A pH self-stabilized peritoneal dialysis solution packaging system

Abstract

The application relates to a pH self-stabilizing peritoneal dialysis solution packaging system, and relates to the technical field of peritoneal dialysis. The packaging system comprises a double-chamber inner bag and an outer packaging bag. The double-chamber inner bag comprises an A chamber filled with a first drug solution containing a bicarbonate buffer component and a B chamber filled with a second drug solution containing a lactate buffer component. A limited gas phase buffer cavity is formed between the outer packaging bag and the double-chamber inner bag. The outer packaging bag comprises a main barrier area and a limited-speed CO2 diffusion window. By arranging the limited gas phase buffer cavity, presetting the CO2 partial pressure and the limited-speed CO2 diffusion window, the CO2 exchange rate of the packaging system is regulated, so that the bicarbonate buffer system remains relatively stable during storage. The pH drift caused by the too fast escape or excessive retention of CO2 during storage is reduced, the carbonate system fluctuation is reduced, and the pH stability and long-term storage stability of the mixed peritoneal dialysis solution are improved.

Description

Technical Field

[0001] This application relates to the field of peritoneal dialysis technology, specifically to a pH-self-stabilizing peritoneal dialysis fluid packaging system. Background Technology

[0002] Peritoneal dialysis is a renal replacement therapy that utilizes the peritoneum as a semipermeable membrane for solute exchange and water removal, and is widely used for the long-term treatment of patients with end-stage renal disease. Peritoneal dialysis fluid, as a key medium in the peritoneal dialysis process, directly affects dialysis efficiency, biocompatibility, and patient comfort due to its composition and physicochemical properties. With the development of peritoneal dialysis technology, neutral or near-physiological pH peritoneal dialysis fluids have gradually become an important development direction to improve biocompatibility and reduce the irritating effect of traditional acidic peritoneal dialysis fluids on peritoneal tissues. Since these types of peritoneal dialysis fluids typically contain buffer systems, electrolytes, and osmotic agents, maintaining stable physicochemical properties during production, storage, and transportation is of great importance.

[0003] Current peritoneal dialysis solutions are typically stored and transported using multi-layered composite packaging materials and double-chamber bag structures to separate and preserve different components, while meeting the requirements for sealing, mechanical strength, sterilization adaptability, and moisture barrier properties. Existing packaging technologies primarily focus on optimizing the barrier properties, mechanical properties, heat-sealing performance, and long-term storage stability of the packaging materials. This is achieved by selecting different composite film materials and packaging structures to improve the product's shelf life and transport reliability. Simultaneously, to meet the needs of industrial production and clinical use, the packaging system must also consider the requirements of multiple stages, including drug filling, terminal sterilization, transportation and storage, and pre-use mixing.

[0004] However, with the increasing use of neutral peritoneal dialysis fluid, existing packaging systems still have limited precision in controlling the physicochemical stability of the fluid during long-term storage. In particular, under long-term storage conditions containing buffered solutions, the lack of synergistic design between the packaging structure and the fluid system means that the acid-base stability of the fluid after storage needs to be further improved.

[0005] Therefore, there is an urgent need to provide a pH-self-stabilizing peritoneal dialysis fluid packaging system that can take into account both the characteristics of the drug solution buffer system and the structural characteristics of the packaging system, so as to improve the pH stability and product consistency of peritoneal dialysis fluid after long-term storage. Summary of the Invention

[0006] This application provides a pH-self-stabilizing peritoneal dialysis fluid packaging system that takes into account both the characteristics of the drug solution buffering system and the structural characteristics of the packaging system, so as to improve the pH stability and product consistency of peritoneal dialysis fluid after long-term storage.

