JP2003088582A - Peritoneal dialysate and storage vessel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce the damage to a living body by a wrong operation in administration or unmixing in a neutral peritoneal dialysate which is stored divisionally as two solutions of acidic solution and alkali-side solution, and administered to the abdominal cavity by mixing the two solutions in use. SOLUTION: An administration outlet is provided on the alkali-side solution side of a peritoneal dialysate storage vessel, and the pH or osmotic pressure of the alkali-side solution is regulated in a prescribed range.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to peritoneal dialysis in which dialysis is carried out by storing and draining in the abdominal cavity of a patient with renal failure, and more particularly to peritoneal dialysis fluid in consideration of safety and a container containing the dialysate. .

[0002]

2. Description of the Related Art According to recent reports, an acidic peritoneal dialysis solution has been cited as one of the causes of decreased peritoneal function. There is also a theory that an acidic peritoneal dialysis solution not only lowers the peritoneal function, but also lowers the immunopotency of intraperitoneal lymphocytes, which easily causes peritonitis. Thus, even though acidic peritoneal dialysis fluid is considered to be unfavorable to the living body, if glucose, which is an osmotic pressure adjusting agent, is sterilized and stored in a neutral region, it will be decomposed, so that the acid side region will be decomposed. There was a situation that I was adjusting.

However, from the viewpoint of biocompatibility and improvement of the above-mentioned harmful effects, neutral peritoneal dialysis fluid has been attracting attention, and researches for suppressing the above-mentioned decomposition of glucose by devising a preparation method, a storage container and a chemical solution composition have been conducted. It is widely practiced. For example, there is a method in which an acidic concentrated liquid containing glucose, calcium, magnesium, or a lactate and an alkaline concentrated liquid containing bicarbonate are separately stored, stored, and mixed at the time of use. Thereby, the decomposition of glucose can be prevented, and the formation of insoluble salts of calcium and magnesium can be prevented.

Japanese Patent Application Laid-Open No. 9-87182 discloses such a preparation method and a chemical composition. Alternatively,
Patent No. 278144 is a method of mixing two liquids, an acidic liquid concentrate containing no lactate and an alkaline liquid concentrate containing bicarbonate.
No. 7 is disclosed. Also, glucose and calcium,
As a method for mixing an acidic concentrated liquid containing magnesium and a liquid containing lactate, JP-A-8-
There is 131542. Furthermore, JP-A-8-16419
As described in No. 9, there is also one in which a neutral peritoneal dialysate is prepared with one agent.

[0005]

However, the above methods and preparations have not been satisfactory in terms of safety during administration. As described above, in order to prevent the decomposition of glucose, the peritoneal dialysis fluid is divided into two fluids and stored.
Although the method of mixing the liquids was adopted, there was a problem caused by the division into two liquids. In other words, it is the damage to the abdominal cavity that would be expected if only one of the solutions before mixing (acidic concentrated solution or alkaline concentrated solution) was mistakenly injected into the abdominal cavity of a patient.

Further, not only the above-mentioned erroneous operation (injection of unmixed single liquid), but also injection after mixing, for some reason, both liquids can be injected into the abdominal cavity without being sufficiently mixed. There is also a nature. The problems expected in such a case are described below. First, an acid concentrate with a pH of 5 or less,
Injecting only an alkaline solution having a pH of 10 or more into the abdominal cavity causes cell damage and abdominal pain.

Further, when the osmotic pressures of the divided liquids are different and only one of the low or high osmotic pressure is injected into the abdominal cavity, the following problems are expected. Depending on the osmotic pressure, cells rupture at low osmotic pressure,
Conversely, in the case of high osmotic pressure, cells contract. In any case, it is a situation that is not preferable for performing the normal function of the peritoneum. In some cases, it may be associated with abdominal pain. It cannot be said that the conventional two-liquid split type peritoneal dialysate or the peritoneal dialysate storage container has been sufficiently considered with regard to the safety in the above case, that is, the Fail Safe mechanism.

