JPS636046B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a separation agent used when a blood sample is separated into serum or plasma and blood cells by centrifugation.

In recent years, testing of blood components in clinical laboratory departments has become extremely important, and the number of tests performed has continued to increase. Among these, many serological tests use only serum or plasma as a sample, and it is necessary to separate serum or plasma from blood cells as a pre-test procedure.

For this reason, conventionally, serum or plasma has been collected only by centrifugation to precipitate the blood cell portion and then sucking it up with a pipette. However, this method does not provide sufficient separation and is very time-consuming. Recently, various methods have been devised to easily collect serum or plasma with high yield.

One method is to add a substance having a specific gravity intermediate to that of serum or plasma to a blood sample, and use centrifugation to position the substance between the two to form a partition wall.

According to this method, it is possible to separate serum or plasma only by decantation, and time and labor can be reduced. The form of this material for forming partition walls is classified into three types: solid form, liquid form, and mixture thereof.

Solid forms include, for example, polystyrene powder or pellet materials, but when these are used, the rate of serum or plasma collection is unavoidably reduced, and the function as a septum is impaired. Due to the insufficiency, there are various drawbacks such as contamination of blood cells into serum or plasma and the tendency of the septum itself to be destroyed.

Acrylic polymers are also known as liquid polymers.

However, in general, when trying to obtain a high viscosity liquid polymer from monomers such as acrylic polymers, there are difficult manufacturing problems such as the removal of impurities depending on the reaction control and reaction method. many.

Further, as a mixture of solid and liquid, for example, there is a mixture of silicone and silica powder added as a viscosity and specific gravity adjusting agent, but this has the disadvantage of being expensive.

In addition, many liquid compounds with specific gravity of 1.03 to 1.08 are known, and by combining solid forms of substances, various fluids with specific gravity of 1.03 to 1.08 can be obtained.

Many of these can form a partition wall between serum or plasma and blood cells by centrifugation.

However, when most of them come into contact with blood, they have some kind of effect on measured values, causing erroneous judgments in clinical tests.

In addition, the serum separating agent may be used after being stored for a long period of time in a testing laboratory, and there is also a risk that it may be exposed to high temperatures due to sunlight or the like during storage. For this reason, even if there are products that do not affect the measured values immediately after manufacture, there are many that change in quality during storage and affect the measured values.

The present invention can be used not only immediately after manufacturing, but also when stored for a long period of time.
In addition, as a result of extensive research into creating a serum or plasma separation agent that would not affect the measured values even if exposed to high temperatures, we developed a mixture of liquid chlorinated substances and liquid compounds containing epoxy groups. This was accomplished by discovering that this objective could be achieved by using a fluid, and the gist of this was to use a liquid chlorinated product obtained by chlorinating liquid polybutene or liquid polybutadiene, epoxidized soybean oil, and epoxidized linseed oil. , a liquid compound containing an epoxy group selected from epoxidized safflower oil and epoxidized fish oil, and has a specific gravity of 1.03 to 25°C.
1.08 and the viscosity at 25℃ is 5000~
A serum or plasma separation agent characterized by being a 5000000 centipoise fluid.

The liquid chlorinated product used in the present invention is obtained by chlorinating liquid polybutene or liquid polybutadiene, which are polymeric substances with a relatively low degree of polymerization, and the specific gravity of the liquid chlorinated product at 25°C is 1.03~1.10, viscosity is 10000~10000000
Preferably, it is centipoise.

The above-mentioned chlorination can be carried out by blowing chlorine gas into the polymer as described above and reacting it under irradiation with ultraviolet rays.

Further, as the liquid compound containing an epoxy group, epoxidized soybean oil, epoxidized linseed oil, epoxidized safflower oil, epoxidized fish oil, etc., which have good compatibility with the above-mentioned liquid chlorinated products, are used.

The serum or plasma separating agent of the present invention is a fluid obtained by mixing the above liquid chlorinated product and a liquid compound containing an epoxy group to form a fluid having a specific gravity of 1.03 to 1.08 at 25°C and a viscosity of 5000 to 5 million centipoise. be. In order to mix the above-mentioned two, they may be added together and mixed uniformly by a conventional method.
The amount of the liquid compound containing an epoxy group to be used is preferably 5 to 70 parts by weight based on 100 parts by weight of the total amount of the liquid chlorinated product and the liquid compound.

When mixing the above-mentioned two, it is necessary that the specific gravity and viscosity of the resulting mixture satisfy the above-mentioned conditions, so the mixing amount can be determined in advance by experiment.

In addition, in order to adjust the viscosity or specific gravity of the separating agent of the present invention, fine powder of an inorganic material such as silica, or particulate material of a polymer such as polystyrene, polymethyl methacrylate, or acrylonitrile-styrene copolymer can be mixed. In this case, the specific gravity and viscosity at 25°C when the fine powders and granules are mixed are in the range of 1.03 to 1.10 and 5,000 to 5,000,000 centipoise, respectively.

In order to separate serum or plasma from blood cells using the separation agent of the present invention, it is sufficient to add the separation agent to sample blood and perform a centrifugation operation. Since a partition wall is formed by the inventive separation agent, serum or plasma can be easily and accurately removed.

