WO2023033639A1

WO2023033639A1 - A system and method for preparing home-made peritoneal dialysis dialysate

Info

Publication number: WO2023033639A1
Application number: PCT/MY2021/050070
Authority: WO
Inventors: Khing Hong LOKE; Chun Mun LOKE; Mei Juan LOKE
Original assignee: Kaisen Technology Sdn Bhd
Priority date: 2021-09-02
Filing date: 2021-09-02
Publication date: 2023-03-09

Abstract

The present invention relates to a system and method for preparing home-made peritoneal dialysis dialysate, more particularly the present invention relates to a system and method for preparing home-made peritoneal dialysis dialysate, wherein the system comprising a water source (10) for supplying water, and an ultrapure water device (11) for producing water for injection from the water source (10), a first distribution device (21) connected with a first concentrate bag (31) for determining distribution volume of a first concentrate, and a second distribution device (22) connected with second concentrate bag (32) for determining distribution volume of a second concentrate the system is configured for mixing the water for injection, and the first concentrate and the second concentrate for producing home-made peritoneal dialysis dialysate.

Description

A SYSTEM AND METHOD FOR PREPARING HOME-MADE PERITONEAL DIALYSIS DIALYSATE

FIELD OF INVENTION

The present invention relates to a system and method for preparing home-made peritoneal dialysis dialysate, more particularly the present invention relates to a system and method for preparing home-made peritoneal dialysis dialysate via mixing water for injection and dialysate and electrolytes concentrate for producing peritoneal dialysis dialysate for Automated Peritoneal Dialysis (“APD”) and Continuous Ambulatory Peritoneal Dialysis (“CAPD”).

BACKGROUND ART

Peritoneal Dialysis (“PD”) dialysate has to be produced in the Good Manufacturing Practice (“GMP”) certified manufacturing site and regulated by health authority as medicine worldwide. Therefore, PD dialysate, which is home-made, has to fulfil health authority requirements.

There are international standards commonly known as Pharmacopeia such as the United States Pharmacopeia (“USP”), European Pharmacopoeia (“EP”) and Japanese Pharmacopoeia (“JP”), which are specified for the requirements of Water-for-lnjection (“WFI”) use for the preparation of PD dialysate. PD dialysate can be prepared by mixing pharmaceutical ingredients with WFI according to the PD dialysate formulations.

Chronic kidney disease (CKD) is a global health problem which affects approximately 12% of the world’s population, and it is increasing worldwide and has become a concern due to its burden as a huge disease. There were approximately 2.6 million people, globally receiving kidney replacement therapy (KRT) in 2010 and this number is estimated to increase up to 5.4 million by 2030. Dialysis remains the primary mode of KRT for kidney failure patients worldwide and there has been a growing interest in peritoneal dialysis (PD) in view of its clinical advantages, particularly it improved quality of life, and patients are more satisfied over hemodialysis (HD), plus it is cost-effective for healthcare providers, policymaker and payor.

There are three dextrose concentration formulations of PD dialysate for PD patients to perform dialysis at home, which are 1.5% dextrose, 2.5% dextrose and 4.25% dextrose. Nephrologists will prescribe 1.5% dextrose for patients categorized in low transporter profile and 2.5% dextrose for patient categorized in high transporter profile. When patients are experiencing fluid overload, nephrologists will prescribe 4.25% dextrose PD dialysate to help patients to remove excess water from the body. Occasionally, nephrologists might change the prescribed dextrose concentration of the PD dialysate based on the clinical outcome of the patient.

Each PD patient requires to use 8 liters to 10 liters of PD dialysate a day for dialysis at home. This causes service providers to deliver a large volume of dialysate to patient homes via intra or inter cities. In practice, service providers will plan a monthly delivery of PD dialysate to a patient’s home to reduce the transportation costs. Thus, patients will need to have adequate storage space and keep one month supply of PD dialysate at home. When a prescription is changed, service providers will be required to deliver the right PD dialysate to the patient and the unused PD dialysate will become redundant and discarded. This results in wastage of valuable resources, hence increasing cost of home PD.

Traditionally, PD dialysate manufacturers produce 1.5% dextrose, 2.5% dextrose and 4.25% dextrose PD dialysate in large production batch at the GMP certified manufacturing site to optimize production costs and kept as inventory waiting for delivery to patients. The PD dialysate manufactured are subject to shelf life approved by the health authority. It is common that PD dialysate manufacturers will require to discard expired batch of PD dialysate inventory. Recently, there are efforts made by the industry and researchers to develop an on-demand system to prepare hemodialysis acid and bicarbonate concentrate and reconstituted dialysate for hemodialysis treatment at patient’s homes. However, there is no single party currently produces PD dialysates with an on-demand system at home which shows positive outcomes.

There are several prior documents that disclose system and method for preparing dialysis solution. US2021038798A1 discloses an automated peritoneal dialysis (APD) device, system and method, which utilizes mechanisms to admix customized dialysate solutions from multiple sources, while maximizing volumetric accuracy. US2018078690A1 discloses a peritoneal dialysis system which includes a water treatment device including a water treatment processor and a first memory and a peritoneal dialysis (“PD”) machine including a PD processor and a second memory. WO2021016188A2 discloses hollow fiber membrane filtration devices for the production of dialysis fluid by forward osmosis, and a method and system for preparing ready- to-use dialysis fluid from raw water and liquid dialysis concentrate by forward osmosis.

However, the prior art fails to disclose a home-made PD dialysate system to produce PD dialysate at the patient's home by purifying the city tap water (city water) or bottled drinking water into WFI grade as specified by Pharmacopeia, which the WFI produced at home used as an excipient with PD dialysate and electrolytes concentrate which will be used for producing PD dialysate for immediate use as prescribed by nephrologist and renal nurses.

