DE3200647A1 - METHOD AND ARRANGEMENT FOR PRODUCING A PYROGEN-FREE SOLUTION FOR MEDICAL PURPOSES - Google Patents

Description

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METHOD AND ARRANGEMENT FOR MANUFACTURING A PYROGENh ¹ REIEN SOLUTION FOR MEDICAL PURPOSES

The invention relates to a method and an arrangement for the preparation of a sterile and pyrogen-free solution for medical purposes, e.g. for peritoneal dialysis.

As is known, peritoneal dialysis essentially consists in delivering dialysis fluid into the patient's abdominal cavity to introduce dio from a salt solution and additional substances, nowadays dextrose or another sugar, to increase the osmosis capacity of the liquid exists. In the abdominal cavity, this fluid comes into contact with the peritoneum, that because of its abundance of blood vessels, an exchange of substances between the blood and the fluid thus enabling an equilibrium to be re-established in the electrolytic state of the patient. In addition, because of its high osmotic power, the dialysis fluid absorbs water from the rest of the body, so that a The patient's kidney function was reduced by dialysis can be. When the exchange between the blood and the dialysis fluid has taken place, the fluid becomes removed again using the same catheter and inserted into usually weighed to determine the effectiveness of the dehydration.

The amount of dialysis fluid and how long it remains in the abdominal cavity depends heavily on the circumstances. However, it can be assumed that an average of two liters Dialysef 1 are four times uid introduced in the day and remain until next jeweiIs time of introduction in the abdomen with a good approximation.

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Nowadays, peritoneal dialysis is done with prepackaged dialysis fluids in plastic bags that are sterile and made pyrogen-free. Each sack contains an average of two liters.

The method used today for preparing the bags for the dialysis fluid essentially consists of the following Stages :

a) Prepare the dialysis fluid in large quantities with all the substances needed in the solution including dextrose;

b) filling the liquid into the bags and sealing the bags;

c) sterilization of the filled bags in an autoclave.

The bags prepared in this way are then stored and distributed to the patients as required.

While the use of prepackaged bags is widespread, there are major disadvantages associated with the Strongly restrict the area of application.

On the one hand, the sack causes contamination of the liquid due to the various impurities in the base material of the Sack or because of the impurities that occur during the manufacturing process get inside (powder, plasticizing residues of lubricants etc.) · On the other hand, the sterilization temperature must be limited to one word, because of the durability of the plastic material is determined and in which there is a transfer of external substances present in the container the liquid takes place. These impurities and / or external substances would generally not pose any particular problems for the patient if dialysis treatment were only given occasionally; but since the patient is permanent is subject to dialysis treatment, these substances unfortunately accumulate in the body and can be dangerous Reach poison level.

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Treatment of the dextrose-containing solution in an autoclave causes some of the dextrose to break down 5-Hydroxy-methyl-furan, from which formal and levulin acids are formed. This results in a sharp decrease in pH of the solution, so that the organism must continuously and actively intervene to restore a balanced pH state. In the long run, this leads to an increasing reduction in the effectiveness of the peritoneum. The breakdown of the Dextrose is promoted by light and therefore continues during the storage time. Since it is not possible all Using bags as soon as they are made reduces the usefulness of older bags for proper use the dialysis fluid they contain.

Since the sterilization for a large number of bags takes place together and at the same time within an autoclave, and there the length of the time available for sterilization is limited due to the reasons mentioned above, it can happen that individual bags do not reach the required minimum temperature. The sterilization is then imperfect, so that Bacterial residues can remain in the liquid and can rise to high levels during storage, depending on their length can reproduce.

Since, after all, the cost of the bags and the connecting lines connected to them are the same or even greater than that The costs of the dialysis fluid they contain are, this'method of manufacture and sterilization is suitable the dialysis fluid bad for economic reasons for the high frequency of dialysis cycles required for this type of treatment. In addition, the bags used cannot will be used again.

The object of the invention is to provide a method for the production of one which can be used for peritoneal dialysis Specify solution as well as an arrangement for the implementation of the

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Method that has the above-mentioned disadvantages of the known Proceedings no longer exhibit.

