JPH1010122A - Composition for serum or plasma separation - Google Patents

Abstract

(57) [Summary] [PROBLEMS] To produce no odor due to radiation sterilization and to have no effect on serum or plasma biochemical test values due to hemolysis, etc.
Provided is a serum or plasma separation composition which does not cause phase separation of components and has good serum or plasma separation properties and storage stability equivalent to those of the prior art. In addition, in addition to the above, there is provided a serum or plasma separation composition which has a small flow during storage in a horizontal position and hardly causes deterioration of reversibility with time. A composition for separating serum or plasma comprising an oligomer of cyclopentadiene, an organic gelling agent, and a dispersing agent for the organic gelling agent. The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde. The dispersant of the organic gelling agent is a polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a composition for separating serum or plasma used for centrifugation utilizing the difference in specific gravity of blood components.

[0002]

2. Description of the Related Art Conventionally, there has been known a blood test container in which a thixotropic composition for separating serum or plasma, for example, a mixture of silicone and silica is previously contained in the bottom of a blood collection tube (Japanese Patent Application Laid-Open No. 51-1979). No. 83654). When blood is collected in the blood collection tube, left for a suitable time, and then centrifuged, the centrifugal force causes the gel-like serum or plasma separation composition to have fluidity. Further, since the gel-like composition for separating serum or plasma has a specific gravity of the serum or plasma component and an intermediate specific gravity of that of the clot or blood cell component, it gradually rises in the collected blood from the bottom of the tube to form a serum or plasma layer. And a blood clot or blood cell layer, so that a serum or plasma component and a blood clot or blood cell component can be separated. The serum or plasma component thus separated from the blood clot or blood cell component can be easily removed from the blood collection tube and subjected to various tests, and can be stored without being transferred to another container.

As the main components of such a thixotropic serum or plasma separating composition, in addition to the above-mentioned silicones, α-olefin-maleic acid diester copolymers (Japanese Patent Application Laid-Open Nos. 2-16815
No. 9), a polyester-based polymer (JP-A-61-2333).
No. 68), acrylic polymers (JP-A-53-42283).
No.), chlorinated polybutene (JP-A-57-9718),
Cyclopentadiene resin (JP-A-1-295163)
No.), hydroxyl group, ester group,
A modified product of cyclopentadiene resin having an ether group, an epoxy group, or the like introduced therein (Japanese Patent Application Laid-Open No. 2-95257) is known. Such a main component acts as a specific gravity adjusting agent like silica, and at the same time imparts thixotropic properties. Inorganic fillers that also act as gelling agents, substances having polar groups at both ends of molecules such as propylene glycol and ethylenediamine (JP-A-1-295163), condensates of sorbitol and aromatic aldehydes ( 2-1681
An organic gelling agent such as No. 59) is blended as necessary.

[0004] However, silicone is poorly compatible with inorganic fillers and hardly reacts at present due to a curing reaction caused by sterilization by radiation (γ-ray, electron beam, etc.), and α-olefin-maleic acid is not used at present. Diester copolymer, polyester polymer, acrylic polymer,
Those having a polar group, such as a modified product of cyclopentadiene resin, have relatively little effect on the measurement of clinical test items in blood, but have a drug concentration in blood (for example, phenobarbital, which is an antiepileptic drug, Carbamazepine, phenytoin, etc.).

[0005] On the other hand, in the case of using chlorinated polybutene, chlorine gas is generated at the time of incineration disposal after use, so that there is a problem that the incinerator is damaged or the environment is adversely affected.

Japanese Patent Application Laid-Open No. Hei 4-203965 discloses a composition for separating serum or plasma which does not have such disadvantages, and discloses an oligomer of cyclopentadiene and a condensate of sorbitol and an aromatic aldehyde as an organic gelling agent. Have been proposed. This composition for serum or plasma separation solves the above-mentioned problems of the prior art,
Dimethyl sulfoxide (hereinafter abbreviated as DMSO) or N, N-dimethylacetamide (hereinafter abbreviated as DMA) is used as a dispersant for the organic gelling agent. In a composition containing DMSO, radiation is used. (Γ-ray,
When sterilization is performed, dimethyl sulfide is generated by the decomposition of DMSO, causing a problem of foul smell. In the case of DMA, the DMA may cause hemolysis by contact with blood, There is a problem that a correct measurement value may not be given in measurement of a specific biochemical test item in blood.

[0007] The composition for separating serum or plasma is
There has been a problem that an oily component may be separated from the composition during storage (hereinafter, this phenomenon is referred to as phase separation).
This oil component is a low molecular weight component contained in the oligomer of cyclopentadiene in the above composition, and the low compatibility of this component with silica added as an organic gelling agent and / or a specific gravity adjusting agent is low. Cause of separation.
When this phase separation occurs, when the blood collection tube containing the above composition is turned over or turned over, the oily component adheres to the tube wall or plug, and blood collection is performed using this blood collection tube. When serum or plasma is separated from the clot or blood cells by centrifugation or the like, the oily components float in the serum or plasma layer,
As a result, when testing the components contained in serum or plasma,
The component clogs the sampling needle for serum or plasma of the test device and affects the test value. Furthermore, when phase separation occurs, there is a problem that the homogeneity of the composition is impaired and the partition wall stability is reduced.

An oligomer of cyclopentadiene,
When a serum or plasma separating composition comprising an organic gelling agent and a dispersant of an organic gelling agent is accommodated in the bottom of a blood collection tube, and the blood collection tube is stored sideways (hereinafter referred to as “side-up storage”). In some cases, the composition caused a flow (hereinafter, this is referred to as "flow"). When this flow occurs, the composition spreads on the side wall of the blood collection tube. When blood is collected in this blood collection tube and centrifuged, the composition floats from the bottom of the tube, and a partition formed in the middle between the serum layer or plasma layer and the clot layer or blood cell layer has a sufficient thickness. The partition walls are broken, and the partition walls are broken due to expansion of the blood clot. The cause of the flow is the lack of thixotropic property of the composition, which is solved by increasing the amount of the above-mentioned organic gelling agent. However, when the amount of the organic gelling agent is increased, thixotropic properties increase with time, and the reversibility during centrifugation is deteriorated. In the worst case, the reversibility may not be achieved.

[0009]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems. One of the objects of the present invention is to provide a biochemical examination of serum or plasma caused by hemolysis or the like, which does not generate an odor due to radiation sterilization. No effect on the value, no phase separation of the components, and good serum or plasma separation properties equivalent to the prior art,
An object of the present invention is to provide a serum or plasma separation composition having storage stability and the like.

Another object of the present invention is to provide a composition for separating serum or plasma, which, in addition to the above, has a small flow during storage in a horizontal position and hardly causes deterioration of reversibility with time. .

[0011]

SUMMARY OF THE INVENTION The present invention has been made to achieve the above object, and provides the following several compositions.

The organic gelling agent comprises an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant of the organic gelling agent. The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde. A composition for separating serum or plasma (hereinafter, referred to as a first composition), which is a polyoxyethylene polyoxypropylene block copolymer having an HLB value of 0 to 9.0.

The organic gelling agent comprises an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant of the organic gelling agent. The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde. A polyoxyethylene polyoxypropylene block copolymer having an HLB value of 0 to 9.0, and a tertiary amine compound having two methyl groups and an alkyl group having 10 or more carbon atoms.
The amount of the secondary amine compound is cyclopentadiene oligomer 1
A composition for separating serum or plasma (hereinafter, referred to as a second composition) in an amount of 0.03 to 0.5 part by weight based on 00 parts by weight.