Therefore, there is a need for a system and method for overcoming the challenges of prior art.

SUMMARY OF INVENTION

The present invention aims to provide a system and method for preparing home-made peritoneal dialysis dialysate though tele-prescription by nephrologist and renal nurses. It is an object of the present invention to provide a system for preparing home-made peritoneal dialysis dialysate comprising a water source for supplying water, and an ultrapure water device for producing water for injection from the water source, a first distribution device connected with a first concentrate bag for determining distribution volume of a first concentrate, and a second distribution device connected with second concentrate bag for determining distribution volume of a second concentrate, the system is configured for mixing the water for injection, and the first concentrate and second concentrate for producing peritoneal dialysis dialysate.

It is another object of the present invention to provide a system for preparing home-made peritoneal dialysis dialysate comprising a water source for supplying water, and an ultrapure water device for producing water for injection from the water source, a first distribution device connected with a first concentrate bag for determining distribution volume of a first concentrate, and a second distribution device connected with second concentrate bag for determining distribution volume of a second concentrate, wherein the system is configured for mixing the water for injection, and the first concentrate and second concentrate for producing peritoneal dialysis dialysate, wherein the system comprises a recombination bag for receiving the water for injection, and the first concentrate and the second concentrate for recombining and reconstituting the water for injection with the first concentrate and the second concentrate for producing home-made peritoneal dialysis dialysate.

It is yet another object of the present invention to provide a method for preparing home-made peritoneal dialysis dialysate comprising the steps of initially producing water for injection from a water source, distributing a predetermined volume of a first concentrate and a second concentrate, and mixing the water for injection with the first concentrate and the second concentrate for producing peritoneal dialysis dialysate, wherein the step of mixing the water for injection and the first concentrate and the second concentrate is for recombining and reconstituting the water for injection with the first concentrate and the second concentrate by a recombination bag for producing home-made peritoneal dialysis dialysate.

The system and method of the present invention provides a solution of producing home-made peritoneal dialysis dialysate at every patient's home by using tap water or bottled drinking water, and subsequently purifying the water into water for injection which meets the international pharmacopeia requirement and standards, which helps more kidney patients to benefit from the home peritoneal dialysis in a more cost effective and economical way, and so as to increase worldwide accessibility of dialysis treatment.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

To further clarify various aspects of some embodiments of the present invention, a more particular description of the invention will be rendered by references to illustrations in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the invention and are therefore not to be considered limiting of its scope. The invention will be described and explained with additional specificity and detail through the accompanying drawings in which:

Figure 1 illustrates a schematic representation of the system for preparing home-made peritoneal dialysis dialysate in accordance with the present invention.

Figure 2A illustrates a schematic representation of a pre-treatment module of an ultrapure water device in accordance with the present invention.

Figure 2B illustrates a schematic representation of an ultrafiltration module of an ultrapure water device in accordance with the present invention. Figure 3 illustrates a schematic representation of a first distribution device connected with a first concentrate bag and a second distribution device connected with a second concentrate bag in accordance with the present invention.

Figure 4A illustrates a schematic representation of a first concentrate bag in accordance with the present invention.

Figure 4B illustrates a schematic representation of a second concentrate bag in accordance with the present invention.

Figure 5 illustrates a schematic representation of a 3-way connecting tubing for connecting water for injection source, dextrose or biocompatible osmotic agent concentrate bag and electrolytes concentrate bag to a recombination bag in accordance with the present invention.

Figure 6A illustrates a schematic representation of two recombination bags for automated peritoneal dialysis treatment in accordance with the present invention.

Figure 6B illustrates a schematic representation of a single recombination bag for CAPD (continuous ambulatory peritoneal dialysis) treatment in accordance with the present invention.

Figure 7 illustrates a schematic representation of an application of the system and method for preparing home-made peritoneal dialysis dialysate in accordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Reference will now be made in detail to the preferred embodiments of the present invention, and results of which are illustrated in the accompanying drawings. The applicant has a PCT application with a PCT application number PCT/MY2019/000043 and a national phase application in the United States with the serial number 17/290,202 for an invention titled “SYSTEM FOR PERITONEAL DIALYSIS” claiming an invention directed to a system for peritoneal dialysis comprising a device for receiving dialysis fluid from a fluid package containing the dialysis fluid and delivering the dialysis fluid into peritoneum of a patient via a delivery channel and draining out drain fluids from the patient via a draining channel into a draining package, wherein the device further comprises a fill sensor for monitoring pressure of the delivery channel in the event of delivering the dialysis fluid, and a drain sensor for monitoring pressure of the draining channel in the event of draining out drain fluids, and the device is configured for delivering the dialysis fluid to the patient in a manner that the delivery is based on clinical conditions of the patient, wherein the delivery channel and the draining channel are configured within a Y-connector tubing system, and the Y connector tubing system is connected to an infection detection kit via the draining channel for testing and determining infection in the peritoneum of the patient via the drain fluids. The PCT application has received an International Preliminary Report on Patentability (IPRPII) with positive outcome.

The preferred embodiment of the present invention is applicable for use in the automated portable peritoneal dialysis cycler as claimed in the said PCT application. However, it should be noted that the preferred embodiment of the present invention is a standalone system and method for preparing home-made peritoneal dialysis dialysate, which is applicable to any relevant and compatible peritoneal dialysis cycler for peritoneal dialysis treatment.

