JPH06148174A - Blood separation agent and blood separation tube - Google Patents

Abstract

(57) [Summary] [Object] An object of the present invention is to provide a blood separating agent which is less likely to cause blood cell congestion and drug adsorption and has excellent storage stability, and a blood separating tube containing the separating agent in a bottomed tube. A blood separating agent containing a copolymer of ethylene and an α-olefin having 6 or more carbon atoms as an essential component, and a blood separating tube containing the separating agent in a bottomed tube. [Effects] The blood separating agent of the present invention has little blood cell accumulation, variation in test values over time, and little drug adsorption in blood. In addition, since it has excellent hydrophobicity, it does not change the shape of the separating agent over time even if the viscosity is not high, and the amount of drug adsorbed is small,
Further, since the viscosity does not change with time, it is possible to provide a blood separation tube having excellent physical properties and stability.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a blood separating agent.
More specifically, when separating the serum part and blood clot part in blood, or the plasma part and blood cell part by their specific gravity differences, a partition wall is formed between both components by giving an intermediate specific gravity of both components. The present invention relates to a blood separating agent which can be used for the purpose of facilitating the separation operation of these both components, and a blood separating tube containing the same in a bottomed tube.

[0002]

2. Description of the Related Art Conventionally, as a separating agent used for separating blood, a resin such as silicone oil, chlorinated polybutene, polyisobutene, acrylic polymer, α-olefin / maleic acid diester polymer is used as a main component. In some of these, inorganic fine particles such as silica and clay or an organic gelling agent were added for adjusting specific gravity and viscosity. The resin as the main component is basically hydrophobic, and the inorganic fine particles provide a thickening effect and thixotropic property, and the organic gelling agent increases the thixotropic property without imparting the thixotropic property. It gives a viscous effect.

However, in a system to which inorganic fine particles are added, if the specific gravity is to be an intermediate specific gravity between the serum portion and the blood clot portion, the addition amount of the inorganic fine particles becomes several percent or less with respect to the separation layer forming material. , Sufficient viscosity, thixotropy
Property cannot be imparted, the separating agent contained in the bottomed tube flows out during long-term storage, and accurate separation cannot be performed by changing the shape, and the separating layer forming material and inorganic fine particles are separated. There was a drawback. Furthermore, in the system in which the inorganic fine particles are added, it is basically impossible to increase the viscosity of the resin or oligomer used as the separation layer forming material, and therefore it is easy to adsorb drugs such as lidocaine and the blood cell components during centrifugation. Since the separation layer is easily formed while hugging the blood cells, there is a drawback that blood cells remain in the serum portion, that is, the phenomenon of so-called blood cell lump easily occurs.

On the other hand, Japanese Patent Application Laid-Open No. 62-197765 discloses a material for forming a separation layer to which an organic gelling agent is added. This is basically a homogeneous system and has been gelled due to the gel forming ability of the organic gelling agent,
It has excellent long-term storage stability and the components are difficult to separate. However, since the gel strength increases with time, as a result of long-term storage, the separating agent is less likely to migrate to the intermediate layer between the serum portion and the blood clot portion during centrifugation, which makes it impossible to perform an accurate separation operation. Was. Further, the system to which the organic gelling agent is added has a drawback that the viscosity is lowered when the separating agent is transferred to the intermediate layer by centrifugation, and blood cells are lumpy and drug adsorption is poor.

[0005]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention The inventors of the present invention have conducted extensive studies in order to achieve the object of providing a blood separating agent which is free from the above-mentioned drawbacks and is excellent in practical use. As a result, ethylene and carbon atoms of 6 are obtained. The inventors have found that a blood separating agent, which contains the above-mentioned copolymer with α-olefin as an essential component and preferably contains a tackifier, is excellent in the accumulation of blood cells and the adsorption of a drug, and has arrived at the present invention.

[0006]

[Means for Solving the Problems] That is, the present invention provides a blood separating agent and a separating agent containing a copolymer of ethylene and α-olerefin having 6 or more carbon atoms as an essential component, and more preferably containing a tackifier. There is provided a blood separation tube having a bottom tube. Hereinafter, the present invention will be described in detail.

