Flexible bag for dialysis concentrate with sealed overpouch - Patent application

Abstract

The present invention relates to a disposable flexible bag for dialysis concentrate that includes a primary bag and an overpouch designed to ensure that the overpouch remains on the primary bag during use of the concentrate to prevent water evaporation that may lead to an out-of-specification condition towards the end of the use period.

Description

[Technical Field]

[0001] The present invention relates to a disposable flexible bag for dialysis concentrates, comprising a primary bag and an overpouch. The bag arrangement is designed to ensure that the overpouch remains on the primary bag during use of the concentrate to prevent water evaporation, which may lead to an out-of-specification condition towards the end of the use period. The present invention is primarily targeted at concentrates intended for multi-day use, where water loss may be an issue. [Background technology]

[0002] Peritoneal dialysis (PD) is a type of dialysis therapy commonly used to treat loss of kidney function. Peritoneal dialysis uses a dialysis solution (also called dialysate) that is infused into the patient's peritoneal cavity through a catheter implanted in the peritoneal cavity. The dialysate contacts the patient's peritoneal membrane, which is located within the peritoneal cavity. Waste, toxins, and excess water flow from the patient's bloodstream through the peritoneal membrane and into the dialysate. The movement of waste, toxins, and water from the bloodstream into the dialysate occurs due to diffusion and osmotic pressure; i.e., an osmotic gradient occurs across the peritoneal membrane. The used dialysate is drained from the patient's peritoneal cavity, removing the waste, toxins, and excess water from the patient. The above-described cycle is then repeated.

[0003] There are various types of peritoneal dialysis treatments, including continuous ambulatory peritoneal dialysis ("CAPD"), automated peritoneal dialysis ("APD"), and continuous flow peritoneal dialysis ("CFPD").

[0004] CAPD is a manual dialysis treatment in which a patient connects an implanted catheter to a drain, allowing used dialysate to drain from the peritoneal cavity. The patient then manually allows unused dialysate to flow from the solution bag, through the patient's indwelling catheter, and into the patient's peritoneal cavity. The patient then disconnects the catheter from the solution bag, allowing the dialysate to dwell in the peritoneal cavity in order to transfer waste, toxins, and excess water from the patient's bloodstream into the dialysate. After the dwell period, the patient may repeat the manual procedure described above. In CAPD, patients perform the drain, fill, and dwell cycle several times a day, for example, approximately four times a day.

[0005] Automated peritoneal dialysis ("APD") is similar to CAPD in that the dialysis treatments include drain, fill, and dwell cycles. However, APD machines automatically perform three to four cycles of peritoneal dialysis treatments, typically overnight while the patient sleeps. Typically, APD machines are fluidly connected to an implanted catheter, one or more solution bags, and a drain bag.

[0006] An APD machine pumps fresh dialysate from a dialysate source through a catheter into the patient's peritoneal cavity, allowing the dialysate to dwell in the cavity to allow for the transfer of waste, toxins, and excess water from the patient's bloodstream into the dialysate solution. The APD machine then pumps used dialysate from the peritoneal cavity through the catheter and into a drain. APD machines are typically computer-controlled so that dialysis treatment occurs automatically when the patient is connected to the dialysis machine, for example, while the patient is asleep. That is, the APD system automatically and continuously pumps fluid into the peritoneal cavity, allows dwell, and then repeats the process of pumping fluid out of the peritoneal cavity.

[0007] Similar to the manual process, several drain, fill, and dwell cycles occur during APD. A "final fill" is typically used at the end of APD and remains in the patient's peritoneal cavity when the patient is disconnected from the dialysis machine for the day. APD eliminates the need for the patient to manually perform the drain, dwell, and fill steps.

[0008] As mentioned above, both CAPD and APD involve the use of solution bags containing fluids pumped into the patient's peritoneal cavity. The preparation of such bags requires great care and skill. The bags must be leak-proof, the materials from which they are made must be safe and sufficiently inert to avoid the leakage of substances into the fluid that could unintentionally transfer to the patient, the materials must be strong and flexible enough to withstand manufacturing, handling, and storage, and must not be opaque to allow visual inspection of the contents, for example, to identify undesirable discoloration or precipitation. Of course, the bags must be made within specific specifications. The solution bag and its contents must also be sterilizable to a level such that the solution is safe for delivery to the patient. Finally, the bags must also be properly labeled so that the user or caregiver can ensure the patient is receiving the correct PD solution.

