Peritoneal dialysis solution, peritoneal dialysis solution set, composition used in peritoneal dialysis, and method for performing peritoneal dialysis

Abstract

To provide a means for appropriately managing water balance while enhancing total sodium removal in incremental peritoneal dialysis. [Solution] A peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, said peritoneal dialysis solution being used in combination with another peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, said peritoneal dialysis solution and said other peritoneal dialysis solution being used separately for peritoneal dialysis, in which an amount of 1.5 to 2.0 L is injected into the peritoneal cavity of a subject, retained, and drained, twice in total per day, said peritoneal dialysis solution being used once per day, and said other peritoneal dialysis solution being used once per day.

Description

[Technical Field]

[0001] The present invention relates to peritoneal dialysis solutions, peritoneal dialysis sets, compositions for use in peritoneal dialysis, and methods for performing peritoneal dialysis. [Background technology]

[0002] Stepwise peritoneal dialysis (incremental peritoneal dialysis) is a method that relies on residual renal function and involves small bag exchanges of peritoneal dialysis fluid in the early stages while residual renal function is maintained. According to Non-Patent Document 1, the sodium concentrating ability of the kidneys of dialysis patients is reduced, and urinary sodium concentrations are around 70 mEq / L regardless of urine volume. Therefore, incremental peritoneal dialysis limits urinary sodium excretion. When compared per fluid removal amount, the sodium removal amount of peritoneal dialysis is greater than that of the residual kidney. However, when peritoneal dialysis fluid bag exchanges are performed twice, the total sodium removal amount combined is insufficient. This leads to gradual accumulation of sodium in the body, potentially leading to fluid overload, a clinical issue.

[0003] Patent Document 1 discloses a means for appropriately managing the balance of water and sodium without causing hyponatremia and avoiding adverse effects on residual renal function. However, this is limited to typical peritoneal dialysis prescribed three to five times a day, and does not disclose any solutions to the problems associated with twice-daily peritoneal dialysis, which is dependent on residual renal function.

[0004] Depending on the degree to which sodium removal is enhanced by peritoneal dialysis, compensatory responses of the remaining functioning nephrons may occur, affecting urinary sodium excretion, resulting in a failure to improve total sodium removal or a change in urine volume that may worsen water balance.

[0005] There are many unknowns, and no research reports have clarified the effect on urinary sodium excretion when increasing the amount of sodium removed by peritoneal dialysis in the early stages when residual renal function is maintained. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2019 / 168063 [Non-patent literature]

[0007] [Non-Patent Document 1] Nakayama M. Why should we use a low sodium dialysis solution for peritoneal dialysis? Perit Dial Int. 2024 Mar;44(2):89-97. Summary of the Invention [Problem to be solved by the invention]

[0008] Therefore, an object of the present invention is to provide a means for appropriately managing water balance while enhancing total sodium removal during incremental peritoneal dialysis. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems, and as a result have found that the above problems can be solved by using a peritoneal dialysis solution containing 1.5 to 1.8 w / v % glucose and 120 to 130 mEq / L sodium in combination with a peritoneal dialysis solution containing 1.35 to 1.5 w / v % glucose and 132 to 135 mEq / L sodium, thereby completing the present invention.

[0010] That is, the above problems can be solved by the present invention having the following configuration, and the present invention includes the following aspects and configurations.

[0011] One aspect of the present invention is (1) A peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, The peritoneal dialysis solution is used in combination with another peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, The peritoneal dialysis solution and the other peritoneal dialysis solution are used for peritoneal dialysis in which 1.5 to 2.0 L of each peritoneal dialysis solution is injected into, retained in, and drained from the peritoneal cavity of a subject twice a day, in total, and the peritoneal dialysis solution is used once a day, and the other peritoneal dialysis solution is used once a day; (2) The peritoneal dialysis solution according to (1) above preferably contains 123 to 128 mEq / L of sodium; (3) The peritoneal dialysis solution according to (1) or (2) above preferably further contains 2.0 to 4.0 mEq / L of calcium; 0.5 to 1.5 mEq / L of magnesium; 86.0 to 98.0 mEq / L of chlorine; and 35 to 40 mEq / L of an alkalizing agent; (4) In the peritoneal dialysis solution according to any one of (1) to (3) above, it is preferable that the other peritoneal dialysis solution further contains 2.3 to 4.0 mEq / L of calcium; 0.5 to 1.5 mEq / L of magnesium; 95.0 to 105.5 mEq / L of chlorine; and 35 to 40 mEq / L of an alkalizing agent.