A copolymer of ethylene and α-olerefin having 6 or more carbon atoms is a liquid at 25 ° C., and finally the specific gravity of the blood separating agent is in the intermediate region between the serum component and the blood cell component. If so, a low-viscosity copolymer to a high-viscosity copolymer can be used. Practically, a copolymer having a viscosity in the range of 200 to 600,000 cps at a temperature of 25 ° C. is suitable in terms of giving stable and appropriate fluidity and gelation property. When a copolymer of ethylene and an α-olefin having a carbon number of 5 or less is used as a blood separating agent, a dimer of ethylene or α-olefin, a trimer or a trimer of α-olefin is formed on the surface of a serum component forming an upper layer when separating blood. It is not preferable because low molecular weight compounds such as a monomer float. Since a copolymer of ethylene and an α-olefin having 6 or more carbon atoms does not have a polar group in the molecule, drug adsorption does not occur and stable measurement results can be obtained. Further, since it has hydrophobicity, the shape of the separating agent does not change with time, and the viscosity does not change with time, so that it has excellent physical properties and stability.

Tackifiers are generally thermoplastics,
It is a compound that is solid or semi-solid at room temperature and has a softening point of about 5 to 150 ° C and a molecular weight of about 200 to 1500. The tackifier, when incorporated into the copolymer of ethylene and α-olefin, acts viscoelastically and interfacially to improve the adhesiveness and wettability with the adherend.

Among the tackifiers, natural resin tackifiers include, for example, rosin, dammar, polymerized rosin, partially hydrogenated rosin, glycerin ester rosin, glycerin ester rosin partially hydrogenated product, glycerin ester rosin fully hydrogenated product, Polymerized glycerin ester rosin, pentaerythritol ester rosin, partially hydrogenated pentaerythritol ester rosin, polymerized pentaerythritol ester rosin, α-pinene, β-pinene polymer, polyterpene resin such as dipentene polymer, polyterpene resin Hydrogenated products, terpene phenols and the like.

Examples of synthetic resin tackifiers include olefin and diolefin polymers, cyclopentadiene resins, aromatic petroleum resins, hydrogenated products of aromatic resins, phenol resins, alkylphenol-acetylene resins, styrene resins. , Xylene-based resin, coumarone-indene resin, vinyltoluene-α-methylstyrene copolymer resin, and the like.

When the tackifier is added, it must be blended in consideration of compatibility, viscosity and the like of a copolymer of ethylene and an α-olefin having 6 or more carbon atoms, which is a material for forming a separation layer. In order to obtain the tackifying effect, it is usually desirable to add 0.1 to 70 parts by weight to 100 parts by weight of the copolymer of ethylene and α-olefin. If the addition amount of the tackifier is too large, the compatibility between ethylene and a copolymer of α-olefin having 6 or more carbon atoms becomes poor, leading to separation, or increase in viscosity and adverse effect on centrifugation. Exert.

The preferred physical properties of the blood separating agent of the present invention are:
The specific gravity at 25 ℃ is between serum and blood cells, ie 1.030〜
It is 1.060 and the viscosity is in the range of 200,000-5,000,000 cps.
The blood separating agent of the present invention includes inorganic powders such as clay, silica, mica, talc, clay, diatomaceous earth, bentonite and mica, organic additives such as plasticizers, various organic solvents and silicones, chlorinated polybutadiene, poly ( A polymer oil such as (meth) acrylic acid ester may be added as appropriate. As the method for producing the blood separating agent of the present invention, a copolymer of ethylene and an α-olefin having 6 or more carbon atoms is used at a temperature of 80 to 200.
When the mixture is heated to ℃ and a tackifier is added thereto, a predetermined amount is added, and the mixture is heated and stirred for several hours, or dispersed by a roll or a kneader.

[0013]

EXAMPLES Next, the present invention will be described more specifically by way of examples, but the present invention is not limited to the following examples unless it exceeds the gist thereof. Further, in the examples, "parts" represents parts by weight unless otherwise specified.

Example 1 Mixed α-C12 and C14
Copolymer of olefin and ethylene (molecular weight about 5000:
(Own product) 100 parts and 5 parts of silica powder were kneaded with a triple roll to obtain a blood separating agent having a viscosity of 400,000 cps and a specific gravity of 1.035.
1 g of the obtained separating agent was put in a 15 cc test tube, 10 cc of whole blood sample was further put, and left for 1 day and then centrifuged at 1200 G for 10 minutes. The separating agent was located in the intermediate layer between the blood cell portion and the serum portion, There was no hemification of the blood cells in the part or transfer of the components in the blood cells to the serum part. The amount of lidocaine adsorbed was 9.1% / 8 hrs.