[0009] The dialysate used in all of the above dialysis techniques primarily contains electrolytes such as sodium, magnesium, calcium, potassium, an acid / base buffer system, and optionally glucose or glucose-like compounds. All components in the dialysate are selected to control the level of electrolytes and acid-base balance in the blood and, in the case of glucose or glucose-like compounds, to remove waste materials from the blood by establishing an osmotic gradient.

[0010] As is clear from the above, patients require large amounts of ready-to-use PD fluid daily to perform the necessary steps. These large amounts of PD fluid must be prepared, transported, and then stored at the patient's home, which adds cost to treatment and burden to the patient and their caregivers. Therefore, ready-to-use PD fluid should preferably be prepared in the patient's home from different types of concentrates by mixing the PD concentrate with purified water, which is also prepared in the patient's home. In such cases, the concentrate is typically provided in a bag, while the purified water required for mixing is provided, for example, from a water purification device that purifies tap water. The concentrate is typically provided in two parts: a buffer concentrate with electrolytes having a nominal dilution factor of about 20, and a glucose concentrate containing 50% glucose, both having a volume of, for example, 1 L. Electrolytes can also be provided separately from the buffer in two different concentrates.

[0011] The use of multi-therapy concentrates allows for cost savings due to shipping less product with less weight and volume per treatment, reducing waste due to less container material required per treatment, and reducing patient burden because unpacking, placing, and connecting the smaller, less heavy concentrate containers can be done at intervals greater than daily changes, e.g., 7-14 days.

[0012] In the medical field, primary bags are used to receive, store, transport, and ultimately deliver dialysis solutions. Often, these primary bags are placed within a secondary container, such as an overpouch, to maintain the integrity and volume of the medication contained within the primary container. The overpouch is typically removed or opened before use to expose the primary bag and connect it to a tubing set, as described, for example, in International Publication Nos. 2004 / 066857 and 2006 / 116287, which disclose easily openable overpouches that allow for easy insertion and removal of the primary bag. The overpouch is then typically discarded.

[0013] The mix of such concentrates is predetermined in both manual and automated procedures based on the concentrate specifications, so evaporation of water from the bag must be avoided as long as the concentrate is used to prepare ready-to-use dialysis fluid for PD treatment.

[0014] During storage and transport of the concentrate, water evaporation is essentially prevented by the overpouch. However, the evaporation rate increases significantly before and during use when the overpouch is removed, which can occur at elevated temperatures, or at least at room temperature, and can last up to four or five days. In addition, the evaporation rate relative to the volume held by the concentrate bag increases during use because the concentrate's surface-to-volume ratio increases as the concentrate volume decreases faster than the container surface available for water diffusion from the container. This means that the rate at which the concentrate concentration increases increases over use, reaching its highest point toward the end of the use period. Therefore, there is a risk that the concentrate concentration will be out of specification, especially toward the end of use.

[0015] Therefore, there is a need for a method for reducing or preventing the concentration buildup of concentrates used to prepare PD fluids during use, including providing a disposable flexible bag for dialysis concentrates that is designed to prevent or at least reduce water evaporation during use. The present invention provides a solution to this problem, which can have serious consequences for patients. Summary of the Invention

[0016] The Applicant is faced with the problem of developing a disposable flexible bag for dialysis concentrate that is suitable for preventing or at least reducing evaporation of water during the time of use, which entails an increase in the concentration of the dialysis concentrate and, consequently, the risk of preparing a dialysis solution for use in PD that does not have the final concentration required for the treatment.

[0017] After extensive experimentation, the applicant has found a solution that allows for maintaining an overpouch that can be used for the complete life of the concentrate product, including sterilization, transport, storage and use, including during the time of use, thereby preventing or at least reducing water evaporation and concentration build-up from the concentrate during use in PD treatment.

[0018] The solution involves a primary bag holding the concentrate liquid, housed in a sealed overpouch intended to protect the primary bag and its outlet connector from contamination and prevent water loss during storage and use, while allowing easy and safe use of the concentrate bag with a PD cycler.