According to the invention, this object is achieved by a method in which water and a concentrated salt solution are mixed in a first stage and then filtered so that that a calibrated solution is created, and in a second stage this calibrated solution is transferred to a vessel is, in which a predetermined amount of heat is supplied during a predetermined period of time. The arrangement for Implementation of this method is characterized according to the invention in that it has a first section, in the drinking water and a concentrated saline solution are mixed and filtered and a filtered and calibrated one Solution is generated, and that behind the first section, a second section is provided, the means for dispensing a having predetermined amount of heat to the calibrated solution during a predetermined period of time. The invention will explained in more detail below on the basis of a preferred exemplary embodiment with the aid of the drawings.

Fig. 1 shows partially in section an arrangement according to the invention.

FIG. 2 shows a side view of an example of the use of the dialysis solution produced in the arrangement according to FIG. 1.

In Fig. 1 an arrangement 1 is shown for the production of solutions that are used for peritoneal dialysis. This arrangement essentially contains a section 2 for mixing and filtering and, downstream from this, a section 3 for sterilization. The section 2 has an inlet pipe 4, which is via a demineralizer 5 in not shown WeisQ connected to the drinking water supply is. On the output side, this section has an outlet pipe 6 which is in series with an inlet pipe 7 of section 3.

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The latter has an outlet line 8 in which a valve 9 sits and in use a connecting line from the arrangement 1 to the catheter 10 attached to the patient 11 (see Fig. 2).

Section 2 contains a revolving loop when viewed more closely 13, in which a pump 14, a conductivity measuring probe 15 and a filter 16 are arranged.

The circulation loop 13 is supplied with drinking water via an antibacterial and anti-pyrogenic filter 18 while a concentrated saline solution from a container 19 via a pump 20, the operation of which is monitored directly by the measuring probe 15 is fed to the loop, usually this is Filter 16 of the membrane type, the membrane of which has a high permeability, so that all residues or impurities, even on an organic basis, which could still be present in the solution circulating in the loop, in the filter be held back.

The section 3 consists essentially of a vessel 23 in that the solution to be sterilized is let in with the aid of a pump 24 located in the tube 7. The vessel 23 is with a bottom 25 is provided to which the outlet line 8 is connected. At the top the vessel 23 is sealed with an expansion chamber 26 via a tube 27 of small cross-section and a valve located in this tube. 28 connected. In a Certain height of the tube 27, a level probe 30 is arranged, which an electrical switch-on signal for the valve 28 and the Pump 24 generated. In an upper wall 31 of the vessel 23 there is a temperature measuring probe 32 which is used to measure the temperature Generated in the vessel 23 proportional electrical signal and this signal to a display instrument 33, which is usually is calibrated in temperature degrees, and supplies to a supply circuit 34. The latter supplies depending on the output signal the temperature measuring probe 3 2 one usually

- Clam the bottom 25 of the vessel 23 attached armored resistance 35 with electricity. In addition, a cooling coil 36 is provided which protrudes into the vessel 23 and from a pump 3 7 is supplied with cold water. Finally, a magazine 38 is connected to the side of the vessel 23, the tablets 39 contains of dextrose in an anhydrous state. In particular, the magazine 38 consists essentially of a cup that with the interior of the GeEäßes 23 via a door 40 in connection stands. This door closes the magazine 38 and is held closed by a spring, not shown. With help of a manually operated piston 41, it is possible to press the tablets 39 into the vessel 23.

The vessel 23, the output line 8 and the magazine .38 are enclosed by a further vessel 42, in particular has a door 43. The line 8 can be pulled out through this door so that the patient can remove dialysis solution can.

As FIG. 2 shows, the free end of the line 8 is firmly connected to a branch 45 of a tubular T-piece 46. A Another branch 47 of this T-piece can be attached to the catheter 10, overcoming the elastic reaction of a spring 48 in the Catheter 10 can be connected itself. Finally, a third branch 4 9 of the T-piece is connected to a line 50, through which the dialysis solution flows off when the pa I.ion I die Desires to empty the abdominal cavity.

In the connecting zone between the T-piece 46 and the calciner 10 there is also a heating resistor 51, which is supplied by a power supply circuit 52 and usually held in a manner not shown by a pair of pliers or another tool generally designated by the reference numeral 53 that good heat transfer from resistor 51 to T-piece 46 and catheter 10 prior to filling the Allows dialysis fluid to enter the patient's abdominal cavity.

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In Fig. 2, a measuring container 54 can be seen in which the Dialysis solution flows into it from the abdominal cavity after use. This measuring container is on a scale 55, on the associated Indicating instrument 56 the weight of the solution used can be read off directly.

The process for preparing the dialysis solution essentially consists of three stages, namely a first stage, in the drinking water is filtered and mixed with the concentrated solution contained in the container 19 (section 2) is, a second stage in which the filtered solution is sterilized (section 3), and a third stage, during the anhydrous dextrose tablets 39 are placed in the vessel 23.

More precisely, during the first stage the drinking water is first cleaned in a demineralizer 5, its characteristics can vary depending on the desired degree of purity of the water. Then the drinking water is filtered in the filter 18 and fed into the circulation loop 13, in which the water with the concentrated solution present in the container 19 is mixed. Entering the concentrated solution is through the Conductivity measuring probe 15 controlled, via the Pump 20 until the solution in circulation loop 13 reaches the desired concentration.

When the concentration of the solution in the loop 13 corresponds to the target value, the pump 24 is switched on, which the Ultra-pure and practically sterile solution is drawn through the filter 16 and transferred into the vessel 23. During this Transfer, the level probe 30 holds the valve 28 open so that air that was in the vessel 23 into the expansion chamber 26 can escape. When the level of the solution in the vessel 23 reaches the range of the level measuring probe 30, the latter switches the pump 24 and at the same time closes the valve 28. Now the actual sterilization begins, during which the

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Resistor 28 rapidly raises the temperature of the solution to the predetermined value, for example between 120 and 14O ⁰ C under direct control of the temperature measuring probe 32nd The dextrose also experiences the increase in temperature, but it is still in the anhydrous state since it is still separated from the solution by the tightly closed door 40. The degradation of the dextrose is therefore negligible.

After a specified time, the power supply to the Resistance 3 5 ended and cold water is fed into the cooling coils 36 with the aid of the pump 37, so that the Solution rapidly cools to a value close to body temperature. A dextrose tablet 39 is now placed in the vessel 23 pressed in using the piston 41 and mixes with the solution that has just been sterilized. After a few minutes of waiting, during which the dextrose can dissolve (a stirrer can also be provided for this purpose), the arrangement is 1 ready to deliver the solution to the patient. Before the transfer (Fig. 2), the tubular T-piece 46 is attached to the The catheter 10 carried by the patient is brought up without, however, already being hydraulically connected to it. Under Under these conditions, the supply circuit 52 supplies a current to the heating resistor 51, thereby creating the T-piece on site and the catheter sterilized. At the end of this process, branch 47 of tee 46 is hydraulically attached to the catheter 10 connected and the patient can empty the abdominal cavity by transferring the used solution into the measuring container 54. The sterile solution in the vessel 23 is then transferred into the abdominal cavity by the valve 9 on the The bottom of the vessel 23 is opened. When this process has also ended, the valve 9 is closed and preferably with the aid of the resistor 51, the local sterilization of the T-piece and the catheter is repeated. The T-piece 4 6 will then removed from the catheter 10 and stowed together with the associated outlet line 8 in the vessel 42.

An examination of the characteristic values of the method described shows that the object on which the invention is based is thus achieved will.

Firstly, since the plastic bag is superfluous, the disadvantages associated therewith are also eliminated, so that there is a risk of contamination the dialysis solution practically no longer exists. There are also no inconsiderable costs for the sack and the associated connecting lines for each dialysis cycle .

Since the dextrose is sterilized in an anhydrous state, the breakdown to 5-Ilydroxy-Methyl-Furan is correspondingly significantly reduced. Since the solution is used immediately, those associated with slow degradation by light are also omitted Disadvantage. Instead of dextrose, another substance, for example bicarbonate, can now also be added to the dialysis solution and / or an amino acid are introduced which is completely decomposed by heat and which also reacts with the Time decreases, so that such a substance could not be used heretofore.

By suitably setting the conductivity measuring probe 15 it is possible to freely choose the concentration of the salts in the dialysis solution, which is undoubtedly advantageous from the point of view the flexibility of the arrangement with it.

Since the procedure described above involves the sterilization of the solution from time to time and only for a few moments before using the solution itself, it is clear that the sterilization is proceeding under the best conditions that a possible bacterial residue does not have enough time to reproduce to a dangerously high level.

