Neutral peritoneal dialysis solution and preparation method thereof

Abstract

The invention relates to the technical field of medical drugs, and particularly discloses a neutral peritoneal dialysis solution and a preparation method thereof. The neutral peritoneal dialysis solution comprises a small chamber solution and a large chamber solution in a mass ratio of 1: (1.5-2), the small chamber solution comprises glucose, icodextrin, lactate, a first electrolyte, a viscosity regulator and an acidity regulator; the pH value of the solution in the small chamber is 3.3-3.8; the large-chamber solution comprises sodium bicarbonate, a second electrolyte and an alkaline regulator; the pH value of the solution in the large chamber is 8.8-9.4. Glucose and icodextrin in a specific proportion are compounded to serve as a penetrant, the ultrafiltration performance of dialysate can be remarkably improved, redundant water in the body of a patient is removed, meanwhile, solute removal is driven through the permeation effect, water balance of the patient is maintained, and electrolyte and acid-base balance in the body is adjusted. By adjusting the concentration and dosage of each component of the dialysate, the synergistic effect of each component is exerted to a greater extent.

Description

Technical Field

[0001] The present invention relates to the technical field of medical drugs, and particularly to a neutral peritoneal dialysis solution and a preparation method thereof. Background Art

[0002] Peritoneal dialysis (PD) is an effective means for treating uremia. Peritoneal dialysis uses the peritoneum as a dialysis membrane, injects dialysis solution into the abdominal cavity. On one side of the peritoneum, the plasma in the capillaries and the dialysis solution in the abdominal cavity on the other side rely on their solute concentration gradient and osmotic gradient, and through the principles of diffusion and ultrafiltration, to remove the retained metabolic wastes and excessive water in the body, and at the same time supplement the necessary substances through the dialysis solution. Continuously replacing the fresh dialysis solution for repeated dialysis can achieve the treatment purposes of removing toxins, removing excess water, correcting acidosis and electrolyte disorders.

[0003] Currently, lactate or bicarbonate is mostly used as a buffer for peritoneal dialysis solution in clinics. The bicarbonate peritoneal dialysis solution, also known as neutral peritoneal dialysis solution, has better biocompatibility compared with the lactate peritoneal dialysis solution. The double-chamber bag packaging makes glucose in a lower pH environment, minimizing the glucose degradation products (GDPs), and the infusion pain of patients is also improved. The osmotic agent of the neutral peritoneal dialysis solution is glucose, which can be quickly absorbed by the peritoneum and is also easily metabolized after entering the blood. However, the glucose concentration of the existing neutral peritoneal dialysis solution may be relatively low. During the long-term dialysis process, the glucose concentration drops too fast after being absorbed by the peritoneum, resulting in the inability to continuously maintain an effective osmotic pressure gradient, relatively low osmotic pressure, limited ultrafiltration efficiency, and unsatisfactory dehydration effect for patients with severe body fluid retention; the solute clearance efficiency is relatively low. For patients with high levels of uremic toxins, more frequent dialysis or combined with other therapies is required. Summary of the Invention

[0004] In view of the above problems, the present invention provides a neutral peritoneal dialysis solution and a preparation method thereof. By using a specific ratio of glucose and icodextrin as a compound osmotic agent, the ultrafiltration performance and solute clearance efficiency of the neutral peritoneal dialysis solution are significantly improved. At the same time, by controlling the dosage and concentration of each component, the glucose degradation products are minimized, and the peritoneal function is improved.

[0005] To solve the above technical problems, the technical solution provided by the present invention is: In a first aspect, the present invention provides a neutral peritoneal dialysis solution, comprising a small chamber solution and a large chamber solution with a mass ratio of 1:(1.5 - 2); The small chamber solution includes: glucose at 37.5 g / L to 62.7 g / L, icodextrin at 82.5 g / L to 110 g / L, lactate at 3.0 g / L to 3.2 g / L, a first electrolyte at 6.7 g / L to 7.0 g / L, a viscosity regulator and an acid regulator at 3.5 g / L to 3.8 g / L; the pH of the small chamber solution is 3.3 to 3.8; The large chamber solution includes: sodium bicarbonate at 3.5 g / L to 3.7 g / L, a second electrolyte at 4.9 g / L to 5.0 g / L, and an alkaline regulator; the pH of the large chamber solution is 8.8 to 9.4.