An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, and a dispersant of the organic gelling agent, wherein the oligomer of cyclopentadiene has a softening point of 70 to 1
Has a melt viscosity at 40 ° C. and 180 ° C. of 30 to 500 centipoise, and the viscosity reducing agent is a phthalate;
The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and the dispersant of the organic gelling agent is 1.0 to 9.0 H
A serum or plasma separation composition (hereinafter, referred to as a third composition) selected from the group consisting of a polyoxyethylene polyoxypropylene block copolymer having an LB value, 1-methyl-2-pyrrolidone, and a mixture thereof; Thing).

An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, a dispersant of an organic gelling agent, and a specific gravity modifier, wherein the cyclopentadiene oligomer has a softening point of 70 to 140 ° C. and a melting point of 180 ° C. Viscosity 30 ~
500 centipoise, the viscosity reducing agent is a phthalic acid ester, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and the dispersing agent of the organic gelling agent is 1.0.
Is selected from the group consisting of polyoxyethylene polyoxypropylene block copolymers having an HLB value of ~ 9.0, 1-methyl-2-pyrrolidone and mixtures thereof, wherein the specific gravity modifier is paraffin chloride. The ratio of the viscosity reducing agent is 30 to 130 parts by weight and the ratio of the specific gravity adjusting agent is 1 to 100 parts by weight of the cyclopentadiene oligomer.
A composition for separating serum or plasma (hereinafter, referred to as a fourth composition) in a range of １００100 parts by weight.

An oligomer of cyclopentadiene, a compatibilizer, a viscosity reducing agent, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the cyclopentadiene oligomer has a softening point of 70 to 140 ° C. and a melting point of 180 ° C. Viscosity 30-5
The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, the compatibilizing agent is a low molecular weight styrene-based thermoplastic resin, the viscosity reducing agent is a phthalic acid ester, and the organic gelling agent is an organic gelling agent. 1.0 to 1.0
A polyoxyethylene polyoxypropylene block copolymer having an HLB value of 9.0, 1-methyl-2-pyrrolidone and a mixture thereof, wherein the amount of the compatibilizer is cyclopentadiene oligomer A composition for separating serum or plasma (hereinafter referred to as a fifth composition) in an amount of 0.1 to 15 parts by weight based on 100 parts by weight.

The cyclopentadiene oligomer comprises a cyclopentadiene oligomer, a viscosity reducing agent, an organic gelling agent, and a dispersant for the organic gelling agent.
Has a melt viscosity at 40 ° C. and 180 ° C. of 30 to 500 centipoise, and the viscosity reducing agent is a phthalate;
The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and the dispersing agent of the organic gelling agent is selected from the group consisting of N, N-dimethylacetamide, N, N-dimethylformamide and a mixture thereof. The amount of the dispersant of the organic gelling agent is cyclopentadiene oligomer 10
A composition for separating serum or plasma (hereinafter, referred to as a sixth composition) in an amount of 0.01 to 0.4 part by weight relative to 0 part by weight.

A polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0, comprising a main component and an organic gelling agent, wherein the organic gelling agent is a mixture of sorbitol and an aromatic aldehyde. A composition for separating serum or plasma, which is a condensate (hereinafter, referred to as a seventh composition).

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION The above-mentioned first to seventh compositions will be individually described in detail.

First Composition First, the first composition comprising an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant for the organic gelling agent will be described.

Oligomers of Cyclopentadiene The oligomers of cyclopentadiene used in the first composition include oligomers in which cyclopentadiene is multimerized and oligomers in which dicyclopentadiene is obtained by dimerizing cyclopentadiene. Is included. The oligomer can be produced by multiplying cyclopentadiene or dicyclopentadiene using, for example, a Diels-Alder reaction or the like. This is sometimes called dicyclopentadiene resin (DCPD resin). When the oligomer is used as a component of the first composition, it is preferable that the oligomer be hydrogenated to saturate the remaining double bond. The oligomer may contain a trace amount of a polar residue derived from a polymerization initiator, but since it has almost no polar group in the molecule, does not cause adsorption of biological components or drugs in blood.

Further, the above-mentioned oligomer is relatively easy to obtain, having a specific gravity of 1.0 or more, unlike ordinary olefin or α-olefin-based polymers. This is because the polymer molecules are densely packed, and there is almost no evaporation loss at 100 ° C. Therefore, when this cyclopentadiene oligomer is used in a composition for separating serum or plasma, there are no problems such as delay of blood coagulation due to volatile components, adhesion of blood clots to blood collection tubes, and no bad odor.

The specific gravity of the oligomer at 25 ° C. is as follows:
It is preferably 1.00 to 1.10, and more preferably 1.02 to 1.08, which is an intermediate value between serum or plasma and a clot or blood cell. If the specific gravity is out of this range, it becomes difficult to adjust the specific gravity of the composition to a suitable range. The oligomer having a specific gravity in the above range can be easily obtained by selecting polymerization conditions and the like.

Organic gelling agent The organic gelling agent used in the first composition is a condensate of sorbitol and an aromatic aldehyde. Examples of the organic gelling agent include dibenzylidene sorbitol, tribenzylidene sorbitol, methyl-substituted dibenzylidene sorbitol, and the like. Among these, dibenzylidene sorbitol is particularly preferred from the viewpoint of imparting thixotropy to the composition when blended with an oligomer of cyclopentadiene.

Since the gelling agent does not have water absorption or water solubility, the composition does not become turbid due to water absorption even if it is in contact with a blood sample for a long period of time. It is not absorbed by the agent and concentrated. in addition,
Since the above-mentioned gelling agent has both a hydrophobic group (benzyl group) and a hydrophilic group (hydroxyl group), it is compatible with both hydrophobic compounds and hydrophilic compounds. Hardly cause phase separation.

In order to exhibit good thixotropic properties in the composition, it is preferable to disperse the organic gelling agent in a hydrophobic medium having no polar group or having a small polar group content. The above-mentioned oligomer of cyclopentadiene is preferably used as the neutral medium.

If the amount of the organic gelling agent is too small, the composition will have insufficient thixotropy and the composition will easily flow during storage, and the partition walls will be easily broken when the composition is used, and if it is too large, Since the thixotropic property of the composition becomes excessive and the partition walls are hardly formed even by centrifugation, 100 parts by weight of cyclopentadiene oligomer is used.
0.02 to 3 parts by weight is preferable, and 0.02 to 1 part by weight is more preferable.

The dispersant for the organic gelling agent used in the first composition is a polyoxyethylene polyoxypropylene block copolymer having a predetermined HLP value.

When the HLB value of the above block copolymer is too small, the organic gelling agent cannot be sufficiently dispersed in the above block copolymer, the thixotropy of the composition becomes insufficient, and the partition wall stability decreases. When the composition is too large, the composition lacks hydrophobicity and dissolves in the blood when the composition is used, lyses the blood, and the components in the red blood cells are mixed with the serum or plasma. 9.0, preferably in the range of 4.0 to 6.0.

The HLB value has been conventionally used as an index indicating the degree of hydrophilicity and hydrophobicity of a general nonionic surfactant having a structure of hydrophilic part-hydrophobic part. , Griffin's formula, but like the block copolymer used in the composition,
This formula cannot be applied to those having a structure of hydrophilic part-hydrophobic part-hydrophilic part, so the HLB value in the present invention refers to the one defined by the following empirical formula. Things.

