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Title:
METHOD AND SUPPLY BAG FOR PROVIDING A MEDICAL SOLUTION
Document Type and Number:
WIPO Patent Application WO/2000/057833
Kind Code:
A1
Abstract:
Method and supply bag of providing a medical solution, for example a peritoneal dialysis solution intended to be used for performing peritoneal dialysis. The supply bag comprises an electrolyte compartment (31) comprising an electrolyte solution and a powder compartment (36) comprising bicarbonate powder. The supply bag is sterilised including electrolyte solution and bicarbonate powder. Shortly before use, the powder compartment is opened to allow the bicarbonate powder to dissolve in the electrolyte solution in the electrolyte compartment. Preferably, there are also at least one osmotic agent compartment (32, 33) comprising an osmotic agent, normally glucose. The supply bag is sterilised inclusive the electrolyte solution, osmotic agent and bicarbonate powder.

Inventors:
BECKER HELMUT (DE)
WIESLANDER ANDERS (SE)
OLSSON LARS-FRIDE (SE)
Application Number:
PCT/SE1999/000482
Publication Date:
October 05, 2000
Filing Date:
March 25, 1999
Export Citation:
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Assignee:
GAMBRO LUNDIA AB (SE)
BECKER HELMUT (DE)
WIESLANDER ANDERS (SE)
OLSSON LARS FRIDE (SE)
International Classes:
A61J1/00; A61J1/10; A61J1/20; A61M1/28; A61M1/16; (IPC1-7): A61J1/00; A61M1/28
Domestic Patent References:
WO1997005852A11997-02-20
WO1994025084A11994-11-10
WO1997005851A11997-02-20
Foreign References:
US4630727A1986-12-23
US5536469A1996-07-16
Attorney, Agent or Firm:
Spitmann, Knut H. (Gambro Lundia AB Patent Dept. P.O. Box 10101 S- Lund, SE)
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Claims:
CLAIMS
1. Method of providing a medical solution, for example a peritoneal dialysis solution intended to be used for performing peritoneal dialysis, characterised by providing a supply bag having multiple compartments; providing electrolyte solution in an electrolyte compart ment; providing bicarbonate powder in a powder compartment; sterilising the supply bag inclusive the electrolyte solution and bicarbonate powder; shortly before use, dissolving the bicarbonate powder in said electrolyte solution to provide said medical solution comprising bicarbonate.
2. Method as claimed in claim 1, characterised by providing an osmotic agent compartment; sterilising the supply bag inclusive the electrolyte solution, osmotic agent and bicarbonate powder; shortly before use, dissolving the bicarbonate powder in said electrolyte solution; shortly before use, mixing said osmotic agent with said electrolyte solution, to provide a peritoneal dialysis solution comprising bicarbonate and an osmotic agent.
3. Method as claimed in claim 2, characterised in that said osmotic agent is glucose solution.
4. Method as claimed in claim 2 or 3, characterised in that said osmotic agent compartment comprises glucose, calcium chloride and magnesium chloride and optionally sodium chloride, and that said electrolyte compartment comprises sodium chloride and optionally sodium lactate.
5. Method as claimed in any one of the previous claims, characterised in that said bicarbonate powder is provided in a pouch of a web material, which maintains said powder bicarbon ate inside the pouch but allow fluid to pass for dissolution of the powder contained in the pouch.
6. Method as claimed in any one of claims 14, charac terised in that said bicarbonate powder is provided in a powder cartridge, which is sealed and sterilised separately, before being introduced in the powder compartment.
7. Method as claimed in claim 6, characterised by provid ing dissolution of the bicarbonate powder in said powder car tridge by breaking frangible pins to gain access to the inte rior of said cartridge.
8. Method as claimed in any one of claims 17 character ised by providing a dissolution compartment arranged so that electrolyte solution from the electrolyte compartment must pass the powder compartment to enter the dissolution compartment.
9. Method as claimed in any one of claims 18, charac terised by providing a supply tube for supplying peritoneal dialysis solution to a patient and connected to a dissolution compart ment, passing said electrolyte solution through said powder compartment and further to said dissolution compartment for dissolution of said powder bicarbonate.