[0006] Compared with the prior art, for the neutral peritoneal dialysis solution provided by the present invention, icodextrin is a macromolecular polysaccharide formed by the polymerization of multiple glucose molecules. It has a large molecular weight and is not easily permeable through the peritoneum. During peritoneal dialysis, it can form a stable and persistent osmotic pressure gradient, which is suitable for nocturnal peritoneal dialysis with a long dwell time in the abdomen, and can effectively remove excess water in the patient's body. By using a specific ratio of glucose and icodextrin compounded as an osmotic agent, the characteristics of the two are complemented to a certain extent, which can significantly improve the ultrafiltration performance of the existing neutral peritoneal dialysis solution, remove excess water in the patient's body, and at the same time drive the removal of solutes through osmosis to maintain the water balance of the patient and regulate the body's electrolyte and acid-base balance. Due to the relatively high viscosity of icodextrin, it may increase the risk of dialysis tubing blockage during use, and it provides a good growth environment for bacteria and other microorganisms, which may increase the incidence of infectious complications such as peritonitis. Therefore, on the premise of not affecting the basic functions of the neutral peritoneal dialysis solution and the safety of patients, the present invention adds a specific amount of viscosity regulator to reduce the viscosity of the small chamber solution.

[0007] The present invention adjusts the concentration and dosage of each component of the neutral peritoneal dialysis solution, giving full play to the synergistic effect of each component to a greater extent, better maintaining the stability of the acid-base balance of the neutral peritoneal dialysis solution, improving the peritoneal physiological environment, increasing the permeability of the peritoneum to solutes, and thus enhancing the solute clearance rate. By controlling the high-concentration osmotic agent in a specific pH environment, the present invention can minimize glucose degradation products and advanced glycation end products (AGEs), avoid preventing angiogenesis and peritoneal fibrosis, improve peritoneal function, and protect residual renal function and urine volume. By limiting the concentration and dosage range of each component of the large chamber solution, the present invention ensures the quality stability of sodium bicarbonate during sterilization and storage. By controlling the pH value and dosage range of the small chamber solution and the large chamber solution, it can ensure that the pH of the peritoneal dialysis solution after mixing is between 6.8 and 7.8, which is more in line with the physiological state of the human body, while maintaining the optimal biocompatibility, reducing the infusion pain, and improving the compliance.

[0008] Through a large number of experiments, the present invention has found that using a specific ratio of glucose and icodextrin compounded as an osmotic agent has the following advantages: (1) Little impact on blood sugar: Different from using glucose as an osmotic agent, icodextrin is basically not absorbed by the peritoneum into the blood circulation and will not cause a significant increase in blood sugar. This is particularly important for patients with diabetes complicated with renal failure who need peritoneal dialysis, which can reduce the risk of hyperglycemia-related complications and facilitate the control and management of the patients' blood sugar; (2) Light metabolic burden: Icodextrin is metabolized slowly in the body and will not be metabolized and decomposed as quickly as glucose, thus reducing the metabolic burden on patients. It is particularly suitable for patients with insulin resistance or metabolic dysfunction and helps to maintain the metabolic balance in the patients' bodies; (3) Good biocompatibility: Icodextrin has less irritation to the peritoneum and good biocompatibility. Long-term use can reduce the occurrence of complications such as peritoneal fibrosis and adhesions, which is beneficial to protecting peritoneal function, prolonging the effective use time of peritoneal dialysis, and improving the dialysis quality and quality of life of patients.

[0009] Preferably, the viscosity regulator is polyethylene glycol or dextran.

[0010] In the present invention, polyethylene glycol belongs to a non-ionic surfactant, which can change the intermolecular interaction in the solution, reduce the aggregation degree of icodextrin molecules, and thus reduce the viscosity, which is beneficial to improving the dialysis efficiency and ultrafiltration effect; low molecular weight dextran can also reduce the viscosity of the icodextrin solution to a certain extent, and has little impact on the osmotic pressure and other properties of the dialysis fluid.

[0011] More preferably, the viscosity regulator is polyethylene glycol.

[0012] Through a large number of experiments, the present invention has found that polyethylene glycol has good water solubility, low viscosity and good biocompatibility. Compared with dextran, polyethylene glycol has a smaller molecular weight, better fluidity, and a more obvious viscosity reduction effect on neutral peritoneal dialysis fluid. At the same time, polyethylene glycol has less irritation to peritoneal tissue and human cells, will not cause obvious immune reactions or other adverse reactions, and will not have a significant impact on the physiological function of the peritoneum. In addition, polyethylene glycol has relatively stable chemical properties and will not react chemically with glucose, icodextrin and other components in the peritoneal dialysis fluid, will not cause the deterioration of the dialysis fluid components or produce harmful substances, and can ensure the chemical stability of the dialysis fluid.