[0007] The pH-self-stabilizing peritoneal dialysis fluid packaging system provided in this application adopts the following technical solution: A pH-self-stabilizing peritoneal dialysis fluid packaging system includes a double inner bag and an outer packaging bag; The dual-chamber bag includes chamber A and chamber B. Chamber A contains a first solution containing a bicarbonate buffer component, and chamber B contains a second solution containing a lactate buffer component. The outer packaging bag covers the outside of the double inner bag, and a confined gas phase buffer cavity is formed between the outer packaging bag and the double inner bag; The outer packaging bag includes a main barrier area and at least one rate-limiting CO2 diffusion window; The main barrier region is a multilayer composite membrane structure; The volume of the confined gas phase buffer chamber is 30–300 mL; The initial CO2 partial pressure in the confined gas phase buffer chamber is 3–12 kPa; The effective diffusion area of ​​the rate-limiting CO2 diffusion window is 0.2–20 cm². 2 ; The mixture of chambers A and B forms a peritoneal dialysis solution with a pH of 6.8–7.6.

[0008] By employing the above technical solution, the bicarbonate buffer component and the lactate buffer component are stored in separate compartments, reducing adverse interactions between the buffer components, electrolytes, and permeabilizers during storage. Simultaneously, a pre-defined gaseous environment for CO2 is provided through a confined gaseous buffer chamber, and the exchange rate of CO2 with the external environment is limited by a rate-limiting CO2 diffusion window. This prevents CO2 from rapidly dissipating or stagnating for extended periods, thereby reducing the risk of the mixed drug solution's pH shifting towards alkalinity or acidity. The combined effect of the main barrier zone and the rate-limiting CO2 diffusion window gives the outer packaging bag both overall barrier properties and locally controllable permeability, which helps maintain the gas-liquid balance of the bicarbonate system, reduces the risk of calcium and magnesium ion precipitation, and improves the pH stability and infusion comfort of the mixed drug solution after storage.

[0009] Optionally, the peritoneal dialysis fluid formed after mixing chambers A and B contains: The bicarbonate concentration was 18–35 mmol / L. The lactate concentration is 5–20 mmol / L. The molar ratio of bicarbonate to lactate is 1.5 to 5:1.

[0010] By adopting the above technical solution, bicarbonate in the mixture can provide immediate buffering capacity close to the physiological environment, while lactate can provide auxiliary buffering and metabolic-related buffering sources. When the two are combined within the aforementioned concentration and ratio range, insufficient buffering capacity due to an excessively low bicarbonate ratio can be avoided, as can excessively high bicarbonate ratios leading to oversensitivity to changes in CO2 partial pressure. This limitation allows the drug solution formulation to form a more suitable buffering base with the restricted gas-phase buffer chamber and the rate-limiting CO2 diffusion window, which is beneficial for obtaining a relatively pH-stable mixed peritoneal dialysis solution even after long-term storage.

[0011] Optionally, the buffer capacity β of the peritoneal dialysis fluid formed by mixing chambers A and B is 10–30 mmol / (L·pH).

[0012] By adopting the above technical solution, the mixture exhibits moderate resistance to pH fluctuations, making it less prone to drastic pH shifts when CO2 partial pressure changes only slightly. Simultaneously, this buffer capacity range avoids excessively low buffer capacity, which would make the pH susceptible to CO2 escape, and excessively high buffer capacity, which would lead to delayed acid-base regulation or decreased physiological adaptability of the drug solution. This buffer capacity, combined with the volume of the limited gas-phase buffer chamber and the diffusion capacity of the rate-limiting CO2 diffusion window, helps improve the packaging system's tolerance to CO2 disturbances during storage, thereby enhancing the pH stability of the mixed drug solution.

[0013] Optionally, the multilayer composite film structure includes one of PA / EVOH / PE, PET / EVOH / PE, COC / PE, and PET / AlOx / PE.

[0014] By adopting the above technical solution, the main barrier zone can achieve a balance of mechanical strength, heat-sealing performance, oxygen barrier performance, water vapor barrier performance, and CO2 barrier performance through the composite characteristics of multiple materials. Materials such as PA and PET are beneficial for improving the mechanical support of the outer packaging bag, while EVOH, COC, or AlOx layers are beneficial for improving gas barrier performance, and the PE layer is beneficial for achieving heat sealing. This structure can reduce disordered gas exchange in the non-window areas of the outer packaging bag, making CO2 exchange mainly controlled by the rate-limited CO2 diffusion window, thereby improving the consistency and repeatability of packaging system parameter design.