10. Method as claimed in any one of claims 19, charac terised by providing a fluid in a dissolution compartment, passing said fluid through said powder compartment to dissolve said bicarbonate powder comprised therein, and into said electrolyte solution to thereby increase the pH of said electrolyte solution to provide a pH of the peritoneal dialysis solution of between 7.1 and 7.4.
11. Supply bag for providing a peritoneal dialysis solu tion intended to be used for performing peritoneal dialysis, characterised by a supply bag having; an electrolyte compartment comprising an electrolyte solution; a powder compartment comprising bicarbonate powder; said supply bag being sterilised including electrolyte solution and bicarbonate powder ; connection means for connecting, shortly before use, the powder compartment comprising bicarbonate powder with said electrolyte compartment comprising said electrolyte solution to dissolve the powder bicarbonate thereby to provide a peritoneal dialysis solution comprising bicarbonate.
12. Bag as claimed in claim 11, characterised by an osmotic agent compartment comprising an osmotic agent; whereby said supply bag is sterilised inclusive the electrolyte solution, osmotic agent and bicarbonate powder; connection means for connecting, shortly before use, the powder compartment comprising bicarbonate powder with said electrolyte compartment comprising said electrolyte solution to dissolve the powder bicarbonate; connection means for connecting, shortly before use, the osmotic agent compartment comprising osmotic agent with said electrolyte compartment comprising said electrolyte solution to introduce said osmotic agent into said electrolyte solution, thereby to provide a peritoneal dialysis solution comprising bicarbonate and an osmotic agent.
13. Bag as claimed in claim 12, characterised in that said osmotic agent is glucose solution.
14. Bag as claimed in claim 12 or 13, characterised in that said osmotic agent compartment comprises glucose, calcium chloride and magnesium chloride and optionally sodium chloride, and that said electrolyte compartment comprises sodium chloride and optionally sodium lactate.
15. Bag as claimed in any one of claims 1114, charac terised in that said bicarbonate powder is provided in a pouch of a web material, which maintains said powder bicarbonate inside the pouch but allow fluid to pass for dissolution of the powder contained in the pouch.
16. Bag as claimed in any one of claims 1114, charac terised in that said bicarbonate powder is provided in a powder cartridge, which is sealed and sterilised separately, before being introduced in the powder compartment.
17. Bag as claimed in claim 16, characterised by frangible pins arranged in said cartridge to provide access to the inte rior of said cartridge for dissolution of the bicarbonate powder in said powder cartridge.
18. Bag as claimed in any one of claims 1117 character ised by a dissolution compartment arranged so that electrolyte solution from the electrolyte compartment must pass the powder compartment to enter the dissolution compartment.
19. Bag as claimed in any one of claims 1118, charac terised in that said electrolyte compartment is connected to said powder compartment, which at its other end is connected to the dissolution compartment, which at its other end is con nected to a supply tube for delivering said peritoneal dialysis solution to a patient.
20. Bag as claimed in any one of claims 1119, charac terised by a dissolution compartment comprising a fluid, con nection means for passing said fluid through said powder com partment to dissolve said bicarbonate powder comprised therein, and into said electrolyte solution to thereby increase the pH of said electrolyte solution to provide a pH of the peritoneal dialysis solution of between 7.1 and 7.4.
21. Bag as claimed in claim 20, characterised in that said bicarbonate powder is provided in an amount of g per liter of peritoneal dialysis solution to provide a final bicarbonate concentration of 215 mM.
Description:
TITLE: METHOD AND SUPPLY BAG FOR PROVIDING A MEDICAL SOLUTION FIELD OF INVENTION The present invention relates to a method and a supply bag for providing a medical solution such as a peritoneal dialysis (PD) solution intended to be used for performing peritoneal dialysis, for example continuous ambulatory PD (CAPD) or auto- matic PC (APD).