Referring to Figure 1, the figure illustrates a schematic representation of the system (505) for preparing home-made peritoneal dialysis dialysate in accordance with the present invention comprising a water source (10) for supplying water, and an ultrapure water device (11) for producing water for injection from the water source (10), a first distribution device (21) connected with a first concentrate bag (31) for determining distribution volume of a first concentrate, and a second distribution device (22) connected with second concentrate bag (32) for determining distribution volume of a second concentrate, wherein the system is configured for mixing the water for injection, and the first concentrate and the second concentrate for producing home-made peritoneal dialysis dialysate. In the preferred embodiment of the present invention, the system (505) is shown comprising more than one recombination bag (14) for receiving the water for injection from the ultrapure water device (11) and for receiving the first concentrate containing dextrose or biocompatible osmotic agent concentrate and for receiving the second concentrate containing electrolytes concentrate from the first distribution devices (21) and the second distribution device (22) for recombining and reconstituting the water for injection with the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate for producing home-made peritoneal dialysis dialysate in the recombination bag (14). The first distribution devices (21) and the second distribution device (22) are preferably configured for determining distribution volume of the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate to the recombination bag (14). The water source (10) is any one of tap water or bottled drinking water, and the water for injection produced from the ultrapure water device (11) and the home-made peritoneal dialysis dialysate produced from the system (505) conform to the international pharmacopeia requirements and standards, especially the US Pharmacopeia (USP) definition of water for injection (WFI) which are requirements and standards specified in feed water use for preparation of dialysate for peritoneal dialysis procedure. Also shown is PD cycler (15) and a channel and package for drain (16) during the peritoneal dialysis procedure.

Referring to Figure 2A and Figure 2B, the figures illustrate, respectively a schematic representation of a pre-treatment module (110A) and internal modules, and an ultrafiltration module (110B) and internal modules, of an ultrapure water device (11) in accordance with the present invention. The ultrapure water device (11) is preferably portable. The process starts from feeding water from a water source (10) either tap water or bottled drinking water into the ultrapure water device (11) and the water flows through multiple stages of filtration processes for purifying feed water and producing water for injection, and of which the water for injection is stored in a pair of 5 liters bag in aseptic condition, and also of which the water for injection conforms to the international pharmacopeia requirements and standards.

The Figure 2A illustrates a water source (10) that feeds water supply to the pre-treatment module (110A) through internal modules in a housing of a pretreatment filter (104) for pretreating water by removing particles and organic compounds from water using polymer fiber material, with a pressure sensor (108) for measuring incoming water pressure, at least a filtration module (105), in which the preferred embodiment of the present invention preferably comprises but not limited to two units of the filtration module (105) for removing organic compounds and free chlorine from water using active carbon material, a pump (106) for stepping up pressure for delivering feed water, and a pair of reverse osmosis filter (107) for reverse osmosis filtration process, and the flow of water continues into the ultrafiltration module (110B) for producing water for injection, of which the water for injection conforms to the international pharmacopeia requirements and standards.

The pretreatment filter (104) is a sediment module that comprises of polymer fiber material for pretreating water by removing large particles and organic compounds from tap water or bottled drinking water, and protects the subsequent filtration components including the reverse osmosis filter (107) against mineral scaling, organic fouling and chlorine oxidation. The filtration module (105) comprises of active carbon material for removing organic compounds and free chlorine from the water source (10). The quality of feed water from the water source (10) should achieve a total dissolved solids level of < 220 ppm (lesser than 220 parts per million) before flowing through the pretreatment filter (104) and the filtration module (105) and the subsequent ultrafiltration module (110B) for producing water for injection which conforms to the international pharmacopeia requirements and standards. The ultrapure water device (11) is configured for receiving feed water from the water source (10) either from tap water or bottled drinking water. Unlike tap water that is supplied from the city water system which has a flow pressure of 96kPa (14 psi) or 100kPa (1 bar), the bottled drinking water does not have a similar flow pressure. In the preferred embodiment of the present invention, there is a pump (106) provided between the filtration module (105) and the pair of reverse osmosis filter (107). The pump (106) will step up the pressure for delivering feed water from either tap water or bottled drinking water which conforms to the international guidelines, more particularly to the World Health Organization (WHO) guidelines for drinking- water quality that flows through the pretreatment filter (104) and the filtration module (105) to the pair of reverse osmosis filter (107). The pump (106) ensures consistent flow rate of treated water from the pretreatment filter (104) and filtration module (105) to the pair of reverse osmosis filter (107) for achieving required output volume.

The pair of reverse osmosis filter (107) comprise of a two-stage reverse osmosis filtration process. Each of reverse osmosis filter (107) is composed of 3 layers of materials, which are the ultra-thin layer of polyamide barrier film, intermediate layer of microporous size polysulfide filtration material and a polyester core support structure. The pair of reverse osmosis filter (107) removes heavy metal ions, sub-visible particles, organic compounds and bacteria. Treated water after the reverse osmosis filter (107) is able to achieve a level of < 10 parts (lesser than 10 parts) per billion of total organic compounds, a resistivity level of > 18 (more than 18) megohm centimeters at room temperature, a conductivity level of < 0.05 (lesser than 0.05) microsiemens per centimeter at room temperature and < 0.1 (lesser than 0.1) colony forming units per milliliters which comply with international pharmacopeia requirements as purified water. The reverse osmosis filter (107) in pair modules according to the preferred embodiment is able to produce a consistent flow rate of one liter every two minutes. However, it should be noted that the reverse osmosis filter (107) is not limited to a single or paired units. The pressure sensor (108) is provided after the pretreatment filter (104) sediment module. The pressure sensor (108) is for measuring incoming water pressure after the pretreatment filter (104) for ensuring the incoming feed water pressure meets the system requirement and ensuring the reverse osmosis filter (107) is able to remove heavy metal ions, sub-visible particles, organic compounds and bacteria. The pressure sensor (108) serves as an indicator of the remaining lifespan of the pair of reverse osmosis filter (107) modules and configured for providing an indicator for replacement of the pair of reverse osmosis filter (107).

