JPH0455760A - Blood segregating agent - Google Patents

Abstract

PURPOSE:To obtain a blood specimen which is stable for a long time and has excellent segregating state so as not to give an effects on the inspected value of serum and the like by mixing an inactive filler and a viscosity adjusting agent into a main agent whose main components are xylene resin and liquid- state rubber. CONSTITUTION:An inactive filler and a viscosity adjusting agent are mixed into a main agent whose main components are xylene resin and liquid-state rubber. The specific gravity at 20 deg.C is made to be 1.03 - 1.07. The xylene resin of the main component is the hypochromic, transparent, glucose-state resin obtained from methaxylene and formalin. The xylene resin is the oligomer wherein the methaxylene is bonded to methylene, dimethyl ether, acetal or the like and the average molecular weight is 300 - 600. The viscosity of the xylene resin at 30 deg.C is 2,000 - 20,000cp. The xylene resin has the sufficient tackiness and is the resin having the excellent miscibility with other macromolecular compounds.

Description

DETAILED DESCRIPTION OF THE INVENTION "Industrial Application Field" The present invention relates to a blood separation agent used for separating whole blood into serum and blood clots by centrifuging a blood sample.

"Prior Art" Among clinical test items, blood tests are indispensable in the diagnosis of diseases, etc., and are regarded as extremely important clinically. Especially in serological tests, etc., various testing methods have been developed, and the number of tests and test items have increased significantly. In this serological test, the test is mainly performed using serum or plasma (hereinafter referred to as serum, etc.) separated from the whole surface, so as a pre-test procedure, the blood sample collected in a blood collection tube such as a Spitz is collected as serum or plasma. It is necessary to separate the blood into blood cells or blood clots (hereinafter referred to as blood clots, etc.).

Conventionally, in this blood separation operation, a collected whole blood sample is placed in a blood collection tube such as a spitz tube, and the sample is centrifuged to separate serum as a specimen. The supernatant of the blood sample separated by this centrifugation, such as serum, is collected as a sample.

However, in this centrifugation operation, the state of separation between serum, etc. and blood clots, etc. is extremely unstable, and blood cells in the clots that settle out due to a slight impact may contaminate the serum, etc. Extreme care was required when handling the specimens.

Various attempts have therefore been made to improve the unstable separation of blood samples after centrifugation and to facilitate testing operations.

An example thereof is a method using a blood separating agent described in Japanese Patent Publication No. 57-24508. This method uses a gel-like substance made of a mixture of silicone oil and hydrophobic fine powder to separate serum, etc.
The above-mentioned gel-like substance is prepared to have a specific gravity between those of serum etc. and blood clots, etc., and by adding this gel-like substance to a blood sample and centrifuging it, it is possible to form an intermediate between the two components such as serum etc. and blood clots. This method takes advantage of the property of forming partition walls between the walls.

[-Problem to be Solved by the Invention] However, when using a two-legged blood separation agent for blood samples, the partition wall formed at the boundary between serum, etc. and blood clots (hereinafter referred to as blood separation partition) Because it is brittle and lacks compactness, if a separated blood sample is accidentally dropped as described above, the formed blood separation barrier will be destroyed.

In addition, this blood separation agent has poor adhesion to synthetic resin materials (polypropylene, etc.) used as materials for blood collection tubes, so when this blood separation agent is added to a blood sample in a spitz to form a blood separation barrier, The formed blood separation partition wall has poor adhesion to the Spitz wall. Therefore, this blood separation partition wall has a problem in that it forms a groove in its Spitz contact portion that connects serum, etc. and blood clot, etc., and blood cells in the blood clot mix with serum, etc. through this groove.

In addition, when this blood separation agent comes into contact with a blood sample, it may adsorb or alter the blood components of the blood sample, which may affect each test value in a blood test, making it difficult to perform an accurate test. Problems such as not being able to do so have been pointed out.

The present invention has been made in view of the above circumstances, and when separating a blood sample used for a blood test into serum etc. and blood clots etc., it is possible to obtain a blood sample that is stable for a long period of time and has a good separation state.
The purpose of the present invention is to provide a blood separating agent that does not affect test values in any way when serum etc. of obtained blood samples are tested.

"Means for Solving the Problems" This invention is made by mixing an inert filler and a viscosity modifier into a main component mainly consisting of xylene resin and liquid rubber.
By providing a blood separation agent characterized by having a specific gravity of 1.03 to 1.07 at 20°C, the above problem has been solved.

