GB2091126A - Preparing a solution for peritoneal dialysis - Google Patents

Abstract

A process for preparing a sterile and apyrogenic solution usable in the medical field, conveniently for peritoneal dialysis comprises, a) preparation eg in a recirculating mixing loop (13) of a calibrated solution by diluting a concentrated saline solution (19) with water; b) filtration (16) of the said calibrated solution; c) heating and subsequent cooling of the said calibrated solution, eg in vessel (23) equipped with heater (35) and cooling coil (36); d) introduction (39) into the said calibrated solution of substances readily decomposed by heat and/or degradeable in time, eg dextrose, and previously rendered sterile and apyrogenic. <IMAGE>

Description

SPECIFICATION A process for preparing a solution for peritoneal dialysis and a machine for performing this process The present invention relates to a process for preparing a solution for peritoneal dialysis and a machine for performing such process.

As is known, the peritoneal dialysis treatment substantially consists in transferring a dialysing liquid into the abdominal cavity of a patient, which liquid is constituted by a saline solution to which there is added a substance, at present dextrose or other sugars, so as to increase its capacity for osmosis. Within the abdominal cavity the liquid mentioned above comes into contact with the peritoneal membrane which, being richly vascularised, allows an exchange of substances between the blood and the liquid itself in such a way as to re-establish equilibrium in the electrolytic state of the patient; moreover, because of the high osmotic capacity the dialysing liquid also absorbs water from the rest of the body in such a way as to cater for the inefficiency in the renal function of the patient restricted to the action of dialysis.When the exchange between the blood and the dialysing liquid is complete, the liquid is discharged to the outside by means of the same catheter and, generally, is weighed to evaluate the efficiency of the water removal.

The quantity of dialysing liquid and the length of time for which it remains in the abdomen vary widely according to circumstances; it is possible, however, to assume with good approximation that on average two litres of liquid are transferred four times each day, this liquid being left in the abdominal cavity until the time of the next transfer.

Currently periotoneal dialysis is performed using a prepared liquid pre-packaged in bags of plastics material certified to be sterile and apyrogenic, each of which has on average a capacity of two litres.

The process currently followed for preparing the dialysing liquid bags comprises substantially the following stages: a) preparation of dialysing liquid in large quantities with all the substances which must be present in the solution, including the dextrose; b) filling the bags with this liquid and sealing the bags themselves; c) sterilisation in an autoclave of the bags filled with dialysing liquid.

The bags, now prepared, are then stored and progressively distributed to patients.

Although the use of pre-packed bags is universaly adoped, it has several serious defects which greatly limit its diffusion.

First of all, the bag causes pollution of the liquid because of the various impurities present in the base material of the bag itself, or else introduced during the working phases (powders, plasticisers, residues of lubricants etc.) Moreover, the temperature of sterilisation cannot exceed a value fixed by the strength of the plastics material and that at which a transfer to the liquid of extraneous substances present in the container take place. The impurities and/or the extraneous substances would not in general give rise to particular problems to the patient if the dialysis treatment took place only occasionally; unfortunately, since the patient must be continually subjected to the dialysis treatment, these accumulate in the organism until they reach dangerously toxic percentages.

The treatment in an autoclave of the solution containing dextrose involves the degradation of a part of the dextrose to 5 hydroxy-methylJuran which subsequently transforms into formic and levulinic acids. This causes a consequent violent lowering of the pH of the solution which imposes on the organism a continuous and active intervention in order to re-establish the balanced pH state, and causes over a long time a progressive reduction in the characteristics of the peritoneal membrane. The degradation of the dextrose is encouraged by light and therefore continues whilst the materials are stored; since it is not possible to utilise all the bags as soon as they are prepared it is apparent that the more "elderly" bags are less suitable for correct use of the dialysing liquid contained in them.

Since the sterilising treatment is effected for a large number of bags all collected within the interior of the autoclave and since the length of time available for performing the sterilisation itself is limited for the reasons explained above, it can happen that some bags do not reach the minimum required temperature value. The sterilisation is therefore imperfect and a residual bacterial charge can remain which multiplies during the storage period and which can reach very high levels if this period is particularly long.

Finally, since the cost of the bags and of the associated connection lines is equal to if not greater than the cost of the dialysing liquid contained in them, such method of production, preservation and sterilisation of the dialysing liquid is hardly convenient from the economic point of view given the high frequency of dialysing cycles required by the type of treatment concerned and the impossibility of recovering the used bags.

The object of the present invention is that of providing a process for the preparation of a solution for peritoneal dialysis and a machine for performing such process, which will be free from the above specified known disadvantages.