The Figure 2B illustrates the internal modules in a housing of the ultrafiltration module (110B) including a microprocessor (102) for decoding and processing information, and an embedded scanner (103) for receiving tele-prescription information, and the flow of water continues from the pre-treatment module (110A) of the ultrapure water device (11) into at least an ultrafiltration filter (110), in which the preferred embodiment of the present invention comprises and an ultraviolet disinfection device (109) for disinfecting residual of organic compounds and bacteria, preferably but not limited to four units of the ultrafiltration filter (110) for membrane filtration of water, an endotoxin filter (111) for filtering endotoxin from water passing through, a peristaltic pump (112) for delivering a predetermined volume of water for injection based on an algorithm generated by the microprocessor (102) after decoding the tele-prescription information from the embedded barcode scanner (103), and a dispensing port (113) for dispensing the water for injection. The ultraviolet disinfection device (109) is for disinfecting residual of bacteria, viruses, molds, algae, and other microorganisms that passed through the pair of reverse osmosis filter (107) shown in Figure 2A. The ultraviolet disinfection device (109) produces 185 to 253.7 nanometer wavelength ultraviolet light which can inactivate or destroy the DNA of microorganisms and prevent microorganisms from growing.

The ultrafiltration filter (110) is a filtration device that have a pore size around 0.01 to 0.05 micron and functions as a molecular sieve. It separates dissolved molecules based on size, often known as the molecular weight. The ultrafiltration filter (110) is composed of a tough, thin, selectively permeable membrane that retains most macromolecules above the size of 0.1 micron including colloids, microorganisms and pyrogens. Only pyrogen-free water with molecules size of smaller than 0.01 to 0.05 micron are allowed to pass through.

The last filtration module is the endotoxin filter (111). The USP has defined the requirements for water for injection which allows a lower value of 0.25 unit of measurement for endotoxin activity per milliliter. The treated water with molecules smaller than 0.01 micron from multiple stages of ultrafiltration is fed into the endotoxin filter (111) as feed water. The endotoxin filter (111) is composed of filtration material with a pore size of 0.02 micron which only allows endotoxin free water to pass through its filtration. The peristaltic pump (112) delivers the endotoxin free water for injection produced to the dispensing port (113) and the water for injection is stored in a pair of 5 liters bag in aseptic condition for the next process of recombination with dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate and reconstitute into the prescribed home made on-demand dialysate solution. Based on the algorithm generated by microprocessor (102), the system (505) is able to produce variable volume of water for injection and recombine with dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate and reconstituted into a series of peritoneal dialysis dialysate prescribed by a nephrologist via tele-prescription.

Referring to Figure 2A and Figure 2B, the original feed water either from tap water or bottled drinking water of the water source (10) will be purified into water for injection which conforms to the international pharmacopeia requirements and standards, after the water passes through the multiple stages of the pretreatment filter (104) and the filtration module (105) to the reverse osmosis filter (107), the ultraviolet disinfection device (109), the ultrafiltration filter (110) and the endotoxin filter (111). This ultrapure water for injection produced by the system (505) is subsequently used as feed water for the subsequent recombination process and reconstitute into the prescribed home-made on-demand peritoneal dialysis dialysate solution.

Referring to Figure 3, the figure illustrates a schematic representation of a first distribution device (21) connected with a first concentrate bag (31) of dextrose or biocompatible osmotic agent concentrate, and a second distribution device (22) connected with a second concentrate bag (32) of electrolytes concentrate in accordance with the present invention. The first distribution device (21) and the second distribution device (22) are for dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate distribution respectively, and are configured for determining variable volume of the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate by a microprocessor and an embedded barcode scanner for scanning and decoding tele-prescription into an algorithm, and configured for controlling a peristaltic pump and controlling a solenoid valve for administering a predetermined volume of the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate required into the recombination bag (14) for the recombination process with water for injection and reconstitute prescribed dialysate according to embedded tele-prescription by the nephrologist and renal nurse. The first distribution device (21) and the second distribution device (22) are preferably configured for determining variable volume of dextrose or biocompatible concentration and electrolytes concentrate.

The function of the first distribution device (21) and the second distribution device (22) are for administering a set volume of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate, via a tubing configuration. The first distribution device (21) is shown in Figure 3, connected with first concentrate bag (31) via a tubing (202), and the second distribution device (22) is connected with second concentrate bag (32) via another tubing (202). Further, it is shown in the Figure 3 that a 3-way connection tube (201) is used for connecting the first distribution device (21) and the second distribution device (22) to the recombination bag (14) for recombination process of the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate with water for injection.

The distribution process is initiated by a user, scanning an embedded barcode at the barcode scanner of the first distribution device (21) and the second distribution device (22), received via tele-prescription from cloud computing to the user’s for activating the the first distribution device (21) and the second distribution device (22). The barcode scanner then decodes the tele-prescription into an algorithm and processed by the microprocessor. The peristaltic pump will then administer the set volume of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate into the recombination bag (14). Also, the microprocessor generates an algorithm for instructing the solenoid valve to open and to allow the peristaltic pump to start administering the set volume of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate into the recombination bag (14) and for the solenoid valve to close when the set volume of dextrose or biocompatible osmotic agent concentrate, and electrolytes concentrate have been completed distribution into the recombination bag (14).

Based on the algorithm generated by the microprocessor, the first distribution device (21) and the second distribution device (22) are able to distribute variable volume of dextrose or biocompatible osmotic agent concentrate, and electrolytes concentrate and recombine with water for injection in the dialysate recombination bag (14) into a series of peritoneal dialysis dialysate prescribed by a nephrologist via tele-prescription.

Referring to Figure 4A and Figure 4B, the figures illustrate, respectively a schematic representation of the first concentrate bag (31) of dextrose or biocompatible osmotic agent concentrate and the second concentrate bag (32) of electrolytes concentrate in accordance with the present invention. The first concentrate bag (31) and the second concentrate bag (32) are preferably made of medical grade polymer film with a closure system which conforms to the international pharmacopeia requirements and standards.

The Figure 4A shows a first concentrate bag (31) in a 600ml of 50% dextrose concentrate or appropriate biocompatible concentrate solution. The 50% dextrose concentrate solution is used for recombination and reconstitution of 1.5%, 2.5% and 4% (or higher) dextrose concentration peritoneal dialysis solution and widely prescribed for use, except for patients which experience low ultrafiltration rate during long dwell. End stage kidney failure patients are not able to discharge additional water from the body through urination. When the water is building up in the patient's body, the patient is required to discharge the excess water through dialysis. In this situation, the peritoneal dialysis patients will need to use a high concentration of dextrose peritoneal dialysis solution to extract the water during dwell time of the peritoneal dialysis exchange by using a 4% or higher dextrose concentration to remove the excess water from patient’s body using the 4% or higher dextrose concentration to extract the water content in the blood verses across the peritoneum membrane during dwell time.

The appropriate biocompatible concentrate solution is specifically used for patients which experience low ultrafiltration for long dwell. There are end stage kidney failure patients which require a longer dwell exchange to remove the excess water through dialysis in order to achieve a better ultrafiltrate outcome. In this situation, the peritoneal dialysis patients will need to use an appropriate biocompatible peritoneal dialysis solution using non-dextrose as an osmotic agent to extract the water during the longer dwell time of the peritoneal dialysis exchange to protect the peritoneum membrane from deterioration due to dextrose degradation products. This biocompatible peritoneal dialysis solution is usually prescribed at the end of peritoneal dialysis exchange during the last filling. The Figure 4B shows a second concentrate bag (32) in a 500ml of electrolytes concentrate solution which contains of Sodium Chloride (NaCI) 53.8 g, Calcium Chloride (CaCI2 2H2O) 1.83 g, Magnesium Chloride (MgCI2 6H2O) 0.508 g, and Sodium Lactate (C3H5NaO3) 44.8 g. The electrolytes concentrate is used to maintain electrolytes balance in the patient’s body.

Referring to Figure 5, the figure illustrates a schematic representation of a 3-way connection tube (201) for connecting water for injection source, dextrose or biocompatible osmotic agent concentrate bag and electrolytes concentrate bag to a recombination bag in accordance with the present invention. The 3-way connection tube (201) is a medical grade PVC tube, which conforms to the international pharmacopeia requirements and standards, with an internal diameter of 3.0mm to 3.2mm and an outer diameter of 4.0mm to 4.2mm, and each end of the 3-way connection tube (201) is connected with a luer lock connector (203).

Referring to Figure 6A, the figure illustrates a schematic representation of a single (2L bag) and a twin (8L bag) recombination bag (14) in accordance with the present invention, and in this embodiment, the present invention is for automated peritoneal dialysis treatment, in that a user is required to use each recombination bag (14) for automated peritoneal dialysis treatment. The illustrated recombination bags are used in the “2L + 8L system” for fluid extraction and is configured to solve the health problem associated with excess fluid retention in the patient's body. The “2L + 8L system” is used to prepare a bag of 2 liters volume of peritoneal dialysis dialysate with 4% (or higher) dextrose concentration peritoneal dialysis solution to increase the osmosis impact to remove excess water in the blood verses across the peritoneum membrane during the first dwell exchange from the patients.

The “2L + 8L system” comprises 2 recombination bags, that are the 2 liters recombination bag (14) and the 8 liters recombination bag (14). The 8 liters recombination bag (14) preferably comprises a configuration of twin 4 liters bag, connected via bridge tubing (306). Each recombination bag (14), i.e. the 2 liters recombination bag (14) and the 8 liters recombination bag (14), each of which comprises an inlet (302) with a connector (305), and an outlet (301) with a cycler port (304). Connector (305) is connected to a 3-way connection tube (201) shown in Figure 5 in an aseptic manner via luer lock connector (203). The cycler port (304) is subsequently connected to an automated peritoneal dialysis tubing set in an aseptic manner. The outlet (301) is fitted with a cycler port (304) for connection with an automated peritoneal dialysis cycler which delivers the recombined and reconstituted peritoneal dialysis solutions to patients in an automated peritoneal dialysis treatment.

The inlet (302) is known as the port for water for injection, dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate, and the outlet (301) is known as the port for dialysate. The connector (305) at the inlet (302) is preferably an infection prevention connector.

The first step is to prepare the recombination process for the 2 liters bag. The process starts with connecting the 3-way connection tube (201) with the inlet (302) by twisting the female luer connector (203) of the 3-way connection tube (201) in clockwise direction onto the infection prevention connector (305) at the inlet (302) of the 2 liters bag. The 3-way connection tube (201), and the luer connectors (203) are as shown in Figure 5.

As described in the foregoing description, the process is initiated by a user, by scanning an embedded barcode at the barcode scanner of the first distribution device (21) and the second distribution device (22) shown in the Figure 3, of which the barcode is received via teleprescription from cloud computing to the user’s mobile device for activating the first distribution device (21) and the second distribution device (22). The barcode scanner then decodes the tele-prescription into an algorithm and processed by the microprocessor. Subsequently, a set volume of the water for injection will be produced and a set volume of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate are distributed to the 2 liters recombination bag (14) for recombination and reconstitution into peritoneal dialysis dialysate with 4% (or higher) dextrose concentration peritoneal dialysis solution.

Upon completion of the delivery of water for injection and distribution of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate into the 2 liters bag, the system will alert the user that the recombination process has been completed and further instructs the users to disconnect the 2 liters recombination bag (14) and prepare for the recombination process of the 8 liters recombination bag (14).

For disconnecting the 2 liters recombination bag (14), the user is required to disconnect the 3- way connection tube (201) from the inlet (302) of the 2 liters recombination bag (14) by twisting the female luer connector (203) in anti-clockwise direction from the infection prevention connector (305) at the inlet (302). The 3-way connection tube (201), and the luer connectors (203) are as shown in Figure 5. For the preparation of 8 liters recombination bag (14) for recombination process and reconstitution into peritoneal dialysate with either 1.5% or 2.5% dextrose concentration peritoneal dialysis solution prescribed by nephrologist via teleprescription, the user initiates by re-connecting the 3-way connection tube (201) with the inlet (302) by twisting the female luer connector (203) in clockwise direction onto the infection prevention connector (305) at the inlet (302) of the 8 liters bag.

There are end stage kidney failure patients which require a longer dwell exchange to remove the excess water through dialysis in order to achieve a better ultrafiltrate outcome. In this situation, the peritoneal dialysis patients will need to use a biocompatible peritoneal dialysis solution using non-dextrose as an osmotic agent to extract the water during the longer dwell time of the peritoneal dialysis exchange to protect the peritoneum membrane from deterioration due to dextrose degradation products. This biocompatible peritoneal dialysis solution is usually prescribed at the end of peritoneal dialysis exchange during the last fill. The following table 1 shows the compositions of dialysate reconstituted at home for extra fluid extraction under automated method:

Referring again to Figure 6A, the figure illustrates a schematic representation of a single (2L bag) and a twin (8L bag) recombination bag (14) in accordance with the present invention, and in another preferred embodiment, the present invention is used for automated peritoneal dialysis treatment, of which the illustrated recombination bags are used in the “8L + 2L system” for long dwell to fill a 2 liters biocompatible peritoneal dialysis solution at the last exchange for better ultrafiltration outcome to the patient. The “8L + 2L system” is for preparing 8 liters recombination bag (14) dialysate volume of either 1.5% or 2.5% dextrose concentration peritoneal dialysis solution for the initiate exchange and a 2 liters recombination bag (14) with biocompatible peritoneal dialysis solution at the last exchange. The “8L + 2L system” comprises 2 recombination bags, that are the 8 liters recombination bag (14) and the 2 liters recombination bag (14). The 8 liters recombination bag (14) preferably comprises a configuration of twin 4 liters bag, connected via bridge tubing (306). Each recombination bag (14), i.e. the 2 liters recombination bag (14) and the 8 liters recombination bag (14), each of which comprises an inlet (302) with a connector (305), and an outlet (301) with a cycler port (304). Connector (305) is connected to a 3-way connection tube (201) shown in Figure 5 in an aseptic manner via luer lock connector (203). The cycler port (304) is subsequently connected to an automated peritoneal dialysis tubing set in an aseptic manner. The outlet (301) is fitted with a cycler port (304) for connection with an automated peritoneal dialysis cycler which delivers the recombined and reconstituted peritoneal dialysis solutions to patients in an automated peritoneal dialysis treatment.

The first step is to prepare the recombination process for the 8 liters bag. The process starts with connecting the 3-way connection tube (201) with the inlet (302) by twisting the female luer connector (203) of the 3-way connection tube (201) in clockwise direction onto the infection prevention connector (305) at the inlet (302) of the 8 liters bag. The 3-way connection tube (201), and the luer connectors (203) are as shown in Figure 5.

As described in the foregoing description, the process is initiated by a user, by scanning an embedded barcode at the barcode scanner of the first distribution device (21) and the second distribution device (22) shown in the Figure 3, of which the barcode is received via teleprescription from cloud computing to the user’s mobile device for activating the first distribution device (21) and the second distribution device (22). The barcode scanner then decodes the tele-prescription into an algorithm and processed by the microprocessor. Subsequently, a set volume of the water for injection will be produced and a set volume of dextrose or biocompatible osmotic agent concentrate and one bag of electrolytes concentrate is distributed to the 8 liters recombination bag (14) process and reconstitution into peritoneal dialysis dialysate with either 1.5% or 2.5% dextrose concentration peritoneal dialysis solution.

Upon completion of the delivery of water for injection and distribution of dextrose or biocompatible osmotic agent concentrate and one bag of electrolytes concentrate into the 8 liters bag, the system will alert the user that the recombination process has been completed and further instructs the users to disconnect the 8 liters recombination bag (14) and prepare for the recombination process of the 2 liters recombination bag (14).

For disconnecting the 8 liters recombination bag (14), the user is required to disconnect the 3- way connection tube (201) from the inlet (302) of the 8 liters recombination bag (14) by twisting the female luer connector (203) in anti-clockwise direction from the infection prevention connector (305) at the inlet (302) of the 8 liters recombination bag (14). The 3-way connection tube (201), and the luer connectors (203) are as shown in Figure 5.

