JPH09220281A - Sterilizing method for body fluid treating device and sterilized body fluid treating device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To drastically reduce the damage to a body fluid treating device by sterilization while maintaining the effect of sterilization at the time of subjecting the body fluid treating device to radiation sterilization and to provide the body fluid treating device which is safe and useful for the living body sterilized by this sterilization method. SOLUTION: This sterilization method comprises subjecting the body fluid treating device to radiation sterilization in the state of impregnating the device with at least one kind of antioxidant soln. selected from sodium pyrrophosphite, sodium phosphite, sodium hydrogensulfite, acetone sodium bisulfite, sodium formadehyde sulfoxylate, sodium hydrosulfite and 1-ascorbic acid.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a body fluid treatment device used for treating body fluids such as blood, plasma, and lymph fluid, changing the composition ratio thereof, and changing the function of structures, and sterilization thereof. Regarding the method. In recent years, due to advances in science and technology such as medicine and engineering, various types of body fluid treatment devices, such as body fluid treatment devices for returning body fluid components that have changed due to various diseases to a normal state, and body fluid treatment devices for altering the immunity of living organisms, etc. Has been developed and is improving the therapeutic effect on various diseases. For example, an artificial kidney for returning blood components of renal failure patients to normal, an artificial lung for sending oxygen into the blood, cancer,
Ascites treatment equipment for returning useful components such as albumin in ascites fluid stored due to cirrhosis to blood, used for collagen diseases, autoimmune diseases, etc.Malignant such as autoantibodies and immune complexes in blood Blood cells for filtering plasma containing substances /
Plasma separator, filtration filter for removing only high molecular weight substances including malignant substances in plasma by filtration, adsorber for selectively adsorbing only malignant substances in plasma, poisoning from the blood of drug-poisoned patients Adsorber for adsorbing the inducer,
An adsorber that adsorbs bilirubin, which increases in the blood of patients with liver disease, an adsorbent that adsorbs blood group substances in the blood of incompatible blood type pregnant patients, and blood cells that remove leukocytes and lymphocytes from the blood of patients with autoimmune diseases Separation filter, blood cell separation filter for removing leukemia cells from leukemia patient blood,
A cell stimulating device or the like for stimulating immunocompetent cells in blood to induce a specific function can be given as an example of the body fluid treatment device.

[0002]

Body fluids treated with a body fluid treatment device are usually
The body fluid treatment device is usually sterilized and used to prevent denaturation of the body fluid during the treatment of the body fluid in many cases. Sterilization methods include heating methods (flame method, dry heat method, high-pressure steam method, circulating steam method, boiling method, intercalation method), filtration method, irradiation method (radiation method, ultraviolet ray method, high-frequency method), gas method, There are chemical liquid methods (Japanese Pharmacopoeia, 11th revision, general test method (7) sterilization method and aseptic operation method), but for sterilization of body fluid treatment device, usually high pressure steam sterilization method, radiation (gamma ray) sterilization method, gas (Ethylene oxide) method is often used. However, since sterilization means killing or removing all microorganisms in a substance, it is easily conceivable that the sterilization of the body fluid treatment apparatus itself would cause great damage. In fact, particularly, the body fluid treatment device is greatly damaged by the radiation sterilization method, and the constituent materials of the body fluid treatment device are decomposed, colored, etc., and when the body fluid is processed, the low-molecular substances elute from the body fluid treatment device to the body fluid side. The problem of getting lost comes up. In particular, a body fluid treatment device (for example, an adsorbent in which a protein, peptide, amino acid, or the like is immobilized on a carrier, a cell stimulating material, or the like) using radiation-unstable proteins, peptides, amino acids, or the like as a constituent material, is easily modified by radiation. There was a problem with a body fluid treatment device or the like using a polymer.

[0003]

