DE4211455C1 - Continuous prepn. of blod dialysis fluids - uses precise concns. of aq. concentrates tailored to patient's requirements - Google Patents

Abstract

Continuous prepn. of dialysis fluids having a precise compsn. with regard to an individual patient's requirements, comprises dilution of aq. concentrates to provide solns. contg. Na+ (0.127-0.141 mol/dm3), K+ (0.001-0.003 mol/dm3), Ca2+ (0.001-0.002 mol/dm3), Mg2+ (0-.0004-0.001 mol/dm3), Cl-(0.092-0.113 mol/dm3), HCO3-(0.035 mol/dm3), OAc-(0.002-0.003 mol/dm3), and opt. additives, e.g. glucose or other sugars (up to 3 g/dm3), monitored carefully so that the NaCl/NaHCO3 molar ratio is kept at 2.0-3.0. Equipment for supplying these solns. and monitoring the amts. of each concentrate is provided. USE - The equipment and process facilitate blood dialysis.

Description

The invention relates to a method and a device for Preparation of dialysis fluid for hemodialysis. The Hemodialysis as a medical treatment in patients including with impaired or lost kidney function its diverse technical aspects is in the Literature extensively described.

When hemodialysis for a treatment about 120-180 Liters of dialysis fluid needed. It refers to an aqueous solution of typically the following composition:

component Concentration (mmol / liter) Na + 139 K + 2.5 Ca ++ 1.65 mg ++ 0.6 Cl 111 HCO3- 32 Acetate- 3

In addition, the dialysis fluid glucose or other Contain sugars in a concentration up to 3 grams / liter.

Since the dialysis fluid in their application only by a thin membrane is separated from the patient's blood by the one intensive diffusive exchange takes place, it must not contain harmful admixtures and should be as germ-free as possible his.  

The problems of a suitable, the physiological requirements adapted composition of the dialysis fluid z. In detail in the book "Replacement of Renal Function by Dialysis "(Editor: W. Drukker, F.M. Parsons, J.F. Maher; Martinus Nÿhoff Medical Division, The Hague 1978) in the main section "The Composition of Dialysis Fluid" (Author: F. M. Parsons, A.M. Davison). It is known and will be out This publication shows that an adaptation of the Zu Composition of the dialysis fluid to the individual Disease condition of the individual patient to the essential medical needs counts.

Because of the large amount of liquid that lasts for 4 to 6 hours Treatment is required, it is appropriate to dialysis to prepare liquid at the place of use.

In principle, the simplest method is to work in one correspondingly large container with the required amount of water the weighed salts and other components. This Procedures in an early stage of hemodialysis was common, but requires a lot of time and manual work. It also causes big problems that Solution to keep sterile or at least low in germs.

Therefore, methods and devices have been developed in which the dialysis fluid by means of automatic dosing is prepared continuously or in smaller quantities. This usually happens in the way that a prefabricated liquid concentrate in a given volumetric ratio (by default, 1 volume concentrate to 35 parts of finished solution) is diluted with water. This procedure is commonly known by the term proportioning.

For this methodology, which is common today, will be from the pharmaceutical industry liquid concentrates in diverse Variations of the composition delivered. For economic Reasons, it is rare today, such Concentrates in the hospital to prepare.  

Proportioning method and corresponding devices for Preparation of dialysis fluid by dilution of liquid Hemodialysis concentrates are z. In the following patent public disclosures:

DE-AS 22 00 481,
DE-AS 20 55 333,
DE-OS 23 64 824,
DE-OS 21 40 677,
DE-OS 20 41 113,
US-PS 33 47 416.

Such known devices can be used either as so-called Central supplies should be designed with the aim of a larger Number of hemodialysis machines of a treatment center, e.g. In a hospital, from a central point via a line supply system with dialysis fluid, or they can as separate facilities for each dialysis machine be designed, if necessary, as an integral part of each Dialysis machine.

In the latter case, the single dialysis machine to a ver connected to the supply line for water, via the recycled and in its toxicological and bacteriological quality controlled water is supplied. The concentrate, the trade usual in containers of z. B. 10 liters of content is in each case provided in this container the dialysis machine and via a hose led into the container of the Device recorded.

A big advantage of this procedure is that for the treatment every single patient a particularly suitable concentrate can be selected according to the physiological condition of the patient and the peculiarities of the treatment Objectives. Such under the term  "Customization" known adaptation is generally considered important accepted.

