JPS5968672A - Sealant for separating serum - Google Patents

Abstract

PURPOSE:To enable sepn. of a blood serum and blood cell with high accuracy in a short time without generation of oil by constituting a sealant for separating serum of a copolymer consisting of two kinds of polymerizable monomers having a specific compsn. CONSTITUTION:A sealant for separating serum is constituted of a kind of polymerizable monomer A expressed by the general formula CH2=C<->R<1>-COOR2, for example, methyl methacrylate, and other one kind of polymerizable monomer B expressed by the general formula CH2=C<->R<1>'-X-C<->R<1>''=CH2, for example, ethylene glycol diacrylate, and the weight ratio thereof is made the monomer A/ the monomer B=99.5/0.5-97.0/3.0. Since the formation of a polymer is prevented by the addition of the monomer B, no oil is produced and the sepn. of a blood serum and blood cell is accomplished with high accuracy in a short time.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a sealan for serum separation, and more specifically, the present invention relates to a sealan for serum separation, and more specifically, the present invention relates to a sealan for separating serum and blood cells, and more specifically, the present invention relates to a sealan for separating serum and blood cells, and more specifically, the present invention relates to a sealan for serum separation. Concerning serum-separated phase norant without the occurrence of.

Blood chemical components tJi are essential for modern medical care, and serum is separated from whole blood and used as a sample. The conventional method for separating serum from whole blood was to put blood ltk in a test tube and centrifuge it to separate serum and blood cells, without removing the former with a pipette. This method not only requires skill and effort in separating serum and blood cells in order to collect as much serum as possible while avoiding contamination with blood cells, but also requires care to avoid contamination with pipettes. There was a problem.For this reason, it is preferable to use one clean pipette for each sample, but it takes an unexpectedly long time to regenerate the pipette.Therefore, recently, high-precision separation of serum from whole blood has been developed. For example, when blood is centrifuged in 811 to be separated into serum and blood cells, a material with a specific gravity intermediate between these two layers can be inserted to separate the two layers. Attempts have been made to form a septum on the serum and then decant it without using a pipette to collect the desired serum. Such septum materials are broadly classified into solid materials and liquid materials. However, the solid (A material) does not have a sufficient separation function, and its constituent Iy, (blood 11 + 1 IJ)
In addition, blood cells often escape from the inside of the solid material or from the gap between the solid material and the tube wall, adversely affecting clinical tests. Furthermore, if a shock or unnatural movement is applied, the formed saw partition wall will be destroyed, so it is necessary to ensure sufficient sufficiency at the time of transfer. On the other hand, liquid materials
Liquid materials using liquid resins such as silicone resins, polyester resins, and acrylic resins are being put into practical use because their use eliminates the drawbacks of the solid paulownia wood. Among these liquid resins, those with appropriate specific gravity and A' viscosity can be used as is.If you want to impart thixotropic properties, or if you do not have appropriate specific gravity and viscosity, you can use silica etc. may be used by dispersing it in 11ν-shaped resin. These liquid materials have the disadvantage that either they have a defective ability to contain serum and blood cells, or a portion of them becomes oily (hereinafter referred to as oil) and floats on the surface of the serum. This oil gets mixed into the serum phase through decantation, clogging the piping of automated clinical analyzers and adversely affecting clinical analysis data.

Therefore, an object of the present invention is to provide a serum that can effectively separate serum and blood cells without causing oil content when separating serum and blood cells using a fluid material that acts as a partition. The purpose of the present invention is to provide a separation sealant.

The generation of oil here means that the sealant for serum separation is *'tr
: Sealan 1 is partially non-uniform when forming a separation layer between T and blood cells.
- refers to the phenomenon in which sealant floats on top of serum, and this sealant floating on top of serum is called oil.

In order to achieve the above object, the inventors conducted intensive research and found that by using a copolymer having a specific composition or a sealant for serum separation containing the copolymer, it is possible to prevent the generation of oil. The present inventors have discovered that serum and blood cells can be separated with high precision and in a short time without any problems, and have completed the present invention.

The gist of the present invention is (1) general formula C112=CG OO
R2 (wherein R1 represents a hydrogen atom or a methyl group, R
, 2 represents an alkyl group having 1 to 18 carbon atoms); and R,'
R,'' 1 (n) General formula CH2= C-X -C= CR2 (in the formula, represents a hydroxyalkyl group of numbers 1 to 6 or -(CH2CH20)n - (n = 1 to '4), and Y is A sealant for serum tilt characterized by comprising a copolymer with at least one polymerizable monomer (B) represented by a hydrogen atom, a chlorine atom, or a bromine atom.

The polymerizable monomer (A) constituting the sealant for serum separation of the present invention is a so-called alkyl acrylate or alkyl methacrylate, such as methyl (meth)acrylate (meaning methyl acrylate or methyl acrylate, hereinafter the same), Examples include ethyl (meth)acrylate, n-butyl (meth)acrylate, iso-butyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, lauryl (meth)acrylate, tritesyl methacrylate, stearyl methacrylate-1, etc. . Among these, 2-ethylhexyl methacrylate, lauryl methacrylate, or a copolymer obtained from a combination of these two monomers has an appropriate viscosity and is easy to handle, and it is easy to adjust specific gravity, viscosity, etc. For the sake of
It is preferable because it facilitates dispersion of silica and the like.

On the other hand, specific examples of the polymerizable monomer (B) include ethylene glycol diacrylate, propylene glycol diacrylate, neopentyl glycol diacrylate,
l, 6-hexane thiolne acrylate, diethylene glycol diacrylate, triethylene glycol diacrylate, tetraethylene glycol diacrylate, ethylene glycol dimethacrylate, propylene glycol dimethacrylate-1, neopentyl glycol dimethacrylate, ■, 6--\ Kizanthiol dimethacrylate, diethylene glycol dimethacrylate I
・, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, 1,2,3-propane 1-liol di(meth)acrylate, and Schinirhensen.

The copolymer constituting the serum separation sealan of the present invention is obtained by copolymerizing one or more of the above polymerizable monomers (Δ) and one or more of the polymerizable monomers (B). obtained by. The copolymerization may be carried out by a commonly used method, such as bulk polymerization, emulsion polymerization, H'l! a. When using turbid polymerization, water, emulsifiers, dispersion stabilizers, etc. are removed before use. However, a method using solution polymerization is generally preferred from the viewpoint of synthesis and post-treatment. Solution polymerization is carried out by polymerizing a monomer mixture in the presence of an inert solvent and a radical or ionic initiator, and after the polymerization is substantially completed, the inert solvent is removed by distillation etc. The copolymer obtained can then be put to practical use.

The copolymer constituting the serum separation sealant of the present invention is
Preferably, monomer (A)/monomer (B) = 99.9
10.1~90.0/10.0 (weight ratio), preferably 99.5/0.5~! It is composed of 37.0/3.0.

If the amount of i1χ-mer (B) is less than 0.1, there is no effect of suppressing the generation of oil (and if it is more than 10, the resulting copolymer may significantly thicken or become kelized). It cannot be put to practical use.Although it is not clear whether the addition of the monomer (B) can prevent the generation of oil, the addition of the monomer (B) produces an oil that is different from that of ordinary copolymers. It was recognized that the copolymer can be used alone as a sealant for serum separation, or it can be made into a sealant for surface separation by adding viscosity and specific gravity modifiers, etc. It is.

When used alone as a sealant for serum separation, the copolymer has a specific gravity of 0.94 to 1.05 and a viscosity of 20 to 50.
Preferably, the range is 0.00 voise. When the specific gravity and viscosity of the copolymer are outside the above ranges, it is common to add a viscosity and specific gravity regulator to adjust the specific gravity and viscosity to fall within these ranges.

Examples of materials used for adjusting specific gravity or viscosity include silica, barium sulfate, alumina, calcium carbonate, talc, Henton, and other organic kelizing agents. When adding these regulators, a silane coupling agent, a titanium coupling agent, etc. can also be added in order to stabilize the dispersion. When adding these modifiers to the copolymer, roll milling,
It is necessary to sufficiently knead and disperse the mixture using a kneader or the like.

The sealant for serum separation according to the present invention can be placed in advance at the bottom of a blood collection tube, or can be put into practical use by filling a capsule that can be placed in a blood collection tube. After collecting blood into a blood collection tube containing the sealant for serum separation according to the present invention, or when using a capsule-filled product, after collecting blood into a blood collection tube and placing the capsule on top of the blood collection tube, By centrifuging, the serum is divided into two parts and the blood cells are separated into two parts using a serum separation sealant as a partition wall.The serum can be removed by decantation and subjected to clinical tests.

Next, the present invention will be specifically explained with reference to production examples and examples, and it goes without saying that the scope of the present invention is not limited to these examples. In the examples, "parts" and "1%" refer to "parts by weight" and "% by weight" unless otherwise specified.

Production Example 1 600 parts of xylene was charged into a reaction vessel equipped with a stirrer, a reflux condenser, a thermometer, a dropping funnel, and a nitrogen gas introduction tube, and the mixture was maintained at 130°C. Next, a mixture of 990 parts of lauryl methacrylate, 10 parts of ethylene glycol methacrylate, and 1.30 parts of t-butylperoxy-2-ethylhexanony was added dropwise to the reaction vessel at a uniform rate over a period of 3 hours under a nitrogen stream. did. 30 minutes after the dropwise addition was completed, a mixture of 70 parts of xylene and 5 parts of L-butylperoxy-2-ethylhexanony I was added, and the mixture was further aged for 2 hours.
A copolymer solution was obtained. This copolymer solution was heated to 140 mL under reduced pressure.
After removing the solvent at 25°C for 5 hours, a copolymer (1) having a viscosity of 130 voids and a specific gravity of 0.945 was obtained.

Production Example 2 Xylene 600 IX was charged into a reaction vessel similar to Production Example 1 and maintained at 140°C. Next, add 2 to the reaction vessel.
- A mixture of 997 parts of ethylhexyl methacrylate, 3 parts of ethylene glycol dimethacrylate, and 1.60 parts of t-butylperoxy-2-ethylhexanony was added dropwise at a constant speed over a period of 3 hours under a nitrogen stream. Dripping completed 3
After 0 minutes, 50 parts of xylene and mo-butylperoxy-2
A mixture of -ethylhexanonite was added, and the mixture was further aged for 2 hours to obtain a copolymer solution. This copolymer solution was desolventized at 140°C under reduced pressure for 5 hours to obtain a copolymer (2) having a viscosity of 970 voices at 25°C and a specific gravity of 0.972.

Production Example 3 In a reaction vessel similar to Production Example 1, 600 parts of xylene was charged and maintained at 130°C. Next, a mixture of 495 parts of lauryl methacrylate, 495 parts of 2-ethylhexyl methacrylate, 10 parts of ethylene glycol dimethacrylate, and 30 parts of t-butyl-2-ethylhexanonite was added to the reaction vessel for 3 hours under a nitrogen stream. It was dripped at a constant speed.

Thirty minutes after the dropwise addition was completed, a mixture of 70 parts of xylene and 5 parts of mo-phthyl peroxy-2-ethylhexanoate was added, and the mixture was further aged for 2 hours to obtain a copolymer solution. This copolymer solution was desolventized under reduced pressure at 140"C for 5 hours.
A copolymer (3) having a viscosity of 665 voids and a specific gravity of 0.964 at 5°C was obtained.

Production Example 4 In a reaction vessel similar to Production Example 1, 600 parts of xylene was charged and maintained at 130°C. Next, 950 parts of lauryl methacrylate, 50 parts of tetraethylene glycol dimethacrylate, and 2-butylperoxy-2 were added to the reaction vessel.
A mixture of 5.0 parts of -ethylhexanonyl was added dropwise at a uniform rate over a period of 3 hours under a nitrogen stream. Thirty minutes after the dropwise addition was completed, a mixture of 70 parts of xylene and 15 parts of t-butylperoxy-2-ethylhexanoate was added, and the mixture was further aged for 2:1 to obtain a copolymer solution. This copolymer solution was desolventized under reduced pressure at 140°C for 5 hours to obtain a copolymer (4) having a viscosity of 680 voices and a specific gravity of 0.949 at 25°C.

600 parts of toluene was charged into a reaction vessel similar to Production Example 1, and maintained at 112°C. Next, this reaction vessel was
A mixture of 1-980 parts of -phthyl acrylate, 20 parts of 3-ethylene glycol cymethacrylate, and 120 parts of -phthyl baroxy-2-nitylhexanony was added dropwise at a constant speed over a period of 3 hours under a nitrogen stream. . Thirty minutes after the completion of the dropwise addition, a mixture of 70 parts of toluene and 5 parts of t-phthyl baroxy-2-ethyl No. Noate was added, and the mixture was further aged for 2 hours to obtain a copolymer/8 liquid. This copolymer 1 volume 1 Oi
was desolventized at 140°C under reduced pressure for 5 hours to obtain a copolymer (5) with a viscosity of 1200 voices and a specific gravity of 1.041 at 25°C.
I got it.

Example 1 Preneact (
0.2 part of isopropyl steroyl titanate-1 (manufactured by Ajinomoto Co., Inc.) was added and thoroughly mixed.

Next, Aerosil R972 (silicon dioxide fine powder:
I] 11 parts of Kiaeshi 2 (manufactured by Sil Co., Ltd.) and 1 part of Aerosil
30 (same as R972) 10 parts and Neolite 5P20
0 (Calcium carbonate fine powder: Takehara Chemical Co., Ltd. 1i
u) 0.5 part was added and kneaded with a kneader.

After thoroughly dispersing this kneaded material in a three-roll mill, it was vacuum degassed and the specific gravity at 25°C was 1.045 to 1.05.
A thixotropic serum separation sealant with a viscosity of 1,500 voids and a shear rate of 1 second was obtained.

The obtained sealan for serum separation) 1.3mj! 10rn
After filling the bottom of the β blood collection tube and storing it at the product temperature and 40℃ for one month, each blood collection tube contains approximately 6 ml! Blood is drawn,
After standing still for about 30 minutes, centrifugation was performed at 2500 rpm for 10 minutes.

Example 2 100 parts of the copolymer (2) of Production Example 2 was added with 1 to 0
．． 15 parts were added and mixed. Next is Aerosil 300
15 parts and 2000.5 parts of Neolye I.
．． 045~], 050, shearing... viscosity at 1 speed 1 second 370
A 0-voice thixotropic sealant for serum separation was obtained. The operations of filling blood collection tubes, storage, and serum separation were performed in the same manner as in Example 1.

Example 3 100 parts of the copolymer (3) of Production Example 3 was added with 0.
15 parts were added and mixed. Then Aerosil 380 17
1 part and 2000.5 parts of Neolyte T-5P were added, and the same operation as in Example 1 was performed to obtain a thixotropic serum separation sealant having a ratio i of 1.050, a shear rate of 1 second, and a viscosity of 3100 voices. The filling, storage, and serum separation operations were performed in the same manner as in Example 1.

Example 4 To 100 parts of the copolymer (4) of Production Example 4, 0.17 parts of a silane coupling agent (vinyltris(β-methoxyconyl-oxy)silane manufactured by Toshi Silicone Co., Ltd.) was added and mixed. Then, the mixture was mixed. 7-engine U sill 3809 parts, Aerosil 130
10 parts and 2000.5 parts of Neolite Sl' were added, kneaded, dispersed, and degassed in the same manner as in Example 1 to obtain a specific gravity of 1.040 to 1.
．． 045, a thixotropic serum separation sealan 1~ having a viscosity of 2800 voices and a shear rate of 1 second was obtained. The operations of filling, blood sampling, and serum separation were performed in the same manner as in Example 1.

Copolymer of Harusan Production Example 5 (51,100 parts was added to 120°C;
Then, 1 part of Kerol'I'' (condensation product of higher polyhydric alcohol and henzaldehyde: Shin Nippon Rika Co., Ltd.) was added to the stirred mixture and dissolved.Next, Neolite 5
After adding 112,001 parts and thoroughly mixing and dispersing with a mixer, the mixture was degassed to obtain a thixotropic serum separation sealant with a specific gravity of 1.045 to 1.050, a shear rate of 1 second, and a viscosity of 2,000 voids. Filling, blood sampling, and serum separation were performed in the same manner as in Example 1.

Example 6 The copolymer (5) of Production Example 5 was used alone as a sealant for serum separation.

Filling, blood sampling, and serum separation were carried out in the same manner as in Example 1 using the serum separation sealant of Example I-9 of Japanese Patent Publication No. 54-63797.

Comparative Example 2 After blood was collected into commercially available product A (filled in a glass blood collection tube) in the same manner as in Example I, 1N of blood was drawn into a dark blue sample.

The results obtained in each of the above categories are as shown in the table below.

Margin below

Claims (1)

[Claims] 1, CI) - general formula Cl-12= C-G OOR2 (
At least one polymerizable monomer (A) represented by the formula (formerly hydrogen atom or methyl group, R2 represents an argyl group having 1 to 18 carbon atoms), and 121' and R, respectively. independently represents a hydrogen atom or methi(CH2CII20) n (n = 1 to 4), Y represents a hydrogen atom, a chlorine atom or a bromine atom)
A serum serum ester characterized by comprising a copolymer with at least one polymerizable monomer (B) that is Body (13) -99,91
0.1 to 90.0/10.0 (weight ratio) according to claim 1] & Blood 11\ Seesont for separation. ;3. Monomer (Δ) or lauryl methacrylate 1-(1)4 monomer (1(Δ) or 2-conidel methacrylate) 5. The sealant for serum separation according to claim 1, wherein the monomer (8) is lauryl methacrylate-I and 2-
The sealan for serum separation according to claim 1, which is ethylhexyl methacrylate-1. 6. The sealant for serum separation according to claim 1, which is monoffi (B) or ethylene glycol dimethacrylate. 7. The specific gravity of the copolymer at 25°C is 0.94 to 1.
Any one of claims 1 to 6 which is 05
The sealant for blood ln separation described in section 1.