[0012] Another aspect of the present invention is (5) a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; a second peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; The first peritoneal dialysis solution and the second peritoneal dialysis solution are each used individually for peritoneal dialysis, in which a total of 1.5 to 2.0 L of each solution is injected into the subject's peritoneal cavity, retained, and drained, twice a day, and in this case, the first peritoneal dialysis solution is used once a day, and the second peritoneal dialysis solution is used once a day, making this a peritoneal dialysis solution set.

[0013] Another aspect of the present invention is (6) A composition for use in peritoneal dialysis, The composition contains 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, The composition is used in combination with other compositions for peritoneal dialysis containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, The composition and the other composition are each injected into the abdominal cavity of a subject in an amount of 1.5 to 2.0 L, twice a day, followed by retention and drainage; The composition is used once per day and the other composition is a once per day composition.

[0014] Another aspect of the present invention is (7) A method of performing peritoneal dialysis on a single subject per day, The method includes administering a first peritoneal dialysis solution to the single subject once per day, and administering a second peritoneal dialysis solution to the single subject once per day; the first peritoneal dialysis solution contains 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; the second peritoneal dialysis solution contains 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; administering the first peritoneal dialysis solution includes injecting 1.5 to 2.0 L of the first peritoneal dialysis solution into the peritoneal cavity of the single subject, allowing the first peritoneal dialysis solution to pool in the peritoneal cavity, and draining the first peritoneal dialysis solution from the peritoneal cavity; administering the second peritoneal dialysis solution includes injecting 1.5 to 2.0 L of the second peritoneal dialysis solution into the peritoneal cavity of the single subject, allowing the second peritoneal dialysis solution to pool in the peritoneal cavity, and draining the second peritoneal dialysis solution from the peritoneal cavity; The infusing of the first peritoneal dialysis solution and the infusing of the second peritoneal dialysis solution are methods that are independent of each other. [Effects of the Invention]

[0015] According to the present invention, a means for appropriately managing water balance while increasing total sodium removal in incremental peritoneal dialysis can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0016] An embodiment of the present invention will be described below, but the present invention is not limited to the following embodiment.

[0017] In this specification, the range "X to Y" means "X or more and Y or less." Unless otherwise specified, operations and measurements of physical properties are performed at room temperature (20 to 25°C) and a relative humidity of 40 to 50% RH.

[0018] <Peritoneal dialysis solution> One aspect of the present invention is a peritoneal dialysis solution comprising 1.5 to 1.8 w / v % glucose and 120 to 130 mEq / L sodium, The peritoneal dialysis solution is used in combination with another peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, The peritoneal dialysis solution and the other peritoneal dialysis solution are each used individually for peritoneal dialysis, in which 1.5 to 2.0 L of each solution is injected into the peritoneal cavity of a subject, retained, and drained twice a day, and the peritoneal dialysis solution is used once a day, while the other peritoneal dialysis solution is used once a day. With this configuration, water balance can be appropriately managed while increasing the total sodium removal amount during incremental peritoneal dialysis.

[0019] The peritoneal dialysis solution according to this embodiment (also referred to herein as the "first peritoneal dialysis solution") contains 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium. The first peritoneal dialysis solution preferably contains 123 to 128 mEq / L sodium, more preferably 125 to 128 mEq / L sodium. In one embodiment, the first peritoneal dialysis solution contains 1.6 w / v% glucose and 126 mEq / L sodium.