However, this advantage comes with several disadvantages:

• a) For staff working on dialysis centers, this means Transport of relatively heavy concentrate containers (typ. 10 kg) a considerable burden.
• b) The storage of different concentrates in such large containers requires considerable effort. For one Dialysis station with 20 treatment stations is the typical Stock quantity for a week in the order of 200-300 containers.
• c) residues of unused concentrate, which after the Treatment in the container are left out normally not used for hygienic reasons become. The removal of these remnants, which are quite up can be up to 30 percent of the actual requirement quantity, actually means a waste and poses beyond that a not inconsiderable environmental impact represents.
• d) The used empty containers, which are usually are canisters of high quality thermoplastics, are according to the prior art and under Berück consideration of economic / organizational criteria for not reusable for the same purpose. Your repatriation in the raw material cycle through recycling is however also not a very economical process.

In addition, complicating the fact that the dialysis fluid only with a few restrictions from a single one Solution concentrate can be produced. The concentrate is in fact stable only if it contains no bicarbonate, d. H. if as secondary anion after chloride acetate instead of the physiological per se more suitable bicarbonate is used. That too Today widespread use of acetate in dialysis In this respect, liquid is only considered as a technical conditional remedy and is not optimal from a physiological point of view. For differentiation  you use the name for this form of dialysis Acetate dialysis.

The physiologically generally considered more favorable so-called Bicarbonate dialysis, in the bicarbonate (HCO₃-) as a secondary Anion after chloride is present in the dialysis fluid and at most small amounts of acetate used as a stabilizing additive requires the use of two separate concentrates, namely a bicarbonate concentrate, usually in Form of a pure sodium bicarbonate solution, and a concentrate the other solution components, being the latter the term "acidic bicarbonate hemodialysis concentrate" common is. This designation goes back to the fact that this concentrate usually a small stabilizing additive free Acid (mostly in the form of acetic acid) contains. The mentioned Designation can also give rise to misunderstandings, because the so-called "acidic bicarbonate hemodialysis concentrate" contains no bicarbonate itself. Concentrates that Bicarbonate and at the same time the essential components of calcium and magnesium, are not useful to produce because in them calcium and magnesium in the form of carbonates as insoluble Dregs would precipitate. In bicarbonate dialysis Thus, for reasons of pharmaceutical stability, the Bicarbonate concentrate separately from the so-called "acidic" Kon concentrate of the other components of the solution (including calcium and Magnesium salts), and those for the bicarbonate Dialysis provided hemodialysis machines must be two separate Proportioning facilities for these two concentrates be equipped.

The risk of precipitation of carbonates arises in this Procedure only after mixing the components. She is at However, hemodialysis is only of minor importance since Ver duration of the finished dialysis solution in the piping system of the Hemodialysis machine including the dialyzer only in the Order of magnitude of about one minute. Much more critical this problem is in peritoneal dialysis, in dialysis solutions of similar composition into the abdominal cavity of the patient  be filled and remain there for up to 12 hours. In DE-OS 39 17 251 is proposed with regard to this, the pH Value of bicarbonate solution fraction by adding acid below 7.6, as this causes the tendency to precipitate the mixing with the other solution components ver. Ver is reduced. As a variant to this is also the possibility provided, the acid in the form of a separate acid solution be and only immediately before use with the Sodium bicarbonate solution to mix. This method or its Variant could also be found in basic bicarbonate hemodialysis However, it is there because of the mentioned different conditions of use of lesser usefulness.

Another problem of bicarbonate hemodialysis in the previously in practice usual form is that the commercial concentrated bicarbonate solution, the so-called basic Bicarbonate hemodialysis concentrate, not autosteril. The Bicarbonate concentrate must therefore be sterile with increased care produced and sterile until consumed in suitable containers be stored. With regard to this problem, WO 81/03 180 proposed to use sodium bicarbonate at the place of use by combining sodium carbonate (soda) with chlorine water to produce acid (hydrochloric acid) and / or acetic acid, wherein Both the sodium carbonate solution and the acid in first separated, autosterile concentrates provided should be. This method eliminates the mentioned problem, but requires a considerable additional equipment Effort for the proportioning of the components. In particular is a fail-safe regulation and monitoring of the pH value the generated solution necessary, since a malfunction of Pro portioning devices for the strongly basic or strong acidic solution components to immediate severe damage of the patient. This may be a major reason be that this procedure so far no entry into practice has found.  

In view of the above handling and storage Today, it is common practice to concentrate on a central concentrate supply. This is parallel to the Wasserver supply network to a concentrate supply network with taps the individual dialysis stations for connecting the dialysis machines Installed. This concentrate supply network is out Concentrated large containers of 300-1000 liters content. This large container installed at a convenient location are ordered by the contracted pharmaceutical company in Exchange service as needed.

