line XY in FIG. B ₉ Pig. 10 shows an axial section through an artificial kidney which is constructed as a cylindrical filter and uses a porous membrane according to the invention as a filter element,

11 shows an axial section through a cylindrically constructed. artificial kidney that has a combination of filters and dialysis device, with a porous Membrane used in the invention as a working element will,

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12 is a diagrammatic partial view of a model of a sieve filter membrane according to the invention,

Figure 15 is an electron microscope photograph of a part the front of a porous according to the invention FiItermembrane, which is particularly useful in an artificial Filter-type kidney is usable with the image in a scanning electron microscope and a enlargement factor of 8000 is made,

14 - a corresponding photograph from the rear

of the same membrane pattern with a magnification factor from 2,500,

Fig. 15 is an electron microscope photograph of the front of a pattern made according to a conventionally known Method according to the following Example 1 has been prepared, with the enlargement factor 4-000 is

Fig. 16 is a corresponding photograph of the back side of the same membrane pattern with a magnification factor from 4-000,

17 is an electron microscope photograph of the front of a pattern of a porous according to the invention Membrane with a magnification factor of 4-000 and

Fig. 18 is a corresponding photograph of the back side of the same membrane pattern with a magnification factor from 4-000.

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A cellulose acetate membrane filter for artificial kidneys according to the invention is formed with a large number of fine pores penetrating the membrane material. Each of these pores emerges on both sides of the membrane in the form of a smoothly curved circular or substantially circular opening shape which has an opening diameter of 0.01-10 Å . These openings of the fine pores in the form of smoothly curved circular shapes or essentially circular opening shapes are generally very suitable for filtering off rod-like or elliptical particles, and they exhibit particularly favorable filter effects.

The expression "curved smoothly circularly or substantially circular shape "for describing the pore openings is defined below. First, the determination is made that the pore opening has a "smoothly curved" shape.

When a plurality of straight lines parallel to or perpendicular to the major or the minor axis of the pore shape, see A in Fig. 1, drawn crosses $ eae these straight lines always at two points, the pore opening shape curve. In this case, the spacing of these straight lines from one another is 1/10 of the larger one crossed by the lines.

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E.g. is in 71g. 1 the forum form A in a drawn line shown; it has a smaller Aohse & and a larger Aohse b · The group of parallel straight lines is duroh horizontal dashed lines are shown, which go parallel to the minor axis a. One of those straight lines that Line 1, crosses the pore shape curve at four points. Therefore, the solid Porm curve is not "smoothly curved" · A Part of the contour curve must therefore be supplemented, such as duroh the dlok dashed curve line is indicated

The term "circular or substantially circular" should be defined in such a way that e.g. in the case of an ellipse the ratio of the smaller eur larger Aohse atb at least Must be 0.75 «.

If at least 90 $> of the total pores correspond to the definitions given here, the condition "smoothly circularly curved or substantially circular shape" can be regarded as fulfilled.

In the case of the cellulose acetate porous membrane of the present invention should the ratio of the opening areas a duroh that Material passing through pore on both sides of the membrane should be at least 3.0 · The meaning and effect of this The ratio of the opening areas of the pore is referred to on the Pig. 2A and B explained.

Fig. 2A shows a relationship by means of a comparison

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drawn conventional membrane of the second type mentioned above. In this membrane, the pore opening durometers of a pore on both sides of the membrane are essentially the same.The pore opening durometer is generally 0.4 ti to a few µ, and the thickness of the membrane is usually in the order of magnitude of 50-100. The length of the pore channel is generally about 100% close to the pore opening durometer, so that there is necessarily a considerable resistance to the elderly · Since the pore diameter fluctuates slightly along the entire pore channel, the fine cables to be filtered can be caught in the inlet opening or in the middle of the pore channel significantly impaired »resulting in a major disadvantage«

FIG. 2B shows a similar representation of an embodiment according to the invention porous membrane »also considerably simplified ·

The surface of the membrane "which has the smaller pore opening" is used for nitriding The surface is hereinafter referred to as the "front side". The pore diameter can be on this front between OfOl ^ n and 10 / u lie · This pore opening diameter Can be realized optionally on average · For the nitration of beer, pore opening sizes of 0.6 - 2.0 / u are extremely important suitable. For the preparation of pure water »suitable for use in the electronics industry are preferred

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Pore sizes averaging 0.4 M should be used. · For medical purposes, eg for catalytic kidneys, pore sizes of 0.01-0.1 / U are extremely useful. The diameter of the membrane can generally be between 50 and 500 λΐ and is set according to the particular purpose of the membrane.

In the practical tests associated with the invention it has been demonstrated that the opposite membrane surface on which the larger pore openings can be seen and which is hereinafter referred to as "BUokseite", in has nothing to do with filtration efficiency, though it determines the mechanical strength of the membrane

With the Versuohon it has been found that if the on pore opening diameter appearing on the reverse side at least makes up the triple of the one on the front, the membrane has a favorable filter performance and a superior one RUokwasohkeit shows.

If each pore of the porous membrane on the front and back of the membrane is circular or substantially has circular opening, as the practical experiments have shown, the mechanical strength of the membrane increased considerably.

