Device, method, and membrane for peritoneal dialysis

Abstract

A device for peritoneal dialysis comprising: a receptacle at least partially defined by a biocompatible semi-permeable membrane, the receptacle configured to allow a dialysate to be flowed into the receptacle and to hold therein the dialysate when the receptacle is in a peritoneal cavity of a patient, the receptacle further configured to allow the dialysate to be removed from the receptacle; wherein the membrane is configured to prevent passage of glucose through the membrane while allowing passage of fluid including waste products from the patient's blood through the membrane.

Description

DEVICE, METHOD, AND MEMBRANE FOR PERITONEAL DIALYSISTechnical Field

[0001] The present disclosure relates to a device, method, and membrane for peritoneal dialysis.Background

[0002] During peritoneal dialysis (PD), a dialysate is introduced into the peritoneal cavity of a patient who may be a person having end-stage kidney disease (ESKD). The osmotic gradient exerted by the dialysate results in the patient’s peritoneum acting as an exchange membrane through which fluid including waste products in the patient’s blood are drawn into the dialysate in the peritoneal cavity. These waste products are removed from the patient when the dialysate is eventually drained from the patient after the PD cycle has been completed.

[0003] Conventional dialysates typically have high glucose concentrations in order to exert the necessary osmotic gradient for passage of the excess fluid and waste products through the peritoneum into the dialysate. However, this results in glucose absorption by the patient due to passage of glucose across the peritoneum from the dialysate into the patient’s blood stream. Such glucose absorption can lead to hyperglycaemia and worsening glycaemic control in diabetic patients. High glucose concentrations in the dialysate has also been associated with peritoneal membrane inflammation and infection. The resultant cardiometabolic burden has severe consequences for PD technique longevity, morbidity and mortality.

[0004] To reduce the absorption of glucose from the dialysate, glucose-sparing dialysates have been proposed. To date, there are only two commercially available glucose-sparing dialysates which use Icodextrin or amino acid as the osmotic agent to exert the osmotic gradient needed for exchange across the peritoneum to take place. These solutions have a very slow ultrafiltration profile and are associated with risk of fluid overload in the patient. In addition, these glucose-sparing solutions only replace up to 50% of daily glucose absorption.

[0005] There is therefore a need to provide a way to perform PD that can achieve adequate ultrafiltration of toxins with reduced glucose absorption from the dialysate in diabetic patients, in order to prevent elevated glycated haemoglobin (Hbalc), that also addresses the issues faced with using glucose-sparing dialysates.Summary

[0006] According to a first exemplary aspect, there is provided device for peritoneal dialysis comprising: a receptacle at least partially defined by a biocompatible semi-permeable membrane, the receptacle configured to allow a dialysate to be flowed into the receptacle and to hold therein the dialysate when the receptacle is in a peritoneal cavity of a patient, the receptacle further configured to allow the dialysate to be removed from the receptacle; wherein the membrane is configured to prevent passage of glucose through the membrane while allowing passage of fluid including waste products from the patient’s blood through the membrane.

[0007] The device may further comprise a flexible tube having an open proximal end, wherein a first part of the membrane is attached to the tube at a proximal end of the receptacle such that the membrane defines a closed volume from the proximal end of the receptacle to a distal end of the receptacle, wherein a fluid communication is provided between the lumen of the tube and the closed volume, wherein the receptacle is configured to be in a collapsed state for insertion of the receptacle into a peritoneal cavity of a patient, and wherein the receptacle when in the peritoneal cavity is configured to be in an expanded state when expanded by dialysate in the receptacle.

[0008] The distal end of the tube may be a closed end, wherein a second part of the membrane is attached to the distal end of the tube at a distal end of the receptacle, and wherein the tube is provided with perforations along the tube between the proximal part and the distal end of the tube, thereby providing the fluid communication between the lumen of the tube and the closed volume.

[0009] The distal end of the tube may be a free open end within the closed volume, thereby providing the fluid communication between the lumen of the tube and the closed volume.

[0010] The membrane may be configured to be compactly provided around the tube when the receptacle is collapsed and to be spread out into a substantially flat membrane defining a balloon-shape for the receptacle when the receptacle is expanded by dialysate in the receptacle.

[0011] The membrane may be provided with a configuration of folds known as a herringbone tessellation.

[0012] The receptacle may comprise at least one hollow fibre.

[0013] The receptacle may comprise a plurality of hollow fibres held together by an inner frame for deployment and retraction of the receptacle.

