Flexible pouch for dialysis concentrates with sealed outer pouch

Abstract

The present invention relates to a disposable flexible pouch for dialysis concentrate comprising a main pouch and an outer pouch, the disposable flexible pouch being designed to ensure that the outer pouch remains on the main pouch during use of the concentrate in order to prevent evaporation of water which may lead to an overproof situation near the end of the use period.

Description

Technical Field

[0001] The present invention relates to a disposable flexible bag for dialysis concentrate, comprising a main bag and an outer bag. The bag assembly is designed to ensure that the outer bag remains attached to the main bag during use of the concentrate to prevent water evaporation, which could lead to an out-of-specification condition near the end of its use. The present invention is primarily targeted at concentrates intended for multi-day use, where water loss could be problematic. Background Art

[0002] Peritoneal dialysis ("PD") is a dialysis treatment commonly used to treat loss of kidney function. Peritoneal dialysis uses a dialysis solution (also called dialysis fluid) that is infused into the patient's peritoneal cavity through a catheter implanted in the peritoneal cavity. The dialysis fluid contacts the patient's peritoneum, which is located in the peritoneal cavity. Waste products, toxins, and excess water enter the dialysis fluid from the patient's bloodstream through the peritoneum. Transfer of waste products, toxins, and water from the bloodstream into the dialysis fluid occurs due to diffusion and osmosis, i.e., an osmotic gradient occurs across the peritoneum. The used dialysis fluid is drained from the patient's peritoneal cavity to remove waste products, toxins, and excess water from the patient's body. Subsequently, the above cycle is 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 the patient connects an implanted catheter to a drain port and allows spent dialysis fluid to drain from the peritoneal cavity. The patient then manually allows fresh dialysis fluid to flow from a solution bag through the patient's indwelling catheter and into the patient's peritoneal cavity. The patient can then disconnect the catheter from the solution bag to allow the dialysis fluid to remain in the peritoneal cavity, thereby transferring waste, toxins, and excess water from the patient's bloodstream to the dialysate solution. After the dwell period, the patient can repeat the manual procedure. In CAPD, the patient performs a drain, fill, and dwell cycle several times a day, for example, about four times a day.

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

[0006] The APD machine pumps fresh dialysate from a dialysate source through a catheter into the patient's peritoneal cavity and allows the dialysate to reside in the peritoneal cavity so that transfer of waste products, toxins, and excess water from the patient's bloodstream to the dialysate solution can occur. The APD machine then pumps spent dialysate from the peritoneal cavity through a catheter to a drain. The APD machine is typically computer-controlled so that dialysis treatment occurs automatically when the patient is connected to the dialysis machine, for example, while the patient is sleeping. That is, the APD system automatically and continuously pumps fluid into the peritoneal cavity, allows it to reside, then pumps the fluid out of the peritoneal cavity and repeats the process.

[0007] As with manual procedures, several drain, fill, and dwell cycles occur during APD. A "last fill" is typically used at the end of APD, and this "last fill" remains in the patient's peritoneal cavity when the patient is disconnected from the dialysis machine for the day. APD relieves the patient from having to manually perform the drain, dwell, and fill steps.

[0008] As mentioned above, both CAPD and APD involve the use of a solution bag that contains the fluid to be pumped into the patient's peritoneal cavity. Preparing such a bag requires great care and skill. The bag must not leak, the material from which the bag is made must be safe and inert enough to avoid leaking substances into the fluid that could be inadvertently transferred to the patient, and the material must be strong and flexible enough to withstand manufacturing, handling, and storage, and should not be opaque to allow visual inspection of the contents, for example, to identify undesirable discoloration or precipitation. Of course, the bag must also be manufactured within certain specifications. The solution bag and its contents must also be sterilizable to a certain level so that the solution is safely delivered to the patient. Finally, the bag must also be appropriately labeled so that the user or caregiver can be sure that the patient is receiving the correct PD solution.