[0008]

In order to solve the above problems, the present invention is characterized by the following means. First, if there is an error in the preparation of peritoneal dialysate,
Alternatively, even if the dialysate is in an insufficiently mixed state, measures have been taken to prevent the injection of the acidic concentrated solution into the abdominal cavity of the patient (which causes a greater damage to the abdominal cavity at the time of injection). In other words, the peritoneal dialysate storage container is provided with a preventive means for preventing the acidic concentrated liquid from being independently injected into the living body. Secondly, the characteristics of the alkaline concentrate, that is, the pH or the osmotic pressure is set within a predetermined range so that the damage to the living body is small even when the alkaline concentrate is administered alone into the abdominal cavity of a patient. .

With the above structure, even if a single solution is injected without being mixed, the alkaline concentrated solution is injected, and therefore, the acidic concentrated solution is injected into the abdominal cavity, which causes a larger damage to the abdominal cavity. can avoid. Further, even when the alkaline concentrated liquid is injected alone, the pH and osmotic pressure of the (intraperitoneal) stored liquid are buffered in a short time, so that the damage to the living body is reduced.

Then, the kind and concentration of the pH adjusting agent are adjusted so that the physical characteristics of the alkaline concentrate are within a predetermined range.
The fact that the liquid ratio is specified is one of the features of the present invention, although it is secondary. With these configurations, the physical characteristics of the alkaline concentrate can be kept within a range where biocompatibility can be maintained, and as a result, damage to the living body when the alkaline concentrate is injected alone can be reduced.

That is, the first aspect of the present invention is as follows. First, it is separated into two liquids, an acidic concentrated liquid that does not contain a blood alkaline agent and contains glucose, and an alkaline concentrated liquid that does not contain glucose and contains a pH adjusting component and a blood alkaline agent. Stored in a peritoneal dialysis solution, wherein the pH of the alkaline concentrate is in the range of 7 to 9, and the osmotic pressure of the concentrate is 280 to 460 mOs.
It is a peritoneal dialysate characterized by being in the range of m.

[0012] The pH adjusting component is the peritoneal dialysis solution, which is sodium hydrogen carbonate having a concentration of 1 to 5 mM.

The blood alkalinizing agent is the peritoneal dialysate, which is a lactic acid compound (inorganic salt).

The peritoneal dialysis solution has a pH of the acidic concentrated solution in the range of 3 to 4.

In addition, the ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to
The peritoneal dialysate in the range of 1: 2.

Further, the second aspect of the present invention is as follows. A container in which a peritoneal dialysate is separated and stored into two liquids, an acidic concentrated liquid containing glucose and an alkaline concentrated liquid containing no glucose and containing a pH adjusting component and a blood alkalizing agent, The container has a first storage part for storing the acidic concentrated liquid and a second storage part for storing the alkaline concentrated liquid, and both the storage parts before mixing both liquids (acidic concentrated liquid and alkaline concentrated liquid) ( The first container, the second container) are shut off, and the container has a communication means that allows the two containers to communicate with each other at the time of mixing, and when administered into the patient's body, substantially the only liquid from the container. A peritoneal dialysis solution storage container is characterized in that a liquid outlet serving as an outflow means is provided in the second container.

The pH of the alkaline concentrate is 7 to 7.
The peritoneal dialysate storage container in the range of 9.

Further, the peritoneal dialysate storage container has a pH of the acidic concentrated liquid in the range of 3 to 4.

Further, in the container for storing the peritoneal dialysate, the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM.

The osmotic pressure of the alkaline concentrate is 2
The container for storing the peritoneal dialysate in the range of 80 to 460 mOsm.

Further, the ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to
The storage container for the peritoneal dialysate in the range of 1: 2.

Further, the peritoneal dialysate storage container has the liquid outlet formed in a region opposite to the side where the communication means is provided in the second container.

Further, the peritoneal dialysate storage container has a circuit set for injecting the liquid contained in the container into the abdominal cavity of the patient at the outlet of the container.

Further, in the container for storing peritoneal dialysate, the blood alkalizing agent is a lactic acid compound (inorganic salt).