[0014] According to a second exemplary aspect, there is provided a method of peritoneal dialysis (PD) using a device comprising a receptacle at least partially defined by a biocompatible semi-permeable membrane, wherein the membrane is configured to prevent passage of glucose through the membrane while allowing passage of fluid including waste products from the patient’s blood through the membrane, the method comprising:(a) inserting the receptacle into the peritoneal cavity of the patient;(b) introducing dialysate into the receptacle;(c) allowing PD to occur as a result of the osmotic gradient exerted by the dialysate that draws fluid containing waste products from the patient’s bloodstream across the peritoneum through the membrane into the receptacle while glucose is prevented by the membrane from leaving the receptacle; and(d) removing dialysate from the receptacle.

[0015] The method may further comprise withdrawing the receptacle from the peritoneal cavity of the patient after step (d).

[0016] According to a third exemplary aspect, there is provided a membrane for use in a device for peritoneal dialysis, the membrane configured to at least partially define a receptacle configured to allow a dialysate to be flowed into the receptacle and to hold therein the dialysate when the receptacle is in a peritoneal cavity of a patient, the receptacle further configured to allow the dialysate to be removed from the receptacle, the membrane being biocompatible and semi-permeable, the membrane configured to prevent passage of glucose through the membrane while allowing passage of excess fluid including waste products from the patient’s blood through the membrane.

[0017] The membrane may be configured to be compactly provided around a tube when the receptacle is collapsed and to be spread out into a substantially flat membrane defining a balloon-shape for the receptacle when the receptacle is expanded by dialysate in the receptacle.

[0018] The membrane may be provided with a configuration of folds known as a herringbone tessellation.

[0019] The membrane may be formed of one or more materials of natural, synthetic, or semisynthetic origin including ceramics, celluloses, cellophanes, regenerated cellulose, celluloseester (CE), and polyvinylidene difluoride (PVDF), nanoporous alumina, polysulfone, cellulose triacetate, and polytetrafluoroethylene (PTFE).

[0020] The membrane may comprise a plurality of pores that are configured to filter substances having a molecular weight ranging from 50 to 20,000.

[0021] The pores may each have a pore size ranging from 2 nm to 5 nm and the plurality of pores are spaced apart from one another by a distance ranging from 50 pm to 100 |im.

[0022] The pores may be provided in an ordered manner and spaced apart by a same distance from one another.

[0023] The membrane may have a thickness ranging from 50 p.m to 100 p.m.

[0024] The membrane may have a hydrophilic wetting tension exceeding 80 dynes / cm and a tensile strength exceeding 40 N / m along its weakest axis.Brief Description of the Drawings

[0025] In order that the invention may be fully understood and readily put into practical effect there shall now be described by way of non-limitative example only exemplary embodiments of the present invention, the description being with reference to the accompanying illustrative drawings.FIG. 1 is a schematic illustration of a longitudinal cross-sectional view of a first exemplary embodiment of a device.FIG. 2 is a schematic illustration of a longitudinal cross-sectional side view of a second exemplary embodiment of the device.FIG. 3 is a schematic illustration of a part of a partially expanded folded membrane of the device of FIG. 1 and FIG. 2.FIG. 4 is a schematic illustration of a lateral cross-sectional view of an alternative exemplary embodiment of a receptacle of the device.FIG. 5 is a flowchart of a method of peritoneal dialysis.Detailed Description

[0026] Exemplary embodiments of a membrane 10, a device 100, and a method 200 for peritoneal dialysis (PD) will be described with reference to FIGS. 1 to 5 in which the same reference numerals are used across the figures to refer to the same or similar parts.

[0027] In general, the device 100 comprises a receptacle 110 at least partially defined by a membrane 10. The receptacle 110 is configured to allow a dialysate to be flowed into the receptacle 110 and to hold the dialysate 99 therein when the receptacle 110 is in a peritoneal cavity of a patient (not shown). The membrane 10 is a biocompatible semi-permeable membrane 10 configured to prevent passage of glucose through the membrane 10 while allowing passage of excess fluid including waste products from the patient’s blood through the membrane 10. When the receptacle 110 holds dialysate 99 in the peritoneal cavity, the dialysate 99 continues to exert the required osmotic gradient for passage of fluid including waste products from the patient’s bloodstream across the peritoneum and through the membrane 10 into the receptacle 110, while the membrane 10 prevents glucose from leaving the receptacle 110 to cross the peritoneum. In this way, by using the device 100, glucose from the dialysate 99 does not enter the patient’s bloodstream during PD. After the PD cycle has been completed, the device 100 is configured to allow the dialysate 99 to be removed from the receptacle 110.