[0013] More preferably, the polyethylene glycol includes at least one of PEG-200, PEG-400 or PEG-600.

[0014] More preferably, the dextran includes at least one of dextran 20, dextran 30 or dextran 40.

[0015] The present invention selects a viscosity regulator with a small molecular weight, which has better fluidity and more obvious viscosity reduction effect.

[0016] Preferably, the lactate salt includes sodium lactate.

[0017] Preferably, the first electrolyte includes 0.5 g / L to 0.72 g / L of calcium chloride, 6.0 g / L to 6.2 g / L of sodium chloride, and 0.1 g / L to 0.2 g / L of magnesium chloride.

[0018] Preferably, the second electrolyte includes sodium chloride.

[0019] Preferably, the acidic regulator includes hydrochloric acid.

[0020] Preferably, the basic regulator includes sodium hydroxide.

[0021] Preferably, the neutral peritoneal dialysis solution includes 725 mL of small chamber solution and 1275 mL of large chamber solution; The small chamber solution includes: 27.2 g to 45.4 g of glucose, 59.9 g to 79.7 g of icodextrin, 2.24 g of sodium lactate, 0.515 g to 0.368 g of calcium chloride, 4.42 g of sodium chloride, 0.102 g of magnesium chloride, 2.25 g of viscosity regulator, and 0.381 g of hydrochloric acid; The large chamber solution includes: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, and 0.225 g of sodium hydroxide.

[0022] Exemplarily, in the small chamber solution of the present invention, the dosage of glucose can be 27.2 g or 45.4 g; the dosage of icodextrin can be 59.9 g or 79.7 g; the dosage of calcium chloride can be 0.515 g or 0.368 g. In the present invention, the specific dosage of the osmotic agent can be adjusted according to the actual needs of the patient, and the dosage of calcium chloride can be adjusted according to the improvement effect on hypermagnesemia.

[0023] Preferably, the mass ratio of the small chamber solution to the large chamber solution is 1:(1.7 - 1.8).

[0024] Preferably, the pH of the system after mixing the small chamber solution and the large chamber solution is 7 - 7.4.

[0025] In a second aspect, the present invention provides a method for preparing the neutral peritoneal dialysis solution as described above, comprising the following steps: S1. Weigh each component of the small chamber solution according to the designed ratio. Under an inert atmosphere, add glucose, icodextrin, lactate, the first electrolyte, and a viscosity regulator to the water for injection, then add an acidic regulator to adjust the pH of the resulting mixed system to 3.3 - 3.8, and filter to obtain the small chamber solution. S2. Weigh each component of the large chamber solution according to the designed ratio. Under an inert atmosphere, add sodium bicarbonate and the second electrolyte to the water for injection, then add a basic regulator to adjust the pH of the resulting mixed system to 8.8 - 9.4, and filter to obtain the large chamber solution. S3. According to the designed mass ratio, under an inert atmosphere, respectively fill the small chamber solution and the large chamber solution into a double - chamber bag, stopper and seal it, sterilize it, and then package it with a vacuum high - barrier bag to obtain a neutral peritoneal dialysis solution.

[0026] The preparation method of the neutral peritoneal dialysis solution provided by the present invention is completed under an inert atmosphere throughout the process, which can protect each component from external interference, ensure a sterile environment. At the same time, it can also ensure that bicarbonate is not decomposed during the whole preparation process, thus ensuring the quality of the neutral peritoneal dialysis solution. The present invention uses a vacuum high - barrier bag with barrier properties to water vapor, oxygen, and carbon dioxide and achieving a negative pressure effect by vacuum pumping. It can not only meet the general safety protection performance of dust prevention and bacteria prevention, avoid physical damage, ensure the integrity and quality of the neutral peritoneal dialysis solution are not affected, but also has the protection effect of waterproof and gas leakage prevention, ensure that the concentration of each component is within the designed range, and keep the best quality of the double - chamber bag product within the shelf life, thereby improving the treatment effect of peritoneal dialysis.

[0027] When the patient uses it, just open the vacuum high - barrier bag and squeeze the large and small chambers forcefully to open the virtual welding part of the double - chamber bag, so that the small chamber solution and the large chamber solution can be mixed.