[0015] Optionally, the CO2 permeability of the main barrier zone is no greater than 0.5 cm. 3 / (m 2 ·day·atm).

[0016] By adopting the above technical solution, the main barrier zone can effectively reduce CO2 permeation over a large area of ​​the outer packaging bag, preventing large-scale CO2 escape through non-designed areas, and ensuring that CO2 exchange in the packaging system is mainly concentrated in the rate-limiting CO2 diffusion window. This limitation helps reduce the impact of overall permeability fluctuations of the outer packaging bag on the CO2 partial pressure in the confined gas phase buffer chamber, increases the control weight of the rate-limiting CO2 diffusion window on the CO2 exchange rate, and thus enhances the predictability and batch stability of the pH stabilization effect of the packaging system.

[0017] Optionally, the rate-limiting CO2 diffusion window is a local thin barrier layer window, and the thickness of the EVOH layer in the local thin barrier layer window is 0.5 to 5 μm.

[0018] By adopting the above technical solution, the rate-limited CO2 diffusion window can achieve a higher but still limited CO2 permeability relative to the main barrier region by locally reducing the thickness of the EVOH barrier layer, allowing CO2 to be exchanged through the window at a controlled rate. This structure avoids the sealing and contamination risks caused by direct openings, while also differing from the complete suppression of exchange state of an overall high-barrier membrane. This facilitates localized rate-limited CO2 migration while maintaining the integrity of the outer packaging bag, thereby reducing the possibility of a significant shift in the pH of the mixed drug solution due to rapid CO2 escape or long-term retention.

[0019] Optionally, the rate-limiting CO2 diffusion window is a CO2 high-permeability membrane insert window, which includes one of a polysiloxane modified membrane, a TPU / siloxane blend membrane, and a PE microporous membrane.

[0020] By adopting the above technical solution, the rate-limited CO2 diffusion window can achieve localized and controllable permeability by utilizing the high CO2 permeability of the insert material itself, and the CO2 exchange capacity of the window can be adjusted by the insert area and material selection. Polysiloxane-modified films or TPU / siloxane blend films have high gas permeability and flexibility, while PE microporous films are conducive to forming stable microporous diffusion channels. Therefore, this structure is beneficial for maintaining high barrier properties in the main barrier area of ​​the outer packaging bag while providing a designable, manufacturable, and verifiable local CO2 diffusion path, thereby improving the packaging system's ability to regulate the dynamic balance of CO2.

[0021] Optionally, the rate-limiting CO2 diffusion window is a microchannel window, which includes multiple microchannels. The diameter of the microchannels is 1 to 100 μm, the number is 5 to 500, and the length is 50 to 1000 μm.

[0022] By adopting the above technical solution, the rate-limiting CO2 diffusion window can be constrained by the diameter, number, and length of microchannels, limiting the CO2 diffusion path and diffusion resistance. This allows CO2 exchange capacity to be adjusted not solely based on the membrane material itself, but also through microstructural parameters. When the diameter, number, and length of the microchannels are within the aforementioned ranges, it avoids excessively large channels leading to excessively rapid CO2 exchange, and also avoids insufficient CO2 exchange due to channels that are too small or too long. This facilitates the formation of stable and controllable CO2 migration channels and improves the packaging system's adaptability to peritoneal dialysis solutions with different buffer capacities.

[0023] Optionally, the outer side of the microchannel window is covered with a hydrophobic and breathable membrane.

[0024] By adopting the above technical solution, the hydrophobic and breathable membrane can reduce the risk of liquids, water vapor condensates, or external contaminants entering the packaging system through the microchannels while allowing gas to pass through, thus making the microchannel window both breathable and protective. This structure can improve the structural reliability of the microchannel window after storage, transportation, and sterilization, avoid contamination or blockage caused by direct exposure of the microchannels, and maintain the controlled migration capability of CO2, thereby improving the safety and stability of the packaging system in long-term use.

[0025] Optionally, the preparation method of the pH self-stabilizing peritoneal dialysis fluid packaging system includes the following steps: S1. Prepare the first and second solutions separately, and fill them into chambers A and B of the double-chamber bag respectively; S2. Prepare an outer packaging bag including a main barrier region and a rate-limiting CO2 diffusion window; S3. Place the inner double bag into the outer packaging bag to form a confined gas phase buffer chamber between the inner double bag and the outer packaging bag; S4. Introduce a mixed gas containing CO2 into the confined gas phase buffer chamber, so that the initial CO2 partial pressure in the confined gas phase buffer chamber is 3-12 kPa. S5. Heat seal the outer packaging bag.

[0026] By employing the above technical solution, this preparation method first maintains the relative separation of the bicarbonate buffer component and the lactate buffer component during storage through compartment filling, reducing the risk of pH drift and precipitation caused by direct mixing during storage. Then, by pre-preparing an outer packaging bag with a main barrier zone and a rate-limiting CO2 diffusion window, the outer packaging bag forms a controllable CO2 diffusion area based on overall barrier properties. Subsequently, by bagging, quantitatively filling with a CO2-containing mixed gas, and heat-sealing, a confined gas-phase buffer chamber with a preset volume and preset CO2 partial pressure is formed between the inner bag of the two compartments and the outer packaging bag. This method enables the simultaneous establishment of the drug solution compartment structure, the local diffusion structure of the outer packaging, and the gas-phase buffer environment during the preparation process, thereby improving the structural consistency of the packaging system, the controllability of the gas environment, and the stability of batch production. It also facilitates obtaining peritoneal dialysis fluid packaging products with a relatively stable mixed pH after storage.

[0027] In summary, this application includes at least one of the following beneficial technical effects: 1. By placing an outer packaging bag outside the double-chamber bag and forming a confined gas phase buffer chamber between the outer packaging bag and the double-chamber bag, and by setting a rate-limiting CO2 diffusion window on the outer packaging bag, the packaging system is transformed from a traditional simple high-barrier structure into a structure with controlled CO2 exchange capacity. Since the confined gas phase buffer chamber can provide a preset CO2 gas phase environment, and the rate-limiting CO2 diffusion window can limit the migration rate of CO2, it can prevent rapid CO2 escape or long-term retention, thereby reducing the risk of pH drift in the bicarbonate buffer system caused by changes in CO2 partial pressure and improving the pH stability of the mixed solution after storage. 2. A first solution containing bicarbonate buffering component and a second solution containing lactate buffering component are stored separately in separate compartments. This ensures the bicarbonate and lactate systems remain relatively independent during storage, reducing interactions between buffering components, electrolytes, and permeabilizers. They are then mixed before use, allowing the buffering capacities of bicarbonate and lactate to work synergistically. Because the concentrations and molar ratios of bicarbonate and lactate are within a specific range, the system's sensitivity to changes in CO2 partial pressure is reduced while maintaining buffering capacity, thus helping to maintain a relatively stable acid-base environment in the mixture. 3. Further limiting the buffer capacity β of the mixed solution, the volume of the restricted gas-phase buffer chamber, and the diffusion capacity of the rate-limiting CO2 diffusion window, so as to match the buffer capacity of the drug solution with the gas exchange capacity of the packaging system. Since the buffer capacity determines the ability of the drug solution to resist pH changes, and the gas-phase buffer chamber and the rate-limiting CO2 diffusion window together determine the CO2 exchange process, their synergistic effect can improve the system's tolerance to CO2 disturbances during storage, reduce the impact of external environmental changes on the acid-base state of the drug solution, and thus improve the long-term pH stability of the mixed solution; 4. An outer packaging structure combining a main barrier zone and a rate-limiting CO2 diffusion window is adopted. The main barrier zone is used to suppress gas exchange in non-designed areas, while the rate-limiting CO2 diffusion window provides a controlled CO2 migration channel. Compared with a uniform barrier structure, this structure enables CO2 exchange to mainly occur in the preset area, thereby improving the controllability and consistency of gas exchange behavior, reducing the impact of overall packaging material permeability fluctuations on system performance, and contributing to improved batch-to-batch stability and consistency in industrial production. 5. When the rate-limiting CO2 diffusion window employs a localized thin barrier layer, a high-permeability membrane insert, or a microchannel structure, a designable CO2 migration path can be provided while maintaining packaging integrity and sealing. Specifically, the localized thin barrier layer achieves controlled permeation by reducing the thickness of the local barrier layer; the high-permeability membrane insert utilizes the material's inherent high CO2 permeability to achieve localized diffusion; and the microchannel structure adjusts diffusion resistance through channel size and number. All of these structures facilitate controlled CO2 exchange and improve the packaging system's adaptability to different drug formulations and buffer capacity systems. 6. The preparation method involves compartmentalized filling, constructing a confined gas-phase buffer chamber, filling with a pre-set CO2 partial pressure mixed gas, and heat-sealing to form a packaging system. This allows the drug solution system, outer packaging structure, and gas phase environment to be established simultaneously during the preparation process. Because the packaging system forms a pre-set gas environment and controlled diffusion structure during the preparation stage, it can improve the consistency of product structure and the stability of the gas environment, which is beneficial for achieving mass production and ensuring the stability of product performance after storage. Detailed Implementation Example 1