Since the separating agent of the present invention has the above-mentioned structure, serum or plasma can be easily and precisely extracted by using the separating agent of the present invention, and furthermore, serum or plasma can be extracted not only immediately after production but also when stored for a long period of time. Even after exposure to high temperatures during storage,
This separation agent does not have any adverse effect on the test values of the separated serum or plasma.

Examples of the present invention will be described below.

Example 1 Liquid polybutene with a specific gravity of 0.86 and a viscosity of 4000 centipoise at 25°C was charged into a flask, and chlorine gas was blown into it at a flow rate of about 60ml per minute, while stirring and maintaining the temperature at 70 to 75°C. Irradiated with ultraviolet light.
After reacting in this state for 8 hours, dechlorination was performed under reduced pressure at 80°C to obtain a reaction product with a specific gravity of 1.07 and a viscosity of 2 million centipoise (25°C). Epoxidized soybean oil was added to this so that the content in the composition was 10% by weight, and the mixture was stirred well at 80°C.

This mixture has a viscosity of 900,000 centipoise and a specific gravity of
It was 1.05 (25℃). Approximately 2 g of this mixture was placed in a polystyrene Spitz tube, 8 ml of sample blood was added, and centrifugation was performed at 2500 rpm for 5 minutes.
The reaction product formed a partition wall between the serum and the blood clot, and it was possible to separate the serum by decantation. In addition, using blood collected from five subjects, serum tests were conducted for 26 items such as proteins, serum enzymes, and inorganic ions with and without using this mixture as a serum separating agent. When these serum test values were compared, results that could be considered to be almost the same were obtained, and it was found that the use of this serum separating agent had no effect on the serum test values.

In addition, we conducted measurements for each of the above items on serum obtained using this serum separating agent stored at 50°C for 30 days and serum obtained immediately after production, but they were found to be exactly the same. I got some measurements that seemed to work.

Example 2 Epoxidized linseed oil was added to the same chlorinated polybutene as obtained in Example 1 at a content of 30% in the composition.
In addition to the weight percentage, specific gravity 1.06, viscosity
When a serum separation agent of 100,000 centipoise (25°C) was prepared and serum was fractionated in the same manner as in Example 1, the partition wall formed between the serum and the blood clot was separated even by decantation. It was not easily destroyed and serum fractionation was easy. Using the same method as in Example 1, serum test values were compared when no serum separating agent was used, when the separating agent was used immediately after manufacture, and when the separating agent was used after being stored at 50°C for 30 days. In both cases, measurements that could be considered the same were obtained.

Example 3 Epoxidized safflower oil was added to the same chlorinated polybutene as obtained in Example 1 in a composition with a different content.
In addition, a serum separating agent with a specific gravity of 1.06 and a viscosity of 100,000 centipoise (at 25°C) was prepared, and the serum was fractionated in the same manner as in Example 1. The partition walls formed in the above were not easily destroyed even by decantation. Furthermore, in the same manner as in Example 1, serum test values were compared when no serum separating agent was used, when the separating agent was used immediately after manufacture, and when the separating agent was used after being stored at 50°C for 30 days. However, in both cases, we obtained measured values that could be considered the same.

Example 4 Epoxidized fish oil was added to the same chlorinated polybutene as obtained in Example 1 so that the content in the composition was 30% by weight, and the specific gravity was 1.06 and the viscosity was
When a serum separation agent of 100,000 centipoise (25°C) was prepared and serum was fractionated in the same manner as in Example 1, the partition wall formed between the serum and the blood clot was separated even by decantation. It was not easily destroyed. Furthermore, in the same manner as in Example 1, serum test values were compared when no serum separating agent was used, when the separating agent was used immediately after manufacture, and when the separating agent was used after being stored at 50°C for 30 days. However, in both cases, we obtained measured values that could be considered the same.

Example 5 Liquid polybutadiene was chlorinated in the same manner as in Example 1 to give a specific gravity of 1.07 and a viscosity of 1.8 million centipoise (25°C).
A reaction product was obtained. Add epoxidized soybean oil to this so that the content in the composition is 10% by weight,
A serum separating agent with a specific gravity of 1.05 and a viscosity of 800,000 centipoise (at 25°C) was prepared by stirring well at 80°C.

When serum was fractionated in the same manner as in Example 1 using this serum separating agent, it was found that the septum formed between the serum and the blood clot was not easily destroyed by decantation. Ta. Furthermore, in the same manner as in Example 1, serum test values were compared when no serum separating agent was used, when the separating agent was used immediately after manufacture, and when the separating agent was used after being stored at 50°C for 30 days. However, in both cases, we obtained measured values that could be considered the same.

Claims (1)

[Claims] 1. A liquid chlorinated product obtained by chlorinating liquid polybutene or liquid polybutadiene is mixed with a liquid compound containing an epoxy group selected from epoxidized soybean oil, epoxidized linseed oil, epoxidized safflower oil, and epoxidized fish oil. A serum or plasma separating agent characterized in that it is a fluid having a specific gravity of 1.03 to 1.08 at 25°C and a viscosity of 5,000 to 5,000,000 centipoise at 25°C.