In the case of bicarbonate dialysis, the concentrate supply network however, be carried out in duplicate to avoid the bicarbonate Concentrate and the "acid" concentrate of the remaining solution components to be supplied separately to the dialysis machines.

With the process of central concentrate supply omitted the mentioned transport and storage problems for the Concentrate within the dialysis station, which are bulk containers reusable, and the residual amounts of concentrate that may be have to be discarded are comparatively very low.

A serious disadvantage of the central concentrate supply However, so far is that an individual adaptation of the Together to the needs of the individual dialysis patient is no longer possible because of a concentrate supply network Only one type of concentrate can be distributed in each case. The doctor is therefore forced to use a "medium" concentrate composition choose the needs of a hypothetical "average patients. "Because of very different views about the correct composition of the concentrate for the "Durch patients "is the pharmaceutical industry forced, even for the central concentrate supply in large Contain a variety of different composite concentrates to produce and keep ready so that part of the conceivable rationalization effect is lost again.

The invention was based on the object, a method and a to provide for its implementation suitable device in the said disadvantages are at least largely avoided.

This object is essentially achieved by the main claim specified feature combination solved. Further embodiments emerge from the dependent claims and the following Description of exemplary embodiments.

The drawings belonging to the description shows

Fig. 1 is a schematic representation of a hemodialysis device with means for preparing the dialysis fluid according to the invention,

Fig. 2 is a schematic diagram of another device for the dosage of the serving for individual adjustment additive concentrate,

Fig. 3 shows the functional diagram of a device for the supply of a dialysis machine with a dry concentrates produced from base for separate feeding of dialysis solution serving for individual adjustment of the liquid additive concentrate,

Fig. 4 shows the scheme of a device for hemodialysis with additional devices for the disinfection / sterilization,

Fig. 5 shows the scheme of a device for supplying several hemodialysis machines with a product obtained from dry substances basic concentrate and metering devices for the individual additive concentrate to the individual dialysis machines.

An essential measure according to the invention is instead of a concentrate of individually matched together use at least two concentrates, namely (a)  a quantitatively far more prevalent, in terms of its together uniformly defined basic concentrate of constant Amount ratio of the solution components and (b) an additional Concentrate of individual to certain typical physiological Situations of patients adapted composition, in the following referred to simply as "individual concentrate".

It is included that the basic concentrate in turn by to replace two partial basic concentrates, as far as the pharma ceutical durability requires this.

In a further embodiment, the invention provides that the Basic concentrate as solution components only sodium chloride and Sodium bicarbonate contains or by two partial basic concentrates is replaced, one of which as a solution components mainly Sodium chloride and a minimum of sodium bicarbonate, the other as solution components mainly sodium bicarbonate and a maximum of low sodium chloride contains.

For the latter embodiment provides an advantageous next formation of the invention, the two partial basic concentrates as Dry concentrates, waiving the water content to use.

Example 1

The following concentrates are used:

a) First partial concentrate (NaHCO3 concentrate):
1 molar sodium bicarbonate solution

b) Second partial basic concentrate (NaCl concentrate):
3.22 molar sodium chloride solution

c) individual concentrate  with the following range of variation of the solution components (Data refer to 1 liter of the individual concentrate):

0-2450 mmol Na +
175-525 mmol K +
175- 350 mmol Ca ++
70-175 mmol Mg ++
0-3675 mmol Cl-
350-595 mmol acetate
0-350 g of glucose (as monohydrate) and / or sorbitol.

The Proportionierungseinrichtung works so that to 100 liters the finished dialysis fluid following concentrate volumes attributable to:

NaHCO3 concentrate: 3.50 liters,
NaCl concentrate: 2.86 liters,
Individual concentrate: 0.57 liters.

As a result, depending on the composition of the individual concentrate, a dialysis fluid with the following concentra tion areas:

That for a total of dialysing fluid of 180 liters required concentrate amounts are:

NaHCO3 concentrate: 6.3 liters,
NaCl concentrate: 5.1 liters,
Individual concentrate: 1.0 liter.

Even for such a large Dialysierflüssigkeitsmenge that already the upper limit of the need for a normal dialysis treatment reached or exceeded, so after this Procedure one liter of the individual concentrate.

The two partial basic concentrates are in a dialysis station meaningfully, as in many dialysis stations customary, supplied via a central concentrate supply. The Individual concentrate, on the other hand, can only be considered in view of its low level Quantity readily from the practitioner to the dialysis machine be transported, as well as other materials for the Implementation of the treatment will be needed.

