JPH02304026A - Liquid for peritoneal lavage - Google Patents

Abstract

PURPOSE:To provide a safe liquid for peritoneal lavage, containing Na<+>, Ca<++>, Mg<++>, Cl<-> and organic acid anion at specific concentrations, having an osmotic pressure falling within a specific range and causing minimized water-absorption and disturbance of the balance of serum electrolytes. CONSTITUTION:The objective peritoneal lavaging liquid contains 125 to 150mEq/l of Na<+>, 1 to 5mEq/l of Ca<++>, 0.5 to 2mEq/l of Mg<++>, 90 to 120mEq/l of Cl<-> and 10 to 60mEq/l of anions of organic acid (e.g. acetic acid, lactic acid or citric acid) and has an osmotic pressure of 285 to 320mOsm/kg. The liquid is further compounded with <=5mEq/l of K<+>, an osmotic pressure regulator to raise the osmotic pressure to be slightly higher than the osmotic pressure of blood (e.g. sugar or low-molecular polyhydric alcohol) and an adhesion- preventing agent (e.g. chitosan or sodium alginate) to prevent the post-operative intraabdominal adhesion.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a peritoneal lavage fluid.

[Conventional technology]

The peritoneal lavage method is performed for the purpose of cleaning the peritoneal cavity at the time of gastrointestinal perforation, eliminating intraperitoneal bacteria after surgery, or eliminating bacterial toxins at the time of peritonitis. Conventionally, as a peritoneal washing fluid,
Physiological saline has been used. However, since a large amount of physiological saline is used each time, there are problems in that water absorption and serum electrolyte balance are disturbed.

[Problem to be solved by the invention]

An object of the present invention is to provide a safe peritoneal lavage fluid that minimizes water absorption and disturbance of serum electrolyte balance.

[Means to solve the problem]

In order to achieve the above object, the present inventors conducted detailed studies on the dynamics of water and electrolytes in an electrolyte solution administered intraperitoneally through animal experiments. As a result, the preferred electrolyte
By finding the concentration range and osmotic pressure range, we were able to complete the present invention.

That is, the present invention provides an aqueous solution containing at least sodium ions, calcium ions, magnesium ions, chloride ions, and anions of a pharmacologically acceptable organic acid, wherein the concentration of each electrolyte is within the following range, and The present invention provides a peritoneal lavage fluid characterized by having an osmotic pressure within the range of 285 to 320 m/kHz.

Na' 125-155 mEq/I
Ca" 1~5 mEq/ffMg"
0.5~2 mEq/42CI-90~
120 mEq/j2 Organic acid Noanio7 10-60 mEq#! In the present invention, examples of the anion of a pharmacologically acceptable organic acid include anions such as acetic acid, lactic acid, citric acid, malic acid, and tartaric acid, and at least one anion selected from these
It only needs to contain seeds.

The concentration range of 10 to 60 mEq/ff means the total amount of organic acid salts dissolved in water that are hydrolyzed and include those present as non-dissociated organic acids.

The peritoneal lavage fluid of the present invention is based on the above-mentioned composition, but in a preferred embodiment, it can contain important electrolytes in the body. Care must be taken to ensure that the concentration is not too high, which causes it to migrate into the body through the peritoneum and cause serious hyperkalemia symptoms.
It is desirable to increase or decrease the amount within a range of up to Eq/1 depending on the patient's condition.

Furthermore, in a preferred embodiment, the osmolality is adjusted to be isotonic with the serum osmolarity (285-29 (] m O
s m/kg) and then add glucose, fructose,
Il of Sho Tang et al! osmotic pressure of low-molecular-weight polyhydric alcohols such as glycerol, nidosilyl, etc.
IE3 IIIj agent was added to make it slightly hypertonic (300mOs).
For example, prescriptions with a weight of about 100 m/kg) can be mentioned. In addition, since intra-abdominal adhesions often become a problem after surgery, chitozan, thorium alginate, etc., which have a preventive effect,
A very small amount of low molecular weight dextran or the like may be added.

The peritoneal cavity washing solution 3) of the present invention constructed as described above can also be effectively and safely used for washing the thoracic cavity for the same purpose.

The peritoneal lavage fluid of the present invention can be easily produced by operations similar to those of ordinary infusion production methods. For example, sodium.