[0028] Preferably, in S1 - S2, the filtration uses a 0.2 - μm polyethersulfone (PES) folded filter element.

[0029] Preferably, in S1, in the small chamber solution, the number of particles ≥10 µm ≤ 10 particles / mL, and the number of particles ≥25 µm ≤ 1 particle / mL.

[0030] Preferably, in S2, in the large chamber solution, the number of particles ≥10 µm ≤ 10 particles / mL, and the number of particles ≥25 µm ≤ 1 particle / mL.

[0031] Preferably, in S3, the filling pressure is 1.0 bar - 2.0 bar, and the filling temperature is 5°C - 50°C.

[0032] Preferably, in S3, the sterilization uses water - bath sterilization, the sterilization temperature is 115°C - 130°C, and the sterilization time is 10 min - 15 min.

[0033] The present invention uses water bath sterilization and completes the sterilization process under overkill conditions by controlling the sterilization conditions, and the F0 value can reach more than 12. Specific embodiments

[0034] In order to make the objectives, technical solutions and advantages of the present invention clearer, the following further describes the present invention in detail with reference to embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0035] In the present invention, unless otherwise specified, all materials are commercially available products.

[0036] Example 1 This example provides a neutral peritoneal dialysis solution, which includes 725 mL of small chamber solution and 1275 mL of large chamber solution. The pH of the system after mixing the small chamber solution and the large chamber solution is 7.2.

[0037] The small chamber solution consists of the following components: 27.2 g of anhydrous glucose, 59.9 g of icodextrin, 2.24 g of sodium lactate, 0.515 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of PEG-200, 0.381 g of hydrochloric acid and water for injection. The pH of the small chamber solution is 3.6.

[0038] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, 0.225 g of sodium hydroxide and water for injection. The pH of the large chamber solution is 9.2.

[0039] The preparation method of the above neutral peritoneal dialysis solution includes the following steps: S1, Weigh each component of the small chamber solution according to the designed ratio. Under an inert atmosphere, add anhydrous glucose, icodextrin, lactate, the first electrolyte and the viscosity regulator to water for injection, then add an acidic regulator to adjust the pH value of the obtained mixed system, and filter it with a 0.2 μm PES pleated filter element to obtain the small chamber solution.

[0040] S2, Weigh each component of the large chamber solution according to the designed ratio. Under an inert atmosphere, add sodium bicarbonate and the second electrolyte to water for injection, then add a basic regulator to adjust the pH value of the obtained mixed system, and filter it with a 0.2 μm PES pleated filter element to obtain the large chamber solution.

[0041] S3, According to the mass design ratio, under an inert atmosphere, fill the small chamber solution and the large chamber solution into a double-chamber bag at 1.5 bar and room temperature respectively; stopper and seal, sterilize in a water bath at 121 °C for 12 min, and then package it with a vacuum high-barrier bag to obtain the neutral peritoneal dialysis solution.

[0042] Example 2 This embodiment provides a neutral peritoneal dialysis solution, which includes 725 mL of small chamber solution and 1275 mL of large chamber solution. The pH of the system after mixing the small chamber solution and the large chamber solution is 7.0.

[0043] The small chamber solution consists of the following components: 27.2 g of anhydrous glucose, 79.7 g of icodextrin, 2.24 g of sodium lactate, 0.368 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of PEG-400, 0.381 g of hydrochloric acid and water for injection. The pH of the small chamber solution is 3.7.

[0044] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, 0.225 g of sodium hydroxide and water for injection. The pH of the large chamber solution is 9.1.

[0045] The preparation method of the above-mentioned neutral peritoneal dialysis solution includes the following steps: S1 - S2 are the same as those in Embodiment 1 and will not be elaborated here.

[0046] S3, according to the mass design ratio, under an inert atmosphere, at 1.0 bar and room temperature, the small chamber solution and the large chamber solution are respectively filled into a double-chamber bag; after capping and sealing, it is sterilized in a water bath at 115 °C for 15 min, and then externally wrapped with a vacuum high-barrier bag to obtain the neutral peritoneal dialysis solution.

[0047] Embodiment 3 This embodiment provides a neutral peritoneal dialysis solution, which includes 725 mL of small chamber solution and 1275 mL of large chamber solution. The pH of the system after mixing the small chamber solution and the large chamber solution is 7.4.