HLB value = 0.098 × (cloud point of block copolymer measured by the following measurement method) +4.02 The method of measuring the cloud point was as follows: 0.5 g of the block copolymer.
Was dissolved in 5 ml of a 98% aqueous solution of ethyl alcohol, and 25
The solution is titrated with a 2% aqueous phenol solution while stirring at a temperature of 0 ° C., and the turbidity of the solution is used as the endpoint. The number of ml of the 2% aqueous phenol solution required for the titration is defined as the cloud point.

The above block copolymer is marketed in various grades by many manufacturers, but the above HLB
There is no particular limitation as long as the value is 1.0 to 9.0, and any of them can be used.

When the amount of the dispersant of the organic gelling agent is too small, the dispersibility of the organic gelling agent is reduced and the thixotropy of the composition becomes insufficient. When the amount is too large, the viscosity of the composition is reduced, Further, the compatibility with the oligomer of cyclopentadiene is reduced, and the thixotropic property of the composition is reduced. Therefore, 0.1 to 15 parts by weight, preferably 0.1 to 5 parts by weight, per 100 parts by weight of the cyclopentadiene oligomer is used. Parts by weight are more preferred.

Specific Gravity Adjusting Agent If necessary, a specific gravity adjusting agent may be added to the first composition to adjust the specific gravity of the serum or plasma separating composition to a desired specific gravity. Examples of such a specific gravity adjuster include inorganic powders such as silica, bentonite and titanium oxide, and fine polymer powders such as polystyrene and polyurethane. The average particle size of the specific gravity adjusting agent is preferably 500 μm or less from the viewpoint of easy mixing and dispersion in the composition.

If the amount of the specific gravity adjusting agent is too large, the difference in specific gravity between the cyclopentadiene oligomer and the specific gravity adjusting agent is large, so that separation of both is likely to occur. Weight parts or less,
More preferably, it is in the range of 10 parts by weight or less.

A viscosity reducing agent may be further added to the first composition, if necessary, to adjust the viscosity. The viscosity reducing agent is not particularly limited as long as it does not affect blood components or blood coagulation. For example, phthalic acid esters or benzoic acid esters are suitable.

If the amount of the viscosity reducing agent is too large, the specific gravity difference between the oligomer and the cyclopentadiene oligomer is large, so that separation of the oligomer and the cyclopentadiene easily occurs. Department,
More preferably, it is in the range of 10 parts by weight or less.

Preferred Specific Gravity of Composition The specific gravity of the first composition is preferably an intermediate gravity between serum or plasma and a clot or blood cell.
Is preferably in the range of 1.03 to 1.08, and more preferably in the range of 1.04 to 1.06.

Suitable viscosity of the composition The viscosity of the first composition may be determined by the usual centrifugation operation, such that the composition is located in the middle of the serum or plasma layer and the clot or blood cell layer, From the viewpoint of easiness of the work of storing blood collection tubes and the like in a blood test container, it is preferably 5 to 25 ° C.
It is 1 million centipoise, more preferably 60,000 to 500,000 centipoise.

Method of Use In order to use the first composition, the composition is generally stored in advance in a bottomed tubular container used as a vacuum type or non-vacuum type blood collection tube. Then, by injecting the collected blood into a bottomed tubular container containing the composition by a predetermined method and performing a centrifugal separation operation, the blood components may be separated from serum or plasma and blood clots or blood solids by a difference in specific gravity. (Such as blood cells), and the composition is interposed between a serum or plasma portion located at an upper portion and a clot portion or a solid content in blood located at a lower portion as a partition wall separating the both, and a separating agent Play a role.

Second Composition Next, a second composition comprising an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant for the organic gelling agent will be described.

The dispersant for the organic gelling agent used in the second composition is as follows.
It comprises a polyoxyethylene polyoxypropylene block copolymer having an HLB value of 0 to 9.0, and a tertiary amine having two methyl groups and an alkyl group having 10 or more carbon atoms.

The above block copolymer and the amount thereof may be the same as those described in the description of the first composition.

The tertiary amine is a tertiary amine having two methyl groups and an alkyl group having 10 or more carbon atoms. When the number of methyl groups is one, a flow occurs in the obtained composition, so that the effect of the addition is not sufficient. If the carbon number of the alkyl group is 9 or less, the compatibility between the tertiary amine and the oligomer of cyclopentadiene decreases, and the effect of the addition is not sufficient. Examples of such tertiary amines include dodecyldimethylamine, tetradecyldimethylamine, hexadecyldimethylamine, and the like.

If the amount of the tertiary amine is too small, the composition tends to flow, and if the amount is too large, the thixotropy of the composition is too large and the reversibility is poor.
0.03 to 0.5 part by weight, preferably 0.03 part by weight, per 100 parts by weight of the oligomer of cyclopentadiene.
5 to 0.3 parts by weight.

An oligomer of cyclopentadiene, which is another essential component of the second composition, and an organic gelling agent; a specific gravity adjusting agent and a viscosity reducing agent, which are optional additional components of the second composition; The preferred specific gravity, preferred viscosity and method of use may be the same as those described in the description of the first composition.

Third Composition A third composition comprising an oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, and an organic gelling agent will be described.

The cyclopentadiene oligomer used in the third composition is an oligomer of the first composition, and has a softening point of 70 to 140 ° C. and a melt viscosity at 180 ° C. of 30. ~
It is 500 centipoise.

If the softening point of the oligomer is too low, the composition tends to undergo phase separation, and if the softening point is too high, it becomes difficult to melt and the production of the composition becomes difficult.
0 ° C., preferably 80 to 110 ° C. In addition,
This softening point means a softening point measured according to JIS K6863-1994 "Testing method for softening point of hot melt adhesive".

If the melt viscosity of the oligomer at 180 ° C. is too low, the viscosity of the composition becomes insufficient, and if it is too high, the viscosity of the composition at low temperatures becomes high, making it difficult to use the composition. ５００500 centipoise, preferably 100 to 500 centipoise. The melt viscosity is measured using the A method in JIS K 6862-1984 “Melt Viscosity Test Method for Hot Melt Adhesives” and a Brookfield B-type viscometer using an A-1 type rotor. Melt viscosity.

As the cyclopentadiene oligomer used in the third composition, those having the following physical properties are particularly preferred.

Specific Gravity The specific gravity at 25 ° C. (based on a floating sedimentation test using a copper sulfate solution) is 1.02 to 1.10, preferably 1.03 to 1.10
1.09. If the specific gravity deviates from the above range, it may be difficult to adjust the specific gravity of the composition appropriately.

Molecular weight The molecular weight distribution by the GPC method is 200 to 5 in number average molecular weight.
00, preferably 300 to 450, and a weight average molecular weight of 600 to 900, preferably 700 to 850. If the molecular weight is less than the lower limit of the above range, the low molecular weight fraction is substantially contained, phase separation is likely to occur, and if it exceeds the upper limit, the viscosity of the resin increases, and it is difficult to obtain the effect of the viscosity reducing agent. There is.

Glass transition point: those having a glass transition point of 50 to 90 ° C., preferably 60 to 80 ° C. according to the DSC method. If the glass transition point is less than the lower limit of the above range, the low molecular weight fraction is substantially contained, and phase separation is likely to occur.If the glass transition point exceeds the upper limit of the above range, the viscosity of the resin increases, and the effect of the viscosity reducing agent is increased. May be difficult to obtain.

A temperature at which the weight loss starts by the TG method is 100 to 400 ° C., preferably 120 to 350 ° C. When the weight loss start temperature is less than the lower limit of the above range, a low molecular weight fraction is substantially contained, and phase separation is easily caused.When the temperature exceeds the upper limit of the above range, the viscosity of the resin increases, and The effect may be difficult to obtain.

Viscosity reducing agent The viscosity reducing agent used in the third composition is a phthalic acid ester because of its excellent compatibility with the cyclopentadiene oligomer. The phthalic acid ester is preferably a diester of phthalic acid. As the diester,
It is preferable that at least one of alcohol residues forming two ester groups has 6 or more carbon atoms. Both diesters having 5 or less carbon atoms tend to have reduced compatibility with cyclopentadiene oligomers. Also, 2
If the carbon number of each of the alcohol residues forming one ester group is too large, it is difficult to adjust the specific gravity of the composition to a suitable range.

Examples of the viscosity reducing agent used in the third composition include butyl pentyl phthalate, dipentyl phthalate, butyl hexyl phthalate, butyl heptyl phthalate, dihexyl phthalate, pentyl heptyl phthalate, butyl nonyl phthalate, and butyl nonyl phthalate. Pentyl octyl, hexyl heptyl phthalate, diheptyl phthalate, heptyl octyl phthalate, dioctyl phthalate, di-2-ethylhexyl phthalate, octyl nonyl phthalate, diisononyl phthalate, octyl decyl phthalate, diisodecyl phthalate, decyl undecyl phthalate , Diundecyl phthalate and butylbenzyl phthalate.

Particularly preferred viscosity reducing agents are phthalic acid diesters having 9 to 11 carbon atoms in each of the alcohol residues forming two ester groups. From the viewpoint of adjusting the specific gravity of the composition, di-2-ethylhexyl phthalate and dioctyl phthalate are most preferred.

If the amount of the viscosity reducing agent used in the third composition is too small, the viscosity of the composition becomes high and it becomes difficult to use the composition. If it is too large, the viscosity of the composition decreases and the viscosity of the composition decreases. It is difficult to use the product, or it becomes difficult to adjust the specific gravity of the composition. Therefore, the amount is preferably 30 to 130 parts by weight, more preferably 50 to 100 parts by weight, based on 100 parts by weight of the cyclopentadiene oligomer. It is.

Dispersant for Organic Gelling Agent The dispersing agent for the organic gelling agent used in the third composition is as follows.
Polyoxyethylene polyoxypropylene block copolymer having an HLB value of 0 to 9.0, 1-methyl-2-
Pyrrolidone and a mixture thereof.

The polyoxyethylene polyoxypropylene block copolymer and the amount thereof may be the same as those described in the description of the first composition.

1-methyl-2-pyrrolidone is preferred because it dissolves the organic gelling agent satisfactorily, does not cause a hemolysis reaction by reacting with blood, and does not decompose upon irradiation with radiation to generate an odor. It is preferably used.

The amount of 1-methyl-2-pyrrolidone is
If the amount is too small, the dispersibility of the organic gelling agent decreases, and the thixotropic property of the composition becomes insufficient. If the amount is too large, a hemolytic reaction is caused.
With respect to 00 parts by weight, 0.05 to 5 parts by weight is preferable,
0.05 to 3 parts by weight is more preferable.

An organic gelling agent, which is another essential component of the third composition, a specific gravity adjusting agent and a viscosity reducing agent, which are optional additional components of the third composition, and their amounts, Suitable viscosities and methods of use may be the same as described for the first composition.

Fourth Composition A fourth composition comprising an oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, a dispersant for the organic gelling agent, and a specific gravity adjusting agent will be described.

Specific gravity adjusting agent The specific gravity adjusting agent used in the fourth composition is chlorinated paraffin. Since it is chemically inert, insoluble in water, odorless and harmless, it is suitable as a component of a serum or plasma separation composition.

Chlorinated paraffins have a chlorination degree of 40% and 45%.
%, 50%, 65% and 70%, all of which can be used. The specific gravity of paraffin chloride at 25 ° C. is 1.
15 to 1.70, which is suitable as a specific gravity adjuster.

If the amount of the specific gravity adjusting agent is too large, the difference in specific gravity between the oligomer of cyclopentadiene and the specific gravity adjusting agent is large, so that separation of the two easily occurs. If the amount is too small, the effect of adjusting the specific gravity is not sufficiently exhibited. The amount is 1 to 100 parts by weight, preferably 5 to 60 parts by weight based on 100 parts by weight of the oligomer.

The oligomer of cyclopentadiene which is another essential component of the fourth composition, a viscosity reducing agent, an organic gelling agent, a dispersing agent for the organic gelling agent, and the amounts thereof, furthermore, a preferable specific gravity, a preferable viscosity and The method of use may be the same as that described in the description of the third composition.

Fifth Composition A fifth composition comprising an oligomer of cyclopentadiene, a compatibilizer, a viscosity reducing agent, an organic gelling agent, and a dispersant for the organic gelling agent will be described.

Compatibilizer The compatibilizer used in the fifth composition is a low molecular weight styrene-based thermoplastic resin, for example, low molecular weight polystyrene. Softening point is 1 according to JIS K 6863-1994
30 to 180 ° C., specific gravity at 25 ° C. by the floatation and sedimentation method is 1.03 to 1.07, number average molecular weight by GCP method is 34,000 to 46,000, and weight average molecular weight by GCP method is A low molecular weight styrene thermoplastic resin having a molecular weight of 69000 to 91,000 is preferred. If the amount of the compatibilizing agent is too small, the compatibilizing effect is insufficient and phase separation occurs.If the amount is too large, the viscosity of the composition becomes large and the composition is not inverted. It is in the range of 15 parts by weight, preferably 0.5 to 10 parts by weight.

The cyclopentadiene oligomer, a viscosity reducing agent, an organic gelling agent, an organic gelling agent dispersant, which are other essential components of the fifth composition, and a specific gravity, which is an optional additional component of the fifth composition, The modifiers and their amounts, as well as the preferred specific gravity, preferred viscosity and method of use, may be the same as those described in the description of the fourth composition.

Sixth Composition A sixth composition comprising an oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, and a dispersant for the organic gelling agent will be described.

The dispersant of the organic gelling agent used in the sixth composition is N,
It is selected from the group consisting of N-dimethylacetamide (hereinafter abbreviated as DMA), N, N-dimethylformamide (DMF) and a mixture thereof.

If the amount of the dispersant of the organic gelling agent in the sixth composition is too small, the dispersing effect of the organic gelling agent is not sufficiently exhibited, and the thixotropy of the organic gelling agent is not exhibited and the partition walls are not stable. If the amount is too large, the blood in contact with the composition at the time of blood collection will lyse and adversely affect the test value.
0.01 to 0.4 parts by weight, preferably 0.05 to 0.1 part by weight.
4 parts by weight.

An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, which are other essential components of the sixth composition, and a specific gravity adjusting agent, which is an optional additional component of the sixth composition; Furthermore, the preferred specific gravity, the preferred viscosity and the method of use may be the same as those described in the description of the fourth composition.

Seventh Composition Finally, a seventh composition comprising a main ingredient and an organic gelling agent will be described.

In the seventh composition, the polyoxyethylene polyoxypropylene block copolymer having a predetermined HLP value used as the main component is the same as that used as the dispersant for the organic gelling agent in the first composition. It may be.

The organic gelling agent may be the same as that described in the description of the first composition.

If the amount of the above-mentioned organic gelling agent is too small, the composition becomes insufficient in thixotropy and the composition easily flows during storage, and the partition walls are easily broken during use of the composition, and the amount is too large. And the thixotropic property of the composition becomes excessive, and partition walls are hardly formed even by centrifugation, so the amount is preferably 5 to 100 parts by weight, based on 100 parts by weight of the polyoxyethylene polyoxypropylene block copolymer, 20 to 70 parts by weight are more preferred.