For the preparation of 2 liters recombination bag (14) for recombination and reconstitution of peritoneal dialysate prescribed by nephrologist via tele-prescription, the user initiates by reconnecting the 3-way connection tube (201) with the inlet (302) by twisting the female luer connector (203) in clockwise direction onto the infection prevention connector (305) at the inlet (302) of the 2 liters recombination bag (14).

The following table 2 shows the compositions of dialysate reconstituted at home for long dwell with biocompatible solution under automated method:

Referring to Figure 5 and Figure 6A, the tube connection techniques as described are aseptic connection which prevent microbial contamination in the dextrose or biocompatible osmotic agent in the first concentrate bag (31) or electrolytes concentrate in the second concentrate bag (32), in the 3-way connection tube (201), and in the recombination bag (14). There are connectors such as the infection preventive connector (305) used in the recombination and reconstitute processes. The infection preventive connector (305) have multiple advantages including a smooth flat surface silicon material as closure which acts as compression seal that can withstand 200kPa (2 bar) pressure resistance which prevents airborne particulate contamination, allows easy disinfection and prevents microbial growth. The infection preventive connector (305) is used to protect the recombination bag (14), the 3-way connection tube (201) and to comply with aseptic conditions at all times during the recombination and reconstitute processes. The outlet (301) is fitted with a cycler port (304) for connection with an automated peritoneal dialysis cycler which delivers the recombined and reconstituted peritoneal dialysis solutions to patients in an automated peritoneal dialysis treatment. Referring to Figure 6B, the figure illustrates a schematic representation of a single recombination bag (14) in accordance with the present invention for an automated recombination process for continuous ambulatory peritoneal dialysis (CAPD) treatment, wherein a user is only required to connect one single bag in a “2L system” for the recombination and reconstitution process. The recombination bag (14) comprises an inlet (302) with a connector (305) and an outlet (301) with a CAPD port (307), wherein the inlet (302) is connected in a 3-way tubing configuration, via a 3-way connection tube (201). The 3-way connection tube (201) and the luer connectors (203) are as shown in Figure 5.

The process starts with connecting the 3-way connection tube (201) with the inlet (302) by twisting the female luer connector (203) of the connection tube (201) in clockwise direction onto the infection prevention connector (305) at the inlet (302) of the 2 liters bag. Connector (305) is connected to 3-way connection tube (201) in an aseptic manner, and the CAPD port (307) is connected to CAPD bags in an aseptic manner. The recombination and reconstitution process involves an automated delivery of water for injection and distribution of dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate into the recombination bag (14) in the “2L system” for automated recombination and reconstitution.

There is an advantage of the automated recombination and reconstitution using the recombination bag (14) as shown in Figure 6A and Figure 6B, wherein the water for injection and the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate delivery into the recombination bag (14) are both combined and mixed at the 3-way tubing configuration at the inlet (302) before entering the recombination bag (14). In this configuration, the water for injection and dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate are continuously delivered into the recombination bag (14) and mix evenly during the entire process of recombination and reconstitution of the home-made peritoneal dialysis solution into the recombination bag (14).

The following table 3 shows the compositions of dialysate reconstituted at home for extra fluid extraction or long dwell with biocompatible solution under automated method:

The said each connector (305) in Figure 6A and Figure 6B, is configured for recombining the water for injection and the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate in an aseptic manner.

Referring to Figure 7, the figure illustrates a schematic representation of an application of the system and method for preparing home-made peritoneal dialysis dialysate in accordance with the present invention, wherein the system (505) is connected to internet of things. In the preferred embodiment of the present invention, the system (505) is shown connected to a cloud computing network, connecting a user (which is the peritoneal dialysis patient) with Bluetooth enabled device such as to receive embedded barcode, embedded barcode scanner provided by the system (505) for receiving embedded tele-prescription over cloud computing prescribed by a nephrologist and renal nurses for users to perform recombination and reconstitution process for producing peritoneal dialysis dialysate at home in aseptic conditions. Referring to Figure 1 , Figure 2A, Figure 2B, Figure 3, Figure 4A, Figure 4B, Figure 5, Figure 6A, Figure 6B, and Figure 7, there is provided a method for preparing home-made peritoneal dialysis dialysate comprising the steps of initially producing water for injection from a water source (10), then distributing a predetermined volume of a first concentrate and a second concentrate, and mixing the water for injection with the first concentrate and the second concentrate for producing peritoneal dialysis dialysate, and mixing the water for injection with the first concentrate and the second concentrate for producing peritoneal dialysis dialysate, in that step of mixing the water for injection and the first concentrate and the second concentrate is for recombining and reconstituting the water for injection with the first concentrate and the second concentrate by a recombination bag (14). The water source (10) is any one of tap water or bottled drinking water, and the water for injection is conforms to the international pharmacopeia, as well as the home-made peritoneal dialysis dialysate conforms to international pharmacopeia, wherein recombining and reconstituting the water for injection with the dextrose or biocompatible osmotic agent concentrate and electrolytes concentrate, is in aseptic manner. The first concentrate preferably is any one of dextrose or biocompatible osmotic agent concentrate, and the second concentrate is preferably an electrolyte concentrate, and wherein the method is automated.

The present invention may be embodied in other specific forms without departing from its essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore indicated by the appended claims rather than by the foregoing description. All changes, which come within the meaning and range of equivalency of the claims, are to be embraced within their scope.