Finally, it is clear that the method and arrangement can be modified and varied as described above,

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without leaving the framework of the discovery.

For example, the magazine 38 could contain dextrose in concentrated solution. By setting the values appropriately For the time and temperature of the sterilization, the dextrose could also be put together directly in the circulating loop 13 be introduced with the concentrated solution from the container 19.

If a membrane filter was also specifically referred to in the case of the filter 16, then section 2 of the arrangement could can also be changed, for example by using other FiI learning animals by ddt; qereiniql <> Drinking water comes from another suitable system.

Finally, the inventive method and the Associated arrangement 1 can also be used instead of for the preparation of a solution for peritoneal dialysis to produce a Manufacture sterile and pyrogen-free solution that is used for other applications in the medical field.

Claims (1)

W 138 D 32 : & ι SOCIETA ¹ ITALIANA FARMACEUTICI RAVlZZA SIFRA. Spa Via Camagre, 41
37 063 ISOLA DELLA SCALA (Verona, Italy) METHOD AND ARRANGEMENT FOR PREPARING A PYROGEN-FREE SOLUTION FOR MEDICAL PURPOSES PATENT CLAIMS 1 - Method of making a sterile and pyrogen-free Solution for medical purposes, for example for peritoneal dialysis, characterized in that in a first stage water and a concentrated silicate solution mixed and then filtered so that a calibrated solution is obtained, and that in a second stage this calibrated solution is transferred to a vessel in which a predetermined Amount of heat is supplied. 2 - The method according to claim 1, characterized in that that the calibrated solution is cooled in a third stage and that substances are added in a fourth stage which are completely degraded by temperature and / or by time, these substances being sterilized beforehand and be made pyrogen-free. 3 - The method according to claim 2, characterized in that that the substances in the fourth stage in the calibrated solution in anhydrous form and / or in concentrated Solution can be added. 4 - arrangement for performing the method according to at least one of claims 1 to 3 / characterized in, that it has a first section (2) in the drinking water and a concentrated salt solution mixed and filtered and a filtered and calibrated solution produced, and that after the first section a second section (3) is provided, the means for emitting a predetermined amount of heat to the calibrated ! Has solution during a predetermined period of time. 5 - Arrangement according to claim 4, characterized in that g e k e η η - ν. I think that in the first section (2) a loop (13) is provided to which drinking water and a concentrated salt solution are fed. 6 - Arrangement according to claim 5, characterized in that g e k e η η-draws, that means (15) are provided for measuring the conductivity of the solution in the circulating loop (13), which control the supply of the concentrated salt solution to the circulation loop (13). 7- - arrangement according to one of claims 5 to 6, characterized it is shown that a membrane filter (16) is inserted into the circulating loop (13) in series. 8 - Arrangement according to one of claims 4 to 7, characterized in that in series in the drinking water inlet an antibacterial and anti-pyrogenic filter (18) is inserted. 9 - Arrangement according to claim 8, characterized in that before the antibacterial and antipyrogenic Filter (18) in the drinking water inlet to a demineralizer (5) is inserted. 320CG / + 7 0O - arrangement according to one of claims 4 to 9, characterized marked is that in the second section (3) a first vessel (23) into which the first section incoming calibrated solution arrives, and heating means (35) are provided which heat the calibrated solution under Control of a Temper.itürmeßsonde (32) feed that the Measures the temperature of the calibrated solution in the first vessel (23). 11 - Arrangement according to claim 10, characterized in that on the upper area of the first vessel (23) an expansion chamber (26) is connected via a pipe (27) into which a valve (28) is inserted. 12 - Arrangement according to one of claims 10 and 11, characterized in that coolant (36) in the first Gofäß are provided to which a cooling fluid is supplied. 13 - Arrangement according to one of claims 10 to 12, characterized characterized in that a magazine (38) is connected to the first vessel (23) via a closure member (40) is in which there are substances that are degraded by heat or substances that are degraded by time will. 14 - Arrangement according to one of claims 10 to 13, characterized in that a line (8) consists of a near the bottom of the first vessel (23) via a valve (9) leads out. 15 - Arrangement according to claim 14, characterized in that a second vessel (42) is the first vessel (23) encloses the magazine (38) and the line (8) and has a door (43) through which the line (8) can be pulled out is.