PRIOR ART Peritoneal dialysis is performed by introducing a perito- neal dialysis solution in the peritoneal cavity of a patient to remove waste products from blood by exchange over the perito- neal membrane of the patient. Moreover, fluid removal takes place by the use of an osmotic gradient provided by an osmotic agent, for example glucose. Electrolytes are balanced by inclu- sion of electrolytes in desired concentrations in the PD solu- tion.

An important function is the replacement of buffer. Often the PD solution comprises lactate which is transferred to the blood. The body converts lactate to bicarbonate, which is the buffer the body uses.

There are suggestions to include bicarbonate as a buffer in the PD fluid replacing lactate fully or partially. However, the use of bicarbonate in solutions which must be sterilised and stored for a prolonged time results in problems, since bicarbonate is metastable and is transformed to carbonate under emission of carbon dioxide. Moreover, the inclusion of calcium and magnesium ions in the PD solution might result in calcium carbonate precipitation.

Examples of prior art patents discussing these and other problems are found in for example: US-A-5 536 469, WO 97/05851, WO 97/05852, WO 97/30694, PCT/SE98/02146.

SUMMARY OF THE INVENTION The first object of the present invention is to solve one or more of the above mentioned problems and provide a method and a PD supply bag including a PD solution comprising bicar- bonate ion.

A second object of the invention is to provide a method and a PD solution bag in which the PD solution is stable over a prolonged storage time and can withstand sterilisation.

A third object of the present invention is to provide a method and a PD supply bag comprising a PD solution where the risk of calcium carbonate precipitation is minimised.

One or more of these and other objects are met with a method of providing a peritoneal dialysis solution intended to be used for performing peritoneal dialysis, comprising the steps of providing a supply bag having multiple compartments; providing electrolyte solution in an electrolyte compartment; providing bicarbonate powder in a powder compartment; sterilis- ing the supply bag inclusive the electrolyte solution and bicarbonate powder; shortly before use, dissolving the bicar- bonate powder in said electrolyte solution to provide a perito- neal dialysis solution comprising bicarbonate.

By dissolving the bicarbonate powder shortly before use, the stable characteristics of the bicarbonate powder is advan- tageously used.

An osmotic agent is mixed with the electrolyte solution shortly before use, which means that the osmotic agent is sterilised separately from the remaining solution and may be sterilised under favourable conditions, such as high concentra- tion and low pH to avoid harmful breakdown components from the osmotic agent, normally glucose.

By providing glucose, calcium chloride and magnesium chloride and optionally sodium chloride in the osmotic agent compartment, while the electrolyte compartment comprises sodium chloride and optionally sodium lactate, and mixing the contents

of the osmotic agent compartment after dissolution of the bicarbonate powder, the risk of precipitation because of local high bicarbonate concentrations are avoided.

The bicarbonate powder may be provided in a pouch of a web material, which maintains said powder bicarbonate inside the pouch but allow fluid to pass for dissolution of the powder contained in the pouch. The pouch may be attached to the supply bag blank during the manufacturing step. Thus, a more accurate dosage of the powder bicarbonate may be obtained.

Alternatively, the bicarbonate powder is provided in a powder cartridge, which is sealed and sterilised separately, before being introduced in the powder compartment. The car- tridge may be provided with frangible pins to gain access to the interior of said cartridge. By sterilising the cartridge separately, the supply bag blank need not be exposed to for example gamma irradiation which might deteriorate the bag material.

In one embodiment of the invention, a dissolution compart- ment is arranged so that electrolyte solution from the electro- lyte compartment must pass the powder compartment to enter the dissolution compartment. When the electrolyte solution passes the bicarbonate powder, it becomes dissolved. The electrolyte solution may be passed several times between the electrolyte compartment to the dissolution compartment and back to promote dissolution of the powder.

In another embodiment the dissolution compartment is arranged between the electrolyte compartment and a supply tube for supplying peritoneal dialysis solution to a patient. Thus, the electrolyte solution must pass the powder compartment to reach the patient, which means that the patient cannot forget to open the bicarbonate compartment.

If it is sufficient to pass the electrolyte solution in a single pass through the bicarbonate powder to obtain full dissolution, such electrolyte solution may be provided in the dissolution compartment and passed from there through the bicarbonate powder to the electrolyte compartment. Then, os- motic agent is added, possibly together with calcium and magne- sium ions.

Other objects, advantages and features of the invention will become apparent from the following detailed description of the invention with reference to several embodiments shown on the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view of a prior art double bag CAPD solution set comprising a Y-connector, for example of the type GEMINI 10 available from Gambro Lundia AB.

Fig. 2 is a schematic view of an alternative supply bag in the PD solution set according to Fig. 1.

Fig. 3 is a schematic view over a first embodiment of a supply bag according to the present invention.

Fig. 4 is a schematic view over a second embodiment of the supply bag according to the present invention.

Fig. 5 is a schematic view over a third embodiment of the supply bag according to the present invention.

Fig. 6 is a cross sectional view of an insert to be used in the supply bag according to Fig. 5.

Fig. 7 is a cross sectional view of an insert similar to Fig. 6 to be used in the supply bag according to Fig. 5.

Fig. 8 is a schematic view of a fourth embodiment of the supply bag according to the present invention.