[0048] The small chamber solution consists of the following components: 45.4 g of anhydrous glucose, 59.9 g of icodextrin, 2.24 g of sodium lactate, 0.515 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of PEG-600, 0.381 g of hydrochloric acid and water for injection. The pH of the small chamber solution is 3.8.

[0049] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, 0.225 g of sodium hydroxide and water for injection. The pH of the large chamber solution is 9.2.

[0050] The preparation method of the above-mentioned neutral peritoneal dialysis solution includes the following steps: S1 - S2 are the same as those in Embodiment 1 and will not be elaborated here.

[0051] S3. According to the quality-designed ratio, under an inert atmosphere, at 2.0 bar and room temperature, the small chamber solution and the large chamber solution are respectively filled into a double-chamber bag; stoppered and sealed, sterilized in a water bath at 130 °C for 10 min, and then externally wrapped with a vacuum high-barrier bag to obtain a neutral peritoneal dialysis solution.

[0052] Example 4 This example provides a neutral peritoneal dialysis solution, including 750 mL of small chamber solution and 1250 mL of large chamber solution. The pH of the system after mixing the small chamber solution and the large chamber solution is 6.8.

[0053] The small chamber solution consists of the following components: 45.4 g of anhydrous glucose, 79.7 g of icodextrin, 2.24 g of sodium lactate, 0.368 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of dextran 20, 0.381 g of hydrochloric acid, and water for injection. The pH of the small chamber solution is 3.5.

[0054] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, 0.225 g of sodium hydroxide, and water for injection. The pH of the large chamber solution is 8.8.

[0055] The preparation method of the above neutral peritoneal dialysis solution is the same as that of Example 1 and will not be elaborated here.

[0056] Example 5 This example provides a neutral peritoneal dialysis solution, including 700 mL of small chamber solution and 1300 mL of large chamber solution. The pH of the system after mixing the small chamber solution and the large chamber solution is 7.7.

[0057] The small chamber solution consists of the following components: 45.4 g of anhydrous glucose, 59.9 g of icodextrin, 2.24 g of sodium lactate, 0.515 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of dextran 40, 0.381 g of hydrochloric acid, and water for injection. The pH of the small chamber solution is 3.3.

[0058] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, 0.225 g of sodium hydroxide, and water for injection. The pH of the large chamber solution is 9.4.

[0059] The preparation method of the above neutral peritoneal dialysis solution is the same as that of Example 1 and will not be elaborated here.

[0060] Comparative Example 1 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 1, except that: the small chamber solution does not contain icodextrin and PEG-200 (i.e., icodextrin and PEG-200 are replaced with the same mass of water for injection), and the other components, their concentrations and dosages are the same as those in Example 1, which will not be elaborated herein.

[0061] Comparative Example 2 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 1, except that: the small chamber solution does not contain PEG-200 (i.e., PEG-200 is replaced with the same mass of water for injection), and the other components, their concentrations and dosages are the same as those in Example 1, which will not be elaborated herein.

[0062] Comparative Example 3 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 2, except that: the pH of the small chamber solution is 4.0 (i.e., part of hydrochloric acid is replaced with the same mass of water for injection), and the pH of the system after mixing the small chamber solution and the large chamber solution is 7.5. The other components, their concentrations and dosages are the same as those in Example 2, which will not be elaborated herein.

[0063] Comparative Example 4 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 3, except that: the pH of the large chamber solution is 8.5 (i.e., part of sodium hydroxide is replaced with the same mass of water for injection), and the pH of the system after mixing the small chamber solution and the large chamber solution is 6.7. The other components, their concentrations and dosages are the same as those in Example 3, which will not be elaborated herein.

[0064] Comparative Example 5 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 1, except that: the dosage of the first electrolyte is different, and the mass ratio of the small chamber solution to the large chamber solution is 1:1. Specifically, it includes 1000 mL of the small chamber solution and 1000 mL of the large chamber solution; the pH of the system after mixing the small chamber solution and the large chamber solution is 7.2.

[0065] The small chamber solution consists of the following components: 27.2 g of anhydrous glucose, 59.9 g of icodextrin, 16.8 g of sodium lactate, 0.9 g of calcium chloride dihydrate, 4.42 g of sodium chloride, 0.102 g of magnesium chloride hexahydrate, 2.25 g of PEG-200, hydrochloric acid (the specific dosage of hydrochloric acid is based on the pH of the small chamber solution being 3.6) and water for injection. The pH of the small chamber solution is 3.6.