Calcium, magnesium, if necessary, potassium chloride and any of the above-mentioned organic acid salts, and further, if necessary, osmotic pressure regulators and anti-adhesion agents, so that the concentration is within the above range and the osmotic pressure is within the range. After dissolving in distilled water and sterile filtering,
Just fill it into a container and sterilize it. The pH is usually kept near neutral.

[For production]

Since the peritoneal lavage fluid of the present invention has a well-balanced formulation of each electrolyte based on experiments using rats, there is little disturbance of the electrolyte balance in the body due to the lavage fluid. In particular, rapid transfer of large amounts of chloride ions from the peritoneum into the body causes acidosis, which is undesirable, but the peritoneal lavage solution of the present invention is significantly improved compared to physiological saline. In addition, since the osmotic pressure is adjusted to be isotonic or slightly high, it absorbs little water and is safe.

In addition, the osmolarity in the present invention is such that human serum osmolality is approximately 2% compared to that of rats (approximately 310 mOsm/kg).
This was derived from the experimental results of Lat.

Regarding the intraperitoneal cleaning effect of the peritoneal cavity washing liquid of the present invention,
It can be expected to have the same effect as conventional physiological saline, which has approximately the same concentration of solutes.

[Example 1] Japanese Pharmacopoeia Sodium Chloride 5 (i, Ig, Japanese Pharmacopoeia Potassium Chloride 2.98 g, Japanese Pharmacopoeia Calcium Chloride (
dihydrate) 1.47g, Japanese Pharmacopoeia magnesium chloride (hexahydrate) 1.02g, Lactic Acid Triud Pharmaceutical Industry (l
@． 67.9 g of special grade 2 (content 72.6%) and 50.0 g of Japanese Pharmacopoeia glucose were dissolved in distilled water at 10°C. The obtained solution was filled into a 500 mR glass bottle, sealed, and sterilized at 12FC in an autoclave for 40 minutes to obtain the desired peritoneal washing fluid.

Table 1 Solute concentration and osmotic pressure Lactate: Lactate anion, Glucose
Niglucose [Examples 2 to 6] In the same manner as in Example 1, peritoneal lavage fluids having the formulations shown in Table 2 were obtained.

Table 2 Solute concentration and osmotic pressure Acetate: Acetate anion + C4trate
: citric acid anion, Glycerol: glycerol.

Xylitol: Xylitol, Chitosan
: Chitosan [Test Example] (1) Test solution Examples L2 and 3, EL-LeFrac No. 1 (Morishita Pharmaceutical Co., Ltd.: Comparative Example A) and physiological saline (Otsuka Pharmaceutical Co., Ltd.: Comparative Example B) were prepared as follows. It was used for experiments.

Table 3 Solute concentration and osmotic pressure in Comparison I. (2) Dynamics of electrolytes and water during intraperitoneal administration Using 8-week-old SD rats (5 rats per group), 40 mR/kg of the test solution was administered intraperitoneally. did. Three hours later, the abdomen was opened under ether anesthesia, intraperitoneal fluid was collected, and electrolyte concentration and osmotic pressure were measured. The results are shown in Table 4.

Table 4 Changes in electrolyte concentration, osmotic pressure, and fluid volume ~: Increase in test fluid, -2 Decrease in test fluid (3) Effect on urine volume by intraperitoneal administration 8-week-old SD rats (1 group of 5)
After administering 40 mfl/kg of the test solution intraperitoneally, the mice were immediately placed in a metabolic cage, and the urine output was measured 8 hours later. From the average urine volume of each group, the ratio of each test solution administration group to the non-administration group was calculated and shown in Table 5.

Table 5 Ratio (%) of mean urine volume of test solution administration group to mean urine volume of non-administration group (%) From the above results, the peritoneal lavage fluid of the present invention has less movement of electrolytes and water than the comparative example, and is safer. I understand that there is something.

〔Effect of the invention〕

The peritoneal lavage fluid of the present invention absorbs little water and has little effect on serum electrolyte balance, so it can be used safely.

Claims (1)

[Claims] (1) An aqueous solution containing at least sodium ions, calcium ions, magnesium ions, chloride ions, and pharmacologically acceptable anions of organic acids, in which the concentration of each electrolyte is within the following range, and the osmotic pressure is 285
A peritoneal lavage fluid characterized in that the concentration is within the range of ~320 mOsm/kg. Na^+ 125-155mEq/l Ca^+^+ 1-5mEq/l Mg^+^+ 0.5-2mEq/l Cl^- 90-120mEq/l Organic acid anion 10-60mEq/l