In the seventh composition, if necessary, a specific gravity adjusting agent and / or a viscosity reducing agent may be added.

When the amounts of the specific gravity adjusting agent and the viscosity reducing agent are too large, the specific gravity difference between the dispersant and the specific gravity adjusting agent is large.
Since separation of both is likely to occur, preferably 40 parts by weight or less, based on 100 parts by weight of the block copolymer,
It is more preferably at most 20 parts by weight.

The preferred specific gravity, preferred viscosity and method of use of the seventh composition may be the same as those described in the description of the first composition.

(Function) Since the composition of the present invention is constituted as described above, the following functions are produced. The effect of the first to sixth compositions A conventional serum or plasma separation composition comprising an oligomer of cyclopentadiene and a condensate of sorbitol and an aromatic aldehyde as an organic gelling agent is characterized in that the organic gelling agent is DMSO or DMA. Once dissolved in an organic solvent as described above, and then blended into a homogeneous mixture of an oligomer of cyclopentadiene and an inorganic fine powder (such as finely divided silica by a gas phase method).

However, the above-mentioned organic solvent remains in the composition and decomposes when irradiated with radiation to cause a bad smell or acts on blood to cause hemolysis. The chemical test values could be abnormal.

In the first to sixth compositions according to the present invention, since a specific polyoxyethylene polyoxypropylene block copolymer is used as a dispersant for the organic gelling agent, DMS
No organic solvents such as O or DMA are required, and thus do not produce malodorous substances upon irradiation. Further, unlike the above organic solvent, the dispersant itself can participate in hydrogen bonding together with the organic gelling agent and the fine silica powder, and can obtain better thixotropic properties than before. In addition, since the dispersant is a hydrophobic polymer compound, there is an advantage that a part of the dispersant is dissolved in blood, serum, and plasma to prevent hemolysis or the like.

The effect of the second composition The composition of the present invention is excellent in storage stability, but when stored for a long period of time, the dispersion of the organic gelling agent in cyclopentadiene in the oligomer gradually progresses. Thixotropic property is likely to increase over time.

In the second composition, a polyoxyethylene polyoxypropylene block copolymer and a third
The secondary action of the tertiary amine allows the organic gelling agent to be uniformly dispersed in the cyclopentadiene oligomer in a short time, thereby preventing the occurrence of poor reversibility due to the increase in thixotropy with time and the flow. Is prevented.

In the conventional serum or plasma separation composition containing an oligomer of cyclopentadiene and an organic gelling agent, the oil component that has been phase-separated mainly contains the oil component in the composition. It is a low molecular weight component contained in the oligomer of cyclopentadiene, and a viscosity reducing agent, an organic gelling agent and the like are partially mixed therein.

In the third to sixth compositions, as the oligomer of cyclopentadiene, one having a very low content of low molecular weight components is used, so that phase separation of the components hardly occurs.
The oligomer of cyclopentadiene is solid at room temperature, but becomes fluid at room temperature by adding a viscosity reducing agent thereto. The third to sixth compositions obtained by adding the above-mentioned specific organic gelling agent, the above-mentioned specific dispersant, and if necessary, a specific gravity adjuster to the oligomer of cyclopentadiene containing the viscosity reducing agent,
The thixotropy and the specific gravity are in a suitable range for a composition for separating serum or plasma, and substantially no phase separation occurs.

Function of Fifth Composition When a cyclopentadiene oligomer having a specific softening point and a specific melt viscosity is used, substantial phase separation does not occur, but a very small amount of a viscosity reducing agent is separated. It may be possible. In particular, phase separation can occur if a longer shelf life is guaranteed than with conventional blood collection tubes.

In the fifth composition, by adding a compatibilizing agent, the compatibility between the oligomer and the viscosity reducing agent is increased, and the phase separation can be almost completely eliminated.

Effect of Sixth Composition In the conventional composition, hemolysis occurred when an effective amount of DMA and / or DMF was added as a dispersant for the organic gelling agent.

In the sixth composition, an oligomer of cyclopentadiene having a specific softening point and a specific melt viscosity and a viscosity reducing agent are used, and DMA and / or DMF are used as an organic gelling agent and a dispersing agent for the organic gelling agent. By adding less DMA and / or DM than in conventional compositions.
The same dispersion effect can be obtained with F. As a result, hemolysis is not caused by a decrease in the concentration of the dispersant.

In the above-mentioned conventional technique, the thixotropic property is expressed as follows:
It is formed by a network structure formed by hydrogen bonding between the organic gelling agent and silica, and the oligomer of cyclopentadiene, which is the main agent, is not involved in this.

On the other hand, in the seventh composition, the thixotropic property is expressed by the network structure formed by a single hydrogen bond of the organic gelling agent, so that the network structure changes over time as in the conventional composition. And phase separation is less likely to occur.

In the above prior art, the silica added to the composition tends to re-aggregate once dispersed in the oligomer of cyclopentadiene, and in this process, the silica and the organic gelling agent have a network structure. Low molecular weight components are extruded and phase separation tends to be promoted.

In the seventh composition, an organic gelling agent is mainly involved in imparting thixotropy. Therefore, when a small amount of silica is used as a specific gravity adjusting agent, even if re-aggregation of silica occurs, phase separation occurs. Is not encouraged.

The polyoxyethylene polyoxypropylene block copolymer is a nonionic surfactant, and uniformly disperses the organic gelling agent, and exhibits good thixotropy. In addition, its HLB value is 1.0-
Since it is 9.0 and is extremely hydrophobic compared to common nonionic surfactants, it is hardly compatible with blood,
Therefore, it does not adversely affect the biochemical test values of blood.

Further, the polyoxyethylene polyoxypropylene block copolymer has a lower temperature dependency of viscosity than the conventional cyclopentadiene oligomer. Therefore, the temperature dependency of the seventh composition is sufficiently smaller than that of the conventional art, and the conventional problem of poor separation of serum or plasma during low-temperature centrifugation hardly occurs.

[0101]

EXAMPLES Next, in order to specifically explain the present invention, some examples of the present invention and some comparative examples for comparison with the examples were given, and the performance of the obtained composition was evaluated.

In each example, is an oligomer of cyclopentadiene, is a viscosity reducing agent, is an organic gelling agent,
Denotes a dispersant of the organic gelling agent (the main agent in Example 19 and Comparative Examples 19 to 20 corresponding to the seventh composition), denotes a specific gravity adjuster, and denotes a compatibilizer.

The specific gravity was measured by a floating / sedimentation method using a copper sulfate specific gravity liquid in a constant temperature room at about 25 ° C., and the viscosity was measured using a Brookfield E-type viscometer at a rotation speed of 1.0 rpm and a measurement temperature of 25 ° C. I went in.

Examples 1 and 2 and Comparative Examples 1 to 5 correspond to the first composition, Example 3 and Comparative Examples 6 to 8 correspond to the second composition, and Examples 4 to 8 and Comparative Examples Example 9 corresponds to the third composition, and Examples 9 to 13 and Comparative Examples 10 to 14 correspond to the fourth composition.
Examples 14 and 15 and Comparative Examples 15 and 1 correspond to the compositions.
6 corresponds to the fifth composition, Examples 16 to 18 and Comparative Examples 17 and 18 correspond to the sixth composition, and Example 19 and Comparative Examples 19 and 20 correspond to the seventh composition.

The materials used as the components of the composition are as follows.