The said object is achieved with the present invention in that it relates to a process for the preparation of a sterile and apyrogenic solution usable in a medical field, conveniently for peritoneal dialysis, characterised by the fact that it comprises a first stage during the course of which there are performed a mixing and subsequently a filtration of water and a concentrated saline solution in such a way as to obtain a calibrated solution; and a second stage during which the said calibrated solution is transferred into a receptacle in which it receives a predetermined quantity of thermal energy within a pre-determined period of time.

The present invention also relates to a machine for performing the process, characterised by the fact that it comprises a first, mixing and filtration section which can be fed with drinkable water and with a concentrated saline solution and which operates to provide a calibrated and filtered solution; and a second section positioned downstream from the said first section and including means for transmitting to the said calibrated solution a pre-determined quantity of thermal energy within a predetermined period of time.

For a better understanding of the present invention there will now be set out the main stages of the process and will also be described a preferred embodiment of a machine forpreparing a solution for peritoneal dialysis, purely by way of nonlimititive example and with reference to the attached drawings, in which: Figure 1 is a schematic view, partially in section, of a machine formed according to the present invention; and Figure 2 is a side view of an example of use of the dialysing solution produced by means of the machine of Figure 1.

With particular reference to Figure 1 a machine for producing solutions for peritoneal dialysis is generally indicated 1 and comprises substantially a filtering and mixing section 2 and a sterilisation section 3 located downstream of the section 2. Section 2 has an inlet tube 4 upstream of which there is located a demineraliser 5 connected, in a manner not illustrated, to a common source of drinkable water, and an outlet tube 6 which is connected in series with an inlet tube 7 of the section 3. This latter has an outlet tube 8 intercepted by a valve 9 and constituting, in use, a connection line of the machine 1 with an associated catheter 10 (see Figure 2) carried by a patient 11.

In more detail, the mixing and filtering section 2 includes a re-circulating duct loop 13 in which there are connected, respectively, a pump 14, a conductivity measuring probe 15 and a filter 16.

The re-circulating duct 13 receives the drinkable water via an anti-bacteriological and apyrogenic filter 18a further receives a concentrated saline solution from a container 19 by means of a pump 20 the operation of which is directly controlled by the conductivity measuring probe 15. Conveniently, the filter 16 is of the type comprising a membrane having a high permeability so asto block the passage from the duct 13 towards the tube 16 of any residue or impurity, even of organic origin, still present in the solution which flows in the duct 13.

The section 3 is substantially constituted by a receptacle 23 into which the solution to be sterilised is supplied by means of a pump 24 connected to the tube 7, The receptacle 23 has a bottom part 25 to which is connected a tube 8 which allows the discharge of the said solution and communicates at the top, in a sealed manner, with an expansion chamber 26 via a duct 27 of narrow section closeable by a valve 28. At a predetermined level of the duct 27 there is mounted a level sensor 30 which generates an enabling electric signal for the valve 28 and pump 24. In an upper wall 31 of the receptacle 23 there is connected a temperature probe 32 which generates an electrical signal proportional to the value of the temperature within the receptacle 23, and supplies this signal to an indicator instrument 33, conveniently calibrated in degrees of temperature, and to a supply circuit 34.This latter, independant on the signal generated by the temperature probe 32, supplies an armoured resistor 35 contained within the receptacle 23 and conveniently fixed to the bottom wall 25 of the receptacle itself. There is also provided a cooling coil 36 mounted within the receptacle 23 and supplied with cold water by means of a pump 37. Finally, to the receptacle 23 there is connected a lateral magazine 38 containing tablets 39 of dextrose in anhydrous state. In particular, the magazine 38 is formed substantially as a cup and communicates with the interior of the receptacle 23 by means of a door 40 which serves to cover the magazine 38 and which is held closed by the action of a spring (not illustrated). There is also provided a manually operable piston by means of which it is possible to press the tablets 39 into the interior of the receptacle 23.

The receptacle 23, the discharge tube 8 and the magazine 38 are contained within a further receptacle 42 which has, in particular, a door 43 to allow the extraction of the tube 8 thus permitting the patient to effect transfer of the dialysing solution.

With particular reference to Figures 1 and 2, the free end of the tube 8 is firmly connected to a branch 45 of a tubular T-shape connector 46. A branch 47 of this latter can be connected into the catheter 10 (see Figure 2) by overcoming the elastic reaction of a spring 48 contained within the catheter 10 itself; Finally, a branch 49 is connected to a tube 50 through which the dialysing solution flows out when the patientwishesto empty the peritoneal cavity.