For the preparation of the porous cellulose acetate membrane is cellulose acetate having an acetyl content from 20 to 62.5 · 1 in an organic solvent with a related weight averhältnie 5-40 $ "· The dissolved solution is

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A sale of a metal was added to the members of groups X - III of the periodic table is selected and has an ionic radius of less than 1.33 A »You solution is then poured into a thin film on a polished surface or plate, which is then subjected to evaporation to remove the solvent, so that a Membrane remains · The membrane eventually becomes that Removes metal salt, creating a large number of very fine pores that pass through the membrane «

As a solvent for the preparation of the cellulose acetate solution Acetone, tetrahydrofuran or Methylenohlorld can be used for cellulose acetate with a higher degree of acetylation can preferably be methylene chloride be used as solvents · JThe main solvent for the Preparation of the cellulose acetate solution should preferably be done with a diluting solvent, such as methanol, ethanol, propanol and / or butanol, in this Pail is nooh note that the thinning solvent has a higher boiling point than the main solvent and also so should be chosen so that it is able to dissolve the metal salt added to the acetate solution «The reason for this is that the acetate solution must be in a single phase state before pouring into a thin slice · According to the Versuohserresults belonging to the invention, a porous membrane according to the invention can not consist of a. Preparing two-phase solution «To prepare the cellulose acetate solution, the type and amount of the diluting solvent should be used after experimental determination of its dissolving effect on the metal salt to be added and its phase separation properties

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be chosen over the main solvent

The concentration of the cellulose acetate in the solution to be used according to the invention is between 5 and 40% by weight, preferably 10-15% by weight, compared to the solvent Porous membranes are too brittle for use. On the other hand, if the above-mentioned highest value of the concentration of 40 wt which are then generally less than 0.01 µ and cannot be observed even through an electron microscope used with the magnification factors mentioned in this specification. With pore sizes reduced to less than 0.01 α , the membrane does not show the filter effect corresponding to a sieve membrane, although instead it is suitable, for example, as a dialysis membrane c can be used to filter molecules β or ions from a solution

To form the Metallealzee in the above sense can Metal ions following the invention are used Sodium (ion radius 0.9 $ A)) potassium (1.33 A)) Lithium (0.66 A), Magnesium (0.82 A), CaIoium (0.99 A)) Aluminum (0.72 A), copper (0.96 A) and - the like «

The usual effect is obtained with these metals

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the following order of preference

Lithium, Sodium, Magnesium, Caloium Zinc Potassium »Aluminum and Copper ·

They opposite to the aforementioned metal ions for the formation of the metal salt or coupling ions can be any negative ions. In practice, however, are for It is most recommended to use the halogen ion or the perchlorate, which allow a great solubility

Metal salts which are particularly preferable in the above sense are CaCl ₂ · 2H ₂ O ₉ MgBr ₂₁ LlCl and the like.

When using Sn, Fe salts and the like, in which the metals to higher than the IV * group of the periodic Systems belong, do not result in usable sieve-like membranes with fully open pores, such as those for the invention have shown belonging clubs

The metal salt is added to the solution in an amount of about 20-200 wt It is necessary to add at least 20 % by weight of metal salt, based on the acetate, to its solution. From the foregoing, it follows that the amount of metal to be added depends on the concentration of the oil acetate

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as well as the types and amounts of the main solvent and the thinning solvent. In general, it is possible to use a three-way coordinate diagram, see eg. Pig. To select 3, the erforderliohen percentage of solvent so that the single phase solution through the path of the micro-phase separation is obtained the conditions for gelling * Specifically, Figure 3 is a Dreieoks coordinate diagram. A Dreikomponentenaystems of CaCl ₂ acetate solution with an acetate-acetone ratio of 10 g / ml lQO. the diagram veransohaulioht the phase separation conditions, the system · In this Fig. a is the area of the two-Phaoen separation B, a micro-phase Trennungebereioh and O Bereioh the homogeneous phase.

In practicing the invention, the amount becomes of the metal salt to be added to the acetate solution that the solution is kept in its homogeneous phase before and during the pouring into a film. During the following Step for the production of the porous membrane consists of removing the solvent by means of evaporation the occurrence of a leakage phase separation caused "

If it is assumed in Fig. 3 that no salting out occurs, "the border must zwisohen the Bereiohen A and B and the zwieohen the Bereiohen B and O converge to the point of 100 # CaCl ₂ '2H ₂ O corresponding to" In the In practice, these limits are roughly set at the 55 1 » and 35 # points. The tendency is that with an increase in the added JIe tall talsmtng · tin tnteprtohtnd increased lowering occurs "

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According to the invention, a sieve membrane suitable for use as a filter is used made from a cellulose acetate solution, the a specially selected metal salt has been added and the solvent is removed from the evaporation, in order to produce a film from which the enclosed Me tallaalζ is then ohemieoh withdrawn · In connection with of the invention are the properties of the membrane taking into account the various types of manufacturing steps been investigated, the following being found let ι

If a metal salt is added in an amount less than two Gev / * #, based on cellulose acetate ₉ , the membrane produced becomes transparent if the ion radius of the metal is greater than 1.35 A let, such as Ba ²⁺ or Sr ^{2 +} ,

2 · When a salt of a metal which has an ionic radius of less than 1.33 Å, such as Na, Ca or the like in Oeetalt of his. Halogen and in an amount of less is used as 20% by weight, based on cellulose acetate, the membrane shows a double-sided structure, as in Usual reverse osmosis membranes

3. When a metal sale, the metal of which has an ionic radius of less than 1.33 Å, in the amount of more than. If 20% by weight is added relative to the cellulose acetate, the membrane produced produces pores, the end openings of which on both sides of the membrane are greater than ο 0.01 ii bind »

With a further increase in the Uetallsalsee beyond 20 wt

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phase separation occurs in the solution before the solution is poured out and continues to produce the membrane is treated. In connection with the invention, however, it has been boobaohtet that a stabilized state of microscopic separation before the first mentioned phase separation exists. The occurrence of this microphaoon separation can clearly be determined by the fact that there is a sudden decrease in the transparency of the Acetate solution is observed, the duroh reduction of the solvent by means of evaporation or duroh increased addition of the metal salt is · The reduction in transparency is based on a sudden and noticeable diminution of the rays of light or of the penetrating light diffuse light, which is continuously and constantly washed in a bath with acetate solution, observed.