[0019] The overpouch permanently seals around and encloses the primary bag and includes two sealed sides: a sealed top and a sealed bottom. The sealed bottom of the overpouch includes a fixed section and a removable section (Figure 1). The sealed top is closed with a permanent seal that cannot be opened during use of the concentrate, while the outlet connector is connected to a line leading to the PD cycler. A permeable seal spans the top outlet connector and is firmly secured to the connector to close the bottom seal of the overpouch from contact with the outside air.

[0020] Thus, the outlet connector of the primary bag extends through the fixed and removable portions and through the sealed lower portion of the overpouch, including intersecting the permanent seal of the lower sealing portion (FIG. 1). Thus, the length of the outlet connector is partially contained within the fixed portion of the sealed lower portion of the overpouch and partially contained within the removable portion of the sealed lower portion of the overpouch. The terminal end and tip of the outlet connector are contained within the removable portion of the sealed lower portion of the overpouch, allowing it to be used during treatment.

[0021] Prior to use, the user removes the sealed, removable lower portion of the overpouch by pulling the overpouch apart, thus making the connector tip accessible and free to connect with the solution generating device, typically a PD cycler.

[0022] Thus, the overpouch can never be removed from the primary bag, which remains permanently sealed within the overpouch by two sides, a sealed top, and a sealed bottom fastener. Similarly, the connector remains covered, but its function is not restricted by the overpouch. Its top is located within the overpouch, which tightly seals around the connector. The bottom is fully accessible. The overpouch's sealing at the bottom end, where the connector is located, and its tight attachment around the primary bag or pouch further increase ease of handling, as the overpouch cannot be unintentionally removed, twisted, or pushed up to expose the primary bag.

[0023] The applicant has found that the above solution prevents or substantially reduces water evaporation during both storage and use of disposable flexible bags for dialysis concentrate and is well suited to be applied safely during treatment. [Brief explanation of the drawings]

[0024] [Figure 1] FIG. 1 shows the configuration of a flexible bag for dialysis concentrate according to the invention before use. [Figure 2] FIG. 2 shows the construction of a flexible bag for dialysis concentrate according to the present invention in use. [Figure 3] FIG. 3 shows a Cartesian plot of the rate of weight loss versus time for three bags containing electrolyte concentrate, as described in Example 2. [Figure 4] FIG. 4 shows a Cartesian plot of the rate of weight loss versus time for three bags containing glucose concentrate, as described in Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0025] While the present invention may be embodied in many different forms, specific embodiments thereof are shown in the drawings and will be further described herein, with the understanding that the present disclosure is an exemplification of the principles of the invention and is not intended to limit the invention to the specific embodiments shown.

[0026] According to the present invention, a disposable flexible bag for storing and providing dialysis concentrate for treatment is provided, which is designed to prevent or at least reduce evaporation during the time of use, and accounts for the above-mentioned requirements.

[0027] The flexible bag according to the present invention comprises a primary bag permanently sealed within an overpouch. As used in this specification and claims, the term "permanently sealed" means that the primary bag remains enclosed within the overpouch throughout its life, i.e., during its manufacture, storage, use and disposal.

[0028] The lower portion of the sealed overpouch comprises a removable portion that can be easily separated to expose the terminal and tip ends of the outlet connector, and a fixed portion that remains completely sealed to prevent exposure of the primary bag to air, thereby preventing or reducing evaporation of water through the primary bag.

[0029] The sealed overpouch should be strong enough to remain intact and substantially airtight during typical sterilization, shipping and storage processes, and during the subsequent 7-10 days of use after the removable portion is separated.

[0030] Furthermore, it is important that the seal strength be permanent and remain that way from the initial construction of the sealed package until the package is intended for use. This is of particular concern when the package is intended to be exposed to extreme temperature fluctuations or mechanical stresses prior to opening, such as during sterilization, packaging, and shipping. PD concentrates require sterilization before use, and it is well known that the most common heat sterilization technique involves the use of an autoclave process to destroy microorganisms at approximately 120°C for a period of 15 to 30 minutes. In this regard, the seal strength must withstand the high temperatures associated with heat sterilization.

[0031] According to the present invention, a particular embodiment is shown in accompanying FIG.

[0032] FIG. 1 shows a primary bag 10 containing a PD concentrate 20 enclosed within a sealed overpouch 30 having opposing first and second sides 40, 50 and opposing sealed top and bottom portions 60, 70.