The xylene resin is preferably an oligomer consisting of meta-xylene and formalin with an average molecular weight of 300 to 600, and whose viscosity at 30°C is 2000c.
It is desirable that it is p~20000 cp.

"Function" The blood separation agent of the present invention is a mixture of a main agent mainly consisting of xylene resin and liquid rubber, an inert filler and a viscosity modifier, so this blood separation agent can be collected together with a blood sample. When placed in a blood vessel and centrifuged, a dense and strong blood separation barrier is formed between serum and blood clots.

Furthermore, since the blood separation agent according to the present invention does not adsorb or alter blood components in a blood sample, accurate test values can be obtained during blood tests.

The present invention will be explained in detail below.

The xylene resin, which is the main component preferably used in the present invention, is a light-colored transparent syrup-like resin obtained from meta-xylene and formalin, and has an average molecular weight of meta-xylene bound by chemical bonds such as methylene, dimethylene ether, and acetal. 300-600 oligomers. This xylene resin has sufficient adhesiveness and is excellent in compatibility with other polymer compounds.

In addition, the liquid rubber used in the present invention has good compatibility with xylene resin, can impart sufficient shape retention to the partition walls formed after centrifugation, and has no interaction with blood. Preferably, it does not affect the components in the blood.

Specifically, butadiene-based liquid rubber is preferred, and among these, liquid acrylonitrile-butadiene rubber having a carboxyl group at the end and obtained by radical polymerization of butadiene and acrylonitrile is particularly preferred. The compounding ratio of this liquid rubber and the above xylene resin is set within a range that can maintain good tackiness and shape retention of the resulting separation agent, xylene resin: liquid rubber (1: O, I ~ 0.5) < weight It is desirable that the ratio be within the range of the ratio.

In addition, the viscosity modifier used in the present invention should not only be able to adjust the viscosity well, but also have a releasing effect such that the blood separating agent smoothly floats from the bottom of the spitz during centrifugation. Liquid paraffin, licorice oil, process resin, and process oil are also suitable. This viscosity modifier has a viscosity of 2 to
15) It is desirable to add at a blending ratio of about % by weight.

Furthermore, the inert filler used in the present invention can be used to adjust the specific gravity of the blood separation agent by increasing or decreasing the amount of the inert filler added, and to impart thixotropic properties to the blood separation agent. It is desirable to have the ability to Specifically, silica is preferably used from the viewpoint of imparting dixotropy, and hydrophobic silica is particularly suitable since there is no risk of silica components leaching into serum. This inert filler is preferably added at a blending ratio of about 3 to 10% by weight based on the base material.

The above-mentioned materials are heated to about 60° C. and then kneaded in a kneader to form the blood separation agent of the present invention.

In order to separate serum, etc. and blood clots, etc. using the blood separation agent of the present invention, it is sufficient to add this blood separation agent to the blood sample to be tested and centrifuge it. A dense and strong partition wall is formed between the blood sample and the blood sample, and the blood sample is separated into serum, etc., and blood clot, etc.

(Example 1) Specific gravity at 20°C is 1.046, viscosity is 20000
cp, xylene resin with an average molecular weight of 350 to 380 (manufactured by Mitsubishi Gas Chemical Co., Ltd., trade name Nikanol LL) 380
9, specific gravity at 25°C is 0907, and viscosity is 400.
00cp, molecular weight 4800, liquid rubber with carboxol group at the terminal functional group (manufactured by Ube Industries, Ltd., product name HY)
CARCT polymer CTB2000x162) 50g
and, as a viscosity modifier, the specific gravity at 20°C is 0.86.
4 liquid paraffin 409 and hydrophobic silica (manufactured by Nippon Aerosil Co., Ltd., trade name Hydrophobic Silica R) as an inert filler.
972) was put into a kneader and kneaded for 20 minutes while heating the inside of the kneader to 60°C. Thereafter, the mixture was degassed under vacuum to obtain a uniform kneaded product.

This kneaded material is a slightly milky white viscous substance with high transparency.
Specific gravity at 0℃ is 1.045, viscosity is 85000cp
Met.

The following experiment was conducted to examine the effect of the obtained blood separation agent on the blood separation barrier and blood test values when it is actually used.