[0028] The membrane 10 may be formed of one or more materials of natural, synthetic, or semi-synthetic origin. Such materials include ceramics, celluloses, cellophanes, regenerated cellulose, cellulose ester (CE), and polyvinylidene difluoride (PVDF), nanoporous alumina, polysulfone, cellulose triacetate, and polytetrafluoroethylene (PTFE).

[0029] The membrane 10 comprises a plurality of pores that are configured to filter substances having a molecular weight ranging from 50 to 20,000 kD. This prevents passage of glucose through the membrane while allowing passage of solutes and liquids such as waste products from a patient’s bloodstream through the membrane.

[0030] In an exemplary embodiment, the pores of the membrane 10 may each having a pore size ranging from 2 nm to 5 nm. The pores may be spaced apart from one another by a distance ranging from 50 pm to 100 pm. Optionally, the pores may be provided in an ordered manner and spaced apart by a same distance from one another. The membrane 10 may have a thickness ranging from 50 pm to 100 pm. The membrane 10 may have a hydrophilic wetting tension exceeding 80 dynes / cm and a high tensile strength exceeding 40 N / m along its weakest axis. Exemplary configurations of the membrane 10 include sheets, plates and hollow fibres.

[0031] In exemplary embodiments of the device 100, such as those shown in FIGS. 1 and 2, the receptacle 110 is configured to be inserted into and deployed within the peritoneal cavity during PD. The receptacle 110 may also be withdrawn from the peritoneal cavity after the PD cycle has been completed if the receptacle 110 is not intended to be implanted in the patient.

[0032] Accordingly, in exemplary embodiments of the device as shown in FIGS. 1 and 2, the receptacle 110 is configured to be expandable from a collapsed state and collapsible from an expanded state. The receptacle 110 is in the collapsed state when the receptacle 110 is being inserted into the peritoneal cavity and when the receptacle 120 is being withdrawn from the peritoneal cavity. The receptacle 110 may be inserted and withdrawn via a PD catheter, a port, or a surgically created passageway through the abdominal wall (not shown). When expanded, the receptacle 110 is capable of containing about 2000 ml of liquid and may have a generally ellipsoidal shape that is about 200 mm long and about 140 mm wide at its widest point.

[0033] In the exemplary embodiment of the device 100 as shown in FIG. 1 , the device 100 includes a flexible tube 120 having an open proximal end 121 and a closed distal end 122. The lumen 124 of the tube 120 may have a diameter of about 1.5 mm. The outer diameter of the tube 120 may be about 2.8 mm. The wall of the tube 120 may be about 0.65 mm thick. A first part 11 of the membrane 10 is attached to the tube 120 at a proximal end 111 of the receptacle 110, and a second part 12 of the membrane 10 is attached to a distal end 122 of the tube 120 at a distal end 112 of the receptacle 110, such that the membrane 10 defines a closed volume 125 around the tube 120 from the proximal end 111 of the receptacle 110 to the distal end 112 of the receptacle 110. The tube 120 is provided with perforations 123 along the tube 120 between the proximal end 111 of the receptacle 110 and the distal end 122 of the tube 120 so that the closed volume defined by the membrane 10 is in fluid communication with the lumen 124 of the tube 120 via the perforations 123. When the receptacle 110 is expanded by dialysate in the peritoneal cavity, the membrane 10 holds a volume of the dialysate 99 around the tube 120 within the receptacle 110.

[0034] An alternative embodiment of the device 100 as shown in FIG. 2 is largely similar to the device 100 shown in FIG. 1 except that the distal end 122 of the flexible tube 120 is a free open end 122 that is not attached to the membrane 10 at a distal end 112 of the receptacle 110. In this embodiment, the tube 120 may or may not be provided with perforations (not shown) as the closed volume 125 defined by the membrane 10 is already in fluid communication with the lumen 124 of the tube via the open distal end 122 of the tube 120.

[0035] Appreciably, for both the embodiments of FIGS. 1 and 2, the tube 120 is configured such that a fluid communication exists between the receptacle 110 and the lumen 124 of the tube 120, i.e., via perforations 123 provided along the tube 120 and or a free open distal end 122 of the tube 120 or other appropriate configurations. In this way, liquid that is introduced into the proximal end 121 of the tube 120 can fill the receptacle 110 via the fluid communication between the lumen 124 of tube 120 and the closed volume defined by the membrane 10.