Example 2 A copolymer of ethylene and α-olefin (Lucant HC-2000:
100 parts of Mitsui Petrochemical Co., Ltd. and 10 parts of aliphatic hydrocarbon resin (ESCOLETS 1305: manufactured by Exxon Chemical Co., Ltd.) were charged, and 1
The mixture was stirred and mixed at 00 ° C for 1 hour. This was kneaded together with 2 parts of silica powder by 3 rolls, and the viscosity was 400,000 cps and the specific gravity was 1.040.
The blood separating agent was obtained. 1 g of the obtained separating agent in a 15 cc test tube
Insert 10cc whole blood sample, leave for 1 day, then 1200G
After centrifugation for 10 minutes, the separating agent was located in the intermediate layer between the blood cell portion and the serum portion, and neither the blood cell lumps in the serum portion nor the components in the blood cells were transferred to the serum portion. Also,
The amount of lidocaine adsorbed was 9.3% / 8 hrs.

Example 3 In a four-necked flask, 100 parts of a mixed α-olefin having 12 and 14 carbon atoms and a copolymer of ethylene and ethylene (molecular weight about 4000: own product) and pentaerythritol ester of partially hydrogenated rosin (pentalin (H: manufactured by Rika Hercules Co., Ltd.) 10 parts were charged and mixed with stirring at 100 ° C. for 1 hour. This was kneaded together with 2 parts of silica powder by a triple roll to obtain a blood separating agent having a viscosity of 400,000 cps and a specific gravity of 1.040. Put 1 g of the obtained separating agent into a 15 cc test tube, and then add a whole blood sample.
When 10cc was put in and left for 1 day and then centrifuged at 1200G for 10 minutes, the separating agent was located in the intermediate layer between the blood cell portion and the serum portion,
Neither the blood cell mass in the serum part nor the transfer of components in the blood cell to the serum part was observed.

[Comparative Example 1] Mixed α-containing 12 and 14 carbon atoms
Copolymer of olefin and dimethyl maleate
100 parts and bentonite powder 2.2 parts, colloidal silica 0.5
The parts were kneaded with three rolls to obtain a blood separating agent having a viscosity of 600,000 cps and a specific gravity of 1.045. 1g of the obtained separating agent was put into a 15cc test tube, 10cc of whole blood sample was put, and left for 1 day.
After centrifugation for minutes, the separating agent was located in the intermediate layer between the blood cell portion and the serum portion, but blood cells remained in the upper portion of the separating layer, and the value of potassium ion in the serum increased with time. The amount of lidocaine adsorbed was 15.0% / 8 hrs.

[Comparative Example 2] Mixed α-containing 12 and 14 carbon atoms
Copolymer of olefin and dimethyl maleate
100 parts of gelol D (condensate of sorbitol and benzaldehyde, organic gelling agent: manufactured by Shin Nippon Rika Co., Ltd.) 0.5 parts were kneaded with 3 rolls, and the viscosity was 500,000 cps and the specific gravity was 1.050. A blood separating agent was obtained. The obtained blood separating agent increased in viscosity over time and completely stopped flowing after one year.

[0019]

The blood separating agent of the present invention does not use a copolymer of ethylene and an α-olefin having 6 or more carbon atoms,
Compared with a conventional blood separating agent containing an inorganic powder or an organic gelling agent, blood cells are less likely to be lumpy, and test values do not fluctuate over time. In addition, there is little drug adsorption in blood. This is probably because it has a viscosity and hydrophobicity that are not present in conventional blood separating agents, and the separating agent layer is formed by wrapping the inner wall of the blood collection tube in an appropriate time without hugging blood cells during centrifugation. Further, since it is excellent in hydrophobicity, it does not change the shape of the separating agent with time even if the viscosity is not high, the amount of drug adsorbed is small, and the viscosity does not change with time.
It is possible to provide a blood separation tube having excellent physical properties and stability.

Claims (4)

[Claims] 1. A blood separating agent which comprises a copolymer of ethylene and an α-olefin having 6 or more carbon atoms as an essential component. 2. The blood separating agent according to claim 1, further comprising a tackifier. 3. The blood separating agent according to claim 1, which has a specific gravity of 1.030 to 1.060 at 25 ° C. 4. A blood separation tube containing the blood separation agent according to claim 1 in a bottomed tube.