[0020] The first peritoneal dialysis solution can further contain components contained in ordinary peritoneal dialysis solutions. Such components include calcium, magnesium, chlorine, an alkalizing agent, etc. The first peritoneal dialysis solution preferably contains 2.0 to 4.0 mEq / L of calcium, 0.5 to 1.5 mEq / L of magnesium, 86.0 to 98.0 mEq / L of chlorine, and 35 to 40 mEq / L of an alkalizing agent.

[0021] Examples of alkalizing agents include lactate ions, bicarbonate ions, etc. The concentration of the alkalizing agent is the sum of the lactate ions, bicarbonate ions, etc. used, and for example, a combination of lactate ions and bicarbonate ions can provide an alkalizing agent of 35 to 40 mEq / L. The alkalizing agent is preferably lactate ions.

[0022] The first peritoneal dialysis solution is used in combination with another peritoneal dialysis solution (also referred to herein as a "second peritoneal dialysis solution") containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium. In one embodiment, the second peritoneal dialysis solution contains 1.35 w / v% glucose and 135 mEq / L sodium.

[0023] The second peritoneal dialysis solution can further contain components contained in ordinary peritoneal dialysis solutions. Such components include calcium, magnesium, chlorine, an alkalizing agent, etc. The second peritoneal dialysis solution preferably contains 2.3 to 4.0 mEq / L of calcium, 0.5 to 1.5 mEq / L of magnesium, 95.0 to 105.5 mEq / L of chlorine, and 35 to 40 mEq / L of an alkalizing agent.

[0024] The alkaline agent contained in the second peritoneal dialysis solution can be the same as the alkaline agent contained in the first peritoneal dialysis solution described above.

[0025] The first and second peritoneal dialysates may further contain other components as needed, as long as the purpose of the present invention is not impaired. For example, the first and second peritoneal dialysates may contain an organic acid or the like depending on the concentration difference between total cations and chloride ions in order to maintain the electrical neutrality of the peritoneal dialysates. Examples of such organic acids include propionic acid, malic acid, fumaric acid, succinic acid, oxalacetic acid, N-acetylglycine, N-acetyl-L-cysteine, glutaric acid, glucuronic acid, ascorbic acid, citric acid, isocitric acid, gluconic acid, N-acetyl-L-aspartic acid, N-acetyl-L-glutamic acid, N-acetyl-L-methionine, N-acetyl-L-proline, N-acetyl-L-valine, N-acetyl-L-glutamine, N-acetyl-L-arginine, N-acetyl-L-histidine, N-acetyl-L-leucine, N-acetyl-L-tryptophan, and salts thereof.

[0026] The pH of the first peritoneal dialysis fluid and the second peritoneal dialysis fluid is usually about pH 5.0 to 7.5, and preferably about pH 6.5 to 7.5.

[0027] The osmotic pressure of the first peritoneal dialysis fluid and the second peritoneal dialysis fluid is usually about 300 to 500 mOsm / kg, and preferably about 330 to 450 mOsm / kg.

[0028] In peritoneal dialysis, typically, 1.5 to 2.0 L of peritoneal dialysis fluid is injected into the patient's peritoneal cavity, allowed to saturate for 4 to 8 hours, and then drained after the desired effect is achieved. The above procedure is considered one session. Incremental peritoneal dialysis is a stepwise introduction method for peritoneal dialysis, in which renal replacement therapy is initiated with a small peritoneal dialysis bag prescription in the early stages when residual renal function is maintained, and the dialysis volume is increased according to the degree of decline in residual renal function (Peritoneal Dialysis and Kidney Transplant Handbook, Chugai Medical Publishing, October 15, 2018). In the peritoneal dialysis of this embodiment, a total of two sessions are performed per day. In the peritoneal dialysis of this embodiment, preferably, two consecutive sessions are performed continuously. The first peritoneal dialysis fluid is used in combination with the second peritoneal dialysis fluid. That is, the first peritoneal dialysis solution is used alone once per day, and the second peritoneal dialysis solution is used alone once per day. In this way, by using the first peritoneal dialysis solution in appropriate combination with the second peritoneal dialysis solution, it is possible to appropriately manage water balance while increasing the total sodium removal amount in incremental peritoneal dialysis.