4 · If the concentration of cellulose acetate in the solution is more than 10 wt. #, add Larger amounts of the metal salt, by the addition of which the micro-phase separation occurs, the mean pore size and the number of pores of the porous membrane is reduced when using 200 wt. # or more of the salt relatively the porous membrane becomes transparent again to the acetate

It should be noted that the invention has only been realized after a detailed analysis of the behavior of the formation of a porous membrane. Here SiOH merkliohe differences have shown daduroh that

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different types of phase separations have been brought about

It is already known to produce a reverse osmosis membrane from a concentrated gelulose acetate solution by adding several percentages by weight of a metal salt ₍ based on acetate, and by removing the solvent by evaporation from a PiIm of the solution, see U8-P3 5.360.459 and 3.415.038 These known processes also show a certain similarity with the present invention, provided that a concentrated cellulose acetate solution is used without the addition of a metal salt Well-made membranes are actually double-sided structures with the metal salt acting only as a kind of swelling agent, whereas in the present invention the metal salt causes the micro-phase separation and the occurrence of salting out.

According to the experiments carried out on the invention, at least one of the following additives can be added to the cellulose acetate solution with the above-mentioned composition are added, the previously added the appropriately selected metal salt had been, the additive to improve the porous membrane, in particular the pore opening adurohmesser make it more uniform, increase the number of pores or porosity and enlarge the mean pore diameter

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Aliphatic monohydric alcohols of the group C ₂ - Cc and their acetic acid esters, saturated cyanohydric monohydric alcohols (such as cyclohexanol> cyolopentanol or the like), aqueous monosoharide solution (such as aqueous solution of polyhydric alcohols such as glucose, sucrose or the like), alkyl esters of aromatic carboxylic acids (Denzosäure alkyl esters, phthalic acid diesters or the like ·!), cyclic hydrocarbons of the C ₅ - C ₁₀ (such as decalin, tetralin, cyclohexane or the like, ·), ethers (such as ethyl ether, diphenyl ether or the like, ·) ·

At least one member from the above group can be added to the cellulose acetate solution containing the Me tallaalζ lends to be removed by treatment with alcohol or water, whichever

Ea is believed to be the reason why the addition of this Additive has the above-mentioned effect, lies in the fact that the micro-phase separation is initiated more easily, which is caused by the addition of the metal salt, and that daa additive the illmoberfläohe due to its favorable Surface tension inherent in the coverage, the rate of evaporation of the acetate tea is advantageously controlled «

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The amount of additive or additives added can be less than 150 wt. ^ And preferably less than 100 wt. 96, based on the solvent of the cellulose acetate. As an example, the use of a cellulose acetate solution is referred to, which is made from acetate and a main solvent to which 1/3 to 1/4 weight of methanol is mixed for dilution, the solution being CaCl ₂ * 2H ₂ O as the metal salt and cyclohexanol as Additive is added.

4 is a graph showing the effect of the change in the addition of CaCl ₂ · 2H ₂ O on an oil acetate solution consisting of acetate, acetone, methanol and cyclohexanol in the ratio 12.5il00i25i62.5, the effect on porosity in percent is shown. The CaCl ₂ * 2H ₂ O - amount is shown in wt i "relative to acetate.. This also applies to Pig "5"

Pig. 5 is a diagram showing the effect on the pore size in yu which occurs when the amount of CaCl ₂ · 2H ₂ O added to the flat acetate solution is changed. "

Like Pig. 4 and 5, occur maxima of the porosity and the pore size at 80-100 i "the amount of addition of CaCl ₂ · 2H ₂ O

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on · This apparition was in no way Position of Ubliohen Reverse Osmooemembranen observed why the invention is an essential difference to the Stand of the Teohnik shows

Fig. 6 is a three-ox coordinate diagram showing the relationship between pore size and the composition of a cellulose acetate solution · A mixed solution of acetate »acetone, methanol and cyclohexanol was used» to which CaOl ₂ · 2H ₂ O was added · In the Diagram corresponds to "SoIn," a solution »which was prepared by dissolving 48g of acetate with a degree of acetylation of 54 # in 300 ml of acetone and further addition of 100 ml of methanol«

This Pig · 6 corresponds to the A ^ range of a membrane product "in which over 97 ^ of the pores have a larger diameter than 0.15 / Uj the B ^ range corresponds to membranes" in which over 97 ^ of the pores have a larger diameter than 0.08 / u · The G ₁ range corresponds to membranes in which over 97 £ of the pores have a diameter of over 0.02 / U * and the D ^ range corresponds to membranes »btl those over 97 £ of the pores larger · Have Durohmtsitr than 0.01 tx

Pig. 7 let tin three-octave coordinate diagram »da · dl · loading Increase in the porosity of the porous holding membrane Composition of the O «llulos« az «tatlöeung shows, where« in · Meowunf from astatine, acetone, methanol and cyclohexanol with

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Addition of CaOIg * 2HgO has been used. "Solnl ¹ " means a solution which has been prepared from 125 g of acetate with a degree of acetylation of 54 $, which has been dissolved in 100 ml of acetone with the addition of 250 ml of methanol.

In Pig. 7, the curves 1, 2, 3, 4, 5 and 6 correspond to the limits of regions with a porosity of βQfi, 70? £, and, respectively

From Pig 6 and 7 it can be seen that the middle The pore size and the porosity of the sieve-like filter membranes are adjusted based on the present invention according to Wunsoh by choosing the types and amounts of the metal salt and the additive accordingly

However, it should be noted that the addition of the aforementioned Additive or the additives has a tendency to distinguish the difference between the two pore opening sizes on the two to reduce the thickness of the membrane to some extent. Too much of the additive also causes the smoothly curved shape of the pore opening in the sense mentioned at the beginning is lost

The cellulose acetate solution thus prepared and adjusted is then processed into membranes, which basically work with evaporation or evaporation of the solvent will. The solution is poured out into a thin head, from which the solvent contained therein is removed by evaporation ■ or evaporation. For this purpose, the Solution B.B

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standing or moving base »depending on the surface, poured and made into a thin piim with the help of a rakela worked out, which interacts with the document. Instead, a cooperating with the document can also be used Parbbefrlohtung used with the same effects be · Sioke of the elm thus applied can in Can be modified depending on the intended use of the membrane filter

From the solution applied or developed into a thin film, the solvent it contains becomes duroh natural Evaporation », so to speak, in a negative way, or instead separated by heating in a positive way« The evaporation · temperature should be set to less than 50 ° C · Palis nioht, there would be a reduction in porosity and occur in the mean pore size "

The remaining amount of solvent is reduced to less than about 15% by weight? » set. The PiIm is washed with water or methanol, which can dissolve the metal salt it contains in order to remove it. After this Wasohvorgang the membrane is dried in any known manner to finally obtain a final product, a daa Dioke of 50 - 500/1 has.