Fig. 9 is a schematic view of a fifth embodiment of the supply bag according to the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS Fig. 1 is a schematic view of a PD solution set compris- ing a supply bag 1, a drain bag 2, a Y-connector 3 and a CAPD- connector 4. The supply bag 1 is connected to one leg of the Y- connector via a supply tube 5 and the drain bag 2 is connected to the Y-connector 3 via a drain tube 6. The final leg of the Y-connector 3 is connected to the CAPD-connecting line- connector 4 via a delivery tube 7, which may be a double tube over a portion of its length. The end of the drain tube 6

connected to the drain bag 2 is provided with a frangible pin 8.

The operation of the CAPD peritoneal dialysis set accord- ing to Fig. 1 is the following. Supply bag 1 is attached to a stand (not shown on the drawing) to position the supply bag 1 at an elevated position, for example 1.7 meter above the floor or higher. For that purpose, supply bag 1 is provided with a hole 9 for engagement with a hook of the stand. The drain bag 2 is placed in a low position attached to the stand. Before placing the drain bag 2, the patient normally opens the frangi- ble pin 8 by applying a gentle pressure sideways to break a weakened part of the pin. The operation of a frangible pin is well known in the art. The opening of the frangible pin 8 establishes a flow path from supply bag 1 via supply tube 5 and Y-connector 3 and further via drain tube 3 and frangible pin 8 into drain bag 2. Thus, solution in supply bag starts to flow along this flow path in order to rinse it, while the patient places the drain bag on the floor. When the flow path has been rinsed, the patient places a clamp 10 on the supply tube 5 to stop the flow.

The patient also connects his patient line to the CAPD- connector 4 using conventional aseptic techniques. The patient line leads from the CAPD-connector to a catheter inserted in the peritoneal cavity of the patient. The patient line com- prises a clamp (not shown on the drawings). When the rinsing is completed, and the patient is connected to the CAPD-connector 4, the patient opens the clamp on his patient line to thereby establish fluid communication between his peritoneal cavity and the drain bag 2 via delivery tube 7, Y-connector 3 and drain tube 6. The spent fluid from the peritoneal cavity is trans- ferred to the drain bag via gravity forces. When the peritoneal cavity is empty, the patient moves clamp 10 from the supply tube 5 and attaches it to the drain tube 6 to establish fluid communication between the supply bag 1 and the peritoneal cavity. Alternatively, a separate clamp 11 on drain tube 6 is closed while clamp 10 on supply tube 5 is opened. Sterile supply solution in supply bag 1 is transferred to the patient's peritoneal cavity by gravity forces to install a fresh dialysis

solution. The above described procedure is a normal CAPD proce- dure performed 4-5 times per day and normally takes about 30 minutes per exchange.

The solution provided in supply bag 1 has a certain compo- sition suitable for peritoneal dialysis. The PD solution com- prises an osmotic agent, a buffer and further electrolytes. The osmotic agent is often glucose or dextrose but several other osmotic agents have been suggested and some of them are used, like icodextrin. The buffer is sodium lactate although sodium bicarbonate has been investigated in clinical trials during the last years. The further electrolytes are sodium chloride, magnesium chloride and calcium chloride. Further substances may be included in the peritoneal dialysis solution like amino acids and medicines such as insulin as is well known in the art.

The supply solution and the entire CAPD set are sterilis- ed after manufacturing, before storage and use, in an autoclave process. The set is introduced in an autoclave and heated to a temperature of approximately 121°C and kept there for approxi- mately 20 minutes.

The GAMBROSOL PD solution provided by Gambro AB has the following composition: sodium 132 mmol/l, calcium 1.75 or 1.35 mmol/1, magnesium 0.25 mmol/1, chloride 96 mmol/1, lactate 40 mmol/1, glucose 15,25 or 40 g/l, and hydrochloric acid to obtain a pH of 5.5. The volume of the supply solution is nor- mally 2 litres, but may vary between 0.5 and 5 litres. The low pH of the supply solution is necessary to decrease carameliza- tion and other breakdown of the glucose during sterilisation and storage.

An alternative supply bag, which may be used in the CAPD set according to Fig. 1, is shown in Fig. 2. The supply bag is in the nature of a multi-compartment bag having an electrolyte compartment 21 and at least one osmotic agent compartment 22, whereby Fig. 2 shows two osmotic agent compartments 22 and 23.