[0029] The subject for peritoneal dialysis is, for example, a mammal, preferably a human. In one embodiment, the subject according to this aspect is a subject who, at the discretion of a physician, requires peritoneal dialysis twice daily. In one embodiment, the subject according to this aspect has an estimated glomerular filtration rate (eGFR) of 15.0 (mL / min / 1.73 m 2 The eGFR of the subjects was 2.7 (mL / min / 1.73 m 2 That is, the eGFR of the subject according to this embodiment can be 2.7 (mL / min / 1.73 m 2 ) or more 15.0 (mL / min / 1.73m 2 ) or less, or 4.8 (mL / min / 1.73 m 2 ) or more 7.7 (mL / min / 1.73m 2 ) can be:

[0030] The infusion volume, retention time, and number of operations are adjusted appropriately depending on symptoms, blood chemistry values, fluid imbalance, age, weight, etc. The infusion and drainage rates are usually 300 mL / min or less.

[0031] The method for preparing the first peritoneal dialysis solution and the second peritoneal dialysis solution is not particularly limited, and a general method for preparing a peritoneal dialysis solution can be used. For example, a method can be used in which glucose; a cation and chlorine ion source such as sodium chloride, calcium chloride, magnesium chloride, sodium lactate, calcium salts, magnesium salts, and sodium bicarbonate; an acid component, and the like are dissolved in water (e.g., water for injection) so that the glucose concentration, sodium concentration, and, if necessary, the concentrations of calcium, magnesium, chlorine, an alkalizing agent, and the like, fall within the above-mentioned ranges.

[0032] The prepared peritoneal dialysis solution is preferably sealed in a soft plastic bag or a glass container, and then subjected to high-pressure steam sterilization or hot water sterilization. Examples of soft plastic materials include polyvinyl chloride, polypropylene, polyethylene, polyester, polyamide, ethylene-vinyl alcohol copolymer, polyethylene terephthalate, polyvinylidene chloride, and ethylene-vinyl acetate copolymer, and a combination of these materials may also be used by laminating them.

[0033] The peritoneal dialysis solution according to this aspect includes the following embodiments: A peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, The peritoneal dialysis solution is used in combination with another peritoneal dialysis solution containing 1.35 to 1.5 w / v % glucose and 132 to 135 mEq / L sodium.

[0034] <Peritoneal dialysis solution set> Another aspect of the present invention is a peritoneal dialysis solution comprising: a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; a second peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; The first peritoneal dialysis solution and the second peritoneal dialysis solution are used separately for peritoneal dialysis, in which 1.5 to 2.0 L of each solution is injected into the subject's peritoneal cavity, retained, and drained, twice a day in total, with the first peritoneal dialysis solution being used once a day and the second peritoneal dialysis solution being used once a day. This configuration allows for appropriate management of water balance while enhancing total sodium removal during incremental peritoneal dialysis.

[0035] In the peritoneal dialysis solution set according to this embodiment, the explanations of the "first peritoneal dialysis solution," "second peritoneal dialysis solution," and "peritoneal dialysis" are the same as those of the peritoneal dialysis solution according to this embodiment described above, and therefore will not be repeated.