The porous membranes of the present invention thus prepared and finished are for practical use done «You can use it due to the pore opening sizes select “membranes with pore sizes from 0.01 to 0.1 / U

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are particularly for use as the main working element In suitable for an artificial kidney

When using the artificial membrane equipped with a porous membrane filter according to the invention, in contrast to the prior art, there is no need to use a circulating buffer solution Unity forms Daduroh results in a significant advantage and progress in this area of Xeohnik *

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Ea is an accepted fact that the rate of urine urination of waoaer or a similar aqueous liquid through a fine pore varies by four times the pore size when a single pore is considered alone and by the square of the pore size when it is assumed porosity of the membrane remains constant · Saher leads an increase of the pore size of 0.01 to 0.05 ^ 0 / u even if the porosity ale consistently assumed to be an acceleration of the Filtergesohwindigkeit 25faohe. Saher becomes duroh yer-

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Use of a sieve membrane filter according to the invention for a artificial kidney achieves that the dimensions are reduced considerably and the carrying capacity of the device is improved.

For porous membranes made in accordance with the invention, the rate of filtration has been measured with different pore sizes for blood filtration; Then the various filtrates have been analyzed «It was found that a ratio of the albumin concentrations of the original blood and the filtrate of 10015 with an average pore size of 0.01 λλ was achieved Ratio changed in the direction of the unit "In these experiments the sole flow rate of the blood to be tested was set to about 200 ml / min."

These blood filtration attempts have also been found to give a significant amount of unexpected selective filtration performance. Table I shows various concentration ratios of the substances contained in blood albumin before and after the filtration, which have been measured in an experimental example in which human blood was carried out using a porous cellulose acetate membrane according to the invention with an average pore size of 0.10 × k and a porosity of 76 # has been filtered «

Table I shows that protein is almost completely absent the membrane according to the invention goes hindu, while urinary

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eüure-Stiokstoff in the blood of an extraordinarily seleotiven Has been subjected to filtration · Such filter properties are of course extremely convenient and desirable when the membrane is used for an artificial kidney of the butterfly type will·

From the foregoing it appears that an artificial kidney, which has a porous membrane according to the invention with an average pore size of 0.01 to 0.1Ou as a filter, the parallel is arranged for the flow direction of the blood to be purified, has the following advantageous features in comparison to excessive devices!

1 «Essentially no promotion of pore clogging ·

2 · The possibility of using an effective porous membrane, the mean pore size of which is about lOfaoha the mean particle size of the substance to be filtered, resulting in the Filtrationsgesohwlndigkeit to about the lOOfaohe is increased

3 Selective filtration performance in relation to the substances to be filtered

4 · Can be designed for a miniaturized, portable and still effective artificial kidney

Several preferred embodiments of an artificial kidney of the Fi3, tert type, for the porous membranes according to the invention are shown in Figs. 8-11 «

BATH ORIGINAL

- 34 -

609883/0451

They Pig 8 and 9 show a first embodiment in the form of an artificial kidney of the flat type In dleoer Embodiment are a blood inlet tube 11, a frame 12, an outlet pipe 1? and a pair of supportive and protective Grid 14 provided for the corresponding membranes 15 » which are arranged parallel to each other

In operation, the inlet tube 11 is connected to a patient's artery, which is not shown, while the outlet tube 13 is connected to the patient's vein, which is also not shown will·

With the help of the blood pressure, waste substances contained in the blood are filtered out through the membranes or gas subscription center 14 serve to prevent excessive deformation of the membranes 15 "which are exposed to blood pressure" at the same time they protect the membranes against mechanical damage from the outside *

Fig. 10 shows a second embodiment of a cylinder type artificial kidney. The apparatus of J ¹ Ig. IO has a blood inlet line 21, an outlet line 22, a pair of porous membranes 23 according to the invention, seals 24 "an outer cylindrical housing 2.5 and an inner hollow cylinder 26"

During use, the blood flows in the direction shown by several solid arrows. «The Piltrat is flowing naoh Durohgang duroh the pores of the membrane in the duroh

ORIGINAL BATHROOM - 35 -

609883/0451

direction shown by dotted arrows,

11 shows a further embodiment of a cylindrically shaped kunetliohen kidney, which can be used as a combined illustration and Osmosis type is carried out. The device is united with one outer cylindrical Gehüuoe 31 »an outer hollow auxiliary θ * cylinder 32, which has an outlet for a circulating buffer solution, an inner hollow cylinder 33 »of an iUllsohioht 34 "which is arranged in the interior of the inner cylinder" a pair of porous membranes 35 'which are parallel to each other arranged are »Diohtungen 36» a blood inlet 37 »a filtrate outlet 33» an inlet for the circulating buffer solution 39 »an outlet 40 in the inner cylinder for the buffer solution (this outlet can serve as an outlet for the piltrate» if the device is used exclusively, in the form of a filter), and an outlet, 41 in the outer cylinder for the buffer solution (this outlet can serve as a filtrate outlet if the device is also in the form of a filter is used)

In operation, the inlet 37 is connected to a patient's artery and the outlet 30 is connected to the patient's vein. In the absence of a buffer solution, waste substances contained in the blood pass through under the influence of blood pressure the membrane 35 and fine, not shown and on the Outside surface of the inner cylinder 33 formed Iitingorinnen hinduoh and are removed through the outlet 41 In the presence of a circulating buffer or osmosis fluid, the connections are made so that between

., -, _rr,, . , _R.,. , BAD ORIGINAL

a countercurrent relationship is established between the two fluids is · For this purpose the inlet and the outlet for the buffer solution are formed at 39 and 4-0 · The buffer liquid is, as usual, circulated under negative pressure.