[0066] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 6.30 g of sodium chloride, sodium hydroxide (the specific dosage of sodium hydroxide is based on the pH of the large chamber solution being 9.2) and water for injection. The pH of the large chamber solution is 9.2.

[0067] Comparative Example 6 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 1, except that: the dosages of the first electrolyte and the second electrolyte are different, and the mass ratio of the small chamber solution to the large chamber solution is 1:1. Specifically, it includes 1000 mL of the small chamber solution and 1000 mL of the large chamber solution; the pH of the system after mixing the small chamber solution and the large chamber solution is 7.2.

[0068] The small chamber solution consists of the following components: 27.2 g of anhydrous glucose, 59.9 g of icodextrin, 2.24 g of sodium lactate, 0.515 g of calcium chloride dihydrate, 0.25 g of magnesium chloride hexahydrate, 2.25 g of PEG-200, hydrochloric acid (the specific dosage of hydrochloric acid is based on the pH of the small chamber solution being 3.6), and water for injection. The pH of the small chamber solution is 3.6.

[0069] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 10.72 g of sodium chloride, sodium hydroxide (the specific dosage of sodium hydroxide is based on the pH of the large chamber solution being 9.2), and water for injection. The pH of the large chamber solution is 9.2.

[0070] Comparative Example 7 This comparative example provides a neutral peritoneal dialysis solution, which is similar to Example 1, except that: the first electrolyte consists of calcium chloride and magnesium chloride, and the small chamber solution does not contain sodium lactate (sodium lactate is in the large chamber solution). Specifically, it includes 725 mL of the small chamber solution and 1275 mL of the large chamber solution; the pH of the system after mixing the small chamber solution and the large chamber solution is 7.2.

[0071] The small chamber solution consists of the following components: 27.2 g of anhydrous glucose, 59.9 g of icodextrin, 0.515 g of calcium chloride dihydrate, 0.102 g of magnesium chloride hexahydrate, 2.25 g of PEG-200, hydrochloric acid (the specific dosage of hydrochloric acid is based on the pH of the small chamber solution being 3.6), and water for injection. The pH of the small chamber solution is 3.6.

[0072] The large chamber solution consists of the following components: 4.62 g of sodium bicarbonate, 2.24 g of sodium lactate, 10.72 g of sodium chloride, sodium hydroxide (the specific dosage of sodium hydroxide is based on the pH of the large chamber solution being 9.2), and water for injection. The pH of the large chamber solution is 9.2.

[0073] Verification test Under the conditions of 25°C and avoiding direct sunlight, after placing the neutral peritoneal dialysis solutions of Examples 1 to 5 and Comparative Examples 1 to 7 for 0 days, 5 months, and 10 months, the viscosity, osmotic pressure, sodium bicarbonate content, and 5-hydroxymethylfurfural (glucose degradation product) content of the neutral peritoneal dialysis solution mixture were measured respectively. The test results are shown in Table 1. Among them, the capillary viscometer method was used for the measurement of viscosity, the freezing point depression method was used for the measurement of osmotic pressure, the method for the determination of sodium bicarbonate content was referred to the method under the determination of "Sodium Bicarbonate Injection" in Part II of the Chinese Pharmacopoeia 2010 Edition, and the method for the determination of 5-hydroxymethylfurfural content was referred to the inspection method of 5-hydroxymethylfurfural under the inspection item of "Compound Sodium Lactate and Glucose Injection" in Part II of the Chinese Pharmacopoeia 2010 Edition.

[0074] Table 1 Performance test results of alloy casting belts of examples and comparative examples

[0075] Clinical studies were carried out using the neutral peritoneal dialysis solutions provided in Examples 1 to 3 and Comparative Example 1 of the present invention. Fifteen-hour single dwell exchanges were performed on 10 peritoneal dialysis patients with a fast peritoneal solute transport rate. The results showed that the average net sodium clearance of the neutral peritoneal dialysis solutions of Examples 1 to 3 was 150 mmol; while the average net sodium clearance of the neutral peritoneal dialysis solution of Comparative Example 1 was 16 mmol; the net ultrafiltration volume, urea clearance rate, and creatinine clearance rate were also significantly improved. This indicates that both the net ultrafiltration volume and sodium clearance of the neutral peritoneal dialysis solution provided by the present invention are significantly increased, which can enhance the clearance of solutes such as uremic toxins, contribute to improving dialysis adequacy, and better maintain the metabolic balance in patients.