[0025]

BEST MODE FOR CARRYING OUT THE INVENTION One embodiment and a preferred embodiment of the present invention will be described below with reference to the drawings. Figure 1
Is the peritoneal dialysate storage container 1 of the present invention. Storage container 1
Has a first storage part 2 for storing an acidic concentrated liquid and a second storage part 3 for storing an alkaline concentrated liquid. Storage container 1
Further, it has a communication means 4 capable of shutting off the two accommodation parts 2 and 3 before mixing and communicating the both accommodation parts at the time of mixing. The communication means 4 may be a communication passage 5 for connecting both storage portions as shown in FIG. 1 and a clamp 6 attached thereto, or a partition wall 7 of both storage portions at the time of mixing as shown in FIG. It may be of the easy peel type that breaks. Although not shown, provision of a port for collecting each of the liquids stored in both of the storage parts and providing a mixed injection into each liquid is not particularly limited.

However, when administered to the peritoneal cavity of a patient, a substantial fluid outlet 8 through which the dialysate flows out from the peritoneal dialysate storage container 1.
Is provided only in the second storage portion 3. If the liquid outlet portion 8 is provided only in the second storage portion 3 instead of in the first storage portion 2, the formation position, the form and the number thereof are not particularly limited,
It can be freely designed as needed. However, if the liquid outlet portion 8 is provided near the partition wall 7 or the communication passage 5, it cannot be said that the acidic concentrated liquid will not directly flow out when the mixing is insufficient, so that the formation of the partition wall or the communication passage is performed. It is preferable to provide the liquid outlet portion 8 on the side opposite to the formed portion.

For example, when the communication passage 5 is formed on the upper left side as shown in FIG. 1, the liquid outlet portion 8 is formed below the right end portion, and as shown in FIG. In the case of being formed at 1, the liquid outlet portion 8 is formed at any of the right end portions. The number of the liquid outlets 8 is practically 1 to 2 at most from the viewpoint of the burden in manufacturing and the effect thereof. Further, the size of the liquid outlet can be designed so that the inflow velocity is calculated back from the amount of dialysate stored and the outlet area required for that purpose is obtained.

Next, regarding the composition and physical characteristics of the dialysate,
Describe. First, the peritoneal dialysate prepared after mixing the two solutions, that is, the solution to be administered intraperitoneally to a patient, has a pH of 6.5 to 5.
It is preferably in the range of 7.5. Further, depending on the necessity of removing water, it is possible to select one having an osmotic pressure of 280 to 480 mOsm after mixing the two liquids or a slightly wider range than that. The composition and physical properties of each liquid are determined in consideration of the physical properties of the finally prepared peritoneal dialysate and the requirements for each liquid.

First, from the viewpoint of acid-base equilibrium, the pH of the acidic concentrate is preferably in the range of 3 to 4 in order to prevent the decomposition of glucose contained in the acidic concentrate before mixing. Then, the pH of the alkaline concentrate is affected by the type of buffering agent added to the concentrate side, that is, the pH adjusting component, and the amount of addition thereof. In other words, if you select sodium hydroxide, which has a low buffering capacity, as the pH-adjusting component, you must raise the pH of the alkaline concentrate, but adjust the pH of sodium bicarbonate that has a high buffering capacity in the slightly alkaline region rather than neutral. When selected as a component, the pH of the alkaline concentrate can be suppressed to a low level.

When the alkaline concentrated solution is directly injected into the body, the pH of the range that is restored in a short time by the buffer function of the living body is expected to be about 7-9.
In order to realize the pH within the range, it is preferable to add sodium hydrogencarbonate having a concentration of 1 to 3 mM.

Next, from the viewpoint of osmotic pressure, a preferred embodiment of the peritoneal dialysate will be described. Considering the stability of glucose contained in the acidic concentrate, it is desirable to add no other component to the acidic concentrate as much as possible. for that reason,
In the conventional dialysate, the osmotic pressure of the acidic concentrate is reduced and the osmotic pressure of the alkaline concentrate is increased to make the osmotic pressure of the peritoneal dialysate after mixing within a range that the living body can tolerate. There is also. However, making the osmotic pressure of one of the liquids extremely high,
On the contrary, when the osmotic pressure of the other liquid is lowered, if the injection is performed by the erroneous operation as described above or the injection is performed when the mixing is insufficient, it causes considerable damage to the abdominal cavity. In particular, when a solution having a low osmotic pressure is injected into the abdominal cavity, the peritoneal mesothelial cells are damaged, which is not preferable.