Oligomers of Cyclopentadiene / Oligomers of Dicyclopentadiene A: Hydrogenated product of cyclopentadiene resin, ECR-
327S, specific gravity 1.04. Oligomers of dicyclopentadiene B: LL101, manufactured by Zeon Corporation, specific gravity 1.04. Oligomers of cyclopentadiene C: KR242, manufactured by Tonex, softening point 106 ° C, melt viscosity 320 ° C at 180 ° C. , Specific gravity 1.07, number average molecular weight about 4
00, weight average molecular weight about 800, glass transition point about 75
° C, weight loss start temperature about 200 ° C ・ Cyclopentadiene oligomer D: KR240, manufactured by Tonex Corporation, softening point 85 ° C, melt viscosity at 180 ° C 7
2 centipoise, specific gravity 1.073, number average molecular weight about 35
0, weight average molecular weight of about 750, glass transition point of about 65 ° C.,
Weight loss start temperature about 130 ° C.

Viscosity-reducing agent and viscosity-reducing agent A: phthalic acid diester in which the alcohol residue is an alkyl group having 9 to 11 carbon atoms, manufactured by Mitsubishi Gas Chemical Company, PL-200. Di-2-ethylhexyl phthalate: Sekisui Chemical Industrial company, DOP.

Organic gelling agent / dibenzylidene sorbitol: Gelol D manufactured by Shin Nippon Rika Co., Ltd.

Organic gelling agent dispersant / organic gelling agent dispersant A: polyoxyethylene polyoxypropylene block copolymer (Adeka Pluronic L-121, HLB value 5.1, manufactured by Asahi Denka Kogyo Co., Ltd.) Dispersant B of organic gelling agent: polyoxyethylene polyoxypropylene block copolymer (Adeka Pluronic L-44, HLB value: 9.5, manufactured by Asahi Denka Co., Ltd.) 1-methyl-2-pyrrolidone: Wako Pure Chemical Industries -DMSO: Wako Pure Chemical Co., Ltd.-DMA: Wako Pure Chemical Co., Ltd.-DMF: Wako Pure Chemical Co., Ltd.-Hexadecyldimethylamine: Nissan Yushi, Nissan tertiary amine PB.

Specific gravity adjuster・ Fine powder silica A: Fine powder silica by gas phase method, DM-30S manufactured by Tokuyama Co., Ltd. ・ Fine powder silica B: Fine powder silica by gas phase method, Aerosil R-812 manufactured by Nippon Aerosil Co., Ltd. -Titanium oxide: manufactured by Yasuhara Sangyo Co., Ltd., Taipaque A-100-Chlorinated paraffin A: manufactured by Wako Pure Chemical Industries, chlorination degree 40%-Chlorinated paraffin B: manufactured by Wako Pure Chemical Industries, 70% chlorination degree.

[0111] compatibilizers, low molecular weight styrene thermoplastic resin: made by Dainippon Ink and Chemicals, Inc, Dick gill styrene # 200.

In each performance test, n means the number of repetitions.

Example 1 Dicyclopentadiene oligomer A 100 parts by weight Viscosity reducer A 5.40 parts by weight Dibenzylidene sorbitol 0.13 parts by weight Dispersant A of organic gelling agent A 0.52 parts by weight Fine powder silica B 2 .30 parts by weight These were kneaded under reduced pressure for 1 hour to prepare a composition. This composition has a specific gravity of 1.05 and a viscosity at 25 ° C. of about 1
It was 40,000 centipoise.

Example 2 The composition obtained in the same manner as in Example 1 was subjected to the test described below.

Comparative Example 1 Instead of dispersant A of an organic gelling agent, DM was used as a component.
A composition was prepared in the same manner as in Example 1, except that 0.52 parts by weight of SO was used.

Comparative Example 2 The composition obtained in the same manner as in Comparative Example 1 was subjected to the test described below.

Comparative Example 3 As a component, DM was used instead of the dispersant A of the organic gelling agent.
A composition was prepared in the same manner as in Example 1, except that 0.52 parts by weight of A was used.

Comparative Example 4 The composition obtained in the same manner as in Comparative Example 3 was subjected to the test described below.

Comparative Example 5 As a component, an organic gelling agent was used in place of dispersant A.
Except for using 0.52 parts by weight of dispersant B of the gelling agent.
Thus, a composition was prepared in the same manner as in Example 1. Performance evaluation Serum or blood obtained in Example 1 and Comparative Examples 1, 3 and 5
The following items were tested for the composition for serum separation.
evaluated.

First, about 1.2 g of the composition was stored in the bottom of a commercially available 10 ml polyethylene terephthalate blood collection tube, and the mouth was sealed with a stopper made of butyl rubber while maintaining the inside of the blood collection tube at a vacuum of 700 mmHg. Sealed. The blood test container thus prepared was subjected to the following tests.

1) Radiation Irradiation Test (n = 50) Irradiation with cobalt 60 gamma rays having a dose of 25 ± 7 kGray was performed. After irradiation, the bottle was opened, the odor was smelled, and the presence or absence of an odor was sensory evaluated.

2) Inversion test and partition wall stability test (n =
10) 4 ml of rabbit fresh blood was dispensed into a blood test container, and after confirming completion of coagulation of blood, centrifugation was performed at 15 ° C. at 1300 G for 10 minutes, and the composition for serum separation was applied from the bottom of the test tube. It was observed whether or not a septum was formed between the serum and the clot by floating (inversion test), and the thickness of the septum was measured.

Further, the blood test container after centrifugation was allowed to stand horizontally for 2 weeks, and the presence or absence of flow (deformation) of the partition was observed (partition stability test).

3) Measurement of biochemical test values (n = 3) 4 ml of rabbit fresh blood was dispensed into a blood test container, and after completion of blood coagulation was confirmed, centrifugation was performed at 15 ° C. at 1300 G for 10 minutes. Was performed, and the separated serum layer was collected.
No oily component was observed in the obtained serum. Using this serum, the following three items were subjected to biochemical tests. As a control test, a serum sampled using a blood test container prepared in the same manner as described above except that the above-mentioned composition for separation was not contained was tested (Analysis request: Fukuyama Clinical Laboratory Center).

Item a: lactate dehydrogenase Item b: creatine phosphokinase Item c: hydroxybutyrate dehydrogenase

The compositions for separating serum or plasma obtained in Example 2 and Comparative Examples 2 and 4 were: 1) Except that in the irradiation test, irradiation was performed with an accelerated electron beam having a dose of 20 ± 10 kGray. The test was performed in the same manner as the test of the composition of Example 1.

Table 1 summarizes the above test results.

[0128]

[Table 1]

In Table 1, the odor was evaluated as “present” when odor of dimethyl sulfide was recognized, and “absent” when no odor was recognized. The partition wall thickness is usually good if it is 5 mm or more. With respect to the flow of the septum, if this flow is present, the stability of the septum is insufficient, and if the blood test container after centrifugation is stored as it is, the clot layer re-enters the already separated serum layer. "No flow" means that the partition is stable and there is no risk of flow. In a biochemical test, if the ratio of the measured value to the control value (measured value / control value) is generally in the range of 0.90 to 1.10.

The measured values of the components in the serum obtained using the compositions of Examples 1 and 2 were equivalent to the measured values of the control test in all items, and the compositions had an adverse effect on biochemical tests. Was found to have no effect. The measured values of the components in the serum obtained using the compositions of Comparative Examples 1 to 5 were higher than the measured values of the control test in any of the items, and did not give correct measured values.