[0033] The sealed overpouch 30 is made by providing a tube of polymeric material having an appropriate diameter and length, inserting the primary bag 10 therein, and then sealing the opposing upper and lower portions 60, 70 together.

[0034] Alternatively, the sealed overpouch 30 can also be made by providing two sheets of polymeric material having an appropriate width and length, interposing the primary bag 10 between such sheets, and then sealing the first and second sides 40, 50 and the opposing top and bottom portions 60, 70 together.

[0035] Dotted lines 80 and 90 represent the permanently sealed top and bottom rims of the secondary bag or permanent overpouch which remain fully closed during use of the bag once removable portion 120 is removed and fixed portion 110 opens at the bottom to allow access to the connector.

[0036] Advantageously, the sealed top 60 includes a hanger hole 100 for hanging the bag on a suitable holder. Although Figure 1 shows two hanger holes 100, the sealed top 60 may include only one hanger hole or more than two hanger holes.

[0037] The sealed lower portion 70 comprises a fixed portion 110 and a removable portion 120. The removable portion 120 can be peeled away along dotted line 130, thereby making the connector accessible.

[0038] The primary bag 10 includes an outlet connector 140 that is fluidly connected to the interior of the primary bag, passes through the permanent seal 90 , and partially through the lower portion 70 of the overpouch 30 .

[0039] 2, prior to use, the user removes removable portion 120 of sealed lower portion 70 by severing removable portion 120 along dotted line 130. Thus, terminal portion and tip 150 of outlet connector 140 are exposed and free to connect to a solution generating device. The substantial portion of outlet connector 140 remains covered by fixed portion 110 of lower portion 70 and resides within a permanently sealed overpouch closed with permanent seal 90.

[0040] The primary bag 10 and overpouch 30 can be realized with films made using any polymeric material conventionally used in PD concentrate packaging, such as polyvinyl chloride (PVC), polyolefins such as polyethylene (PE) and polypropylene (PP), polyesters such as polyethylene terephthalate (PET), copolyesters, polyamides, copolyamides, and polycarbonates. Polyolefins, polyesters, and polyvinyl chloride are preferred polymeric materials. Preferably, the overpouch utilizes a material with low permeability to water vapor, such as polyethylene, polypropylene, or a combination of PE and PP, a PVC / PVdC, or a PVC / PCTFE laminate. If halogen-free packaging is preferred, the primary bag can be made from PVC or a cyclic olefin copolymer, which preferably provides an excellent barrier.

[0041] The film used for the primary and secondary bags, i.e., overpouches, is preferably made from a transparent film to allow visual inspection of the contained concentrate. PE and, for example, PVC are transparent materials that meet this requirement.

[0042] The film of the polymeric material can have a single layer structure or a multilayer structure containing two or more layers of different composition. Useful examples of multilayer films are described, for example, in EP-A-733472 and EP-A-738589.

[0043] The product label can be applied to both the primary bag and the secondary bag. If the overpouch is made from a transparent material, applying the label to the primary bag can offer an additional advantage, as there is less risk of the label being physically damaged or rendered illegible, for example, by moisture. If such application is preferred, the product label can also be applied to the overpouch, since the overpouch is permanently sealed with the primary bag. In the latter case, the material used for the secondary bag or overpouch can also be selected from opaque or non-transparent materials, such as high-barrier foil made of multiple layers of different materials, which may include aluminum, bonded with adhesive or polyethylene, providing a particularly low water vapor transmission rate (WVTR). Water vapor transmission rate is a measure of the passage of water vapor through a substance, such as the material used in the present primary or secondary bag. It is measured in grams per 100 square inches per 24 hours (g / 100 inches). 2 / 24hrs).

[0044] The present invention is further illustrated below by some preparation examples, which are provided for illustrative purposes only, without limiting the present invention in any way.

[0045] Experimental Part Example 1 A sealed overpouch according to the present invention can substantially reduce the risk of out-of-specification (OOS) over a 10-day use period for products stored for different time periods (shelf life), as shown in Tables 1-3 below. The tables summarize the probability of OOS for concentrations of concentrates of two key solutes (dextrose and sodium chloride) stored in PVC 5L primary bags with and without an overpouch. The overpouch was made from a polymeric material consisting of a blend of polyethylene and polypropylene.