[0036] In order for the receptacle 110 shown in FIGS. 1 and 2 to be expandable and collapsible, the membrane 10 is configured to be compactly provided around the tube 120 when the receptacle is collapsed and to be spread out into a substantially flat membrane defining a balloon-shape for the receptacle 110 when the receptacle 110 is expanded by dialysate in the receptacle 110. In the exemplary embodiment of the membrane 10 as shown FIG. 3, the membrane 10 is folded with a configuration of folds M, V in a configuration known in origami as a herringbone tessellation or Miura fold. In FIG. 3, the reference letter M refers to a mountain fold and the reference letter V refers to a valley fold. In the herringbone tessellation or Miura fold configuration, mountain folds M and valley folds V are alternately formed to create multiple, alternating rows of concertina-folded parallelograms 11 , 12, such that across adjacent rows of parallelograms 11, 12, mountain folds M and valley folds V alternate and are connected end to end. With this configuration, the membrane can be compactly provided around the tube 120 and also expanded into a substantially flat sheet.

[0037] In alternative configurations of the device, instead of a balloon-shaped receptacle when the receptacle is expanded with dialysate, the receptacle 110 may take the form of one or more hollow fibres 140 made of the biocompatible semi-permeable membrane 10 that can be filled with dialysate when the receptacle 10 is in the peritoneal cavity. The hollow fibres 140 are open at their proximal ends to allow inflow and outflow of the dialysate into the hollow fibres 140, while the distal end of each hollow fibre 140 is closed to retain the dialysate within the hollow fibre 140. Where the receptacle 10 comprises a plurality of hollow fibres 140 forming a hollow fibre cluster 10, these can be held together by an inner frame (not shown) for deployment and retraction of the receptacle 10. For example, as shown in FIG. 4, the receptacle 10 may comprise a cluster of four hollow fibres 140 adhered to each other or linked together with the support of an internal support structure (not shown) between the hollow fibres 140, or by means of a fluid-permeable mesh (not shown) surrounding the hollow fibres 140. Each hollow fibre 140 may have an internal diameter of 0.5 mm and a wall thickness of 0.125 mm. The length of each hollow fibre 140 may range from 20 cm to 200 cm. The hollow fibre cluster 10 can be introduced into the peritoneal cavity via a catheter or other surgically-created passageway, in a collapsed form or in fully dilated form where each hollow fibre 140 is filled with the dialysate. The hollow fibre cluster 10 may be introduced in a curved manner, folded manner, etc. If the hollow fibres 140 used are of a smaller diameter, the hollow fibre cluster 10 may include more than four hollow fibres 140.

[0038] In an exemplary method of PD (200) using the device 100, as illustrated in FIG. 4, the receptacle 110 1s first inserted into the peritoneal cavity of a patient (210). For the embodimentsshown in FIGS. 1 and 2, the receptacle 110 is inserted in the collapsed state. Dialysate 99 is then introduced into the receptacle 110 (220). For the embodiments shown in FIGS. 1 and 2, dialysate is introduced from the open proximal end 121 of the tube 120 via the fluid communication between the lumen of the tube and the closed volume 125 such that the receptacle 110 is expanded by the dialysate. PD then occurs as a result of the osmotic gradient exerted by the dialysate 99 that draws fluid containing waste products from the patient’s bloodstream across the peritoneum through the membrane 10 into the receptacle 110 while glucose is prevented by the membrane 10 from leaving the receptacle 110 (230). After the PD cycle is completed, the dialysate 99 is removed from the receptacle 110 (240). For the embodiments shown in FIGS. 1 and 2, dialysate is removed from the receptacle 110 via the tube 120 such that the receptacle 110 collapses. In embodiments where the receptacle 110 is not implanted in the patient, the receptacle 110 is withdrawn from the peritoneal cavity after the PD cycle is completed.

[0039] The disclosed device 100 for PD thus advantageously allows PD to occur, while preventing glucose transfer from the dialysate 99 to the patient, thereby mitigating the negative effects of such glucose transfer and also addressing the short-comings of using glucose- sparing dialysates during PD.

[0040] While there has been described in the foregoing description exemplary embodiments of the present invention, it will be understood by those skilled in the technology concerned that many variations in details of design, construction and / or operation may be made without departing from the present invention. It will be appreciated that many further alterations, modifications and permutations of various aspects of the described embodiments are possible that fall within the spirit and scope of the claims. For example, while the receptacle 110 of the device 100 is described as being inserted during PD and withdrawn after the PD cycle is completed, in alternative embodiments, the receptacle 110 may be configured to remain implanted in the peritoneal cavity of the patient.

Claims

Claims1 . A device for peritoneal dialysis comprising: a receptacle at least partially defined by a biocompatible semi-permeable membrane, the receptacle configured to allow a dialysate to be flowed into the receptacle and to hold therein the dialysate when the receptacle is in a peritoneal cavity of a patient, the receptacle further configured to allow the dialysate to be removed from the receptacle; wherein the membrane is configured to prevent passage of glucose through the membrane while allowing passage of fluid including waste products from the patient’s blood through the membrane.