[0028] A pH-self-stabilizing peritoneal dialysis fluid packaging system includes a double inner bag and an outer packaging bag; The double-inner bag includes chamber A and chamber B, and includes the following steps: S1. Prepare the solutions for compartment A and compartment B separately, and fill them into compartments A and B of the double-layer inner bag respectively; S2. Prepare an outer packaging bag including a main barrier region and a rate-limiting CO2 diffusion window; S3. Place the inner double bag inside the outer packaging bag to form a confined gas phase buffer chamber between the inner double bag and the outer packaging bag; S4. Introduce a mixed gas containing CO2 into the confined gas phase buffer chamber; S5. Heat seal the outer packaging bag.

[0029] in: The volume of compartment A is 1500 mL. Each liter of the solution in compartment A contains: sodium bicarbonate 25 mmol / L, sodium chloride 102 mmol / L, potassium chloride 4 mmol / L, and water for injection to make up the volume. The volume of compartment B is 500 mL. Each liter of the solution in compartment B contains: sodium lactate 10 mmol / L, calcium chloride 1.25 mmol / L, magnesium chloride 0.5 mmol / L, glucose 1.5%, and water for injection to make up the difference. The total volume after mixing in both chambers is 2000 mL, pH 7.24, and buffer capacity β18 mmol / (L·pH). The inner bags of both chambers are made of medical-grade PP / PE composite film and separated by a ruptureable diaphragm. The outer packaging bag covers the outside of the inner double-chamber bag, and a confined gas phase buffer chamber is formed between the outer packaging bag and the inner double-chamber bag; the outer packaging bag includes a main barrier area and a rate-limiting CO2 diffusion window; The main barrier region is a PA / EVOH / PE membrane structure, with an EVOH thickness of 15 μm and a CO2 permeability of 0.3 cm⁻¹. 3 / (m 2 (day atm); The rate-limiting CO2 diffusion window is a localized thin barrier layer window with an area of ​​4 cm². 2 EVOH thickness 2 μm; The confined gas phase buffer chamber has a volume of 150 mL, an initial CO2 partial pressure of 6 kPa, and a balance of N2.

[0030] Example 2

[0031] A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that the diffusion window employs a TPU / siloxane blend membrane insert structure; the window area is 3 cm². 2 The volume of the confined gas phase buffer chamber is 180 mL; the buffer capacity β of the mixed solution is 22 mmol / (L·pH).

[0032] Example 3

[0033] A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that: the diffusion window adopts a microchannel structure; the microchannel diameter is 15 μm; the number of microchannels is 80; the length is 300 μm; the confined gas phase buffer chamber volume is 120 mL; and the initial CO2 partial pressure is 5 kPa.