[0036] The peritoneal dialysis set according to this aspect includes the following embodiments: a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; a second peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; a peritoneal dialysis solution set, in which the first peritoneal dialysis solution and the second peritoneal dialysis solution are used alone; one dose of a first peritoneal dialysis solution containing 1.5-1.8 w / v% glucose and 120-130 mEq / L sodium; a dose of a second peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; a peritoneal dialysis solution set for daily use, in which the amount of the first peritoneal dialysis solution used each time is 1.5 to 2.0 L, and the amount of the second peritoneal dialysis solution used each time is 1.5 to 2.0 L; A peritoneal dialysis solution set for performing peritoneal dialysis on a single subject in one day, comprising: a first volume of a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; a second volume of a second peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; the sum of the first volume of the first peritoneal dialysis solution and the second volume of the second peritoneal dialysis solution is at least 3.0 L; a membrane dialysis solution set, wherein the first peritoneal dialysis solution and the second peritoneal dialysis solution are independently infused during peritoneal dialysis so that a total volume of at least 3.0 L is infused into the peritoneal cavity of a single subject in one day; A peritoneal dialysis solution set for performing peritoneal dialysis on a single subject in one day, comprising: one container for holding 1.5 to 2.0 L of a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; one container for holding 1.5 to 2.0 L of a second peritoneal dialysis solution containing 1.35 to 1.5 w / v % glucose and 132 to 135 mEq / L sodium; The peritoneal dialysis solution set is configured so that the first peritoneal dialysis solution and the second peritoneal dialysis solution are independently infused during peritoneal dialysis, and a total volume of at least 3.0 L is infused into the peritoneal cavity of a single subject in one day.

[0037] <Compositions used in peritoneal dialysis> Another aspect of the invention is a composition for use in peritoneal dialysis, comprising: The composition contains 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, The composition is used in combination with other compositions for peritoneal dialysis containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, The composition and the other composition are each injected into the abdominal cavity of a subject in an amount of 1.5 to 2.0 L, twice a day, followed by retention and drainage; The composition is used once per day and the other composition is a once per day composition.

[0038] In the composition used for peritoneal dialysis according to this embodiment, the "composition used for peritoneal dialysis" corresponds to the "first peritoneal dialysis solution" of the peritoneal dialysis solution according to this embodiment, and the "other composition used for peritoneal dialysis" corresponds to the "second peritoneal dialysis solution" of the peritoneal dialysis solution according to this embodiment. Therefore, the explanations for the "composition used for peritoneal dialysis," "other composition used for peritoneal dialysis," and "peritoneal dialysis" are the same as those for the peritoneal dialysis solution according to this embodiment, and therefore will not be repeated.

[0039] Compositions for use in peritoneal dialysis according to this aspect include the following embodiments: 1. A combination for performing peritoneal dialysis on a single subject in one day, comprising: A composition (first composition) containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; and another composition (second composition) containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium, The combination comprises (i) the first composition capable of being independently injected into the peritoneal cavity of a single subject in a volume of 1.5 to 2.0 L once daily in the same day, and (ii) the second composition capable of being independently injected into the peritoneal cavity of a single subject in a volume of 1.5 to 2.0 L once daily in the same day, the total volume of the first and second compositions being such that the first and second compositions are capable of being independently injected into the peritoneal cavity of a single subject in a volume of 1.5 to 2.0 L once daily in the same day.

[0040] <Method of performing peritoneal dialysis> Another aspect of the invention is a method of performing peritoneal dialysis on a single subject per day, comprising: The method includes administering a first peritoneal dialysis solution to the single subject once per day, and administering a second peritoneal dialysis solution to the single subject once per day; the first peritoneal dialysis solution contains 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; The second peritoneal dialysis solution contains 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium. administering the first peritoneal dialysis solution includes injecting 1.5 to 2.0 L of the first peritoneal dialysis solution into the peritoneal cavity of the single subject, allowing the first peritoneal dialysis solution to pool in the peritoneal cavity, and draining the first peritoneal dialysis solution from the peritoneal cavity; administering the second peritoneal dialysis solution includes injecting 1.5 to 2.0 L of the second peritoneal dialysis solution into the peritoneal cavity of the single subject, allowing the second peritoneal dialysis solution to pool in the peritoneal cavity, and draining the second peritoneal dialysis solution from the peritoneal cavity; In this method, the infusion of the first peritoneal dialysis solution and the infusion of the second peritoneal dialysis solution are independent of each other. This configuration allows for appropriate management of water balance while enhancing total sodium removal during incremental peritoneal dialysis.