[0009] The dialysis fluid used in all of the above-mentioned 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 dialysis fluid are selected to control the electrolyte levels and acid-base balance in the blood, and in the case of glucose or glucose-like components, they remove waste materials from the blood by establishing an osmotic gradient.

[0010] As is apparent from the foregoing, patients require large quantities of readily available PD fluid daily to perform the necessary procedures. These large quantities of PD fluid must be prepared, delivered, and subsequently stored at the patient's home, increasing the cost of treatment and placing an increased burden on the patient and their caregiver. It is therefore preferred that readily available PD fluid be prepared at the patient's home from different types of concentrates by mixing the PD concentrate with purified water, also prepared at the patient's home. In this case, the concentrate is typically supplied in bags, and the purified water required for mixing is sourced from, for example, a water purification plant that purifies tap water. The concentrate is typically provided in two parts: a buffer concentrate with electrolytes having a nominal dilution factor of approximately 20 and a glucose concentrate containing 50% glucose, both having a volume of, for example, 1 L. The electrolytes can also be provided separately from the buffer as two different concentrates.

[0011] The use of multiple treatment concentrates can save costs because less product is shipped, each treatment has lower weight and volume, and reduces waste because less container material is required for each treatment. It also reduces patient burden because unpacking, placement, and connection of smaller, less heavy concentrate containers can be performed at greater intervals than daily replacement, for example, 7-14 days.

[0012] In the medical field, primary bags are used to collect, store, transport, and ultimately deliver dialysis solutions. Typically, these primary bags are placed into secondary containers (such as overbags) to maintain the integrity and volume of the medication contained within the primary container. The overbag is typically removed or opened before use to expose the primary bag and connect it to a tubing set. For example, WO2004 / 066857 and WO2006 / 116287 disclose an easily opened overbag that facilitates insertion and removal of the primary bag. The overbag is then typically discarded.

[0013] Since the mixing of the concentrate in both manual and automated procedures is predetermined based on the concentrate's specifications, evaporation of water from the bag must be avoided whenever the concentrate is used to prepare ready-to-use dialysis fluid for PD treatment.

[0014] During storage and transport of the concentrate, the outer bag substantially prevents water evaporation. However, the evaporation rate increases significantly when the outer bag is removed before and during use, which may occur at elevated temperatures or at least room temperature and may last up to four or five days. Furthermore, during use, when the concentrate volume decreases faster than the container surface available for water diffusion from the container, the evaporation rate relative to the volume contained in the concentrate bag increases due to the increased surface-to-volume ratio. This means that the concentrate's rising concentration rate increases with use time and is highest near the end of its use period. Therefore, there is a risk that the concentrate concentration may exceed the permitted concentration limit, particularly near the end of its use period.

[0015] Therefore, there is a need for a method for reducing or preventing the concentration of a concentrate used to prepare PD fluid from rising over time, including providing a disposable flexible bag for the dialysis concentrate that is designed to prevent or at least reduce water evaporation over time. The present invention is provided to address this problem, which can have serious consequences for patients. Summary of the Invention

[0016] The problem faced by the Applicant was to develop a disposable flexible bag for dialysis concentrate suitable for preventing or at least reducing water evaporation during use time, which would carry the risk of increasing the concentration of the dialysis concentrate and thus preparing a dialysis fluid for PD that does not have the final concentration required for treatment.

[0017] After extensive experiments, the applicant has found a solution that allows maintaining an outer bag that can be used throughout the life of the concentrate product, including sterilization, transportation, storage and use, including during the time of use, thereby preventing or at least reducing water evaporation and concentration rise of the concentrate during use in PD treatment.

[0018] The solution includes a primary bag containing the concentrate fluid, wherein the primary bag is contained within a sealed outer bag that protects the primary bag and its outlet connector from contamination and prevents water loss during storage and use, while allowing easy and safe use of the concentrate bag with a PD cycler.