A feature of the device naoh Pig · 11 is · that, if required, by using the buffer liquid a faster and accelerated removal of waste materials and aqueous components from the blood is enabled. Usually the blood can be used without using the buffer liquid be filtered «The inner cylinder 33 acts as a support for the membrane and is on its outside with fine Longitudinal channels for guiding the filtered substances from "formed" when using the buffer liquid, these are used Grooves for washing the inner membrane surface with the liquid.

Various numerical examples for the porous membrane according to the invention and for the method are given below their production will be given first of all in the following used. Terms defined and explained

The pore (opening) iorm and the pore diameter, which appearing on both surfaces of the membrane can be observed by means of a scanning electron microscope definitelyο

The pore (or opening diameter "") - Verhältnie is the relationship between the Porendurohmeasör in the front for Porendurohmeseer at the rear OCE membrane is wid

609883/0451 _B ^ OB.G.NAL

determined from the microscopically observed results «

You porendiohte is made by counting the actual pores »

which have been observed through the electron microscope, and after calculation by a corresponding multiplication

2 per om determined

The porosity or the pore ratio is calculated according to the following formula

Porosity ($ 0-1 - ac 100

2ψ means the visible view of the membrane and P_ the view of the cellulose acetate.

The tensile strength is given for a membrane sample 5 mm wide and 5 om length, held at one end and below room temperature at the other end (25 0) is charged »whereby the determination refers to the fact that a Bruoh within 5 seconds of the introduction the load occurs.

Si · dynamic elasticity is determined by using the test device "Vibron SSV-II ¹¹ , which is manufactured and sold by the Japanese company Τ0Ϊ0 SOKKi KK, the test being carried out at a frequency of 110 Hz and 25 ⁰ O ·

You will measure the speed of piltration Filtrate amount per cell unit of the membrane and per unit of time with an applied pressure difference of 700 mmllg certainly*

Your ability to tiltrate is measured by measuring the amount of piltrate determined at a pressure difference of 700 mmHg «beginning

- 38 -

6 0 9 8 8 3/0451 ^{BAD 0RIGINAL}

a?

with the initiation of the filtration, in which the relationship between the rate of filtration and the rate of flow shows a linear characteristic, and ending at a point in time to which this relationship suddenly and merklioh from the deviates linear characteristics, with a dispersion of styrene / butadiene gumraimiloh as the filtration liquid Used in water with a concentration of 50- $ 00 ppm · The sieve juice is duroh the formula V / V ^ determined »For this purpose, first the filtration speed V _{£ is} determined on a porous membrane. Then the same membrane is pressed on a press machine with a pressure of 800 kg / om at RO ⁰ O for five minutes determined by the membrane pressed in this way «

example 1

250g »100g and 45g cellulose acetate with a degree of acetylation of 54 # were each dissolved in 1000 ml acetone« 600 ml methanol were added to each of these solutions »Then 200, 80 and 36 g CaCl ₂ '2H ₂ O, respectively, were added to these solutions and The solutions were applied to a level, polished glass surface using an Ubliohon applicator device. Then the acetone solvent was spontaneously ^{evaporated at 25 0} O under 60 ° S relative humidity. After 10 minutes after solvent evaporation, the membranes formed were peeled off the glass plate and placed in immersed in a methanol or water bath for cleaning and

lioh dried

5AD ORIGINAL

- 39 -

809883 / 0451-

The diolcenes of these membranes were 300 u, 150 u and 80 u.

The first and third porous membranes made from the solutions with. 250g and 45g of acetate, respectively, were examined on a scanning electron microscope, see the Piß. 1? 14 and 15-16, FIG. 13 shows an electron microscope photograph with 8000x magnification of the front side of the first membrane and FIG. 14 shows a corresponding view in 2500x magnification from the reverse side of the same membrane. The pore openings each show smoothly curved, round opening shapes the front ₍ and on the reverse side, too, each opening shows a smoothly curved , essentially round shape

^ n Figs. 15 and 16 the third membrane is shown, which has been produced from the solution with a lower acetate concentration of 4 »5% by weight» Die Poreneraoheinung is essentially similar to that of a common mem-

bran · On both sides of the membrane the pore shape is very irregular "so that this membrane is unsuitable for use as a sieve membrane filter". Fig. 15 shows the front and FIG. 16 the rear side of the membrane, in each case in a 4000faoh magnified electron microscope photograph.

The various physical properties of these membranes are summarized in Table II

Example 2 Oellulose acetate having a degree of acetylation of 60ji

609883/0451 BAD OHIGINaZ

dissolved in a Löaemittolgoaiöoh made from methylene chloride and methanol. Häherοs is given in Table III. Metal salt and cyclohexanol were added to the solution as indicated, and a porous membrane was made from it manufactured in a similar manner as above.

The composition of the for the preparation of the porous Morabran The liquid used and various physical properties of the membrane are also given in Table III listed.

Example 3

125 g of cellulose acetate with a degree of acetylation of 54-7 »were dissolved in 1000 ml of acetone, and 250 ml of methanol and 625 ml of cyclohexanol were further added to the solution. 100 g of metal salt, as indicated in Table IV, was added to the solution. The solution was then applied, the solvent evaporated, the membrane washed and dried in a manner similar to that described in Example 1. The various metal salts used and the various physical properties of the porous membranes thus produced are also given in the table. Furthermore, comparative examples are given in the table which have been produced using TeBr., SnCl ₂ and Ba (CH ₅ COO) ₂ «

Example '4

125g Gellulooeazetat with a degree of acetylation of 54? »

ml ÄS9 ^ © s gei§ © 1j0 w &@> (! © 2? S ^ SMSig TOS ¹ «!! © ferae2?

883/0 k SI

22652A3

250 ml of methanol and 375 ml of n-butyl acetate added As indicated in Table V, CaBr _{2 was} added to the solution, and the solution was applied to the intestine, the solvent was evaporated and the product was washed and dried in the same manner as explained in Example 1. Various physical properties of the porous membranes produced in this way are also listed in the table _{in relation to the amounts of CaBr 2 used.}

Comparative sample 5 contains a smaller amount of additive ₂ % 10% by weight based on acetate, which results in pore openings with a partially serrated shape, both on the front and on the outer side of the membrane.The porosity is unfavorable in this sample reduced to 30 ^ «

Example 5

125 g of cellulose acetate with a degree of acetylation of were each dissolved in 1000 ml of methylene chloride, tetrahydrofuran and azotone. 250 ml of methanol or ethanol or methanol were added to Biesen's solutions and 5 ml of deoalin. _{100 g of CaCl 2} * 2H ₂ O were added to each of these solutions. Bio solutions were applied, the solvent was evaporated, the product was evaporated and dried, as in Example 1. Various physical properties of the porous membranes obtained in this way are shown in Table VI

compiled*

ORIGINAL BATHROOM - 42 -

s 0 9 e e: / c ■, 51

Example 6

120g cellulose acetate with a degree of acetylation of were dissolved in a solvent mixture that consisted of 1000 ml of methylene chloride and 100 ml of methanol «In the same So three solutions were hergeutellt, which then methanol added in amounts of 300 ml, 900 ml and 1900 ml, respectively “In the pail of the solution bath with the addition of 1900 ml Methanol a noticeable phase separation occurred and only unusable porous membranes could be produced

_{120 g of CaCl 2} · 2H ₂ O and 300 ml of diphenyl ether were added to the solutions with a total amount of methanol of 100 ml, 400 ml and 1000 ml, respectively. The solutions prepared in this way were applied and the solvent was evaporated and the product was washed and dried as in the previous examples to produce porous membrane filters.

In the pail of the solution with a total amount of methanol of 100 ml, the membrane produced, however, showed a noticeably uneven pore distribution due to the phase separation of the CaCl ₂ which occurred during the membrane production step, which caused its precipitation. This membrane had to be discarded as unusable Solution with a total methanol content of 1000 ml that appear on both sides of the membrane

- 43 -

^: 809833/0451 ^BAD ORIGINAL

MO

Pore opening jagged round, so that this membrane (sieve * property 0.50) αϊο must be discarded unusable,

You of the rest of the solution with a total content of 400 ml Membrane made with methanol exhibited smoothly curved, substantially circular pore opening shapes on both Sides of the membrane, which are therefore usable as usable was

Example 7

125 g of cellulose acetate with a degree of acetylation of 54 # were dissolved in 1000 ml of acetone, whereupon 250 ml of methanol and further 125 g of CaCl ₂ · 2H ₂ O were added.

This solution was further each 500 ml of one of the ffable VII indicated auxiliary sweeteners added iodine these solutions were applied by applying, solvent evaporation, Waning and troubling as in the previous examples further processed

The relationship between the various physical Properties of the membranes on the one hand and the type of diluting solvent and additives added on the other hand are illustrated in Table VII.

Example 8

By dissolving cellulose acetate having a degree of acetylation of 54 #, solutions as shown in Table VIII were prepared and these solutions were made into porous membranes further processed according to samples 8 and 9 *

609883/0451 ^BAD ORIGINAL 44 -

Using these pattern membranes, artificial ones were made Nieron entopreohend Piß · IO produced. Table VIIII are essential for blood filtration this pattern 8 and 9 again.

Example 9

100 Q cellulose acetate with a degree of acetylation of ^v Ai » were dissolved in 1000 ml of acetone. 250 ml of methanol and 80 g of GaCl _2. 2H ₂ O and also 600 ml of cyclohexanol were added to the solution Versions processed further »Pig · 17 and 18 each show in 4000faohor magnification the front and the outside of the membrane when viewed with an electron microscope.

This membrane has been used successfully as a membrane filter last stage used for ion exchange the ϊ industrial production of ultra-pure water was used · The electrical resistance of the ion DUstausohwaosöra before the filtration with 15 χ 10 'ohm · ° mj the piltrate showed 100 χ 10 'ohm * cm. Multiple physical

Data for this membrane are given in Table X «

Example 10

100 g of cellulose acetate with a degree of acetylation of $ 54 were dissolved in 1000 ml of acetone. 250 ml of methanol and 80 g of CaCl ₂ * 2H ₂ O were added to the solution. 850 ml of cyclohexanol were further added to the solution and the solution was then processed into a porous membrane in the aforementioned manner.

609883 / 0A51

- Tables I - X -

- PATENT CLAIM) -ÖBIGIN * ¹ -

Table I.

Concentration in blood Concentration in albumin

Geeaat-Eiveiss-crowd Haric acid substance in the blood

uric acid Ha*

Often* 0.05 1.60 1.30 1.20 1.40 1.75 1.35

1.0 - 1.2

609883/0451

Table II

Acetate amount

250 g 100 ε
(Invention) (invention)

45 κ
(Comparison)

Pore opening shape

Y j smoothly curved - smoothly curved circular, · gene round, essentially strongly serrated side shape round shape

back

Smoothly curved, essentially round shape

11 η

very btark

jagged

shape

Porenöff "
tion

0 M.

front

back

O.O5 2.0

0.10 1.0

approx 0.2 approx, QA

Pore diameter,
relationship 40 10 approx. 2 Porosity % 76 77 78 Pore density, number
of pores / cm 72.5 χ 10 ⁸ 2 χ 10 ⁸ 5 x 10 ⁷ tensile strenght
dyn / cm 2.2 χ 10 ² 2.0 χ 10 ² 1.6 χ 10 ² Dynamic Elasti
city, dyn / cm ² 5.0 χ 10 ⁹ 1.5 χ io ⁹ 1.0 χ 10 ⁹ Filter speed
speed, ml / min. 0.5 9 20th Filterable
speed, ml / cm 15th 20th 30th ßiobo property 0.89 0.80 O.5O