Example 3 Dicyclopentadiene oligomer B 100 parts by weight Viscosity reducing agent A 6.00 parts by weight Dibenzylidene sorbitol 0.82 parts by weight Dispersant A of organic gelling agent A 0.82 parts by weight Hexadecyldimethylamine 0 .22 parts by weight Fine powder silica A 1.98 parts by weight These were kneaded under reduced pressure for 1 hour to prepare a composition. The specific gravity of this composition is 1.05, and the viscosity at 25 ° C. is about 2
It was 50,000 centipoise.

Comparative Example 6 Same as Example 3 except that the amount of the component hexadecyldimethylamine was changed to 0.02 parts by weight and the amount of the component viscosity reducing agent A was changed to 6.18 parts by weight. To prepare a composition. The specific gravity of this composition was 1.05, and the viscosity at 25 ° C. was about 200,000 centipoise.

Comparative Example 7 Same as Example 3 except that the amount of the component hexadecyldimethylamine was changed to 0.66 parts by weight and the amount of the component viscosity reducing agent A was changed to 5.55 parts by weight. To prepare a composition. The specific gravity of this composition was 1.05, and the viscosity at 25 ° C. was about 400,000 centipoise.

Comparative Example 8 Dicyclopentadiene oligomer B 100 parts by weight Viscosity reducing agent A 6.20 parts by weight Dibenzylidene sorbitol 0.82 parts by weight DMSO 0.82 parts by weight Fine powdered silica A 1.98 parts by weight The mixture was kneaded for 1 hour to prepare a composition. The specific gravity of this composition is 1.05, and the viscosity at 25 ° C. is about 2
It was 10,000 centipoise.

Performance Evaluation Using the compositions for separating serum or plasma obtained in Example 3 and Comparative Examples 6 to 8, the performance of the following items was evaluated.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Flow test (n = 5) After the blood test container was held horizontally at 60 ° C. and allowed to stand for 7 days, the composition before the test and the flow of the composition after the test from the contact point on the inner surface of the tube. The distance to the tip was measured.

2) Inversion test and partition wall stability test (n =
5) A reversibility test and a partition wall stability test of the composition were performed in the same manner as in the test of the composition of Example 1.

Table 2 summarizes the above test results.

[0140]

[Table 2]

In Table 2, it is preferable that the partition wall thickness is usually 5 mm or more. A flow of 10 mm or less is good. The septum stability was determined to be “good” when the septum did not deform even after 2 weeks of standing, and after 2 weeks of standing, the septum was broken or no septum was formed, and serum and blood clots could not be separated. Was determined to be "poor".

Example 4 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 66.6 parts by weight Dibenzylidene sorbitol 0.1 part by weight Dispersant A of organic gelling agent 0.1 part by weight 1-methyl-2- Pyrrolidone 0.3 parts by weight Fine powder silica A 5.9 parts by weight The components were heated and melted at 130 ° C.
Was added and kneaded for 30 minutes. After cooling to room temperature, the components were added thereto and kneaded under vacuum for 30 minutes to obtain a composition. The specific gravity at 25 ° C. of the obtained composition is 1.05, 25
The viscosity at ° C was about 160,000 centipoise.

Example 5 The amount of the components was changed to 0.4 parts by weight, and 1-methyl-2
-A composition was obtained in the same manner as in Example 4 except that pyrrolidone was not used. 25 ° C. of the obtained composition
Was 1.05, and the viscosity at 25 ° C. was about 160,000 centipoise.

Example 6 A composition was obtained in the same manner as in Example 4 except that the components were not used and the amount of 1-methyl-2-pyrrolidone used was 0.4 parts by weight. The specific gravity of the obtained composition at 25 ° C was 1.05, and the viscosity at 25 ° C was about 160,000 centipoise.

Example 7 Cyclopentadiene oligomer D 100 parts by weight Viscosity reducing agent A 55.6 parts by weight Dibenzylidene sorbitol 0.1 part by weight 1-methyl-2-pyrrolidone 0.4 part by weight Fine powder silica A 5.9 Parts by weight Except for using the above components, the same as in Example 4,
A composition was prepared.

[0146] The specific gravity of the obtained composition at 25 ° C. was 1.
The viscosity at 05 and 25 ° C. was about 160,000 centipoise.

Example 8 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 93.20 parts by weight Dibenzylidene sorbitol 0.12 parts by weight 1-methyl-2-pyrrolidone 0.48 parts by weight Fine silica A 6.20 parts by weight As in Example 4, except that the above components were used.
A composition was prepared. The specific gravity of the obtained composition at 25 ° C was 1.05, and the viscosity at 25 ° C was about 160,000 centipoise.

Comparative Example 9 Dicyclopentadiene oligomer B 100 parts by weight Viscosity reducing agent A 6.20 parts by weight Dibenzylidene sorbitol 0.82 parts by weight DMSO 0.82 parts by weight Fine powder silica A 1.98 parts by weight The composition was kneaded at room temperature under vacuum for 60 minutes to obtain a composition. The specific gravity of the obtained composition at 25 ° C. is 1.0
The viscosity at 5, 25 ° C was about 200,000 centipoise.

Performance Evaluation The performance of the compositions for separating serum or plasma obtained in Examples 4 to 8 and Comparative Example 9 was evaluated for the following items.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Phase Separation Test (n = 5) The blood test container was held on a slope having a 45 ° inclination with the mouth of the blood test container facing downward, and allowed to stand at 60 ° C. for 24 hours. It was examined whether or not the oil component separated (phase separation).

2) Inversion test and partition wall stability test (n =
5) The test was performed in the same manner as the test of the composition of Example 1. In addition, it was observed whether or not oil droplets considered to be due to phase separation of the composition were present in the serum phase after centrifugation.

Table 3 summarizes the above test results.

[0154]

[Table 3]

In Table 3, the phase separation was evaluated as “absent” when no oil component was separated from the composition, and as “present” when separated. The reversibility is defined as “good” when the composition is located between the serum layer and the clot layer to form a partition, and the partition gives a good separation image with a thickness of about 7 mm. " When no oil droplets were generated, the oil droplets were evaluated as “present”. When oil droplets were generated and the hemolytic test was not performed, the oil droplets were evaluated as “present”. The evaluation criteria for the partition wall stability are the same as the criteria for Table 2.

Each of the partition walls formed in the reversibility test had a thickness of about 7 mm. Examples 4 to 8 in reversibility test
The composition of Example 1 gave a good separation image, while the composition of Comparative Example produced oil droplets.

Example 9 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 75 parts by weight Dibenzylidene sorbitol 0.24 parts by weight Dispersant A of organic gelling agent A 0.24 parts by weight 1-methyl-2 -Pyrrolidone 0.72 parts by weight Chlorine paraffin A 25 parts by weight The components were heated and melted at 130 ° C, all the remaining components were added to the melt, and the whole was kneaded for 30 minutes to prepare a composition. This composition had a specific gravity of 1.04 at 25 ° C. and a viscosity of about 120,000 centipoise.

Example 10 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 70 parts by weight Dibenzylidene sorbitol 0.27 parts by weight Dispersant A of organic gelling agent A 0.27 parts by weight 1-methyl-2 -Pyrrolidone 0.80 parts by weight Chloride paraffin A 50 parts by weight Same as Example 9 except that the above components were used.
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 130,000 centipoise.

Example 11 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 50 parts by weight Dibenzylidene sorbitol 0.2 parts by weight Dispersant A of an organic gelling agent A 0.2 parts by weight 1-methyl-2 -Pyrrolidone 0.6 parts by weight Chlorinated paraffin A 50 parts by weight Same as Example 9 except that the above components were used.
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
06, viscosity was about 140,000 centipoise.