[0019] The outer bag is permanently sealed around the main bag and closes the main bag, wherein it comprises two sealed side parts, a sealed upper part and a sealed lower part. The sealed lower part of the outer bag comprises a fixed part and a removable part ( Figure 1 The upper portion of the seal is closed with a permanent seal that is not opened during use of the concentrate while the outlet connector is connected to the line leading to the PD cycler. The permanent seal spans the outlet connector at its upper portion and is tightly secured to the connector to seal the lower sealed portion of the outer bag from contact with ambient air.

[0020] Thus, the outlet connector of the main bag extends through the sealed lower portion of the outer bag ( Figure 1 ), including a connector extending through the fixed portion and the removable portion to intersect the permanent seal of the lower sealing portion. Thus, the length of the outlet connector is partially contained within the fixed portion of the sealed lower portion of the outer bag and partially contained within the removable portion of the sealed lower portion of the outer bag. The distal end and tip of the outlet connector are contained within the removable portion of the sealed lower portion of the outer bag to allow it to be used during treatment.

[0021] Prior to use, the user removes the removable portion of the sealed lower portion of the outer bag by tearing open the outer bag. Thus, the connector tip becomes accessible and free to connect with a solution generating device (typically a PD cycler).

[0022] Thus, the outer bag cannot be removed from the main bag, which is permanently sealed within the outer bag by fixed portions on both sides, the sealed upper portion, and the sealed lower portion. Likewise, the connector remains covered, while its function is not restricted by the outer bag. Its upper portion is located within the outer bag, which is tightly sealed around the connector. The lower portion is fully accessible. The seal of the outer bag at the bottom end where the connector is located and its tight fit around the main bag (or pouch) further enhance ease of handling, as the outer bag cannot be accidentally removed, twisted, or pushed upward to expose the main bag.

[0023] The Applicant has found that the above-described solution prevents or substantially reduces water evaporation during both storage and use of disposable flexible bags for dialysis concentrate and is well-suited for safe application during treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The configuration of a flexible bag for dialysis concentrate according to the present invention before use is shown.

[0025] Figure 2 The configuration of a flexible bag for dialysis concentrate according to the invention during use is shown.

[0026] Figure 3 A Cartesian plot of percent weight loss versus time for three bags containing electrolyte concentrate as described in Example 2 is shown.

[0027] Figure 4 A Cartesian plot of percent weight loss versus time for three bags containing glucose concentrate as described in Example 2 is shown. DETAILED DESCRIPTION

[0028] While the invention may be embodied in many different forms, specific embodiments thereof are shown in the drawings and will be further described herein, it being understood that this disclosure is illustrative of the principles of the invention and is not intended to limit the invention to the specific embodiments shown.

[0029] 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 use time and which meets the above requirements.

[0030] The flexible bag according to the present invention comprises a primary bag permanently sealed within an outer bag. As used in this specification and claims, the term "permanently sealed" means that the primary bag remains enclosed within the outer bag throughout its useful life, i.e., from production, storage, use to disposal.

[0031] The lower portion of the sealed outer bag includes a removable portion that can be easily torn open to expose the end and tip of the outlet connector, and a fixed portion that remains completely sealed to prevent the main bag from being exposed to air, thereby preventing or reducing water evaporation through the main bag.

[0032] The sealed outer bag should be strong enough to remain intact and substantially airtight during typical sterilization, shipping and storage processes, and after the removable portion has been removed, for the subsequent 7-10 days of use.

[0033] It is also important that the seal strength is permanent and remains in place from the initial deployment of the sealed package until the package is intended for use. This is of particular concern when the package is subjected to extreme temperature fluctuations or mechanical stresses prior to opening, such as during sterilization, packaging, and shipping. As is well known, PD concentrates require sterilization before use, and the most common heat sterilization technique involves the use of an autoclave process at approximately 120°C for 15 to 30 minutes to destroy microorganisms. In this regard, the seal strength must withstand the high temperatures associated with heat sterilization.

[0034] According to the present invention, in the attached Figure 1 Specific embodiments are shown in FIG.

[0035] Figure 1 A primary bag 10 containing a PD concentrate 20 is shown enclosed within a sealed outer bag 30 having opposing first and second side portions 40 , 50 and opposing sealed upper and lower portions 60 , 70 .