1.2 g of the blood separation agent of this example was filled into the bottom of a polypropylene spitz (mouth diameter 17xx, capacity 99xQ), and six Spitz filled with this blood separation agent were prepared. These Spitz were injected with seven samples each: human whole blood collected from five test subjects, whole surface of Uno collected from a cow immediately after stratification, and pig whole blood collected from a pig immediately after stratification. A total of 6 blood samples were prepared, 2 blood samples each. Six blood samples of these three types were heated at 20°C.
After leaving it at room temperature for 2 hours, set one tube of each of the three types of blood samples in a centrifuge, and
Centrifugation was performed for 10 minutes at 0°C and 300 rpm. After a further 4 hours (6 hours after Spitz injection), the remaining three tubes were centrifuged in the same manner as the three duplicate tubes. When we observed the appearance of the six centrifuged blood samples obtained in this way, we found that both blood samples centrifuged 2 or 6 hours after Spitz injection had a serum layer and a blood clot layer. A good blood separation barrier was formed between them. Furthermore, human whole blood was centrifuged from among the three types of blood samples, and the serum was collected, and the biochemical test values and electrolyte test values of this serum were tested. As a result of comparing this test value with the serum biochemical test value and electrolyte test value of the blood sample centrifuged without using a blood separation agent,
It can be concluded that both values are almost the same.

In addition, regarding the blood separation agent of this example, the one immediately after manufacture and the one after 2 months of manufacture were mixed on the whole surface of a human body and further centrifuged. As a result of biochemical tests and electrolyte tests performed on these two types of blood samples, no difference was found in the values between the two.

(Example 2) 350 g of the same xylene resin used in the previous example
and a liquid rubber (manufactured by Ube Industries, Ltd., trade name: IYCARCT Polymer CTBNI300X31) with a specific gravity of 0.924.27°C at 25°C and a viscosity of 55000 cp and a molecular weight of 3500. 20y of silicone oil (manufactured by Toshiba Silicone Corporation, trade name TSF451-10) with a viscosity of 10cp at a specific gravity of 0.935.25°C and the same hydrophobic silica 309 used in the previous example as an inert filler. was placed in a kneader and kneaded for 20 minutes while heating the inside of the kneader to 60°C. Thereafter, the mixture was degassed under vacuum to obtain a milky white kneaded product with uniform viscosity.

In order to examine the effect of using the obtained blood separation agent on the blood separation state and blood test values, the blood separation agent was used in the same manner as in the previous example, and after 2 or 6 hours had elapsed after Spitz injection. An experiment was conducted to compare the separation state of centrifuged blood samples and the biochemical test values and electrolyte test values of the blood samples. In addition, with this blood separation agent, biochemical test values and serum of blood samples separated using the blood separation agent immediately after manufacture and blood samples separated using the blood separation agent 2 months after manufacture. Electrolyte test values were measured and compared.

As a result, regarding the separation status of the blood sample and the biochemical test values and electrolyte test values of the blood sample, the blood sample centrifuged 2 hours after Spitz injection and the blood centrifuged 6 hours after injection were determined. The test values of the samples were determined to be almost identical.

In addition, regarding biochemical test values and electrolyte test values, blood samples separated using a blood separation agent immediately after manufacture and blood samples separated using a blood separation agent immediately after manufacture.
The test values of the blood samples separated using the aged blood separation agent were judged to be almost identical.

"Effects of the Invention" As explained above, according to the blood separation agent of the present invention, the blood separation partition formed when a blood sample is centrifuged is dense and has good adhesion to the synthetic resin Spitz wall. Therefore, by putting a blood sample together with the blood separation agent of the present invention into a blood collection tube such as a Spitz and performing a centrifugal separation operation, the Spitz containing the separated blood sample can be kept in an unstable state such as lying on its side for a long time. However, the septum is not destroyed, and a blood sample in a stable separated state can be obtained for a long time.

In addition, this blood separation wall is extremely strong and has excellent shape retention, so even if a blood sample separated using this blood separation agent is subjected to a fairly strong impact such as being dropped, it will maintain a stable separation state. This makes it easier to handle blood samples in blood tests.

In addition, the substances and compounds constituting the blood separation agent of the present invention do not adsorb or alter blood components even when mixed with and brought into contact with blood in a blood sample. Even if the separation is performed, the test values at the time of the blood test are not affected, and therefore accurate test values can be obtained.

Claims (1)

[Claims] 1. The product is made by mixing an inert filler and a viscosity modifier with a main component mainly consisting of xylene resin and liquid rubber, and has a specific gravity of 1.03 to 1.07 at 20°C. A blood separation agent characterized by: 2. The xylene resin is an oligomer of meta-xylene and formalin with an average molecular weight of 300 to 600,
Its viscosity at 30℃ is 2000cp~20000c
The blood separation agent according to claim 1, wherein the blood separation agent is p.