There are considerable advantages associated with this approach: it exists extensive freedom in the individual adaptation of the Composition of the dialysis fluid to the requirements of the individual patient, since the above-mentioned range of variation covers and meets all relevant needs Demand can also be extended. The effort for handling, Transport and storage is compared to the introductory described handling of canisters relatively low. The possibly to be destroyed residual amounts of the individual concentrate are much smaller, and also the recycling of the essential smaller containers in the form of bottles or bags, as in  the infusion technique are used, offers significantly lower Problems.

Another important advantage is that the basic concentrates are uniform. This will disposition and storage simplified, which also leads to corresponding cost reductions should.

A particularly suitable for carrying out the method according to this example apparatus is shown schematically in Fig. 1 represents.

1 denotes a hemodialysis machine of conventional design for bicarbonate dialysis. Components of the hemodialysis machine that are of minor importance for the description of the invention are not taken into account in this schematic representation. The dialysis machine has a built-Proportio ning device. In contrast to a dialysis machine for acetate dialysis, which usually has only one concentrate connection, the dialysis machine for bicarbonate dialysis shown schematically here has a first concentrate port 3 for the supply of pure bicarbonate concentrate and a second Kon zentratanschluß 4 , on the after Prior art, the concentrate of the other solution components is supplied. Notwithstanding this, however, according to the invention, a pure sodium chloride concentrate is supplied via this connection 4 . The water necessary for diluting the concentrates flows via the connection 2 . The said components flow into a mixing vessel 5 , which has a heating device 6 for heating the liquid to body temperature. A volumetric conveyor 7 delivers the liquid from the mixing vessel 5 from. The controller 8 regulates the function of the metering pumping 9 and 10 depending on the flowing through the conveying device 7 liquid volume so that the over the concentrate ports 3 and 4 inflowing concentrate volumes are keitsvolumen in a defined ratio to the forwarded by the conveyor 7 liquid. This also defines the amount of water flowing in via the water connection 2 .

The activity of the proportioning device is monitored according to known prior art by continuous measurement of the electrical conductivity of the liquid formed by diluting the two partial basic concentrates. The liquid flows for this purpose through a conductivity cell 11 , which is connected to a limit value monitoring device 13 .

If the measured electrical conductivity and thus the con centration of the liquid formed by diluting the two partial Grundkonzentrate within the allowable limits, the liquid passes further in the direction indicated by the arrow A through the valve 12 to the terminal 14 and from there via the Line 15 to the dialyzer 16 . The effluent from the dialyzer 16 spent dialysis fluid flows through line 17 , the port 18 , the line 19 and the port 20 in the drain. If the conductivity of the liquid is outside the allowable limits, the valve 12 is switched over by the monitoring device 13 over so that the marked with the arrow A flow path is blocked and instead of the indicated by the dashed arrow B flow path is released. As a result, the flow through the dialyzer is interrupted, and the incorrectly proportioned liquid is directed into the drain.

The individual concentrate is introduced from a container 21 by means of a volumetric pump 22 via the line 23 into the line 15 leading to the dialyzer. The conveying speed of the pump 22 is determined by the drive controller 24 and adjusted so that the desired proportioning of the individual concentrate in relation to the total amount of dialysis fluid results. For monitoring the conveying activity of the pump 22 , a flow sensor ( 25, 26 ) can be provided. In case of a malfunction of the proportioning device for the two partial basic concentrates, which leads to the switching of the flow paths described above, the supply of the individual concentrate must also be interrupted. This is done in the scheme shown by a shutdown signal, which is transmitted from the monitoring device 13 via the control line 27 to the drive controller 24 on.

All necessary for the supply of the individual concentrate parts are expediently taken together to form a unit 27 , which forms a small additional device to the hemodialysis machine 1 .

The individual concentrate can also be introduced at another location in the leading to the dialyzer flow path, z. B. directly into the mixing vessel. 5 This is particularly useful in hemodialysis machines which have facilities for flow balance (eg, in accordance with DE-PS 28 38 414), so that the supplied volume of the individual concentrate is included in the balance.

Another advantageous embodiment of the facilities for the supply of the individual concentrate is shown in the scheme Fig. 2. The line connection 2 of the hemodialysis machine 1 , which is normally intended for connection to the water supply, is used in the present case according to the invention for supplying a solution formed by mixing water and individual concentrate, as described in more detail below.

According to a preferred embodiment of the invention, the metering device 30 is inserted for the Indi vidualkonzentrat in the line 29 , which normally serves the water supply to the terminal 2 of the dialysis machine. The water pipe is interrupted for this purpose. About the line section 29 a of the metering device 30 flows to pure water, while the solution formed by adding individual concentrate to the water passes through the line section 29 b to the terminal 2 of the dialysis machine.

The individual concentrate is introduced from the reservoir 21 via the line 31 , the pump 32 and the line 33 in the line 29 and mixes there with the section on the line 29 a flowing water. This leads to an increase in the electrical conductivity. The difference in the electrical conductivities before and after the feed point is detected by means of the appropriately arranged conductivity measuring cells 34 and 35 .

For a given composition of the individual concentrate and correct adjustment of the delivery rate of the pump 24 accordingly the intended mixing ratio, the conductivity has keitsunterschied a certain amount that is typical for the individual concentrate in question and can be assumed to be known. In order to achieve this setpoint of the conductivity difference, a controller 36 is provided, which detects the conductivity keitsunterschied between the two measuring points and compared with the setpoint and the drive speed of the pump 32 influenced so that the deviation between the ermit th conductivity difference and the setpoint conductivity difference reaches a minimum.

The typical for the individual concentrate setpoint of the conductivity keitsdifferenz may be adjustable by hand, z. B. by means of a keyboard or the like. In a further embodiment of the invention, however, it is provided that the reservoir 21 or a part attached thereto has a coding characterizing the desired conductivity difference and further sizes as required, which is read by a sensor 37 in order to transmit this information to the controller 36 . Optical or magne tables sensors that are suitable for such purposes are known in various designs.

example 2

The following concentrates are used:

a) First partial concentrate (NaHCO3 concentrate):
1 molar sodium bicarbonate solution

b) Second partial basic concentrate with the following solutions (Data refer to 1 liter of this concentrate):

3220 mmol Na +
35 mmol K +
35 mmol Ca ++
14 mmol Mg ++
3285 mmol Cl-
68 mmol acetate

c) Individual concentrate with the following range of variation of the solution components (details based on 1 liter of the individual concentrate):

0-2450 mmol Na +
0-350 mmol K +
0-175 mmol Ca ++
0-105 mmol Mg ++
0-3675 mmol Cl-
0-280 mmol acetate
0-350 g of glucose (as monohydrate) and / or sorbitol.

The Proportionierungseinrichtung works so that to 100 liters the finished dialysis fluid following concentrate volumes attributable to:

First part basic concentrate: 3.50 liters,
Second part basic concentrate: 2.86 liters,
Individual concentrate: 0.57 liters.

As a result, depending on the composition of the individual concentrate, a dialysis fluid with the following concentra tion areas:

In the method according to Example 2, the advantages of the Example 1 preserved. In addition, increased security in the event of failure of the metering device for the Indi achieved full concentrate. If this metering device is not in Function, a dialysis fluid is still being produced, Although its composition is at the lower limit of the physiological Range is, but still no acute threat represents for the affected patient.

The second partial basic concentrate contains in principle the same Solution components such as the previously used bicarbonate-free ("acid") partial concentrate for bicarbonate dialysis, but in lower concentration to preserve the opportunity through Supply of specifically selected components via the individual concentrate the composition of the finished dialysis fluid to the individual requirements of the patient in the desired Way to adapt. Apart from the lower concentration Also differs the ratio of dissolved Salts in the second partial masterbatch according to Example 2 from the corresponding ratio in the previously for the Bicarbonate dialysis of common bicarbonate-free partial concentrates. Based on the mass of dry substances reaches the Total amount of potassium, calcium and magnesium salts in the second partial base concentrate according to Example 2 about 5 percent of Sodium chloride, while the corresponding ratio in so far common bicarbonate-free partial concentrates for the Bicarbonate dialysis is typically more than 6 percent.

For carrying out the method according to Example 2 are the same devices as used for Example 1 have been described.  

example 3

The following example follows example 1, however with the further embodiment that the two partial Basic concentrates at the place of use by dissolving the relevant Salts, namely sodium bicarbonate and sodium chloride won become.

When using individual concentrates with the same Variations of the composition as in Example 1 are then for 180 liters of dialysis fluid following salts as Dry substances needed:

NaHCO3: 530 g instead of about 6.6 kg of the corresponding concentrate,
NaCl: 960 g instead of about 5.6 kg of the corresponding concentrate.

Overall, this reduces the transport weight of approx. 12.2 kg to 1.49 kg, corresponding to about 8: 1. The amount of too additionally required individual concentrate for 180 liters dialyser liquid is still 1 liter.

A particularly advantageous device for carrying out this method is shown schematically in FIG . The dry concentrates are in two cartridges 40 (for NaHCO3) and 41 (for NaCl). By fine sieves or filter 42 at the inlet and outlet of the cartridges flushing of salt particles is prevented. Via a line 42 , the inputs of the two cartridges are connected to the water line. The saline solutions emerging at the cartridge outlets are discharged into the conduit 29 via the metering pumps 44 (for NaHCO 3) and 45 (for NaCl).