In view of the above problems, an object of the present invention is to sterilize a body fluid treatment device by radiation.
In providing a radiation sterilization method that greatly reduces damage to the body fluid treatment device due to sterilization while maintaining the sterilization effect,
Another object of the present invention is to provide a body fluid treatment device that is sterilized by this sterilization method and is safe and useful for living bodies.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies in accordance with the above-mentioned object, and as a result, by carrying out radiation sterilization while impregnating a specific antioxidant solution in a body fluid treatment device, the body fluid It was found that it is possible to significantly reduce the damage to the treatment device, and further, it was confirmed that the body fluid treatment device sterilized by this sterilization method is safe and useful for the living body, and the present invention was completed. It was That is, in the present invention, the body fluid treatment device is selected from at least sodium pyrosulfite, sodium sulfite, sodium hydrogen sulfite, acetone sodium bisulfite, sodium formaldehyde sulfoxylate, sodium hydrosulfite, and 1-ascorbic acid. A method for sterilizing a body fluid treatment device, which comprises sterilizing radiation in a state of being impregnated with one type of antioxidant solution, which is sodium pyrosulfite, sodium sulfite, sodium bisulfite, acetone sodium bisulfite, sodium formaldehyde. The body fluid treatment device is radiation-sterilized in a state of being impregnated with at least one antioxidant solution selected from sulfoxylate, sodium hydrosulfite, and 1-ascorbic acid.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The body fluid treatment device referred to here is a body fluid such as blood, plasma, lymph fluid or bone marrow fluid which is used to change the composition of electrolytes, hormones, proteins, etc. of this body fluid, and red blood cells and white blood cells. Changes the composition of monocytes, granulocytes, lymphocytes and lymphocyte subsets in platelets or leukocytes, or stimulates some lymphocytes, even if the composition does not change, to helper function, suppressor function, killer function It is a processing device for inducing the like, and is a device for causing some change in body fluid. There are various mechanisms for causing a certain change to the body fluid, such as a physical mechanism and a chemical mechanism. For example, dialysis, filtration, adsorption, adhesion, antigen-antibody reaction, utilization of specific gravity difference, salting out, physical Various things such as stimulation can be used. Here is another example of a body fluid treatment device. An artificial kidney for returning the blood components of a patient with renal failure to normal, an artificial lung for supplying oxygen to the blood, and albumin in ascites concentrated and re-injected Ascites treatment device, plasma filtration filter for separating blood cell components and plasma components in blood, centrifugal separator and blood cell separation filter for separating blood cells for each component, selective adsorption of specific components in body fluids Adsorber, a filter for fractionating components in plasma by molecular weight, a filter for selectively removing specific blood cells, stimulating immunocompetent cells in blood to induce specific functions There is a stimulating device for performing the above, and all the processing devices that cause some change to the body fluid are included in those which are not exemplified here. Sterilization in the present invention refers to killing or removing all microorganisms in a substance. In addition, the antioxidant referred to in the present invention refers to an atom, molecule or ion having a property of easily giving an electron to another molecule or the like, but having a property of inhibiting a body fluid treatment device from being changed by oxygen. Things. The antioxidant referred to in the present invention is selected from the following seven types. That is, sodium pyrosulfite, sodium bisulfite, sodium sulfite, acetone-sodium-bisulfite, sodium-formaldehyde-sulfoxylate, sodium hydrosulfite, and 1-ascorbic acid. These antioxidants may be used alone or as a mixture of two or more. Among the above examples, sodium pyrosulfite, sodium acetone bisulfite, sodium formaldehyde sulfoxylate, sodium hydrosulfite, l-ascorbic acid are preferably used in terms of toxicity, handleability, etc. Sodium is preferred.

A method of impregnating a body fluid treatment device with an antioxidant solution is a method of dissolving an antioxidant in an appropriate solvent and contacting the body fluid treatment device, for example, dissolving the antioxidant in water or a physiological salt solution. And a method of dissolving an antioxidant in a solvent such as glycerin or alcohol and filling or impregnating the body fluid treatment device. It is necessary that the body fluid treatment device is impregnated with the antioxidant solution so that the body fluid treatment device can be prevented from being changed by oxygen. When the antioxidant is used in the form of a solution, the optimal concentration of the antioxidant should be determined by the material of the body fluid treatment device, the type of the antioxidant, and the sterilization conditions. .00
1% to 1%, more preferably 0.005% to 0.1%.
It is a concentration of 5%. The sterilization method used in the present invention is an irradiation method, and a gamma ray method is particularly preferred among the irradiation methods. Hereinafter, with respect to an embodiment of the present invention, taking a case of gamma ray sterilization of a hollow fiber type artificial kidney as an example,
This will be described in detail. In the case of gamma ray sterilization, usually 1 to 5 Mr
Generally, gamma rays of ad are irradiated to the hollow fiber type artificial kidney. At this time, the hollow fiber mainly deteriorates, and a low molecular substance may be generated. Such a low molecular weight substance poses a problem since the possibility of elution toward the body fluid when the body fluid is treated with the hollow fiber type artificial kidney cannot be denied. According to the present invention made in order to solve this problem, for example, since a liquid in which a specific antioxidant is dissolved is filled in the container of the hollow fiber type artificial kidney, gamma rays are irradiated. Also, the deterioration of the hollow fiber can be prevented, and the generation of low molecular substances can be greatly suppressed. This is probably because the impregnation with the specific antioxidant solution prevented the oxidative deterioration of the hollow fiber material and suppressed the generation of low molecular substances. The method of impregnating the hollow fiber artificial kidney with the specific antioxidant solution is not limited to the above method, and a method of dissolving the antioxidant in a solution such as glycerin and impregnating the hollow fibers can be used.
The material of the hollow fiber is cellulose acetate, cellulose,
There are various types such as polyacrylonitrile, methyl methacrylate, polysulfone, cellulose deacetate, ethylene vinyl alcohol, etc.Depending on the degree, there is degradation due to gamma ray sterilization, generation of low molecular weight substances, and specific antioxidants to suppress this Impregnating the solution is very useful. Impregnation with an antioxidant solution is also very effective because it can prevent deterioration of the surface of the container and deterioration of an adhesive or the like for binding and bonding hollow fibers.