[0036] The sealed outer bag 30 is prepared by providing a tube of polymeric material having an appropriate diameter and length and sealing the opposing upper and lower portions 60 and 70 together after the primary bag 10 has been inserted.

[0037] Alternatively, the sealed outer bag 30 may be made by providing two sheets of polymer material of appropriate width and length and sealing the first side portion 40, the second side portion 50 and the opposing upper and lower portions 60, 70 together after the main bag 10 has been inserted between the two sheets.

[0038] Dashed lines 80 and 90 represent the permanently sealed upper and lower edges of the secondary bag or permanent outer bag, which also remains completely closed during its use once the removable portion 120 has been removed and the fixed portion 110 is opened at the bottom to allow access to the connector.

[0039] Advantageously, the sealing upper portion 60 includes a hook hole 100 for hanging the bag from a suitable support. Figure 1 Two hook holes 100 are shown, but the sealing upper portion 60 may also include only one hook hole or more than two hook holes.

[0040] The sealing lower part 70 comprises a fixed portion 110 and a removable portion 120. The removable portion 120 can be torn off along a dotted line 130, whereby the connector becomes accessible.

[0041] The primary bag 10 includes an outlet connector 140 that is fluidly connected to the interior of the primary bag and that passes through the permanent seal 90 and partially through the lower portion 70 of the outer bag 30 .

[0042] like Figure 2 As shown, before use, the user removes the removable portion 120 of the sealed lower portion 70 by tearing off the removable portion 120 along the dotted line 130. As a result, the distal portion and tip 150 of the outlet connector 140 become exposed and free to connect to the solution generating device. The majority of the outlet connector 140 remains covered by the fixed portion 110 of the lower portion 70 and is located within the permanently sealed outer bag enclosed by the permanent seal 90.

[0043] The main bag 10 and the outer bag 30 can be made of films made from any polymer material commonly used for PD concentrate packaging, such as polyvinyl chloride (PVC), polyolefins (e.g., polyethylene (PE) and polypropylene (PP)), polyesters (e.g., polyethylene terephthalate (PET)), copolyesters, polyamides, copolyamides, and polycarbonates. Polyolefins, polyesters, and polyvinyl chloride are preferred polymer materials. Preferably, the outer bag uses a material with low permeability to water vapor, such as polyethylene, polypropylene, or a combination of PE and PP, PVC / PVdC, or PVC / PCTFE laminates. The main bag can preferably be made of PVC or cyclic olefin copolymer, which provides an excellent barrier, preferably using halogen-free packaging.

[0044] The films used for the primary bag and the secondary bag (ie, outer bag) are preferably made of transparent films to allow visual inspection of the contained concentrate. For example, PE and PVC are both transparent materials that meet this requirement.

[0045] The film of polymer material may have a single layer structure or a multilayer structure comprising two or more layers of different compositions. Useful examples of multilayer films are described, for example, in EP733472A2 and EP738589A2.

[0046] The product label may be applied to both the primary bag and the secondary bag. In the case where the outer bag is made of a transparent material, applying the label to the primary bag may provide further advantages in that there is a lower risk of it being physically damaged or becoming unreadable, for example due to moisture. If application to the outer bag is preferred, the product label may also be applied to the outer bag since the outer bag is permanently sealed to the primary bag. In the latter case, the material for the secondary bag or outer bag may also be selected from an opaque or non-transparent material such as a high barrier foil made from multiple layers of different materials bonded together with an adhesive or polyethylene and may include aluminum which provides a particularly low water vapor transmission rate (WVTR). Water vapor transmission rate is a measure of the amount of water vapor that passes through a substance, such as the material used for the primary bag or secondary bag of the present invention. It is expressed in grams per 100 square inches per 24 hours (g / 100 in 2 / 24 hours) to measure.

[0047] The present invention will be further described below through several preparation examples, which are provided for illustrative purposes only and are not intended to limit the present invention in any way.

[0048] Experimental part

[0049] Example 1

[0050] As shown in Tables 1-3 below, the sealed outer bag according to the present invention significantly reduces the risk of out-of-specification (OOS) for products stored for various periods of time (shelf life) over a ten-day shelf life. These tables summarize the OOS potential for concentrates of two primary solutes (dextrose and sodium chloride) stored in 5L PVC primary bags with and without the outer bag. The outer bag is made of a polymer material composed of a blend of polyethylene and polypropylene.

[0051] Table 1 Shelf life of 12 months at 25°C

[0052]

[0053] Table 2 Shelf life of 18 months at 25°C

[0054]

[0055]

[0056] Table 3 Shelf life of 24 months at 25°C

[0057]

[0058] The data in Tables 1-3 clearly show that the out-of-specification (OOS) risk is significantly reduced when the outer bag of the present invention is used.

[0059] Example 2

[0060] Another test was performed on 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 outer bag. The outer bag was made of a polymer material consisting of a blend of polyethylene and polypropylene.

[0061] The test was performed as follows. First, the initial weight of each bag was recorded. For each group, one bag was stored with the outer bag closed (Bag A), one bag was stored with the outer bag 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 outer bag (Bag C). Each bag was hung in free air and weighed every few days over the total test period of 35 days.

[0062] For this set of electrolyte concentrate bags, Figure 3 The results for the percentage weight loss for this set of glucose concentrate bags are summarized in Figure 4 The results for percent weight loss are summarized in , where lines A, B, and C represent the trend lines for bags A, B, and C, respectively.

[0063] The results show that the evaporation rate is greatly reduced in bags A and B according to the present invention, both when the outer bag is kept in the closed configuration and in the open configuration during use, compared to bag C without the outer bag. The evaporation rate reduction is calculated to be 71% for the electrolyte concentrate and 79% for the glucose concentrate.

[0064] It will be appreciated that, given the above description of the embodiments of the present invention, 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 main bag (10) having an outlet connector (140) and an outer bag (30), characterized in that The main bag (10) is permanently sealed within the outer bag (30).

2. The disposable flexible bag for dialysis concentrate according to claim 1, characterized in that The outer bag includes a sealed lower portion (70) including a fixed portion (110) and a removable portion (120).

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

4. The disposable flexible bag for dialysis concentrate according to claim 2, characterized in that Upon removal of the removable portion (120), the outlet connector (140) is exposed.

5. The disposable flexible bag for dialysis concentrate according to claim 1, characterized in that The outer bag includes a sealed upper portion (60).

6. The disposable flexible bag for dialysis concentrate according to claim 5, characterized in that The sealing upper portion (60) includes one or more hook holes (100), preferably two hook holes (100).

7. The disposable flexible bag for dialysis concentrate according to claim 1, characterized in that The main bag (10) contains PD concentrate (20).

8. The disposable flexible bag for dialysis concentrate according to claim 1, characterized in that The outer bag (30) has opposing first and second sealed sides (40, 50).

9. A disposable flexible bag for dialysis concentrate according to any one of the preceding claims 1 to 8, characterized in that The main bag (10) and the outer bag (30) are made of a polymer material selected from polyvinyl chloride (PVC), polyolefins such as polyethylene (PE) and polypropylene (PP), polyesters such as polyethylene terephthalate (PET), copolyesters, polyamides, copolyamides and polycarbonates.

10. The disposable flexible bag for dialysis concentrate according to claim 9, characterized in that The main bag (10) is made of PVC.

11. The disposable flexible bag for dialysis concentrate according to claim 9, characterized in that The outer bag (30) is made of a polymer material selected from polyethylene (PE), polypropylene (PP) and mixtures thereof.

12. The disposable flexible bag for dialysis concentrate according to claim 1, characterized in that The primary bag remains sealed within the outer bag throughout its useful life.

13. The disposable flexible bag for dialysis concentrate according to claim 2, characterized in that The portion above the edge (90) of the fixing portion (110) is tightly sealed around the upper portion of the connector (140).

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

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