[0034] Example 4

[0035] A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that: the bicarbonate concentration is 30 mmol / L; the lactate concentration is 8 mmol / L; the buffer capacity β is 22 mmol / (L·pH); the confined gas phase buffer chamber volume is 180 mL; and the window area is 2.5 cm². 2 .

[0036] Example 5

[0037] A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that: bicarbonate concentration is 22 mmol / L; lactate concentration is 15 mmol / L; buffer capacity β is 16 mmol / (L·pH); and window area is 5 cm². 2 The volume of the confined gas phase buffer chamber is 120 mL.

[0038] Comparative Example 1 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that the confined gas phase buffer chamber is eliminated, and the inner bag is directly sealed to the outer packaging bag.

[0039] Comparative Example 2 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that: the rate-limiting CO2 diffusion window is eliminated, and all outer packaging bags adopt a main barrier zone structure.

[0040] Comparative Example 3 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it does not contain a CO2 / N2 mixture and uses ordinary air for sealing.

[0041] Comparative Example 4 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that the restricted gas phase buffer chamber volume is only 10 mL.

[0042] Comparative Example 5 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that the restricted gas phase buffer chamber volume is 500 mL.

[0043] Comparative Example 6 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it has a diffusion window area of ​​0.05 cm². 2 .

[0044] Comparative Example 7 A pH-self-stabilizing peritoneal dialysis fluid packaging system, differing from Example 1 in that: the diffusion window area is 50 cm². 2 .

[0045] Comparative Example 8 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that the EVOH thickness is 15 μm, meaning the diffusion window is the same as the main barrier region.

[0046] Comparative Example 9 A pH-stable peritoneal dialysis fluid packaging system differs from Example 1 in that: bicarbonate concentration is 15 mmol / L; lactate concentration is 20 mmol / L; β = 8 mmol / (L·pH).

[0047] Comparative Example 10 A pH-stable peritoneal dialysis fluid packaging system differs from Example 1 in that: bicarbonate 35 mmol / L; lactate 5 mmol / L; β=35 mmol / (L·pH).

[0048] Comparative Example 11 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it uses a single-chamber bag and does not have chambers A and B.

[0049] Comparative Example 12 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it uses a regular PE outer packaging bag and does not have a main barrier zone.

[0050] Comparative Example 13 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it uses a high-barrier outer bag; does not have a diffusion window; and does not have a buffer chamber.

[0051] Comparative Example 14 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it only has a confined gas phase buffer chamber and does not have a diffusion window.

[0052] Comparative Example 15 A pH-self-stabilizing peritoneal dialysis fluid packaging system differs from Example 1 in that it only has a diffusion window and does not have a confined gas phase buffer chamber.

[0053] Detection example pH testing: Samples from each example and comparative example were stored at 25℃±2℃ and 60%±10% relative humidity, and samples were taken at 0, 1, 2, and 3 months. During sampling, the diaphragm of the double-chamber bag was broken to ensure thorough mixing of chamber A and chamber B. After standing for 5 minutes, the pH of the mixture was measured. The pH was measured according to the pH determination method in the General Chapter of the Chinese Pharmacopoeia, using a pH meter calibrated with standard buffer solution. Carbonate concentration detection: Samples from each example and comparative example were taken and mixed after 0, 1, 2, and 3 months. The converted concentration of carbonate / bicarbonate system in the mixture was determined. The results were expressed as HCO3⁻ in mmol / L. Acid-base potentiometric titration method was used: a quantitative sample was taken and titrated with standard hydrochloric acid solution. The consumption of carbonate / bicarbonate was determined by the potential jump. The interference of buffer bases such as lactate was corrected in combination with blank samples. The specific test results are shown in Tables 1 and 2.

[0054] Table 1 pH

[0055] Table 2. Carbonate concentration, expressed as HCO3⁻, mmol / L

[0056] The performance test data from Examples 1-5 and Comparative Examples 1-15 show that, in the 0-3 month storage period of the embodiments conforming to this technical solution, the pH of the mixed solution only fluctuates slightly and the carbonate concentration remains relatively stable. This indicates that the combined effect of the limited gas phase buffer chamber, the rate-limiting CO2 diffusion window, the main barrier zone, and the specific buffer system can mitigate the impact of excessively rapid CO2 escape or excessive retention on the bicarbonate system.