2. The device of claim 1 , further comprising a flexible tube having an open proximal end, wherein a first part of the membrane is attached to the tube at a proximal end of the receptacle such that the membrane defines a closed volume from the proximal end of the receptacle to a distal end of the receptacle, wherein a fluid communication is provided between the lumen of the tube and the closed volume, wherein the receptacle is configured to be in a collapsed state for insertion of the receptacle into a peritoneal cavity of a patient, and wherein the receptacle when in the peritoneal cavity is configured to be in an expanded state when expanded by dialysate in the receptacle.

3. The device of claim 2, wherein the distal end of the tube is a closed end, wherein a second part of the membrane is attached to the distal end of the tube at a distal end of the receptacle, and wherein the tube is provided with perforations along the tube between the proximal part and the distal end of the tube, thereby providing the fluid communication between the lumen of the tube and the closed volume.

4. The device of claim 2, wherein the distal end of the tube is a free open end within the closed volume, thereby providing the fluid communication between the lumen of the tube and the closed volume.

5. The device of any one of claims 2 to 4, wherein the membrane is configured to be compactly provided around the tube when the receptacle is collapsed and to be spread out into a substantially flat membrane defining a balloon-shape for the receptacle when the receptacle is expanded by dialysate in the receptacle.

6. The device of claim 5, wherein the membrane is provided with a configuration of folds known as a herringbone tessellation.

7. The device of claim 1 , wherein the receptacle comprises at least one hollow fibre formed of the membrane, the hollow fibre having an open proximal end and a closed distal end.

8. The device of claim 8, wherein the receptacle comprises a plurality of hollow fibres held together by an inner frame for deployment and retraction of the receptacle.

9. A method of peritoneal dialysis (PD) using a device comprising a receptacle at least partially defined by a biocompatible semi-permeable membrane, wherein the membrane is configured to prevent passage of glucose through the membrane while allowing passage of fluid including waste products from the patient’s blood through the membrane, the method comprising:(a) inserting the receptacle into the peritoneal cavity of the patient;(b) introducing dialysate into the receptacle;(c) allowing PD to occur as a result of the osmotic gradient exerted by the dialysate that draws fluid containing waste products from the patient’s bloodstream across the peritoneum through the membrane into the receptacle while glucose is prevented by the membrane from leaving the receptacle; and(d) removing dialysate from the receptacle.

10. The method of claim 9, further comprising withdrawing the receptacle from the peritoneal cavity of the patient after step (d).11 . A membrane for use in a device for peritoneal dialysis, the membrane configured to at least partially define a receptacle configured to allow a dialysate to be flowed into the receptacle and to hold therein the dialysate when the receptacle is in a peritoneal cavity of a patient, the receptacle further configured to allow the dialysate to be removed from the receptacle, the membrane being biocompatible and semi-permeable, the membrane configured to prevent passage of glucose through the membrane while allowing passage of excess fluid including waste products from the patient’s blood through the membrane.

12. The membrane of claim 11 , wherein the membrane is formed of one or more materials of natural, synthetic, or semi-synthetic origin including ceramics, celluloses, cellophanes, regenerated cellulose, cellulose ester (CE), and polyvinylidene difluoride (PVDF), nanoporous alumina, polysulfone, cellulose triacetate, and polytetrafluoroethylene (PTFE).

13. The membrane of claim 11 or claim 12, wherein the membrane comprises a plurality of pores that are configured to filter substances having a molecular weight ranging from 50 to 20,000.

14. The membrane of any one of claims 11 to 13, wherein the pores each have a pore size ranging from 2 nm to 5 nm and the plurality of pores are spaced apart from one another by a distance ranging from 50 |im to 100 gm.

15. The membrane of claim 14, wherein the pores are provided in an ordered manner and spaced apart by a same distance from one another.

16. The membrane of any one of claims 11 to 15, wherein the membrane has a thickness ranging from 50 pm to 100 .m.

17. The membrane of any one of claims 11 to 16, wherein the membrane has a hydrophilic wetting tension exceeding 80 dynes / cm and a tensile strength exceeding 40 N / m along its weakest axis.

18. The membrane of any one of claims 11 to 17, wherein the membrane is configured to be compactly provided around a tube when the receptacle is collapsed and to be spread out into a substantially flat membrane defining a balloon-shape for the receptacle when the receptacle is expanded by dialysate in the receptacle.

19. The membrane of claim 18, wherein the membrane is provided with a configuration of folds known as a herringbone tessellation.

20. The membrane of any one of claims 11 to 17, wherein the membrane is in the form of a hollow fibre having an open proximal end and a closed proximal end.

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