The addition of the concentrated salt solutions at the feed point 46 (for NaHCO3) or 47 (for NaCl) leads in each case to an increase in the electrical conductivity. The difference in electrical conductivity in front of and behind the feed point 46 is detected by means of the conductivity measuring cells 48 and 49 , in front of and behind the feed point 47 by means of the conductivity measuring cells 49 and 50 .

With the correct setting of the delivery speeds of the metering pumps 44 and 45 corresponding to the intended proportioning apply to the conductivity differences before and after the Zuführungsstellen certain constant values that must be complied with as setpoints. The delivery speeds of the pumps 44 and 45 are controlled for this purpose by the controllers 51 and 52 so that the respective measured conductivity difference with the corresponding target value of the conductivity difference comes into agreement.

In this way, the port 2 of the hemodialysis machine 1 to a NaHCO3-NaCl solution flows, which already largely corresponds to the final composition of the dialysis fluid, with the exception of the quantitatively small additional components contained in the individual concentrate. The individual concentrate is added downstream according to FIG. 3, in accordance with the arrangement shown in FIG .

In the arrangement of FIG. 3, the previously required internal Proportionierungseinrichtungen the hemodialysis machine 1 can be omitted. As a result, the internal structure of the hemodialysis machine can be considerably simplified, so that the additional expense for the additional equipment provided according to the invention is easily compensated. In addition, there is the advantageous possibility to connect to the line 29 b, which provides the NaHCO 3 -HCl solution, another similar hemodialysis machine 1 a (or more hemodialysis).

example 4

This example follows Example 1, but with the embodiment that in addition to the individual concentrate, by whose composition is an individual adaptation to the pa patient-specific physiological conditions, only a basic concentrate is used, which is essentially a  Solution of sodium bicarbonate and sodium chloride in water.

The following concentrates are used (subsequently changed):

a) basic concentrate with the following solution proportions, based on 1 liter of the basic concentrate:

1870 mmol Na +
1350 mmol of Cl-
520 mmol HCO3-

b) Individual concentrate with the following variation range of Solution shares (data referring to 1 liter of the individual concentrate):

0-2450 mmol Na +
175-525 mmol K +
175- 350 mmol Ca ++
70-175 mmol Mg ++
0-3675 mmol Cl-
350-595 mmol acetate
0-350 g of glucose (as monohydrate) and / or sorbitol.

The proportioning device dilutes the two concentrates so that for 100 liters of the finished solution following concentrate volumes attributable to:

Basic concentrate: 6.80 liters,
Individual concentrate: 0.57 liters.

The dialysis fluid thus obtained has the same choice of Individual concentrate the same composition as a dialysis liquid, which was prepared according to Example 1.

The quantities of the two partial quantities indicated in Example 1 Basic concentrates were chosen so that the usual Adjustment of the internal proportioning device of the hemo dialysis machines for so-called bicarbonate dialysis no change necessary is. This hitherto customary adjustment of the proportions  tioning device generally starts from the arbitrary one Agreement that dialysis concentrates 35 times the concentration of ready-to-use dialysis fluid should. This agreement could - historically - be divided be maintained as long as exclusively bi carbonate-free concentrates (with acetate instead of bicarbonate) used were. With the reintroduction of the physiologically cheaper However, bicarbonate dialysis did not just have to, as above set out the bicarbonate concentrate because of intolerance with the bivalent ions (Ca ++ and Mg ++) as a separate Concentrate to be fed, but it had to for the Bicarbonate concentrate also deviates from the factor 35 Proportioning be introduced. Cause for this is the relatively low water solubility of sodium bicarbonate, which has a permissible concentration of about 1 mol / liter limited. In the finished dialysis fluid a Bicarbonate concentration of 35 mmol / l is then a dilution to the 28.75-fold volume necessary and general common. This is also the case in Example 1 considered.

The method according to Example 4 are investigations with regard to the water solubility of a combination of narium bicarbonate and sodium chloride, with a molar ratio from NaHCO3 to NaCl of about 1: 2.6. It follows that with these solution components a stable, at least 14-fold Concentrate can be produced.

The method of Example 4 offers over the method according to example 1 additional advantages:

• a) If the basic concentrate is distributed over several treatments places over a pipe system is combined NaHCO3-NaCl-Grundkonzentrat only a simple piping system necessary while for bicarbonate dialysis according to previous Method (and also according to the method of Example 1) double piping system is necessary.  
• b) The proportioning device of the hemodialysis machine must - apart from the metering device for the individual concentrate - Only one metering device for the basic concentrate respectively.
• c) The combined NaHCO3-NaCl basic concentrate offers because its high saline concentration lower possibilities for an increase of bacteria than the otherwise for the Bicarbonate dialysis used pure bicarbonate basic concentrate. The significant hygienic problems otherwise with the Bicarbonate dialysis are thus eliminated in part.

