JPS6367657B2 - - 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 pretreatment for the test. 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 provides insufficient separation and is very time consuming. Recently, various methods have been devised to allow serum or plasma to be collected easily and 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 it is possible to reduce time and labor, but it also has the following drawbacks. That is, three types of forms of the above-mentioned partition wall forming material have been proposed so far: solid form, liquid form, and mixtures thereof.
For example, there are polystyrene powder materials or pellet materials, but when these are used,
Since the function as a septum is insufficient, there have been various drawbacks such as contamination of blood cells into serum or plasma and a tendency for the septum itself to be destroyed.

In addition, liquid forms such as liquid acrylic polymers, and solid/liquid mixtures include silicone and silica powder, but these stick strongly to the walls of spitz tubes, so they cannot be removed from the spitz tube after use. When the tube is cleaned and reused, cleaning is time-consuming and troublesome, and it has the disadvantage that it has some influence on the measured values upon reuse, causing erroneous judgments in clinical tests.

The present invention was made as a result of intensive research to eliminate the above-mentioned drawbacks, and the formed partition wall has excellent strength, and the partition wall can be quickly removed after use to clean the Spitz tube. Moreover, it is an object of the present invention to provide a novel serum or plasma separating agent that can separate serum or plasma from blood extremely simply and accurately.

The gist of the present invention is that the specific gravity at 25℃ is 1.03 ~
1.08, the particle size is 0.1 to 5 mm, the ball tack value at 25°C is 3 to 7, and is obtained by polymerizing an acrylic ester or methacrylic ester monomer alone or a monomer that can be copolymerized with these. The present invention relates to a serum or plasma separating agent characterized by comprising fine particles having pressure-sensitive adhesive properties.

The fine particles having pressure-sensitive adhesive properties in the present invention refer to fine particles having the property of adhesively bonding to each other when pressurized, and acrylic pressure-sensitive adhesive fine particles are used. The particle size of these sticky fine particles is preferably 0.1 to 5 mm, and it is preferable that the particle sizes are uniform. Further, the shape is not particularly limited, but a spherical shape is preferable. The specific gravity of the above-mentioned sticky particles is set in the range of 1.03 to 1.08. This means that if the specific gravity of the above-mentioned particles is less than 1.03, the sticky particles will float in the serum or plasma phase. However, if it exceeds 1.08, the adhesive particles will settle in the blood cell phase, making it impossible to form a partition wall between the two layers. Incidentally, in order to adjust the specific gravity of the fine particles, an inorganic substance such as silica may be added to these sticky fine particles.

As an index of the adhesiveness of the fine particles in the present invention, a ball tack value representing adhesive strength is used according to the method of J. Dow, which is commonly used in the field of adhesives. That is, fine particles having the tackiness to be measured are dispersed in an organic solvent such as ethanol, coated on a film substrate such as polyester, and dried.
This is fixed on a table with a slope of 30 degrees. Next, stainless steel balls of various sizes are rolled from the top of the table, starting from the largest ball, and the ball tack value is expressed as the size of the stainless steel ball that can stop in the adhesive-applied area with a length of 10 cm. For example, X/32
When the above conditions are satisfied using inch diameter stainless steel balls, the ball tack value is X.

The adhesive fine particles used in the present invention have a ball tack value of 3 to 7 at 25 DEG C. as measured by the above-mentioned measuring method.

In the present invention, the adhesive fine particles can be produced by mixing an acrylic acid ester monomer such as 2-ethylhexyl acrylate or butyl acrylate alone or with a monomer that can be copolymerized therewith in the presence of an oil-soluble catalyst. If suspension polymerization is carried out in water below, fine particles having acrylic adhesive properties will be obtained. In addition, during the above polymerization, stabilizers include water-soluble polymers such as polyvinyl alcohol and polyacrylic acid, suitable surfactants, etc., and oil-soluble catalysts include peroxides such as benzoyl peroxide and methyl ethyl ketone peroxide. or azobisisobutyronitrile, etc. are used.