[0057] The performance test data from Example 1 and Comparative Example 1 show that after the restricted gas phase buffer chamber was removed, the pH of the sample increased significantly with storage time, while the carbonate concentration gradually decreased. This indicates that without the preset gas phase space, the system's buffering capacity against CO2 loss is reduced, and CO2 escape is more likely to cause the bicarbonate equilibrium to shift towards a more alkaline direction.

[0058] The performance test data from Example 1 and Comparative Example 2 show that after removing the rate-limiting CO2 diffusion window and using a high-barrier structure for all outer packaging bags, the pH of the sample gradually decreased with storage time, while the carbonate concentration slightly increased or remained high. This indicates that a simple high-barrier structure is not conducive to the limited balance of CO2 after sterilization or during storage, and can easily cause CO2 retention and make the mixture acidic.

[0059] The performance test data from Example 1 and Comparative Example 3 show that when ordinary air is used for encapsulation without filling with a preset CO2 / N2 mixture, the pH of the sample gradually increases and the carbonate concentration decreases. This indicates that when the initial CO2 partial pressure is insufficient, the gas phase buffer chamber is unable to maintain the CO2 environment required by the bicarbonate system, which can easily lead to CO2 migrating from the drug solution system to the gas phase or the outside world.

[0060] The performance test data from Example 1 and Comparative Examples 4 and 5 show that when the volume of the restricted gas phase buffer chamber is too small, the gas phase buffering capacity of the system is insufficient and the pH is prone to increase; when the volume of the restricted gas phase buffer chamber is too large, the tendency of CO2 retention is enhanced and the pH is prone to decrease. This indicates that the volume of the gas phase buffer chamber is not arbitrarily set, but needs to be matched with the drug solution buffer system and the diffusion window.

[0061] The performance test data from Example 1 and Comparative Examples 6 and 7 show that when the rate-limiting CO2 diffusion window area is too small, CO2 exchange is insufficient and the sample pH gradually decreases; when the rate-limiting CO2 diffusion window area is too large, CO2 escapes too quickly and the sample pH increases significantly. This indicates that the diffusion window area has a direct impact on the CO2 exchange rate and there is an appropriate range.

[0062] The performance test data from Example 1 and Comparative Example 8 show that when the diffusion window and the main barrier region use the same barrier structure, the sample exhibits a similar trend to that when the diffusion window is removed. This indicates that simply dividing the window area on the outer packaging bag is not enough to produce a technical effect; the window area must have a CO2 rate-limiting diffusion capability that is different from that of the main barrier region.

[0063] The performance test data from Example 1 and Comparative Examples 9 and 10 show that when the buffer capacity of the mixture is too low, the pH is more sensitive to CO2 escaping and tends to rise rapidly; when the buffer capacity is too high, the proportion of bicarbonate in the system is too high, and CO2 retention or equilibrium lag is more likely to cause the pH to drop, indicating that the buffer capacity of the drug solution needs to be matched with the CO2 exchange capacity of the packaging system.

[0064] The performance test data from Example 1 and Comparative Example 11 show that when a single-chamber bag is used, the bicarbonate buffer, lactate buffer, electrolyte, and permeabilizer coexist for a long time during storage, and the pH fluctuation and carbonate concentration change of the sample increase. This indicates that a double-chamber bag is necessary to improve storage stability.

[0065] The performance test data from Example 1 and Comparative Example 12 show that when the outer packaging bag is made of ordinary PE material and no main barrier zone is set, CO2 escapes over a large area through the outer packaging bag, resulting in a significant increase in pH and a significant decrease in carbonate concentration. This indicates that the main barrier zone can reduce CO2 migration in non-designed areas, so that gas exchange is mainly controlled by the rate-limiting CO2 diffusion window.