The advantage mentioned under item (b) above means in practice that hemodialysis, previously only for the so-called acetate dialysis equipped and therefore only with one Dosing device for a concentrate are equipped, well with relatively minor external apparative additions as well can be used for bicarbonate dialysis, even with the general advantage of being able to change the composition of Dialysis fluid individually to the needs of the patient adapt.

A device according to the method of Example 4 is shown schematically in Fig. 4. 1 denotes a hemodialysis machine for acetate dialysis. Its internal structure differs from the hemodialysis machine shown in Fig. 1 for the bicarbonate dialysis essentially by the simpler Ge staltung the Proportionierungseinrichtung. There is only one Kon zentratanschluß 4 available. For metering the concentrate, the volumetric metering pump 10 , while the connection via the water supplied liquid 4 is metered with the volumetric pump 55 . Both pumps 10 and 55 are coupled together and have a common drive 56th This arrangement is just one example of the existing different designs of proportioning devices in dialysis machines for acetate dialysis. It is only important that such a device normally has only one concentrate connection.

Notwithstanding the previous application of such a device, however, the water supply 2 is not pure water supplied in the scheme of FIG. 4, but, similar to the order of FIG. 2, a solution generated from water and the individual concentrate, and the concentrate port 4 is not fed an acetate-containing total concentrate, but the com bined NaHCO3-NaCl-Grundkonzentrat according to Example 4.

In addition, the scheme according to FIG. 4 shows devices which serve for the disinfection / sterilization of the hemodialyzer and for closed lines, wherein the proportioning device for the individual concentrate is also advantageously used for supplying a chemical disinfectant. In a further embodiment of the invention are provided for this purpose:

• a valve 57 in the water supply line 29 a,
• - A locking pot 58 with free fall distance of the water in the water supply line to prevent backflow via the line 29 a in the water supply network. The blocking pot can simultaneously serve as a feeding point for the individual concentrate or for the disinfectant,
• a valve 59 in the water connection 2 of the hemodialysis device leading line 29 b,
• - A valve 60 which connects the line section 29 c between the locking pot 58 and the valve 59 with the discharge line 70 a of the hemodialysis machine,
• - A valve 61 between the drain line 70 a of the hemodialysis machine and the drain line 70 b of the overall arrangement.

The control and regulation device 62 assumes the functions of the controller 36 and additionally serves to control the valves 57, 59, 60 and 61 . For the purpose of disinfection / sterilization of the reservoir 34 is replaced by a container with a disinfecting / sterilizing agent. The sensor 34 detects the deviating coding of the container and accordingly activates the function program of the control and regulation device 62 suitable for sterilization / disinfection. A suitable functional sequence preferably contains the following steps:

The arrangement shown has the advantage that the disinfection / Sterilization also on the connected to the dialysis machine Lines extends, being due to the alternating use of parts of the device both for the supply of the individual concentrate as well as for the supply of the disinfection / Sterilization means considerable simplifications and possibilities result in extensive automation.

A central concentrate supply device for a larger number of hemodialysis machines based on Example 4 is shown schematically in FIG . Among the essential components of this arrangement include two solution container 80 a and 80 b with closable by cover 81 a, 81 b filling openings for filling weighed quantities of sodium bicarbonate and sodium chloride as dry substances. After filling the salts of the container lid is closed and by opening the relevant faucet 82 a and 82 b, the above given to give predetermined amount of water. The solution process for forming the combined NaHCO3-NaCl-concentrate can be accelerated by a stirrer arranged in the container 83 a, 83 b.

The two solution containers are for alternate use provided a quasi-continuous concentrate supply to enable. While in each case a container with concentrate for Supply of dialysis stations is in operation, can in the other Containers are prepared for the next batch of concentrates. The Container volume is typically of the order of 250-300 liters, corresponding to the daily requirement of a dialysis station with 20 hemodialysis machines and two dialyses per device per day.

The position of the three-way valves 84, 85 determines which of the two containers 80 a, 80 b is effectively connected to the ring line 86 . The taken at the bottom of the container in question concentrate flows through the three-way valve 84 and the line section 86 a to the pump 87th This promotes the concentrate in the main section 86 b of the loop with the connection points 90 a, 90 b, 90 c. , , for the concentrate supply of the individual hemodialysis machines. The excess recirculating concentrate passes through a pressure-retaining valve 88 , the line section 86 c and the three-way valve 85 in the respective container.