Therefore, in a two-liquid split type peritoneal dialysis fluid or a dialysis fluid storage container containing the fluid, there is a risk that the concentrated fluid on one side is independently injected into the abdominal cavity and the two fluids are not sufficiently mixed. When assuming the risk of being injected as it is, it is preferable to set the osmotic pressure on the liquid side, which may be injected, in the range of 280 to 460 mOsm. In the present embodiment, it is preferable to set the osmotic pressure in the above range in the concentrated solution on the alkaline side. When the osmotic pressure of the dialysate injected into the abdominal cavity is within the above range, damage or influence on the peritoneal mesothelium or cells in the abdominal cavity can be reduced.

Furthermore, the liquid ratio of the concentrated liquid on the acidic side to the concentrated liquid on the alkaline side is 1: 1.5 to 1: 1 due to the above-mentioned adjustment of the osmotic pressure and the influence of the heat load on each divided liquid during sterilization. A range of 2 is preferable. That is, if the liquid ratio is too large or too small, it is easy to make an error in the prediction of the osmotic pressure after mixing the two liquids, and the heat load applied to the concentrated liquid differs depending on the liquid amount. It becomes difficult to heat sterilize evenly.

The blood alkalinizing agent referred to in the present invention refers to an agent that adjusts the acid-base balance of the blood of a patient through the peritoneum of the patient, and is, for example, a lactic acid compound such as sodium lactate.

[0035]

EXAMPLES Experiment 1. Example of preparation of peritoneal dialysate Composition of each fluid before mixing of peritoneal dialysate, which is an example of the present invention,
The pH and osmotic pressure and the pH and osmotic pressure of the dialysate after mixing are shown below.

(1) Acidic Concentrated Solution Glucose: The following three types of glucose having different glucose concentrations were prepared. a.239.2 mmol / l, b.350.2 mmol /
l, c. 522.7 mmol / l calcium chloride: 5.56 mmol / l magnesium chloride: 1.41 mmol / l 3.5% hydrochloric acid: 0.3 ml / l The acidic concentrate prepared with the above composition has a pH of Is 3.4
6. The osmotic pressure is 270 depending on the glucose concentration.
mOsm (a), 393mOsm (b), 565mOs
m (c) was shown.

(2) Alkaline concentrated solution (pH: 8.1, osmotic pressure: 392 mOsm) Sodium chloride: 151.6 mmol / l Sodium lactate: 54.9 mmol / l Sodium hydrogen carbonate: 2.0 mmol / l

After 720 ml of the above acidic concentrate and 1280 ml of the above alkaline concentrate were respectively housed in two compartments, autoclave sterilization was performed at 115 ° C. for 30 minutes, the compartments were communicated, and the two solutions were mixed. The pH of the peritoneal dialysate after mixing was 7.1 to 7.3, and the osmotic pressure was 34
0-470 mOsm [The average osmotic pressure of each dialysate after mixing with different glucose concentrations is 350 mOsm.
(A), 394 mOsm (b), 460 mOsm
(C)] is shown, and each is shown to be in a physiological region.

Experiment 2. Evaluation of biocompatibility using cultured cells (1) Outline This experiment was conducted as a simulation of the effect on the living body when an acidic concentrate before mixing or an alkaline concentrate was directly administered intraperitoneally . Each test solution shown below was added to V79 cells (hamster lung-derived fibroblasts)
After exposure for 0 minutes, the cell activity after the exposure was evaluated using WST-1 reagent (Takara Shuzo). In this experimental system, the p
The effect of not only H but also osmotic pressure on living cells was compared.

(2) In order to confirm the influence of pH and osmotic pressure on each test solution cell,
The following seven test liquids were used. The peritoneal dialysate used clinically was used as a negative control. Acidic, low osmotic solution Acidic, high osmotic solution Weak alkaline using sodium bicarbonate, low osmotic solution Weak alkaline using sodium bicarbonate, high osmotic solution Strong alkaline using sodium hydroxide , Low osmotic solution solution Strongly alkaline and high osmotic solution control using sodium hydroxide (neutral peritoneal dialysis solution, good biocompatibility) Each test solution should have the component content, pH and osmotic pressure of Table 1. Was prepared.