[0041] In the method of performing peritoneal dialysis according to this embodiment, the explanations of the "first peritoneal dialysis solution," "second peritoneal dialysis solution," and "peritoneal dialysis" are the same as those of the peritoneal dialysis solution according to this embodiment described above, and therefore will not be repeated. [Example]

[0042] The effects of the present invention will be explained using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. In the following examples, the terms "parts" and "%" may be used, but unless otherwise specified, they represent "parts by mass" or "% by mass." Furthermore, unless otherwise specified, each operation is carried out at room temperature (1 to 30°C).

[0043] <Preparation of peritoneal dialysis solution> The required amounts of anhydrous glucose, sodium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, and sodium L-lactate solution were prepared according to the manufacturing method for injections in the General Provisions of Preparations of the Japanese Pharmacopoeia to achieve the glucose, sodium, calcium, magnesium, chlorine, and lactate ion concentrations shown in Table 1, and then filtered through a membrane filter. The filtered dialysis solution was dispensed into polypropylene resin two-compartment containers for peritoneal dialysis that conform to the test method and sealed. The dialysis solution was then sealed in a multilayer laminate film bag and sterilized by high-pressure steam.

[0044] [Table 1]

[0045] <Test example> The following clinical trial was conducted on patients undergoing peritoneal dialysis.

[0046] (Main selection criteria) Patients who met the following criteria and had the ability to consent were eligible for the study. (1) Age: 20 years or older (at the time of obtaining written consent) (2) Gender: Any (3) Patients who have been undergoing stable peritoneal dialysis for 3 months and have been prescribed peritoneal dialysis solution containing 1.35 w / v% glucose at least twice a day, or peritoneal dialysis solution containing 1.35 w / v% glucose and peritoneal dialysis solution containing 2.5 w / v% glucose at least once each. (4) Patients who have been receiving the same prescription for at least 30 days since consent was obtained (5) Patients who are judged by a doctor to require sodium removal based on physical or laboratory findings.

[0047] (Major exclusion criteria) (1) Patients undergoing hemodialysis (2) Patients undergoing automated peritoneal dialysis (3) Patients undergoing peritoneal dialysis therapy only once a day (4) Patients who have achieved appropriate salt restriction management (5) Patients with signs of hypovolemia (6) Patients with persistent hypotension with a systolic blood pressure of less than 100 mmHg in the office (7) Patients with serum sodium concentration less than 130 mEq / L or symptomatic hyponatremia. (8) Other patients who are deemed inappropriate by the investigator or clinical trial physician.

[0048] (Discontinuation criteria) The principal investigator (subinvestigator) discontinued the study if any of the following criteria was met: (1) When the subject or their legal representative requests to discontinue the clinical trial (2) If it is discovered that the patient is not eligible for the clinical trial after the start of the trial. (3) If symptoms worsen and it becomes difficult to continue the clinical trial (4) When an adverse event occurs, making it difficult to continue the clinical trial. (5) Any other case in which the principal investigator or co-investigator recognizes the need for discontinuation.

[0049] (method) Patients undergoing outpatient peritoneal dialysis were randomly assigned to receive either the test drug group or the control drug group for 8 weeks (test drug group: control drug group = 2:1). Table 2 shows the daily prescription breakdown for the test drug group and the control drug group for twice-daily peritoneal dialysis patients who are the subject of this invention.

[0050] [Table 2]

[0051] Each peritoneal dialysis solution was injected into the abdominal cavity at a volume of 1.5 to 2.0 L per session, allowed to dwell for 4 to 8 hours, and then removed after the expected effect was achieved. This procedure was counted as one session, and the procedure was carried out twice a day.

[0052] The infusion volume, retention time, and number of operations were adjusted appropriately depending on symptoms, blood biochemistry values, imbalance of retention, age, body weight, etc. The infusion and drainage rates were usually set at 300 mL / min or less.

[0053] During the evaluation period, the use of peritoneal dialysis fluids other than the first peritoneal dialysis fluid, the second peritoneal dialysis fluid A, and the second peritoneal dialysis fluid B was prohibited. In addition, dialysis therapy other than peritoneal dialysis therapy was prohibited.