The setting of the pressure holding valve 88 determines the pressure prevailing in the main portion 86 b of the loop. Further details of a possible embodiment, for. As the application of multiple pressure holding valves to compensate for hydrostatic pressure differences in systems that provide dialysis equipment on different floors of a building, sterile filter for aeration of the container, automatic metering devices for filling the container and the like are in the scheme Fig. 5 not be taken into account. Also is simplified only single indicated at a closed hemodialysis device, wherein the supply of the individual concentrate selectively to one of the methods described above (Fig. 1, Fig. 4) can be carried out.

Claims (12)

1. A process for the continuous preparation of dialysis fluid, which is individually adapted to the physiological requirements of the individual patient in terms of its composition, by dilution of concentrates in a device for hemodialysis treatment,
wherein the composition of the finished dialysis fluid is selectable in particular in the following typical variation ranges. component Concentration (mmol / liter) Na + 127-141 K + 1-3 Ca ++ 1-2 mg ++ 0.4-1 Cl 92-113 HCO3- 35 (typ.) Acetate- 2-3 and the dialysis fluid may contain other additives, including glucose or other sugars in a concentration of up to 3 g / liter,
characterized by the separate continuous feed

• (a) at least one by far predominant, mainly sodium chloride and sodium bicarbonate-containing, of uniformly defined composition, wherein the sodium chloride content and the sodium bicarbonate content are in a molar ratio of 2.0: 1 to 3.0: 1, and
• (B) at least one individually adapted and selected additional concentrate, which provides the other components of the solution in individually adjusted concentrations, and the continuous dosage of these concentrates during dialysis according to the amount of continuously supplied water for dilution.

2. The method according to claim 1, characterized by the use of two basic concentrates, namely

• a first basic concentrate consisting predominantly of dissolved sodium bicarbonate in a manner known per se,
• - a second basic concentrate, which consists predominantly of sodium chloride dissolved in water and at most low additions of potassium, calcium and magnesium salts in the form of chlorides and / or acetates, the total amount, based on the mass of dry matter, less than 5, 5 percent of the amount of sodium chloride.

3. The method according to claim 2, characterized in that the first concentrate a pure sodium bicarbonate concentrate and the second basic concentrate is a pure sodium chloride concentrate is. 4. The method according to claim 1, characterized by the use a single, uniform basic concentrate that far predominantly of sodium chloride dissolved in water and Sodium bicarbonate exists. 5. The method according to claim 4, characterized in that the Basic concentrate has an addition of potassium salts whose Total content, based on the mass of dry substances, less than 0.5 percent. 6. The method according to any one of claims 1 to 5, characterized gekenn records that the basic concentrate at the point of use by dissolving one essentially of sodium chloride and sodium bicarbonate existing salt mixture is formed. 7. The method according to any one of claims 1 to 6, characterized marked indicates that the basic concentrates are at their point of use  Dry substances separated from each other by continuous dissolution be formed in the flow.   8. The method according to any one of the preceding claims, characterized characterized in that the amount of the individual additive concentrate is less than 1/8 of the total basic concentrate amount. 9. The method according to any one of the preceding claims, characterized characterized in that the second partial basic concentrate and / or the individual additive concentrate have an added acid. 10. Apparatus for carrying out the method according to claim 1 in the form of an additional device for a hemodialysis machine with built-Proportionierungseinrichtung, characterized by a in the water connection ( 2 ) of the hemodialysis machine leading line ( 29, 29 a, 29 b) inserted additional device ( 30 ) a pump ( 32 ), which in terms of its composition individually adapted to the needs of each treated patient additive concentrate from a storage vessel ( 21 ) continu ously in the connected to the water connection of the hemodialysis machine line ( 29 ) promotes. 11. The device according to claim 10, characterized by two in the water connection of the hemodialysis machine leading line ( 29, 29 a, 29 b) inserted measuring cells ( 34, 35 ) for measuring the electrical conductivity of the liquid flowing in the conduit, of which a conductivity measuring cell upstream and the other downstream of the feed point of the individual supplemental concentrate, and a regulator ( 36 ) connected to the conductivity cells for adjusting the rate of delivery of the pump ( 32 ) so that the measured conductivity difference reaches a predetermined set point for the particular additive concentrate used. 12. The apparatus according to claim 11, characterized by a with the controller ( 36 ) connected to the sensor ( 37 ) for reading a to the storage vessel ( 21 ) mounted, the setpoint of the conductivity difference for the additive concentrate indicating coding.