[0046] [Table 1]

[0047] [Table 2]

[0048] [Table 3]

[0049] The data in Tables 1 through 3 clearly demonstrate that the risk of out-of-specification (OOS) is significantly reduced when using the overpouch of the present invention.

[0050] Example 2 Another test was conducted using a set of three PVC 1-liter electrolyte concentrate bags and a set of three PVC 1-liter glucose concentrate bags, with and without an overpouch. The overpouch was made from a polymeric material consisting of a blend of polyethylene and polypropylene.

[0051] The tests were conducted as follows: First, the original weight of each bag was recorded. For each set, one bag was stored with the overpouch closed (Bag A), one bag was stored with the overpouch opened by removing the removable portion 120 of the sealed lower portion 70 and exposing the outlet connector (Bag B), and one bag was stored without the overpouch (Bag C). Each bag was suspended in free air and weighed at intervals of several days for a total test period of 35 days.

[0052] The weight loss rate results are summarized in Figure 3 for the set of electrolyte concentrate bags and in Figure 4 for the set of glucose concentrate bags, where lines A, B, and C indicate the trend lines for bags A, B, and C, respectively.

[0053] The results demonstrate that evaporation rates are strongly reduced in bags A and B, in which the overpouch is maintained in either a closed or open in-use configuration according to the invention, compared to bag C without an overpouch. The calculated evaporation rate reduction was 71% for the electrolyte concentrate and 79% for the glucose concentrate.

[0054] Given the above description of embodiments of the present invention, it will be understood that various modifications may be made by those skilled in the art. Such modifications are intended to be encompassed by the following claims.

Claims

1. A disposable flexible bag for dialysis concentrate comprising a primary bag (10) having an outlet connector (140) and an overpouch (30), wherein the primary bag (10) is permanently sealed within the overpouch (30).

2. 2. The disposable flexible bag for dialysis concentrate according to claim 1, wherein the overpouch comprises a sealed lower portion (70) having a fixed portion (110) and a removable portion (120).

3. 3. The disposable flexible bag for dialysis concentrate according to claim 2, wherein the outlet connector (140) is enclosed within the sealed lower portion (70) during storage.

4. 3. The disposable flexible bag for dialysis concentrate according to claim 2, wherein the outlet connector (140) is exposed when the removable portion (120) is removed.

5. 2. The disposable flexible bag for dialysis concentrate according to claim 1, wherein the overpouch comprises a sealed top portion (60).

6. 6. The disposable flexible bag for dialysis concentrate according to claim 5, wherein the sealed top (60) is provided with one or more hanger holes (100), preferably two hanger holes (100).

7. 2. The disposable flexible bag for dialysis concentrate according to claim 1, wherein the primary bag (10) contains a PD concentrate (20).

8. 2. The disposable flexible bag for dialysis concentrate according to claim 1, wherein the overpouch (30) comprises first and second opposed sealed sides (40, 50).

9. 9. The disposable flexible bag for dialysis concentrate according to any one of claims 1 to 8, wherein the primary bag (10) and the overpouch (30) are made using a polymer material selected from the group consisting of polyvinyl chloride (PVC), polyolefins such as polyethylene (PE) and polypropylene (PP), polyesters such as polyethylene terephthalate (PET), copolyesters, polyamides, copolyamides, and polycarbonates.

10. 10. The disposable flexible bag for dialysis concentrate according to claim 9, wherein the primary bag (10) is made using PVC.

11. 10. The disposable flexible bag for dialysis concentrate according to claim 9, wherein the overpouch (30) is made of a polymer material selected from the group consisting of polyethylene (PE), polypropylene (PP), and mixtures thereof.

12. 10. The disposable flexible bag for dialysis concentrate of claim 1, wherein the primary bag remains sealed within the overpouch for its lifetime.

13. 3. The disposable flexible bag for dialysis concentrate according to claim 2, wherein the portion of the fixing portion (110) above the rim (90) tightly seals around the upper portion of the connector (140).

14. 3. The disposable flexible bag for dialysis concentrate according to claim 2, wherein the portion of the fixed portion (110) above the rim (90) remains completely sealed to prevent the primary bag from being exposed to air when the removable portion (120) is removed.

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