609883/0451

Tabollo III . \ <i ~

Huotor 1 riusstcr 2 riuoter 3 * lluGtor 4 * solution Acetnt, £ 250 100 100 ao 100 120 the Mothylon- ₁₀₀₀
Chloride, ml ^ΊΟϋϋ 1000 1000 **
# · 1000 ** tongue Mothanol, ml 250 80 160 0.08 240 0.15
0.75 ens et Cyclohexanol 2qq
ml 0 0 10 0 5 I together Kind don Mo- M ₀ ^ ₁₁
talloalzoo ^ilßW1 2 CaCl ₂ .2H ₂ O 52 80 ZuGOöotzto
Monco metal 200
onlz c 40 2.4x10 ⁸ 2.0 χ 10 ⁸ Porcnt "Vordres?« · _{0 #}
öff- ooito
nuncß— return ,,
form ooito **
· * 3.0 χ 10 ² 2.0 X 10 ² Pore front. 0.09
fyt \ . XXUwIvO · cL · \ J 0.04
1.0 4.0 x 10 ⁹ 2.0 χ 10 ° Pore diameter - p _O
and relationship 25th 0.87 0.75 Porooity% 73 42 Porondichto, _{2 2} ^ -q8 2.0x1O ⁸ Module d.Zuß- 5
fectiGkoit 2.5x10 ^
dyn / cm ² V Dynamic _Q
Elioticity 3.3x1O ^v
dyn / cm2 4. 9x10 ⁹ SieiDoigensch. 0.85 O.9O

Note 1 ·. ·· OaCl ₂

** ··· smoothly curved, white 1. round shape

609883/0451

Tube parts IY -

Yerv? Ended rietallsala

Physical properties

TeBr *

SnCl ₂

LiCl

Ba-

AL

(CH ₃ COO) ₂ (CH ₃ COO) ₂

ZnSO,

CuCl.

CaCl

Pore yorders.
offngs.
Form rucks. *
* ♦ <0.01
2 * ·
* · *
* · ♦ * · · * ♦ *
♦ ♦ ♦ · * » Pore Yorders
open.
μ Eucks. 2 7200 0.30
2 <0.01
about 2 0.15
1-5 0.20
1.4 0.10
2.0 0.12
1.4 0.45
1.8 Por endurchia. -
relationship 7200 65 6.6 7200 10 7-0 20th 12th 4.0 Porosity, % 60 - 75 .35 60 65 72 63 78 Pore density, no.
of pores / cm? - - 1.OxIO ⁸ - 3X10? 6.5x10 ⁷ 1.2x10 ⁸ 5x10 ⁷ 2.4x10 ⁸ ^ Tensile strength, dyn / cQ ² - - 1.4x10 ² - 2.4x10 ² 2.2x10 ² 1.7x10 ² 2.8x10 ² Dynamic Elasti
city, dyn / ca ^ - ** ♦ · 3.1XiO ⁹ - 6 XiO '' 4.5x10 * 3.0x10 ^ 4.1x10 ⁹ 2.8x10 ^ Piltergeschvindig—
ability, al / ain. * ♦ * · ♦ * · ♦ 60 ♦ ♦♦ · 8th 10 50 30th 80 PiltratioasfnhisTc. ♦ · ♦♦ - 33 ♦ · »· 50 40 25th 20th ./t C Sieve property - 0.80 - - 0.71 0.65 0.77 0.78 0.8 Sun

Note: · ... 2 to observe a pore; * ♦ ·. · Smoothly curved, mostly round pora ··· fi.e-r.4nrp-ri | g-fg serrated round shape; * · ** ... almost ITuIl

Table V

Additional row CaBiu Muotör 5 sample 6 Mustor 7

(Comparison) (invention) (invention)

Phys. characteristic

12.5 g 50 s 100 6

Pore opening front,
form back. * ** * ·
· * Pore opening front.
0, μ back. 0.05
1.0 0.09
1.2 0.09
1.8 Pore diameter ratio 20th 13th 20th Porosity % 58 59 78 Pore density, number
of pores / cm 1.2 x10 ⁷ 4.8 χ 10 ⁷ 6.2 x10 ⁷ Dynamic Elastizi
strength, dyne / cm ² 9.9 x10 ⁹ 7.0 χ 10 ⁹ 3.2 x10 ⁹ 7 filter speed «
speed, ml / min. 0.1 3 11

Noteι · ... Circular, but partly jagged;

•• ... smoothly curved, essentially round shape

609883/0451

Tnbollo VI

Main solvent Methylone
chloride *
* Acetone Phys. properties
Thinning solvent - tetrahydro
• furan 0.20
1.0 Methanol /
Docalin Porcnöffngs .-- Front ooite
form back Methanol / ethanol /
Decalin decalin 5.0 *
* Pore openings - front
0, η back *
* 70 0.45
1.5 Pore diameter ratio 0.35
1.5 5.0x10 ^ö 5.5 Porosity % 4.0 5.OX1O ⁹ 76 Pore density, number of
Pores / cm 72 0.7 ^ 2.2X10 ⁸ Dyii ami echo elasticity,
dyn / cm 2.75X10 ⁸ 2.5x10 ⁹ Siebeigenechaft 5.2 3dO ⁹ 0.75 0.69

Note »* ··· smoothly curved» essentially round shape

609833/0451

Table VII

Thinner, solvent
Physical property Pore opening form Pore opening ^ u
Front. Bucks. Fronts.itäcks. 2.0 Pore diameter
relationship Porosi
activity % Pore density ₂
Δηζ. d. Por en / crT Dynanic
Elasticity ρ
tat, dyn / cn Xthanol ♦ · O.5O 2.2 4.0 78 3.0 χ 10® 2.0 χ 10 ⁹ Isopropyl alcohol • · O.45 2.0 4.9 77 3.O χ 10® 2.2 χ 10 ⁹ σ> H-butyl alcohol 0.35 2.2 . 5-7 77 2.8 χ 10® 2.8 χ 10 ⁹ 098 Sucrose plus
Vasser (2 + 1; 0.55 2.1 4.0 76 2.9 χ 10® 2.8 χ 10 ⁹ GO
CO Ethyl acetate * w O.3O 1-5 7.0 69 2.9 χ 10® 3.1 χ 10 ⁹ O Tetralin • 0.48 1.8 7-2 70 3.1 χ 10® 3.1 χ 10 ⁹ cn Methylcyclohexane * 0.46 1.8 3-9 74 3.1 χ 10® 2.9 χ 10 ⁹ Ethyl ether • ♦ O.45 1.7 4.0 76 3.1 χ 10® 2.9 χ 10 ⁹ Dinethyl phthalate 0.33 1.3 5-2 66 2.8 χ 10® 3.2 χ 10 ⁹ Diethyl phthalate • · O.32 2.0 4.1 67 2.8 χ 10® 3.1 χ 10 ⁹ Dibutylphthal at 0.39 5-1 76 3.O χ 10® 3.0 χ 10 ⁹