[0007]

EXAMPLES Examples of the present invention will be shown below together with comparative examples, but the present invention is not limited thereto.

[0008]

Example 1 7300 cupra ammonium rayon hollow fibers (internal diameter 200 μm, film thickness 11 μm) were potted at both ends with a polyurethane resin, built into a cylindrical outer cylinder to assemble an artificial kidney, and then dialyzed with the blood side. Liquid side 1 each
Wash and fill with 500 ml of aqueous sodium pyrosulfite solution. The concentration of the sodium pyrosulfite aqueous solution in the aqueous solution is
Three levels of 0.01 g / dl, 0.1 g / dl and 0.5 g / dl were set. Thereafter, the artificial kidney was sealed in a polyethylene bag, packed in a cardboard case, and sterilized by irradiating 2.5 Mrad of gamma rays in this state.
Measurement was performed using the filling liquid after the sterilization treatment as a test liquid.

[0009]

[Comparative Example 1] A cupra ammonium rayon hollow fiber type artificial kidney was assembled, and then 2.5 Mrad gamma ray sterilization treatment was performed in the same manner as in Example 1 using pure water, and the filling liquid was used as a test liquid for measurement. I did. The UV absorbance and the visible absorbance of the above test solution were measured.
As a method of measuring the absorbance of ultraviolet light, a 10-mm measurement cell was used, and the absorbance at the point where the absorption was highest between the measurement wavelengths of 220 nm and 350 nm was determined. Filling water of each concentration was used as a comparison solution when measuring the absorbance. Also,
The absorbance in the visible part was measured at a wavelength of 420 nm for the purpose of measuring the yellowing degree of the solution. Table 1 shows the measurement results. In all the data, the results using sodium pyrosulfite showed that the amount of eluted substances was smaller and the degree of yellowing of the solution was lower than that of Comparative Example 1 (when no antioxidant was used). Recognize.

[0010]

Example 2 Using the same artificial kidney as in Example 1, sodium bisulfite (0.01 g / dl) was used as an antioxidant.
Acetone sodium bisulfite (0.1 g / d
l) The same experiment as in Example 1 was performed except that each aqueous solution of sodium formaldehyde sulfoxylate (0.1 g / dl) was used. Table 2 shows the results. As the data of the antioxidant pear, the data of Comparative Example 1 was used. The irradiation dose of gamma rays was 2.5 Mrad. It can be seen that the amount of eluted substances was reduced for all antioxidants and the degree of yellowing of the solution was also improved.

[0011]

Example 3 Cellulose hollow fiber for artificial kidney (inner diameter 200
μm, film thickness of 11 μm) was immersed in an aqueous solution of sodium pyrosulfite (0.1 g / dl) in a glass beaker, packaged with a polyethylene film, and then gamma-rayed in this state.
Irradiated 5 Mrad. Thereafter, the hollow fiber was taken out of the solution, and the tensile strength and elongation of the hollow fiber were measured.

[0012]

Comparative Example 2 Cellulose hollow fibers (same as in Example 3) were immersed in distilled water in a glass beaker, and in this state 2.5M.
By irradiating rad gamma rays, the tensile strength and elongation of the hollow fiber were measured. Table 3 shows the measurement results. Those using sodium pyrosulfite as an antioxidant,
Both the tensile strength and the elongation were superior to those without the antioxidant (Comparative Example 2).

[0013]

As described above, by sterilizing radiation in a state where the body fluid treatment device is impregnated with a specific antioxidant solution, deterioration of the constituent materials of the body fluid treatment device, which has conventionally occurred,
It is possible to significantly reduce the generation of low molecular weight substances due to deterioration, and the radiation-sterilized body fluid treatment device according to the present invention has become a safe and useful body fluid treatment device for living organisms.

Claims (2)

[Claims] 1. A body fluid treatment device comprising sodium pyrosulfite,
Sodium sulfite, sodium hydrogen sulfite, acetone sodium bisulfite, sodium formaldehyde sulfoxylate, sodium hydrosulfite, l-
A method for sterilizing a body fluid treatment device, which comprises sterilizing radiation in a state of being impregnated with at least one antioxidant solution selected from ascorbic acid. 2. At least one antibacterial agent selected from sodium pyrosulfite, sodium sulfite, sodium hydrogen sulfite, acetone sodium bisulfite, sodium formaldehyde sulfoxylate, sodium hydrosulfite, and 1-ascorbic acid. A body fluid treatment device that has been sterilized by radiation while being impregnated with an oxidant solution.