[0076] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, or improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A neutral peritoneal dialysis fluid, characterized in that: It includes a small chamber solution and a large chamber solution in a mass ratio of 1:(1.5-2); The cell solution comprises: 37.5 g / L to 62.7 g / L of glucose, 82.5 g / L to 110 g / L of icodextrin, 3.0 g / L to 3.2 g / L of lactate, 6.7 g / L to 7.0 g / L of a first electrolyte, 3.5 g / L to 3.8 g / L of a viscosity regulator and an acidity regulator; the pH of the cell solution is 3.3 to 3.8; The large chamber solution comprises: 3.5 g / L to 3.7 g / L of sodium bicarbonate, 4.9 g / L to 5.0 g / L of a second electrolyte and an alkaline regulator; the pH of the large chamber solution is 8.8 to 9.

4.

2. The neutral peritoneal dialysis fluid according to claim 1, characterized in that The viscosity modifier is polyethylene glycol or dextran.

3. The neutral peritoneal dialysis fluid according to claim 2, characterized in that The polyethylene glycol includes at least one of PEG-200, PEG-400 or PEG-600; The dextran includes at least one of dextran 20, dextran 30 or dextran 40.

4. The neutral peritoneal dialysis fluid according to claim 1, characterized in that The first electrolyte includes 0.5 g / L to 0.72 g / L of calcium chloride, 6.0 g / L to 6.2 g / L of sodium chloride, and 0.1 g / L to 0.2 g / L of magnesium chloride; The second electrolyte includes sodium chloride.

5. The neutral peritoneal dialysis fluid according to claim 1, characterized in that The lactate includes sodium lactate; The acidic regulator includes hydrochloric acid; The alkaline conditioner includes sodium hydroxide.

6. The neutral peritoneal dialysis fluid according to any one of claims 1 to 5, characterized in that: The neutral peritoneal dialysis solution includes 725 mL of small chamber solution and 1275 mL of large chamber solution; The chamber solution includes: 27.2g~45.4g glucose, 59.9g~79.7g icodextrin, 2.24g sodium lactate, 0.515g~0.368g calcium chloride, 4.42g sodium chloride, 0.102g magnesium chloride, 2.25g viscosity modifier and 0.381g hydrochloric acid; The large chamber solution includes: 4.62 g sodium bicarbonate, 6.30 g sodium chloride and 0.225 g sodium hydroxide.

7. The neutral peritoneal dialysis fluid according to any one of claims 1 to 5, characterized in that The pH of the system after the small chamber solution and the large chamber solution are mixed is 6.8~7.

8.

8. The method for preparing the neutral peritoneal dialysis fluid according to claims 1 to 7, characterized in that: The following steps are involved: S1, weighing the components of the cell solution according to the designed ratio, adding glucose, icodextrin, lactate, the first electrolyte and the viscosity regulator to the water for injection under an inert atmosphere, adding an acidic regulator to adjust the pH of the obtained mixed system to 3.3-3.8, filtering, and obtaining the cell solution; S2, weighing the components of the large chamber solution according to the designed ratio, adding sodium bicarbonate and the second electrolyte to the water for injection under an inert atmosphere, adding an alkaline regulator to adjust the pH of the resulting mixed system to 8.8-9.4, filtering, and obtaining the large chamber solution; S3, according to the quality design ratio, under an inert atmosphere, the small chamber solution and the large chamber solution are respectively canned into double chamber bags, stoppered and sealed, sterilized, and wrapped in a vacuum high barrier bag to obtain a neutral peritoneal dialysis solution.

9. The method for preparing a neutral peritoneal dialysis fluid according to claim 8, characterized in that: In S1, in the chamber solution, the number of particles ≥10 µm is ≤10 particles / mL, and the number of particles ≥25 µm is ≤1 particle / mL; In S2, in the large chamber solution, the number of particles ≥10µm is ≤10 particles / mL, and the number of particles ≥25µm is ≤1 particle / mL.

10. The method for preparing a neutral peritoneal dialysis fluid according to claim 8, characterized in that: In S3, the filling pressure is 1.0 bar to 2.0 bar, and the filling temperature is 5° C. to 50° C.; In S3, the sterilization is carried out by water bath sterilization, the sterilization temperature is 115° C. to 130° C., and the sterilization time is 10 min to 15 min.

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