In the junction region between the connector46 and the catheter 10 there is provided a resistor 51 supplied by a supply circuit 52 and conveniently supported in a manner not illustrated, by a pincer or other tool generally indicated 53 which allows a good transmission of the heat produced by the resistor 51 to the connector 46 and to the catheter 10 before the transfer of the dialysing solution into the patient's abdominal cavity is effected. In Figure 2 there is also shown a calibrated container 54 into which the dialysing solution discharged from the abdominal cavity is made to flow, and a balance 55 with an associated indicator instrument 56 which allows the weight of the above mentioned discharged solution to be read directly.

The process adopted for the preparation of the dialysing solution consists essentially of three stages, that is a first stage in which drinking water is filtered and mixed with the concentrated solution contained in the container 19 (section 2), a second stage in which the sterilisation of the filtered solution takes place (section 3), and a third stage during the course of which the anhydrous dextrose 39 is injected into the receptacle 23.

In more detail, during the course of the first stage the drinking water is initially purified by the demineraliser 5, the characteristics of which can widely vary in dependence of the degree of purity of the water.

Subsquently, the drinking water is filtered in the filter 18 and sent on to the re-circulating duct 13 in which it mixes with the concentrated solution present in the container 19. The injection of concen trated solution is controlled by the conductivity measuring probe 15 which controls the operation of the pump 20 until the solution in the re-circulating duct 13 reaches the desired concentration.

When the concentration of the solution in the duct 13 is right the pump 24 is activated to draw the highly purified and practically already sterile solution through the filter 16 and to transfer such solution to the interior of the receptacle 23. During the transfer stage the level sensor 30 holds the valve 28 open so that the air contained in the receptacle 23 can discharge into the expansion chamber 26. When the level of the solution contained in the receptacle 23 reaches the level at which the sensor 30 is located this latter stops the pump 24 and, simultaneuosly, closes the valve 28. At this point the true and proper sterilisation stage commences, during which stage the resistor 25 rapidly raises the temperature of the solution to the predetermined value, for example lying between 120 and 140 C, under the direct control of the temperature probe 32.The dextrose also experiences the increase in temperature of the solution, but it is still in the anhydrous state in that it is separated from the solution by means of the door 40 which is sealed shut, and therefore it degrades by an entirely negligible amount.

After a predetermfined period of time the resistor 35 is no longer supplied with current and correspondingly cold water is fed into the coil 36 by the pump 37 causing a sudden cooling of the solution so as to make this latter reach a temperature close to body temperature. At this point the dextrose 39 is pressed into the receptacle 23 with the aid of the piston 41 and therefore mixes with the solution which has just been sterilised. After having waited several minutes to permit the dextrose to disolve well (for this purpose the use of an agitator may be provided for) the machine 1 is ready to transfer the solution into the patient. Before performing the transfer (see Figure 2) the tubular connector 46 is brought up to the catheter 10 carried by the patient without, however, this being connected hydraulically to the catheter itself.In these conditions the circuit 52 supplies current to the resistor 51 causing consequentsterilisation, in situ of the connector/ catheter unit; at the end of this operation the branch 47 of the connector 46 is hydraulically connected to the catheter 11 and the patient can thus empty the abdominal cavity by transferring the solution contained therein into the calibrated container 54. The subsequent operation consists in transferring the sterile solution contained in the receptacle 23 into the abdominal cavity and for this purpose the valve 9 located beneath the bottom of the receptacle 23 is opened. When this operation is also completed the vale 9 is closed and, conveniently, by means of the resistor 51,the local sterilisation of the connector/ catheter unit is repeated.The connector 46 is then uncoupled from the catheter 10 and subsequently replaced within the receptacle 42 together with the associated discharge tube 8.

From an examination of the characteristics of the process described above it is possible to observe how it allows the achievement of the above specified objects.

First of all, by eliminating the bag the disadvantages associated with it are totally eliminated so that the probability of contamination of the dialysing solution is now practically nil; moreover, the significant cost of the bag and the associated connection lines no longer appear in the unit cost for each dialysing treatment.

Since the dextrose is now sterilised in the anhydrous state, degradation to 5 hydroxy-methyl-furan is now proportionally very reduced; moreover, the solution being utilised immediately means that the disadvantage connected with the slow degradation caused by light is also eliminated. As well as dextrose it is now possible to introduce into the dialysing solution other substances such as, for example, bicarbonate and/or amino acids which, being readily decomposed by heat and degradable with time cannot at present be introduced into the solution itself.

By acting conveniently on the conductivity measuring probe 15 it is possible to adjust the concentration of salts in the dialysing solution with indubitable advantages from the point of view of the flexibility of the machine 1.

Given that the process described above involves the sterilisation of the solution from time to time and only a few moments before use of the solution itself, it is evident that the sterilisation takes place in the best conditions and that a possible residual bateriological charge does not have enough time to reproduce to a dangerously high level.

Finally, it is clear that the process and the machine 1 described above can have modifications and variations introduced thereto without departing from the scope of the present invention.

For example, the magazine 38 could conveniently contain dextrose in concentrated solution. By accurately pre arranging the values of time and temperature of sterilisation the dextrose itself could also be introduced in the re-circulating duct 13 together with the concentrated solution from the container 19.

Also, although in the description of the filter 16 specific reference has been made to a membrane filter, the section 2 of the machine could be modified, for example by utilising the filters of other type or else by arranging that the purified drinking water comes from a suitable installation provided for this purpose.

Finally, although the process and the machine 1 have been described in relation to the preparation of solutions for peritoneal dialysis, it is apparent that these could be used to prepare sterile and apyrogenic solutions conveniently usable for different applications in the medical field.

Claims (17)

1. A process for the preparation of a sterile and apyrogenic solution usable in medical fields, conveniently for peritoneal dialysis, characterised by the fact that it comprises a first stage during the course of which there are performed a mixing and subsequent filtration of water and a concentrated saline solution in such a way as to obtain a calibrated solution; and a second stage during which the said calibrated solution is transferred into a receptacle in which it receives a pre-determined quantity of thermal energy in a pre-determined time period.

2. A process according to Claim 1, characterised by the fact that it comprises a third phase during which the said calibrated solution is cooled; and a fourth phase during the course of which there are introduced into the said cooled calibrated solution substances which are readily detiorated by temperature and/or degradable in time, these being previously sterilised and rendered apyrogenic.

3. A process according to Claim 2, characterised by the fact in the said fourth stage the said substances are introduced into the said calibrated solution in the anhydrous form and/or in concentrated solution.

4. A machine (1) for performing a process according to at least one of the proceeding claims, characterised by the fact that it comprises a first, mixing and filtration section (2) which can be supplied with drinking water and with a concentrated saline solution and which is operable to provide a filtered and calibrated solution; and a second section (3) positioned downstream from the said first section (2) and including meansfortrans- mitting a pre-determined quantity of thermal energy to the said calibrated solution in a predetermined time period.

5. A machine according to Claim 4, characterised by the fact that the said first section (2) includes a recirculation duct loop (13) to which is supplied drinking water and a concentrated saline solution.

6. A machine according to claim 3, characterised by the fact that it includes means (15) for detecting the conductivity of the said solution in the said re-circulation duct (13), the said means being operable to adjust this supply of the said concentrated saline solution to the said re-circulation duct (13).

7. A machine according to Claim 5 or Clain 6, characterised by the fact that it includes a membrane filter (16) connected in series with the said recirculation duct (13).

8. A machine according to at least one of Claims 4 to 7, characterised by the fact that it includes an anti-bacterial and apyrogenic filter (18) disposed in series with a drinking water supply duct.

9. A machine according to Claim 8, characterised by the fact that it includes a demineraliser connected upstream of the said anti-bacterial and apyrogenic filter (18).

10. A machine according to at least one of Claims 4 to 9, characterised by the fact that the said second section (3) includes a first receptacle (23) into which the said calibrated solution coming from the first said section (2) is supplied, and heating means (35) operable to provide thermal energy to the said calibrated solution under the control of a temperature sensative probe (32) sensative to the temperature assumed by the said calibrated solution in the said first receptacle (23).

11. A machine according to Claim 10, characterised by the fact that it includes an expansion chamber 26 connected to an upper portion of the said first receptacle (23) by means of a tube (27) intercepted by a valve (28).

12. A machine according to Claim 10 or Claim 11, characterised by the fact that it includes cooling means (36) mounted within the said first receptacle and operable to be supplied with a cooling fluid.

13. A machine according to any of Claims 10 to 12, characterised by the fact that it includes a magazine (38) connected to the said first receptacle (23) from which it is separated by sealable closure means (40); the said magazine (38) serving to contain substances which detiorate when heated and/or substances which are degradable-with the passage of time.

14. A machine according to any of Claims 10 to 13, characterised by the fact that it includes a tube (8) which leads out from a region near to the bottom of the said first receptacle (23) and which is intercepted by an associated valve (9).

15. A machine according to Claim 14, characterised by the fact that it includes a second receptacle (42) which houses the said first receptacle (23), the said magazine (38) and the said tube (8), and which has a door (43) which allows the said tube (8) to be extracted.

16. A process as described with reference to the attached drawings and claimed in any of Claims 1 to 3.

17. A machine as described with reference to the attached drawings and claimed in any of Claims 4 to 15.