[0054] (Evaluation items) Using the effluent collected from the patients and the collected urine, the transperitoneal sodium removal and water removal volumes per dialysis session of the peritoneal dialysate, as well as the transperitoneal sodium removal, urinary sodium excretion, total sodium removal, water removal volume, urine volume, and total water removal volumes were calculated and evaluated using the following methods. The results are shown in Tables 3 and 4. [Transperitoneal sodium removal per peritoneal dialysis session (mEq / session)] Transperitoneal sodium removal rate (mEq / time) = (sodium concentration in effluent (mEq / L) × effluent volume (L / time)) - (sodium concentration in dialysis fluid (mEq / L) × infusion volume (L / time)) [Amount of peritoneal dialysis fluid removed per dialysis session (mL / session)] Amount of fluid removed (mL / time) = amount of fluid drained (mL / time) - amount of fluid injected (mL / time) [Daily transperitoneal sodium removal (mEq / day)] Transperitoneal sodium removal (mEq / day) = total daily transperitoneal sodium removal (mEq / time) [Daily urinary sodium excretion (mEq / day)] Urinary Na excretion amount (mEq / day) = Urinary Na concentration (mEq / L) x urine volume (L / day) [Total daily sodium removal (mEq / day)] Total sodium removal (mEq / day) = total daily transperitoneal sodium removal (mEq / time) + (urinary sodium concentration (mEq / L) × urine volume (L / day)) [Amount of fluid removed per day (mL / day)] Amount of fluid removed (mL / day) = Total amount of fluid removed per peritoneal dialysis session (mL / session) per day [Daily urine volume (mL / day)] Urine volume (mL / day) = accumulated urine for one day (mL) [Total water removal per day (mL / day)] Total fluid removal (mL / day) = total fluid removal volume per peritoneal dialysis session (mL / session) + accumulated urine volume per day (mL).

[0055] In Table 3, for the test drug group, the transperitoneal sodium removal and water removal amounts after peritoneal dialysis using the first peritoneal dialysis solution (test drug) are shown, and for the control drug group, the transperitoneal sodium removal and water removal amounts after peritoneal dialysis using the second peritoneal dialysis solution A or B (control drug) are shown.

[0056] Table 4 shows the transperitoneal sodium removal, urinary sodium excretion, total sodium removal, water removal volume, urine volume, and total water removal volume (daily volume) after peritoneal dialysis using the first peritoneal dialysis solution (test drug) and the second peritoneal dialysis solution A or B (standard drug) for the test drug group, and the transperitoneal sodium removal, urinary sodium excretion, total sodium removal, water removal volume, urine volume, and total water removal volume (daily volume) after peritoneal dialysis using the second peritoneal dialysis solution A or B (control drug) and the second peritoneal dialysis solution A or B (standard drug) for the control drug group.

[0057] (statistical analysis) The evaluation results were summarized as mean ± standard deviation, and the mean difference between groups and two-sided 95% confidence intervals for the change from baseline to week 8 were calculated. Comparisons between groups were performed using an independent t-test with a two-sided significance level of 5%. The results are shown in Tables 3 and 4.

[0058] [Table 3]

[0059] [Table 4]

[0060] As shown in Table 3, the first peritoneal dialysis fluid (test drug) removed 16.6 mEq (approximately 1 g of salt equivalent) more sodium per dialysis session than the second peritoneal dialysis fluids A or B (control drugs), with a statistically significant difference. The change in the amount of water removed per dialysis session tended to be 42.4 mL more with the first peritoneal dialysis fluid (test drug) than with the second peritoneal dialysis fluids A or B (control drugs), but no statistical difference was observed.

[0061] As shown in Table 4, the daily transperitoneal sodium removal in the test drug group was 18.5 mEq greater than that in the control drug group, with a statistically significant difference. This was similar to the results for the transperitoneal sodium removal per dialysis session using the first peritoneal dialysate (test drug). In other words, even when the first peritoneal dialysate (test drug) was used in combination with the second peritoneal dialysate A or B, the enhanced sodium removal by the first peritoneal dialysate was reflected.