[0066] The performance test data from Example 1 and Comparative Examples 13, 14, and 15 show that simply using a high-barrier outer bag, setting only a confined gas phase buffer chamber, or setting only a diffusion window cannot achieve the same pH stability and carbonate concentration retention effect as in Example 1. This indicates that the technical effect of this solution is not produced by a single technical means, but is formed by the synergistic effect of the dual-chamber drug solution system, the main barrier zone, the confined gas phase buffer chamber, and the rate-limiting CO2 diffusion window.

[0067] The performance test data from Examples 1-5 show that, under different buffer formulations, different diffusion window structures, and different confined gas phase buffer chamber volumes, the samples can maintain small pH fluctuations and relatively stable carbonate concentrations within 3 months. This indicates that the technical solution is not limited to a single window material or a single formulation condition, and has a certain degree of versatility and feasibility.

Claims

1. A pH-self-stabilizing peritoneal dialysis fluid packaging system, characterized in that, Includes two inner bags and an outer packaging bag; The dual-chamber bag includes chamber A and chamber B. Chamber A contains a first solution containing a bicarbonate buffer component, and chamber B contains a second solution containing a lactate buffer component. The outer packaging bag covers the outside of the double inner bag, and a confined gas phase buffer cavity is formed between the outer packaging bag and the double inner bag; The outer packaging bag includes a main barrier area and at least one rate-limiting CO2 diffusion window; The main barrier region is a multilayer composite membrane structure; The volume of the confined gas phase buffer chamber is 30–300 mL; The initial CO2 partial pressure in the confined gas phase buffer chamber is 3–12 kPa; The effective diffusion area of the limited-speed CO2 diffusion window is 0.2-20 cm 2 ; The mixture of chambers A and B forms a peritoneal dialysis solution with a pH of 6.8–7.

6.

2. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The peritoneal dialysis fluid formed after mixing chambers A and B contains: The bicarbonate concentration was 18–35 mmol / L. The lactate concentration is 5–20 mmol / L. The molar ratio of bicarbonate to lactate is 1.5 to 5:

1.

3. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The buffer capacity β of the peritoneal dialysis fluid formed by mixing chambers A and B is 10–30 mmol / (L·pH).

4. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The multilayer composite membrane structure includes one of PA / EVOH / PE, PET / EVOH / PE, COC / PE, and PET / AlOx / PE.

5. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The CO2transmission rate of the primary barrier zone is no more than 0.5 cm 3 / (m 2 · day · atm).

6. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The rate-limiting CO2 diffusion window is a locally thin barrier layer window, and the thickness of the EVOH layer in the locally thin barrier layer window is 0.5 to 5 μm.

7. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The rate-limiting CO2 diffusion window is a CO2 high-permeability membrane insert window, which includes one of the following: a polysiloxane modified membrane, a TPU / siloxane blend membrane, and a PE microporous membrane.

8. The pH self-stabilizing peritoneal dialysis fluid packaging system according to claim 1, characterized in that, The rate-limiting CO2 diffusion window is a microchannel window, which includes multiple microchannels. The diameter of the microchannels is 1 to 100 μm, the number is 5 to 500, and the length is 50 to 1000 μm.

9. A pH-self-stabilizing peritoneal dialysis fluid packaging system according to claim 8, characterized in that, The microchannel window is covered with a hydrophobic and breathable membrane.

10. A method for preparing a pH-self-stabilizing peritoneal dialysis fluid packaging system according to any one of claims 1 to 9, characterized in that, Includes the following steps: S1. Prepare the first and second solutions separately, and fill them into chambers A and B of the double-chamber bag respectively; S2. Prepare an outer packaging bag including a main barrier region and a rate-limiting CO2 diffusion window; S3. Place the inner double bag into the outer packaging bag to form a confined gas phase buffer chamber between the inner double bag and the outer packaging bag; S4. Introduce a mixed gas containing CO2 into the confined gas phase buffer chamber, so that the initial CO2 partial pressure in the confined gas phase buffer chamber is 3-12 kPa. S5. Heat seal the outer packaging bag.

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