This type of supply bag is disclosed in US patent 5 536 469 issued to Gambro AB. By separating the osmotic agent, in this case glucose or glucose polymer, in a separate compartment and sterilising it in a high concentration and at a low pH, the

degradation of glucose is avoided. By dividing the osmotic agent compartment in two compartments as shown in Fig. 2 as disclosed in WO 97/05851 and WO 97/05852, a single supply bag having options for three different final concentrations of glucose may be provided. The contents of US-A-5 536 469, WO 97/05851 and WO 97/05852 are incorporated herein by reference.

The pH in the multi-compartment bag, in the final prepared solution to be infused into the patient, may be between 6.0 and 6.5. The increased pH compared to the GAMBROSOL solution (pH=5.5) means reduced infusion discomfort/pain for the pa- tients. At the same time, lower concentrations of glucose degradation products are obtained in the Fig. 2 embodiment resulting in a more physiological solution and possibly reduced AGE formation during peritoneal dialysis. This is described in WO 97/30694, applicant Gambro AB, the contents of which is incorporated herein by reference.

The operation of the supply bag according to Fig. 2 is the following. The supply bag is sterilised with the osmotic agent separated in compartments 22 and 23 and the rest of the PD solution in compartment 21. Shortly before use, break pin 24 associated with compartment 22 is broken to allow the glucose solution in compartment 22 to flow into the electrolyte com- partment 21 to mix with the electrolyte solution and form a glucose concentration of 1.5%. Alternatively, frangible pin 25 associated with compartment 23 is broken to transfer the glu- cose in compartment 23 to the electrolyte compartment 21, thereby to provide a glucose concentration of 2.5%. Further alternatively, both break pins 24 and 25 are broken to transfer all glucose in both compartments 22 and 23 to the electrolyte compartment 21 thereby to provide a glucose concentration of 4.0%. The amount of glucose and the concentration thereof in compartment 22 and 23 are adjusted to provide the above men- tioned concentrations in the final mixed solution before the solution is delivered to the patient.

Even the pH of 6.0 to 6.5 obtained in the embodiment shown in Fig. 2 might be considered too low for being provided to the peritoneal cavity. There are research indicating that a physio- logical pH of 7.1 to 7.4 would be preferred. Such a pH can not

be provided with the conventional lactate buffer. Experiments have been performed to replace the lactate buffer wholly or partially with sodium bicarbonate.

If only bicarbonate is used as a buffer, it should nor- mally be provided in a concentration of 35 to 40 mM in the final solution. Some patients may obtain too much buffer and get alkalosis if 40 mM are used, and therefore two or three different concentrations have to be provided.

If a combination of lactate and bicarbonate buffer is used, the sum of the two buffers should be between 35 to 40 mM, for example 25 mM bicarbonate and 15 mM lactate.

According to experiments performed by the present inven- tors, the most important contribution by bicarbonate is to increase the pH to the physiological level of 7.1 to 7.4. In order to provide this pH with a safety margin, the bicarbonate concentration should exceed 2.0 mM. In further experiments the inventors have found that if the bicarbonate concentration exceeds 15 mM, there is risk for calcium carbonate precipita- tion, specifically at long time storage. Therefore, the bicar- bonate concentration should not exceed 15 mM at a calcium concentration below 2.5 mM.

The risk for calcium carbonate precipitation may be re- duced by separating the calcium ions from the bicarbonate buffer during autoclaving and storage. This may be done by including the calcium ions in the osmotic agent compartments 22 and 23 and including the bicarbonate buffer in the electrolyte compartment 21. Further research has revealed that a calcium neutral PD solution may be provided by providing a calcium concentration which is proportional to the glucose concentra- tion as reported in an article entitled"Should dialysate calcium be valid in proportion to the amount of ultrafiltration in peritoneal dialysis dwells? Directions from a computer simulation", published by Bengt Rippe and Lars Levin September 1998 in"Peritoneal Dialysis International", Vol. 18, p. 474- 477, no. 5., September 1998. The contents of the article is incorporated herein by reference and a copy is enclosed here- with.

By including the calcium and magnesium ions in the osmotic agent compartments 22 and 23 and by including them in propor- tion to the glucose concentration, a calcium neutral solution is provided as described in the international patent applica- tion PCT/SE98/02146 with priority from 1997-11-28 (not yet published), the contents of which is incorporated herein by reference and a copy of which is attached hereto.

When using bicarbonate as buffer, there are always prob- lems with the instability of bicarbonate, specifically with PVC bags, which are permeable for carbon dioxide. The bicarbonate is metastable and transformed to sodium carbonate under emis- sion of carbon dioxide. At the same time the pH increases. The increase of pH and the transformation to carbonate increases the risk for calcium carbonate precipitation.