[0062] As shown in Table 4, there was no statistically significant difference in the amount of fluid removed per day between the test drug group and the control drug group, similar to the results per dialysis session for the first peritoneal dialysis solution (test drug). In other words, when the first peritoneal dialysis solution was used in combination with the second peritoneal dialysis solution A or B, it did not affect the amount of fluid removed, but only increased the amount of sodium removed.

[0063] Regarding whole-body sodium balance, as shown in Table 4, there was no difference in urinary sodium excretion between the test drug group and the control drug group, and the total sodium removal was statistically significantly higher in the test drug group by 22.9 mEq compared to the control drug group. This demonstrates that the combined use of the first peritoneal dialysis solution and the second peritoneal dialysis solution A or B increases total sodium removal without affecting urinary sodium excretion due to residual renal function.

[0064] Regarding the total body water balance, the amount of water removed, urine volume, and total water removal were almost the same between the test drug group and the control drug group, as shown in Table 4. This demonstrates that the combined use of the first peritoneal dialysis solution and the second peritoneal dialysis solution A or B has almost no effect on the total body water balance.

[0065] From the above, it can be seen that in patients receiving peritoneal dialysis prescribed twice a day, by using a combination of the first peritoneal dialysis solution and the second peritoneal dialysis solution A or B, it is possible to appropriately manage sodium balance and water balance by increasing only the total sodium removal amount, including peritoneal dialysis and residual renal function, while maintaining the water balance of the entire body.

Claims

1. A peritoneal dialysis solution comprising 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium, The peritoneal dialysis solution is used in combination with another peritoneal dialysis solution containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; The peritoneal dialysis solution is used for peritoneal dialysis in which the peritoneal dialysis solution and the other peritoneal dialysis solution are each used alone twice a day in total, injecting, storing, and draining an amount of 1.5 to 2.0 L into the peritoneal cavity of a subject, and in this case, the peritoneal dialysis solution is used once a day, and the other peritoneal dialysis solution is used once a day.

2. 2. The peritoneal dialysis solution of claim 1, comprising 123 to 128 mEq / L of sodium.

3. 10. The peritoneal dialysis solution of claim 1, further comprising 2.0 to 4.0 mEq / L calcium; 0.5 to 1.5 mEq / L magnesium; 86.0 to 98.0 mEq / L chloride; and 35 to 40 mEq / L alkalinizing agent.

4. 2. The peritoneal dialysis solution of claim 1, wherein the other peritoneal dialysis solution further comprises 2.3 to 4.0 mEq / L of calcium; 0.5 to 1.5 mEq / L of magnesium; 95.0 to 105.5 mEq / L of chloride; and 35 to 40 mEq / L of an alkalinizing agent.

5. a first peritoneal dialysis solution containing 1.5 to 1.8 w / v% glucose and 120 to 130 mEq / L sodium; a second peritoneal dialysis fluid containing 1.35 to 1.5 w / v % glucose and 132 to 135 mEq / L sodium; A peritoneal dialysis set, wherein the first peritoneal dialysis solution and the second peritoneal dialysis solution are each used independently for peritoneal dialysis, in which an amount of 1.5 to 2.0 L is injected into the peritoneal cavity of a subject, retained, and drained, twice a day in total, and in this case, the first peritoneal dialysis solution is used once a day, and the second peritoneal dialysis solution is used once a day.

6. A composition for use in peritoneal dialysis, comprising: the composition comprises 1.5 to 1.8 w / v % glucose and 120 to 130 mEq / L sodium; the composition is used in combination with other compositions used for peritoneal dialysis containing 1.35 to 1.5 w / v% glucose and 132 to 135 mEq / L sodium; the composition and the other composition are each injected separately into the subject's abdominal cavity in an amount of 1.5 to 2.0 L, allowed to dwell, and then drained, a total of twice per day; A composition wherein the composition is used once per day and the other composition is used once per day.

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