Note: · ... smoothly curved, essentially round shape isj

Table VIII

Hubter

Cough 9

Acetate, s
Azοton, ml Hothanoi, ml CaOl ₂ . 21I ₂ O, β cyclohexanol, ml

150 1000 250 180 500

250

1000 700 250

Pore opening front
form back * * Pore opening front
0, u back 0.08
1.9 0.07
2.1 Pore diameter ratio 20th 50 Porosity % 76 76 Surface density, number of
Pores / cm ** 50 χ 10 ⁸ 50 χ 10 ⁸ Tensile strength, dynes / cm 2Λ χ 10 ² 2.5 x 10 ² Dynamic elasticity, dyn / cm 2.7 x 10 ⁹ 2.9 x 10 ⁹ ITilter speed, ml / min 10 6th Filtration capacity, ml / cm ² 50 52 property 0.88 0.89

Noteι * ... smoothly curved, essentially round shape

Tables IX -50-

Poroe membrane
Blood ^ JTilter conditionon template 0.5 8 pattern 9 BLOOD FLOW CONVERSION SPEED, ml / min. 160 19.3 160 Blood pressure, mmllß 160 4.8 160 Entry blood pressure, imaHs 100 165 100 Auoeangs blood pressure, ml 220 79 220 Consumption of blood before attempt Total protein, g / dl 7.2 7.2 Urea nitrogen, mg / dl 16 16 Ilarnoüuro, mg / dl 6.0 6.0 Nq, M.Eq. / dl 152 152 Cl ₁ M.An./dl 80 80 K, M.Xq./dl 5.9 5.9 Ca, M.Eq. / dl 6.4- 6.4 Mg, M.Eq. / dl 1.9 1.9 Increase in blood after attempt Total protein, g / <H 7.2 7.2 Hornetoffnitrogen, mß / äl 10.5 11.0 Uric acid, n ^ / dl 4.2 4.2 ITn, M.Eq. / dl 14.9 150 Cl, M.Eq. / dl 71 73 K, M.Eq. / dl 5.2 5.2 Ca, M.Eq. / dl 5.3 5.2 Mß, M.Eq. / dl 1.9 1.9 FiltrationBßeachwindisskoit, ml / h cm 0.25 0.20 Blutzuoammonaotzunß, semosnen after Bossinn dos
■ ■! «■« ■■■■■ »■■■■■■■!«! ■ »■■■■■» ■■■■■■■■■ UaaaBKaa
Red blood cell count / cc 0 "Yorgucho
0 Total protein, c / dl 0.4 Urea nitrogen, mg / dl 19.4 Uric acid, mR.dl 4.9 Na ₁ m.Eq. / dl 169 Cl ₁ M.Eq. / dl 79

60988 3 / Ü4bl

Table IX - continued

Note t "M. Xq." “Molecular equivalent.

M.JIq./dl · Mugtor 8 Cheerful 9 κ, , M.Eq. / dl 6.7 6Λ Approx , M.Eq. / dl 5.9 5.9 Mg 1.3

609883/04 S1

Table X

Pore opening shape

Front clatt bid, im

borrowed round shape back "

Pore opening front
0, / a back side 2.9
0. ^ 6 Pore diameter - Relationship 6.2 Porosity % 78 Pore density, number of
Pores / cm 5.6 χ 10 ⁸ ρ
Zucfeetigkeiti Kg / om 1.8 χ 10 ² p
Dynamic elasticity, dyn / cm 2.3 x 10 ⁹ p
Filter drainage shrinkage, ml / min.cm 85 Piltration Ability, ml / om ² 60 Siobut property 0.76

S09883 / 0A61

Claims (5)

PATENT CLAIMS: Artificial kidney with a separating the inlet side of the blood and the outlet side of the filtrate Filter, characterized in that a membrane filter (14 ·) with pores with a diameter of 0.01 "to 0.10 / U in a blood stream parallel to it Is arranged flow direction, with a filtration causing the pressure difference between Entry and exit side of the membrane can be produced. 2. Artificial kidney according to claim 1, characterized by a planar arrangement of the filter membrane. 3. Artificial kidney according to claim 1, characterized by a cylindrical arrangement of the filter membrane. 4-, artificial kidney according to claim 1, characterized in that that the outlet side of the membrane can be connected to a buffer solution circuit. §09883 / 04 5 5. Artificial kidney according to claim 1-4, characterized through a cellulose acetate symmetry porous membrane filter made by dissolving cellulose acetate with a degree of acetylation of 20 - 65 »5% in one organic solvent with a weight ratio of 5 - 40% to the solvent and the addition of a thinner Solvent whose boiling point is higher than that of the aforementioned organic solvent, and furthermore, a metal salt whose metal component has an ionic radius of less than 1.33A is a member of group I - III of the periodic table and that is a ratio of 20 - 200% by weight to the acetate has, to the solution, so that a homogeneous solution is created, which on a polished flat surface to a thin film is applied, from which the solvent contained therein is removed by evaporation and the is converted into its gel state by micro-phase separation, whereupon what is contained therein Metal salt is dissolved out to form the porous membrane. S09883 / 0A51 SS Blank page