Claims

26

1. A system for preparing home-made peritoneal dialysis dialysate comprising: a water source (10) for supplying water, an ultrapure water device (11) for producing water for injection from the water source (10), a first distribution device (21) connected with a first concentrate bag (31) for determining distribution volume of a first concentrate, and a second distribution device (22) connected with second concentrate bag (32) for determining distribution volume of a second concentrate; the system is configured for mixing the water for injection, and the first concentrate and the second concentrate for producing peritoneal dialysis dialysate; characterized in that the system comprises a recombination bag (14) for receiving the water for injection, and the first concentrate and the second concentrate for recombining and reconstituting the water for injection with the first concentrate and the second concentrate for producing peritoneal dialysis dialysate.

2. The system according to claim 1 , wherein the water source (10) is any one of tap water or bottled drinking water that conforms to international guidelines of drinking-water quality.

3. The system according to claim 1, wherein the water for injection conforms to the international pharmacopeia.

4. The system according to claim 1 , wherein the home-made peritoneal dialysis dialysate conforms to the international pharmacopeia.

5. The system according to claim 1 , wherein the ultrapure water device (11) comprises a pretreatment module (100A) and an ultrafiltration module (100B).

6. The system according to claim 5, wherein the pretreatment module (100A) comprises: a pretreatment filter (104) for pretreating water by removing particles and organic compounds from water using polymer fiber material; a pressure sensor (108) for measuring incoming water pressure; at least a filtration module (105) for removing organic compounds and free chlorine from water using active carbon material; a pump (106) for stepping up pressure for delivering feed water; and a pair of reverse osmosis filter (107) for reverse osmosis filtration process.

7. The system according to claim 5, wherein the ultrafiltration module (100B) comprises: a microprocessor (102) for decoding and processing information; an embedded scanner (103) for receiving tele-prescription information; a disinfection device (109) for disinfecting residual of bacteria, viruses, molds, algae, and other microorganisms; at least an ultrafiltration filter (110) for membrane filtration of water; an endotoxin filter (111) for filtering endotoxin from water passing through; a peristaltic pump (112) for delivering a predetermined volume of water for injection based on algorithm generated by the microprocessor (102) after decoding the teleprescription information from the embedded barcode scanner (103); and a dispensing port (113) for dispensing the water for injection.

8. The system according to claim 1 , wherein the first distribution device (21) is configured for determining variable volume of the first concentrate by a microprocessor and an embedded barcode scanner for scanning and decoding tele-prescription into an algorithm and controlling a peristaltic pump and controlling a valve for administering a predetermined volume of the first concentrate into the recombination bag (14).

9. The system according to claim 1 , wherein the second distribution device (22) is configured for determining variable volume of the second concentrate by a microprocessor and an embedded barcode scanner for scanning and decoding tele-prescription into an algorithm and controlling a peristaltic pump and controlling a valve for administering a predetermined volume of the first concentrate into the recombination bag (14).

10. The system according to claim 1 , wherein the first concentrate is any one of dextrose or biocompatible osmotic agent concentrate.

11. The system according to claim 1 , wherein the first concentrate comprises composition of 50% Dextrose Monohydrate in 600ml bags.

12. The system according to claim 1 , wherein the second concentrate is an electrolyte concentrate in 500ml bag.

13. The system according to claim 1 , wherein the second concentrate comprises compositions of Sodium Chloride (NaCI) 53.8 g, Calcium Chloride (CaCI2 2H2O) 1.83 g, Magnesium Chloride (MgCI2 6H2O) 0.508 g, and Sodium Lactate (C3H5NaO3) 44.8 g.

14. The system according to claim 1 , wherein the home-made peritoneal dialysis dialysate is used for automated peritoneal dialysis treatment.

15. The system according to claim 1 or 14, wherein the recombination bag (14) for automated peritoneal dialysis treatment subsists as a single or twin bag.

16. The system according to claim 15, wherein the recombination bag (14), comprises an inlet (302) with a connector (305), and an outlet (301) with a cycler port (304).

17. The system according to claim 15, wherein the connector (305) is connected to a 3-way connection tube (201) in an aseptic manner. 29 The system according to claim 15, wherein the cycler port (304) is connected to an automated peritoneal dialysis tubing set in an aseptic manner. The system according to claim 1 , wherein the home-made peritoneal dialysis dialysate is used for continuous ambulatory peritoneal dialysis treatment. The system according to claim 1 or 19, wherein the recombination bag (14) comprises an inlet (302) with a 3-way connector (305) and an outlet (301) with a port (307) and are connected in a 3-way tubing configuration. The system according to claim 20, wherein the connector (305) is connected to a 3-way connection tube (201) in an aseptic manner. The system according to claim 20, wherein the port (307) is connected in an aseptic manner. The system according to claim 1 , wherein the system is connected to internet of things. A method for preparing home-made peritoneal dialysis dialysate comprising the steps: producing water for injection from a water source (10); distributing a predetermined volume of a first concentrate and a second concentrate, and mixing the water for injection with the first concentrate and the second concentrate for producing peritoneal dialysis dialysate; characterized in that the step of mixing the water for injection and the first concentrate and the second concentrate is for recombining and reconstituting the water for injection with the first concentrate and the second concentrate by a recombination bag (14). 30

25. The method according to claim 24, wherein the water source (10) is any one of tap water or bottled drinking water that conforms to international guidelines of drinking-water quality.

26. The method according to claim 24, wherein the water for injection is conforms to the international pharmacopeia.

27. The method according to claim 24, wherein the home-made peritoneal dialysis dialysate conforms to international pharmacopeia.

28. The method according to claim 24, wherein recombining and reconstituting the water for injection with the first concentrate and the second concentrate, is in aseptic manner.

29. The method according to claim 24, wherein the first concentrate is any one of dextrose or biocompatible osmotic agent concentrate.

30. The method according to claim 24, wherein the second concentrate is an electrolyte concentrate.

31 . The method according to claim 24, wherein the method is automated.