According to the present invention, the risk for bicarbon- ate deterioration is avoided by the provision of the bicarbon- ate in the nature of a powder as shown in Fig. 3 and disclosed in German Patent Application No. DE 198 11 276.9-41, inventor Helmut Becker. Fig. 3 discloses the supply bag 30 intended to be used in a CAPD set according to Fig. 1 or in another conven- ient manner. Supply bag 30 comprises an electrolyte compartment 31, a first osmotic agent compartment 32 and a second osmotic agent compartment 33, connected to the electrolyte compartment 31 via frangible pins 34 and 35. So far the supply bag 30 agrees with supply bag 20 of Fig. 2. Moreover, a powder com- partment 36 is provided, located between the first and the second osmotic agent compartments and connected to the electro- lyte compartment 31 via a breakable seal 37. Seal 37 may be opened by pulling in tabs 38,39 attached to the supply bag 30 close to the breakable seal 37. By pulling tabs 38,39, a sufficient force is exerted for severing seal 37 and opening the powder compartment 36 to connection with electrolyte com- partment 31.

The powder compartment 36 comprises sodium bicarbonate powder, which upon breaking of seal 37 falls down in the large electrolyte compartment 31 and mixes with the solution therein to be dissolved. Solution in electrolyte compartment 31 may also flow into powder compartment 36 to dissolve any remaining

powder which has not fallen down into compartment 31. Full dissolution of all bicarbonate powder is thereby obtained.

The amount of bicarbonate powder in compartment 36 is chosen to obtain the desired final bicarbonate concentration in electrolyte compartment 31. The final concentration in electro- lyte compartment 31 may be 35 to 40 mM, if only bicarbonate is used as a buffer, or from 2 to 35 mM, if a combination of bicarbonate and lactate is used as buffer. Preferably the range of bicarbonate in the final prepared PD solution is from 2 to 15 mM.

After dissolution of the bicarbonate powder, frangible pins 34 and 35 are operated to introduce glucose in the elec- trolyte compartment 31 as desired.

It is appreciated that only one osmotic agent compartment may be provided, for example by the exclusion of the second osmotic agent compartment 33. Conversely, several osmotic agent compartments may be provided to increase the variation of glucose. Several bicarbonate powder compartments may also be provided to provide a selection of bicarbonate concentrations in the final solution.

Bicarbonate powder can not be sterilised in the normal autoclave procedure used for PD solutions. A dry powder needs to be heated to much higher temperatures to obtain sterilisa- tion. However, bicarbonate powder will decompose if heated to such a high temperature.

According to the present invention this problem is solved by first providing bicarbonate in powder compartment 36, seal- ing it and exposing the supply bag 30 for gamma radiation for a time sufficient for obtaining a sterile bicarbonate powder in compartment 36. Then, compartments 31,32 and 33 are filled with solution and sealed, and the final product is inserted in an autoclave for sterilising the fluids.

When the bicarbonate powder is exposed to gamma irradia- tion sufficient to obtain sterilisation, it becomes pink.

However, during the following autoclaving 121°C during 20 minutes, the powder substantially retains it's original white colour, as described in EP 424 667, issued to Gambro AB. The colour of the powder is substantially restored to white but it

still maintains a slight pink colour. However, analysis has shown that no harmful components are formed when the powder is dissolved in an electrolyte solution after gamma irradiation and autoclaving.

It is known that bicarbonate powder is difficult to dis- solve. Therefore the powder is provided in small particles, which are faster to dissolve.

A second embodiment of the invention is shown in Fig. 4, which discloses a supply bag 40 comprising an electrolyte compartment 41, a first osmotic agent compartment 42, a second osmotic agent compartment 43, frangible pins 44 and 45, similar to the embodiments shown in Figs. 2 and 3. Between the osmotic agent compartments 42 and 43, there is a powder compartment 46 comprising bicarbonate powder. Furthermore, between the upper portion of the first and second osmotic agent compartments 42 and 43 a dissolution compartment 47 is formed. Powder compart- ment 46 forms a connection between dissolution compartment 47 and electrolyte compartment 41. Tabs 48 and 49 are provided for separating breakable seals, whereby a first breakable seal 50 is arranged between powder compartment 46 and electrolyte compartment 41 and a second breakable seal 51 is arranged between powder compartment 46 and dissolution compartment 47.