[0041]

[Table 1]

(3) Method and Results 10,000 V79 cells were seeded on a 98-well plate and cultured overnight. Each test solution was dispensed into this culture plate and exposed to the cells for 30 minutes. Then WST-1
The cell viability (absorbance ratio to that exposed to the culture medium) was measured by adding a reagent. The results are shown in FIG. Upon exposure to a control neutral peritoneal dialysate, 87% cell survival was confirmed. On the other hand, in each test solution, 67
Although the survival rate was reduced to ~ 80%, compared to the acidic solution of test solution, or the strong alkaline solution of,
It can be seen that the weak alkaline solution of 1 is maintained at a higher level. Further, when compared with the test solution, the hyperosmolarity solution showed higher cell viability.

[0043]

[Effects of the Invention] When exchanging the peritoneal dialysis fluid (bag),
Even if the liquid is injected into the abdominal cavity of the patient due to an erroneous operation by the patient or due to insufficient mixing, the damage to the living body can be further reduced.

[Brief description of drawings]

FIG. 1 is a schematic diagram showing an overall outline of one embodiment of a peritoneal dialysate storage container of the present invention.

FIG. 2 is a schematic view showing the outline of another embodiment of a peritoneal dialysate storage container.

FIG. 3 is a graph showing the effect of each test solution (or control) on cell viability.

[Explanation of symbols]

1. Peritoneal dialysate storage container 2. First storage part 3. Second storage section 4. Communication means 5. Communication passage 6. Clamp (blocking device) 7. Partition 8. Liquid outlet

Claims (14)

[Claims] 1. An acidic concentrated liquid which does not contain a blood alkalizing agent and contains glucose, and does not contain glucose,
A peritoneal dialysis fluid which is separately stored in two solutions of an alkaline concentrate containing a pH adjusting component and a blood alkalizing agent, wherein the pH of the alkaline concentrate is in the range of 7 to 9 and A peritoneal dialysate characterized in that the osmotic pressure of the fluid is in the range of 280 to 460 mOsm. 2. The peritoneal dialysis solution according to claim 1, wherein the pH of the acidic concentrated solution is in the range of 3 to 4. 3. The peritoneal dialysis solution according to claim 1, wherein the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM. 4. The ratio (liquid ratio) of the two liquid amounts of the acidic side concentrated liquid and the alkaline concentrated liquid is in the range of 1: 1.5 to 1: 2. The peritoneal dialysis solution according to the item. 5. The peritoneal dialysis solution according to claim 1, wherein the blood alkalizing agent is a lactic acid compound (inorganic salt). 6. A container in which the peritoneal dialysate is separated and contained into two liquids, an acidic concentrated liquid containing glucose and an alkaline concentrated liquid containing no glucose and containing a pH adjusting component and a blood alkalinizing agent. The container has a first storage part for storing the acidic concentrate and a second storage part for storing the alkaline concentrate, and before mixing both liquids (acidic concentrate, alkaline concentrate) Both of the accommodating parts (first accommodating part, second accommodating part)
(Accommodation part) is cut off, and has a communication means capable of communicating both the storage parts at the time of mixing, and further, when administered into the patient's body, is a liquid outlet part which is substantially the only liquid outflow means from the storage container. A container for storing peritoneal dialysate, characterized in that the container is provided in the second container. 7. The peritoneal dialysate storage container according to claim 6, wherein the pH of the alkaline concentrate is in the range of 7-9. 8. The peritoneal dialysate storage container according to claim 6, wherein the acidic concentrated liquid has a pH in the range of 3 to 4. 9. The peritoneal dialysate storage container according to claim 6, wherein the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM. 10. The osmotic pressure of the alkaline concentrate is 280.
The storage container for peritoneal dialysate according to any one of claims 6 to 9, which is in the range of 460 mOsm to 460 mOsm. 11. The ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to 1: 2.
The peritoneal dialysate storage container according to any one of claims 6 to 10, which is in the range of. 12. The peritoneal dialysis solution storage container according to claim 6, wherein the liquid outlet is formed in a region of the second storage portion opposite to the side where the communication means is provided. 13. The patient's abdominal cavity at the outlet of the container,
The peritoneal dialysate storage container according to any one of claims 6 to 12, wherein a circuit set for injecting the liquid contained in the container is connected. 14. The peritoneal dialysate storage container according to claim 6, wherein the blood alkalinizing agent is an organic acid salt, preferably a lactate salt.