As the above-mentioned monomer, it is particularly preferable to use an acrylic ester or methacrylic ester of a primary or secondary alcohol having 4 to 10 carbon atoms. In addition, monomers that can be copolymerized with these monomers such as styrene, methyl methacrylate, acrylamide, acrylonitrile, etc. may be used in combination, and in particular, if polyfunctional monomers such as divinylbenzene and polyethylene glycol diacrylate are used in combination, a wide range of possibilities can be obtained. Fine particles can be obtained that can maintain a moderate degree of tackiness over a temperature range. After the adhesive fine particles synthesized in this way are thoroughly washed with water to completely remove residual impurities such as stabilizers,
It is important to use it dry.

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. As a result, an upper serum or plasma layer and a lower blood cell layer are separated. Since a partition wall is formed by the separation agent of the present invention in the middle of the membrane, serum or plasma can be easily and accurately collected by decantation or the like.

The serum or plasma separating agent of the present invention is a fine particle with a specific gravity of 1.03 to 1.08 at 25°C and has pressure-sensitive adhesive properties, so it can be easily separated under normal centrifugation conditions without the need for a particularly strong centrifugal force. A partition wall is formed between the serum or plasma layer and the blood cell layer, and the partition wall is formed by adhesive particles bonding to each other due to the pressure during centrifugation, so the partition wall is not destroyed. Serum or plasma separated by decantation or the like can be easily and accurately collected. Furthermore, after serum or plasma is collected, the septum can be easily removed with a spatula, a glass rod, etc. without remaining on the inner wall of the Spittz tube, so the Spitz tube can be cleaned and reused.

Hereinafter, the present invention will be explained by examples.

Example 1 200 parts by weight of ion-exchanged water, 0.5 parts by weight of polyvinyl alcohol (degree of polymerization 1500), 80 parts by weight of butyl acrylate, 15 parts by weight of styrene, 5 parts by weight of divinylbenzene, and 0.3 parts by weight of benzoyl peroxide were charged into a reaction vessel. The mixture was reacted at 80° C. for 10 hours in a nitrogen stream to prepare an aqueous dispersion of sticky fine particles. Fine particles were separated from this dispersion, washed several times with ion-exchanged water to remove polyvinyl alcohol, and then freeze-dried at -50°C to obtain sticky fine particles. The particle size of this fine particle is 0.1~0.5
mm, and the ball tack value was 4. Approximately 2 g of these sticky particles were placed in the bottom of a polystyrene Spitz tube, and then 8 ml of collected blood was added and centrifuged at 3000 rpm for 5 minutes. The particles bonded to each other, forming an upper serum layer and a lower blood cell layer. A partition wall was formed in the middle. This septum was not destroyed by decantation, and serum could be easily collected from the Spitz tube. Furthermore, after serum collection, the septum could be easily removed with a spatula without remaining on the wall of the Spitz canal.

Example 2 200 parts by weight of ion-exchanged water, 0.5 parts by weight of polyvinyl alcohol (degree of polymerization 1500), 70 parts by weight of 2-ethylhexyl acrylate, methyl methacrylate
20 parts by weight, 10 parts by weight of ethylene glycol dimethyl methacrylate, and 0.3 parts by weight of benzoyl peroxide were charged into a reaction vessel and reacted in the same manner as in Example 1, then separated, washed with water, and freeze-dried at -50°C. Adhesive fine particles having a diameter of 1 to 2 mm were obtained. The ball tack value of this fine particle was 4. Approximately 2 g of these sticky particles were placed at the bottom of a glass Spitz tube, and then 5 ml of the collected blood was added.
When centrifuged at 3000 rpm for 5 minutes, the microparticles bonded to each other to form a partition wall between the upper serum layer and the lower blood cell layer. This septum was not destroyed by decantation, and serum could be easily collected from the Spitz tube. Furthermore, after serum collection, the septum could be easily removed with a spatula without remaining on the wall of the Spitz canal.

Claims (1)

[Claims] 1 Specific gravity at 25°C is 1.03 to 1.08, particle size is 0.1 to
5 mm, has a ball tack value of 3 to 7 at 25°C, and has pressure-sensitive adhesive properties obtained by polymerizing an acrylic ester or methacrylic ester monomer alone or a monomer that can be copolymerized with these monomers. A serum or plasma separating agent characterized by comprising: