JP2009244172A - Serum or blood plasma separating compound, and blood testing container - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a serum or blood plasma separating compound which utilizes difference in specific gravity, excels in separation performance, rarely allows floating of oily component in the serum or blood plasma, and also avoids from performance degradation even if being stored under various storage conditions. <P>SOLUTION: The serum or blood plasma separating compound includes rosin-based resin, trimellitic acid ester or pyromellitic acid ester. A serum or blood plasma separating compound includes rosin-based resin 100 pts.wt. in which its softening point is 60-160°C and specific gravity at 25°C is within 1.0-1.1, and trimellitic acid ester or pyromellitic acid ester 50-250 pts.wt. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a serum or plasma separation composition used for separating serum or plasma from blood and a blood test container containing the same, and in particular, a serum or plasma separation composition containing a rosin resin and the composition The present invention relates to a blood test container in which a separation composition is contained.

  Conventionally, in order to separate each component in blood, a method of collecting blood in a blood test container containing a separating agent and centrifuging it has been used. That is, each component was separated by centrifugation using the specific gravity difference of each component in blood.

  In order to quickly and reliably separate serum or plasma from blood cell components and the like, a separating agent having an intermediate specific gravity between serum or plasma and blood cell components is used, and the specific gravity is 1.03 to 1.08, Various serum or plasma separation compositions have been proposed that are more preferably adjusted to a range of 1.04 to 1.06.

  For example, Patent Document 1 describes a serum or plasma separation composition containing a polyester polymer as a main component. Patent Document 2 describes a composition for separating serum or plasma containing an acrylic polymer as a main component, and Patent Document 3 discloses a composition for separating serum or plasma containing a cyclopentadiene resin as a main component. Things are listed.

  Among them, since the viscosity of cyclopentadiene resin has a large temperature dependency, when a serum or plasma separation composition containing cyclopentadiene resin as a main component is used at a low temperature, the composition for serum or plasma separation is used. There was a problem that the fluidity of the liquid became worse. In order to solve such a problem, Patent Document 4 discloses that viscosity adjusting agent 0.8 to 25 parts by weight and organic gelling agent 0.03 to 0.03 parts per 100 parts by weight of liquid cyclopentadiene resin at room temperature. A serum or plasma separation composition comprising 9 parts by weight is disclosed.

Furthermore, in Patent Document 5, the specific gravity can be set finely, the separation performance of serum or plasma and blood cell components using the difference in specific gravity is excellent, and as a composition for separating serum or plasma excellent in stability. In addition, a serum or plasma separation composition containing a hydrogenated cyclopentadiene resin and a phthalate ester which is an aromatic esterified product is disclosed.
JP-A-61-233368 JP-A-53-42283 JP-A-1-295163 JP-A-6-3356 Japanese Patent Laid-Open No. 9-15238

  However, in the serum or plasma separation composition as described in Patent Documents 1 to 5, the contained components are poorly compatible, and the contained oily component tends to be separated. Therefore, the separated oily component may float in the serum or plasma after centrifugation. The blood test container after centrifugation is often put on an automatic analyzer or the like for blood tests. If impurities such as oily components are present in serum or plasma, the sampling nozzle of the automatic analyzer is clogged, Sometimes it adhered to the surface of the electrolyte sensor, which hindered blood tests.

  Furthermore, when designing a composition for separating serum or plasma, it is necessary to make the specific gravity intermediate between serum or plasma and blood cell components. It must be large. However, the specific gravity at 25 ° C. of many polymers and resins is less than 1.0, the specific gravity at 25 ° C. is 1.0 or more, is industrially available, and is easily available. The material was very limited.

  The object of the present invention is generally made of easily available materials, and is excellent in the separation performance of serum or plasma and blood cell components due to the difference in specific gravity, and further, the contained components are not separated. An object of the present invention is to provide a serum or plasma separation composition in which oily components are unlikely to float in the separated serum or plasma, and a blood test container containing the serum or plasma separation composition.

  According to the present invention, a composition for separating serum or plasma containing a rosin resin and trimellitic acid ester or pyromellitic acid ester is provided, thereby achieving the above object.

  More preferably, as the rosin resin, a rosin resin having a softening point of 60 to 160 ° C. and a specific gravity at 25 ° C. in the range of 1.0 to 1.1 is used, and 100 parts by weight of the rosin resin is used. On the other hand, the trimellitic acid ester or pyromellitic acid ester is contained in a proportion of 50 to 250 parts by weight. Thereby, serum or plasma and blood cell components can be separated more rapidly and reliably by a separation method using the specific gravity difference.

  The specific gravity of the serum or plasma separation composition is preferably 1.02 to 1.08, more preferably 1.02 to 1.055. Thereby, the separation of serum or plasma and blood cell components utilizing the specific gravity difference can be performed more rapidly and reliably.

  The blood test container according to the present invention is characterized by containing the serum or plasma separation composition of the present invention. Therefore, after blood is introduced into the blood test container, serum or plasma and blood cell components can be promptly and reliably separated by utilizing the specific gravity difference by centrifugation or the like.

  Details of the present invention will be described below.

  The rosin resin used in the present invention is not particularly limited, and examples thereof include polymerized rosin, rosin-modified phenol resin, rosin ester resins, disproportionated rosin ester resins, and hydrogenated rosin ester resins. Examples of such rosin-based resins include products listed in the trade name: Pine Crystal Series, manufactured by Arakawa Chemical Industry Co., Ltd., that is, product numbers KR-85 (softening point 85 ° C.), KR-614 (softening). 90 ° C.), KE-100 (softening point 100 ° C.), KE-359 (softening point 100 ° C.), and Arakawa Chemical Industries, Ltd. Product names: Superester series However, A-75 (softening point 75 ° C.), A-100 (softening point 100 ° C.), A-115 (softening point 115 ° C.), A-125 (softening point 125 ° C.) and the like are commercially available.

  The softening point of the rosin resin is preferably 60 to 200 ° C, more preferably 60 to 160 ° C, and further preferably 60 to 140 ° C.

  The specific gravity at 25 ° C. of the rosin resin is preferably 1.00 to 1.15, more preferably 1.04 to 1.10. By using a rosin resin having a specific gravity at 25 ° C. within this range, it is possible to easily adjust the specific gravity of the whole serum or plasma separation composition.

  The trimellitic acid ester or pyromellitic acid ester used in the present invention belongs to the aromatic esterified product like the phthalic acid ester, and is not particularly limited as long as it is a trimellitic acid ester or a pyromellitic acid ester.

  As the trimellitic acid ester, trimellitic acid alkyl ester is preferable. As trimellitic acid alkyl ester, specifically, trimellitic acid tri-n-octyl, trimellitic acid triisooctyl, trimellitic acid triisodecyl, etc. Is mentioned.

  As a commercial item of the alkyl ester of the said trimellitic acid, the product name: Monosizer W-700 (trimisooctyl trimellitic acid, specific gravity (25 degreeC / 25 degreeC) 0.990 made from Dainippon Ink Chemical Co., Ltd.), for example. , Viscosity (25 ° C.) 220 mPa.s), Product Name: Monosizer W-750 (trimellitic acid tri-n-octyl, specific gravity (25 ° C./25° C.) 0.984, viscosity (25 ° C.) 93 mPa.s) Product name: Sansosizer TOTM (triisooctyl trimellitic acid, specific gravity (20 ° C / 4 ° C) 0.990, viscosity (30 ° C) 162 mPa.s), product name: Sansosizer TITM, manufactured by Shin Nippon Chemical Co., Ltd. (Triisodecyl trimellitic acid, specific gravity (20 ° C./4° C.) 0.975, viscosity (30 ° C.) 287 mPa.s) Triisooctyl rimellitic acid, specific gravity (20 ° C / 20 ° C) 0.990, viscosity (25 ° C) 218 mPa.s), trade name: TOTM NB (triisooctyl trimellitic acid, specific gravity (20 ° C / 20 ° C)) 0.990, viscosity (25 ° C.) 218 mPa.s), trade name: 711TM (trialkyl trimellitic acid (carbon chain 7-11), specific gravity (20 ° C./20° C.) 0.978, viscosity (25 ° C.) 131 mPa .S).

  The pyromellitic acid ester is preferably an alkyl ester of pyromellitic acid, and specifically includes pyromellitic acid tetraisooctyl ester.

  Examples of the commercially available alkyl ester of pyromellitic acid include, for example, trade name: Monosizer W-7010 (tetraisooctyl pyromellitic acid, specific gravity (25 ° C./25° C.) 0.992 manufactured by Dainippon Ink & Chemicals, Inc. , Viscosity (25 ° C.) 460 mPa.s).

  The blending ratio of the trimellitic acid ester or pyromellitic acid ester is preferably 50 to 250 parts by weight with respect to 100 parts by weight of the rosin resin. When the blending ratio of trimellitic acid ester or pyromellitic acid ester is less than 50 parts by weight, the viscosity of the resulting serum or plasma separation composition becomes too high, and serum or plasma and blood cell components are separated by centrifugation, etc. May require a large centrifugal force for separation. In addition, when the blending ratio of trimellitic acid ester or pyromellitic acid ester exceeds 250 polymerization parts, a large amount is used to adjust the specific gravity of the resulting serum or plasma separating composition between serum or plasma and blood cell components. Therefore, the yield value of the resulting serum or plasma separation composition may increase with time, and the partition wall forming ability may be reduced. More preferably, trimellitic acid ester or pyromellitic acid ester is blended at a ratio of 70 to 150 parts by weight with respect to 100 parts by weight of the rosin resin, and thus it is good without requiring a large centrifugal force. A partition wall for separation can be formed.

  In addition to the rosin resin and trimellitic acid ester or pyromellitic acid ester, the serum or plasma separation composition according to the present invention contains various other components within a range not inhibiting the purpose of the present invention. Also good. Examples of such other components include thixotropy imparting agents, specific gravity adjusting agents, inorganic fine powders, organic gelling agents, and polar organic solvents for adjusting the gelation degree.

  Examples of the organic gelling agent include sorbitol-modified products such as dibenzylidene sorbitol, bis (p-ethylbenzylidene) sorbitol, bis (p-methylbenzylidene) sorbitol, and the like.

  Moreover, as said inorganic fine powder, fine powders, such as a silica, a kaolin, a bentonite, an alumina, a synthetic silicate compound, diatomaceous earth, can be mentioned regardless of crystallinity and an amorphous property.

  Furthermore, examples of the polar organic solvent include acetone, dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), ethylene glycol, and propylene glycol.

  The composition for separating serum or plasma according to the present invention is obtained by mixing the rosin resin and trimellitic acid ester or pyromellitic acid ester and other components added as necessary by an appropriate mixing method. The manufacturing method is not particularly limited.

  The blood test container according to the present invention is characterized in that the composition for separating serum or plasma of the present invention is contained in a container body that has been conventionally used for blood test containers.

  The container body is not particularly limited, and those conventionally used for blood test containers are used.

  The shape of the container body is not particularly limited, but is generally a tubular container having one end opened and the other end closed with a bottom.

  The material constituting the container main body is not particularly limited, and for example, a container main body made of glass or synthetic resin can be used. However, since the serum or plasma separated from the outside can be easily confirmed by visual observation, it is desirable that the container body is made of a transparent material.

  The container body has an opening at least at one end, and the opening is generally sealed with a stopper.

  The plug body is not particularly limited as long as the container body can be hermetically and liquid-tightly sealed, and those conventionally used for blood test containers are used. For example, the most common plug is a rubber plug.

  FIG. 1 is a schematic cross-sectional view showing an example of a blood test container of the present invention. After the serum or plasma separation composition 3 of the present invention is contained in a synthetic resin container main body 1, it is sealed with a rubber stopper 2 to obtain a blood test container.

  When separating serum or plasma from blood using the composition for separating serum or plasma according to the present invention, for example, the following methods can be mentioned.

  Blood as a specimen is introduced into the blood test container in which the serum or plasma separation composition of the present invention is contained at the bottom. And it centrifuges with a centrifuge. Centrifugation precipitates blood cell components, which are solids in the blood, downward, and serum or plasma is obtained as the supernatant. The serum or plasma separation composition forms a partition wall between the blood cell component and the serum or plasma. In order to separate plasma, a conventionally known anticoagulant such as heparin, K salt or Na salt of ethylenediaminetetraacetate may be added to the blood and / or blood test container in advance. In order to separate serum, blood tests can be performed using a known coagulation promoter such as inorganic powder such as silica or diatomaceous earth, serine protease such as thrombin without using an anticoagulant or instead of anticoagulant. It may be stored in a container for use and centrifuged after the introduced blood is coagulated.

  The composition for separating serum or plasma of the present invention is composed of a rosin resin and trimellitic acid ester or pyromellitic acid ester, and the rosin resin and trimellitic acid ester or pyromellitic acid ester are compatible. Therefore, the composition for separating serum or plasma according to the present invention is excellent in stability because it hardly causes separation of components even when stored for a long period of time.

  Therefore, even when serum or plasma is separated using the serum or plasma separation composition of the present invention that has been stored for a long time, oily components are unlikely to float in the separated serum or plasma. Therefore, clean serum or plasma can be reliably separated from blood by using the serum or plasma separation composition of the present invention.

  Conventionally, if the oily component as described above floats in the serum or plasma after separation, the sampling nozzle for collecting the serum or plasma is clogged with the oily component when the sample is applied to an automatic analyzer for blood test, etc. The sensor surface could be contaminated with oily components. On the other hand, according to the present invention, since the oily component can be reliably prevented from being mixed into the serum or plasma as described above, the sampling nozzle is clogged even when applied to an automatic analyzer or the like. Or the surface of the electrolyte sensor is not easily contaminated.

  Further, the rosin resin and trimellitic acid ester or pyromellitic acid ester used in the serum or plasma separation composition of the present invention are generally commercially available, and the selection of the grade and amount to be used is relatively limited. Thus, the specific gravity can be easily adjusted.

  Since the blood test container of the present invention contains the serum or plasma separation composition of the present invention, the components of the serum or plasma separation composition can be separated even when stored for a long period of time. Is less likely to occur and has excellent stability. In addition, since an oily component does not come out from the serum or plasma separation composition, blood is collected in the blood test container and centrifuged to obtain serum or plasma. Can be reliably suppressed.

  Hereinafter, the present invention will be clarified by giving specific examples of the present invention. In addition, this invention is not limited to a following example.

  The materials used in the examples are as follows.

Rosin resin (1): manufactured by Arakawa Chemical Industries, Ltd., trade name: KE-100, softening point 100 ° C., specific gravity (25 ° C./4° C.) 1.085
Rosin resin (2): manufactured by Arakawa Chemical Industries, Ltd., trade name: KE-359, softening point 100 ° C., specific gravity (25 ° C./4° C.) 1.0580
Rosin resin (3): manufactured by Arakawa Chemical Industries, Ltd., trade name: A-75, softening point 75 ° C., specific gravity (25 ° C./4° C.) 1.080
Rosin resin (4): manufactured by Arakawa Chemical Industries, Ltd., trade name: A-100, softening point 100 ° C., specific gravity (25 ° C./4° C.) 1.090
Rosin resin (5): manufactured by Arakawa Chemical Industries, Ltd., trade name: A-115, softening point 115 ° C., specific gravity (25 ° C./4° C.) 1.090
Rosin resin (6): manufactured by Arakawa Chemical Industries, Ltd., trade name: A-125, softening point 125 ° C., specific gravity (25 ° C./4° C.) 1.105
Cyclopentadiene oligomer (1): manufactured by Tonex, trade name: E5690, softening point 90 ° C., specific gravity (25 ° C./4° C.) 1.060
Cyclopentadiene oligomer (2): manufactured by Tonex, trade name: E5380, softening point 85 ° C., specific gravity (25 ° C./4° C.) 1.070
Trimellitic acid ester: manufactured by J Plus Co., Ltd., trade name: TOTM NB (triisooctyl trimellitic acid), specific gravity (25 ° C./25° C.) 0.990, viscosity (25 ° C.) 218 mPa.s s
Organic gelling agent: dibenzylidene sorbitol (DBS), manufactured by Shin Nippon Chemical Co., Ltd., trade name: Gelol D
Polar organic solvent: N-methylpyrrolidone (NMP), reagent grade fine powder silica: amorphous fine powder silica having a specific surface area of 200 m ² / g, manufactured by Nippon Aerosil Co., Ltd., trade name: 200V
(Examples 1-8: Confirmation of solubility of rosin resin and the like in trimellitic acid ester)
The rosin resin (1) to (6) or the cyclopentadiene oligomer (1) to (2) is dissolved in the trimellitic acid ester heated to 140 ° C. by heating and stirring to such an extent that it can be confirmed visually. Thereafter, each solution was stored at room temperature of about 25 ° C. The solubility of the rosin resin or cyclopentadiene oligomer was evaluated by visually observing the next day, one week later, and three weeks after the solution was prepared. The types of blending components, the blending ratio of each component (unit: parts by weight) when the rosin resin or cyclopentadiene oligomer is 100 parts by weight, easiness of dissolution, and compatibility evaluation results over time are shown below. Table 1 shows.

  As is clear from Table 1, the rosin resin showed high solubility in trimellitic acid ester at 140 ° C.

  Although the cyclopentadiene-based oligomer has high solubility in trimellitic acid ester at 140 ° C., a light white turbidity occurred with time after the solution was prepared. This is considered to be due to slight phase separation.

  As described above, the rosin resin showed high solubility with respect to trimellitic acid ester, and the transparency did not deteriorate with time. That is, it was confirmed that these rosin resins have high compatibility with trimellitic acid esters. In addition, it can be seen from the above results that the serum or plasma separation composition using the rosin resin hardly separates the constituent components and hardly causes the oily substance to float.

(Examples 9 to 16: Preparation of serum or plasma separation composition)
Add rosin resin (1) to (6) or cyclopentadiene oligomer (1) to (2), organic gelling agent and gelation degree adjusting agent to trimellitic acid ester heated and stirred at 130 to 140 ° C. The solution was dissolved to such an extent that it could be visually confirmed, and the resulting solution was left to cool to room temperature of about 25 ° C. Fine powdered silica was stirred and dispersed in the solution cooled to room temperature with a planetary mixer to obtain a gel-like composition for serum or plasma separation.

  Table 2 below shows the types of blending components and the blending ratio of each component (unit: parts by weight) when the rosin resin or cyclopentadiene oligomer is 100 parts by weight.

(Evaluation)
Using the serum or plasma separation composition obtained in each Example, 20 blood test containers were prepared in the following manner.

  After storing about 1.5 g of the serum or plasma separating composition obtained in each example in the bottom of 20 7 mL polyethylene terephthalate test tubes, fine silica (average particle diameter) was placed on the inner wall of the test tube. A blood coagulation promoter consisting of an aqueous suspension containing 2% by weight of about 3 μm, crystalline), 2% by weight of carbinol-modified silicone oil and 2% by weight of polyvinylpyrrolidone is sprayed at a rate of about 20 mg / tube and dried. Thus, a blood test container was produced.

  Of the 20 blood test containers prepared as described above, 10 were stored at room temperature of about 25 ° C. for 2 weeks, and the remaining 10 were stored under heating at 60 ° C. for 2 weeks. Thereafter, 3 mL of each citrated blood stored in sheep is collected in all blood test containers, and 1300G each of blood test containers stored at room temperature and 5 blood test containers stored under heating at 60 ° C. Centrifugation under conditions of × 15 ° C. × 5 minutes, and the remaining 5 blood test containers stored at room temperature and 5 blood test containers stored at a temperature of 60 ° C. are each 1300 G × 20 ° C. × 5 minutes Centrifugation under conditions. In each blood test container after centrifugation, the state of separation of plasma and blood cells by the septum formed of the formed serum or plasma separation composition, the presence or absence of hemolysis, and the presence or absence of oily suspended matter were visually observed. The results are shown in Table 3 below.

  As is apparent from Table 3, hemolysis did not occur in any of the storage conditions when stored at room temperature and when stored at 60 ° C., and floating of oily substances was observed. I couldn't. In Examples 14 to 16, the partition walls were thin, and blood cells remained on the crystal side. This is considered to be due to the fact that the serum or plasma separation composition is difficult to move onto blood cells because the specific gravity of the serum or plasma separation composition is large.

  From the above, the serum or plasma separation composition of the present invention has a novel structure, but is excellent in separation performance as a serum or plasma separation composition, and oily components may be mixed into the separated serum or plasma. It can be seen that it does not occur and has excellent stability.

It is a longitudinal cross-sectional view of an example of the blood test container of the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Container body 2 ... Plug body 3 ... Composition for serum or plasma separation

Claims (4)

  A serum or plasma separating composition comprising a rosin resin and trimellitic acid ester or pyromellitic acid ester.   Trimellitic acid ester or pyromellitic acid ester is 50 to 100 parts by weight of rosin resin having a softening point in the range of 60 to 160 ° C. and a specific gravity at 25 ° C. of 1.0 to 1.1. A composition for separating serum or plasma, comprising 250 parts by weight.   The composition for serum or plasma separation according to claim 1 or 2, wherein the specific gravity of the composition is 1.02 to 1.055.   A blood test container containing the composition for separating serum or plasma according to any one of claims 1 to 3.

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