The bicarbonate powder is arranged in a powder pouch 52 at- tached inside powder compartment 46.

In operation, the breakable seals 50 and 51 are broken in that the tabs 48 and 49 are pulled. Then, a gentle pressure is exerted on electrolyte compartment 41 to press fluid through powder compartment 46 into dissolution compartment 47, thereby passing the powder in the powder pouch 52 to dissolve the bicarbonate powder comprised therein. The powder pouch 52 comprises a net or web having meshes of a size which prevents passage of bicarbonate powder particles. By this arrangement, it is avoided that bicarbonate powder falls down into electro- lyte compartment 41 and gathers at the bottom thereof in an un- dissolved state. Moreover, the dosage of bicarbonate powder becomes easier and more controlled.

When dissolution compartment 47 is full of electrolyte solution including some dissolved bicarbonate, the pressure on

electrolyte compartment 41 is removed and the solution is allowed to pass back through powder compartment 46 by gravity to thereby further dissolve bicarbonate powder in pouch 52.

This procedure is repeated until all powder in pouch 52 is dissolved, which can be inspected visually. Normally, two fills of dissolution compartment 47 is sufficient to dissolve all powder in pouch 52 at least for bicarbonate concentrations below 15 mM.

When all powder has been dissolved, all fluid in dissolu- tion compartment 47 is allowed to pass down into electrolyte compartment 41, whereupon frangible pins 44 and/or 45 are opened to provide glucose to electrolyte compartment 41 as described above.

If electrolyte compartment 41 comprises calcium and that solution is passed into contact with powder bicarbonate in compartment 46, there is a risk for precipitation of calcium carbonate due to high local concentration of bicarbonate or carbonate. By the inclusion of calcium in osmotic agent com- partments 42 and 43, this risk is avoided. Calcium is mixed into the final solution when all bicarbonate powder has been dissolved and diluted, whereby the risk for calcium bicarbonate precipitation is completely avoided.

A third embodiment of the invention is shown on Fig. 5, which has the same general layout as Fig. 4, but in which the powder pouch 52 is replaced by a powder cartridge 66. In Fig.

5, supply bag 60 comprises an electrolyte compartment 61, osmotic agent compartments 62 and 63, frangible pins 64 and 65, powder compartment 66, dissolution compartment 67 and powder cartridge 70. Powder cartridge 70 comprises frangible pins 68 and 69, opened to dissolution compartment 67 and electrolyte compartment 61, respectively. Powder cartridge 70 is attached in powder compartment 66 in order to prevent fluid communica- tion between dissolution compartment 67 and electrolyte com- partment 61. No breakable seals are necessary in this embodi- ment.

The arrangement is similar to the second embodiment in Fig. 4. Frangible pins 68 and 69 are broken so that the fluid communication is opened between electrolyte compartment 61 and

dissolution compartment 67. A gentle pressure on electrolyte compartment 61 causes passage of fluid through powder cartridge 40 into dissolution compartment 67. Relief of the pressure on electrolyte compartment 61 means that solution in dissolution compartment 67 passes back through powder cartridge 70 into the electrolyte compartment 61 whereby the powder bicarbonate in cartridge 70 is dissolved.

In the embodiment of Fig. 5, cartridge 70 may be manufac- tured as a separate unit sealed by frangible pins 68 and 69 and sterilised by gamma irradiation or any other known method. The sealed cartridge may be inserted in the supply bag blank 60 and solutions are filled in compartment 61,62 and 63. Then, the bag is sealed and transferred to the autoclave equipment for autoclaving. By this method, exposure of the PVC supply bag blank 61 for gamma irradiation is avoided. Moreover, the risk, that bicarbonate powder particles contaminate the seal area close the breakable seals 50,51 and 37, is avoided.

Fig. 6 is a cross sectional view of a powder cartridge 80 suitable for the supply bag 60 according to Fig. 5. Cartridge 80 comprises frangible pins 81,82 extending from opposing end walls of the cartridge. The cartridge is generally cylindrical or oval and is tapered adjacent both ends. The cartridge may be partially or completely filled with bicarbonate powder depend- ing on the desired concentration and the size of the cartridge.

Fig. 7 discloses another embodiment of the cartridge 90 suitable for use in the supply bag 60 of Fig. 5. Cartridge 90 comprises internal flanges forming elongated flow paths for fluid passing through the cartridge to thereby decrease disso- lution time.

A fourth embodiment of the invention is shown in Fig. 8.

The supply bag 100 comprises an electrolyte compartment 101, osmotic agent compartments 102,103 and frangible pins 104, 105. A dissolution compartment 107 is arranged below electro- lyte compartment 101 between compartment 101 and the peritoneal dialysis solution outlet to supply tube 108. Between electro- lyte compartment 101 and dissolution compartment 107, a powder compartment 106 is arranged, comprising bicarbonate powder, in the nature of a pouch as described in connection with Fig. 4 or

as a powder cartridge as described in connection with Fig. 5.

By this arrangement, the risk that the patient does not break the powder compartment and dissolve the bicarbonate powder, is avoided since the electrolyte solution can not be given off from the supply bag without passing powder cartridge 109. The operation is similar to that described in connection with Figs.

4 and 5.

It is appreciated that the dissolution of the bicarbonate powder may be performed by a cycler in an automatic manner instead of by a gentle pressure applied manually, when the supply bag is used in connection with a cycler, for example cycler PD 101 or PD 200 manufactured by Gambro AB and described in WO 95/20985, applicant Gambro AB, the contents of which is incorporated herein by reference.

The cycler comprises a heater bag connected to the supply bag 100 via supply tube 108. In operation, a suction is exerted from the heater bag (not shown on the drawings) via supply tube 108 to dissolution compartment 107 in Fig. 8. When frangible pins 110,111 in cartridge 109 are broken, the pressure exerted by the cycler to dissolution compartment 107 results in a transfer of fluid from electrolyte compartment 101 to dissolu- tion compartment 107 whereby the powder in cartridge 109 is dissolved. After a while the cycler exerts a pressure in supply tube 108 thereby to push or press the electrolyte solution in the solution compartment 107 back into electrolyte compartment 101 through cartridge 109 whereby further powder is dissolved.

This procedure may be repeated by the machine as many times as necessary without human involvement. Finally, frangible pins 104 and/or 105 are broken to provide the desired glucose and calcium into electrolyte compartment 101.

Fig. 9 discloses a fifth embodiment of the invention. The supply bag 120 comprises an electrolyte compartment 121, two osmotic agent compartments 122 and 123, and frangible pins 124, 125. A powder compartment 126 comprises an insert 127, for example of the type shown in Fig. 6 or 7. The powder compart- ment is arranged between the electrolyte compartment 121 and a supply tube 128, so that the PD fluid must pass through the insert to be able to reach the patient. The supply bag is used

together with a cycler as described above, with reference to Fig. 8, to dissolve all powder in the insert or cartridge. The supply bag may also be used without a cycler for direct infu- sion into the peritoneal cavity of a patient. In that case, insert 127 and the powder therein, may be arranged to dissolve the powder bicarbonate in a slow manner, such as by slow re- lease encapsulation, in order to avoid local high bicarbonate concentrations. Since the fluid is anyhow mixed in the perito- neal cavity, the exact dosage is not critical, specifically if low concentrations of bicarbonate is considered.

As an example, the following compositions may be provided in the different compartments according to the present inven- tion.

An electrolyte compartment comprising 1900 ml and having the following composition: sodium chloride 130-140 mM, sodium lactate 20-38 mM.

A first osmotic agent compartment comprising 60 ml and having the following composition. glucose 50%, calcium chloride 33 mM, magnesium chloride 8 mM, sodium chloride 130-140 mM.

A second osmotic agent compartment comprising 100 ml and having the following composition: glucose 50%, calcium chloride 33 mM, magnesium chloride 8 mM, sodium chloride 130-140 mM.

A powder compartment comprising 0.33-6.7 g of powder bicarbonate. This amount of bicarbonate powder may be comprised in a cartridge having a volume of 10 ml or less.

The invention has been described above with reference to the use as a PD solution. However, the supply bag according to the invention can be used in other applications, such as a supply bag for hemodialysis or replacement solutions in connec- tion with hemodialysis, hemodiafiltration or hemofiltration, specifically for acute hemofiltration or home dialysis. The supply bag according to the invention can also be used for other medical solutions, such as nutritional solutions or infusion solutions comprising bicarbonate and optionally glu- cose or amino acids, or infusion solutions in connection with plasmapheresis.

The invention has been described by reference to a pre- ferred embodiment. The skilled person will appreciated that many variations within the scope of the invention are possible.

Other combinations than those given on the drawings are possi- ble of the different features of each embodiment. The scope of the invention is, therefore, only limited by the following claims.