Example 12 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 100 parts by weight Dibenzylidene sorbitol 0.24 parts by weight Dispersant A of organic gelling agent A 0.24 parts by weight 1-methyl-2-pyrrolidone 0 .72 parts by weight Chlorinated paraffin B 10 parts by weight Same as Example 9 except that the above components were used.
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Example 13 100 parts by weight of oligomer C of cyclopentadiene 100 parts by weight of di-2-ethylhexyl phthalate 0.51 part by weight of dibenzylidene sorbitol 2.02 parts by weight of 1-methyl-2-pyrrolidone 50 parts by weight of paraffin chloride A Except for using the above components, in the same manner as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
04, viscosity was about 120,000 centipoise.

Comparative Example 10 Dicyclopentadiene oligomer B 100 parts by weight Viscosity reducing agent A 6.20 parts by weight Dibenzylidene sorbitol 0.82 parts by weight DMSO 0.82 parts by weight Fine powdered silica A 1.98 parts by weight Was kneaded under normal temperature vacuum for 1 hour to prepare a composition. The specific gravity of this composition at 25 ° C. is 1.05,
The viscosity was about 200,000 centipoise.

Comparative Example 11 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 20 parts by weight Dibenzylidene sorbitol 0.07 parts by weight 1-methyl-2-pyrrolidone 0.29 parts by weight Paraffin A chloride 25 parts by weight Except for using the above components, in the same manner as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
07, the viscosity was about 400,000 centipoise.

Comparative Example 12 Cyclopentadiene oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 140 parts by weight 0.13 parts by weight of dibenzylidenesorbitol 0.5 part by weight 1-methyl-2-pyrrolidone 0.5 part by weight 25 parts by weight of paraffin chloride A Except for using the above components, in the same manner as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
02, the viscosity was about 50,000 centipoise.

Comparative Example 13 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 80 parts by weight Dibenzylidene sorbitol 0.24 parts by weight Dispersant A of organic gelling agent A 0.24 parts by weight 1-methyl-2-pyrrolidone 0 .72 parts by weight Chlorinated paraffin B 0.5 parts by weight Same as Example 9 except that the above components were used.
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
02, the viscosity was about 110,000 centipoise.

Comparative Example 14 Cyclopentadiene Oligomer C 100 parts by weight Di-2-ethylhexyl phthalate 10 parts by weight Dibenzylidene sorbitol 0.27 parts by weight Dispersant A of organic gelling agent A 0.27 parts by weight 1-methyl-2 -Pyrrolidone 0.80 parts by weight Chlorine paraffin A 120 parts by weight Same as Example 9 except that the above components were used.
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
11. The viscosity was about 190,000 centipoise.

Performance Evaluation The performance of the compositions for separating serum or plasma obtained in Examples 9 to 13 and Comparative Examples 10 to 14 was evaluated for the following items.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Phase Separation Test (n = 10) A test was conducted in the same manner as in the test of the composition of Example 4.

2) Inversion test and partition wall stability test (n =
10) The test was performed in the same manner as the test of the composition of Example 4.

3) Irradiation test (n = 50) A test was conducted in the same manner as in the test of the composition of Example 2.

4) Hemolysis test (n = 3) A serum layer was separated from the blood test container subjected to the test of 2) above, and hemoglobin (Hb) in the serum was measured (analysis requesting destination: Fukuyama Clinical Laboratory Center).

Table 4 summarizes the above test results.

[0174]

[Table 4]

In Table 4, the serum Hb concentration was 5 in the hemolytic test.
Hemolysis was considered to be at least mg / dl. The criteria for phase separation, reversibility, oil drop and partition stability are the same as for Table 3 and the criteria for odor are the same as for Table 1.

Example 14 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 73 parts by weight Dibenzylidene sorbitol 0.1 part by weight 1-methyl-2-pyrrolidone 0.4 part by weight Fine powder silica A 6.6 parts by weight 9.5 parts by weight of a low-molecular-weight styrene-based thermoplastic resin Except for using the above components, the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 250,000 centipoise.

Example 15 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 67 parts by weight Dibenzylidene sorbitol 0.09 parts by weight 1-methyl-2-pyrrolidone 0.35 parts by weight Fine silica powder A 6.1 parts by weight 0.9 parts by weight of a low-molecular-weight styrene-based thermoplastic resin Except for using the above components, and in the same manner as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, viscosity was about 150,000 centipoise.

Comparative Example 15 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 67 parts by weight Dibenzylidene sorbitol 0.09 parts by weight 1-methyl-2-pyrrolidone 0.35 parts by weight Fine powder silica A 6.1 parts by weight Except for using the above components, in the same manner as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Comparative Example 16 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 79 parts by weight Dibenzylidene sorbitol 0.1 part by weight 1-methyl-2-pyrrolidone 0.4 part by weight Fine powder silica A 7.2 parts by weight 21 parts by weight of low-molecular-weight styrene-based thermoplastic resin Except that the above components were used, the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, viscosity was about 500,000 centipoise.

Performance Evaluation The following items were evaluated for the serum or plasma separation compositions obtained in Examples 14 and 15 and Comparative Examples 15 and 16.
The performance was evaluated.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Phase Separation Test (n = 10) A test was conducted in the same manner as in the test of the composition of Example 4.

2) Inversion test and partition wall stability test (n =
10) The test was performed in the same manner as the test of the composition of Example 4.

3) Irradiation test (n = 50) A test was conducted in the same manner as in the test of the composition of Example 2.

4) Hemolysis test (n = 3) A serum layer was separated from the blood test container after subjected to the test of 2) above, and hemoglobin (Hb) in the serum was measured (request for analysis: Fukuyama Clinical Laboratory Center).

Table 5 summarizes the above test results.

[0187]

[Table 5]

In Table 5, the evaluation criteria are the same as the criteria for Table 4.

Example 16 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 67 parts by weight Dibenzylidene sorbitol 0.09 parts by weight DMA 0.35 parts by weight Fine powder silica A 6.1 parts by weight The above components were used. Except for the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Example 17 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 66 parts by weight Dibenzylidene sorbitol 0.09 parts by weight DMA 0.09 parts by weight Fine powder silica A 6.0 parts by weight The above components were used. Except for the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Example 18 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 67 parts by weight Dibenzylidene sorbitol 0.09 parts by weight DMF 0.35 parts by weight Fine powder silica A 6.1 parts by weight The above components were used. Except for the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Comparative Example 17 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducing agent A 66 parts by weight Dibenzylidene sorbitol 0.09 parts by weight Fine powdered silica A 6.0 parts by weight The same procedure as in Example 1 was conducted except that the above components were used. Same as 9
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 110,000 centipoise.

Comparative Example 18 Cyclopentadiene oligomer C 100 parts by weight Viscosity reducer A 68 parts by weight Dibenzylidene sorbitol 0.09 parts by weight DMA 0.53 parts by weight Fine powder silica A 6.2 parts by weight The above components were used. Except for the same as in Example 9,
A composition was prepared. The specific gravity of this composition at 25 ° C. is 1.
05, the viscosity was about 120,000 centipoise.

Performance Evaluation The following items were evaluated for the serum or plasma separation compositions obtained in Examples 16 to 18 and Comparative Examples 17 and 18.
The performance was evaluated.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Phase Separation Test (n = 10) A test was conducted in the same manner as in the test of the composition of Example 4.

2) Inversion test and partition wall stability test (n =
10) The test was performed in the same manner as the test of the composition of Example 4.

3) Irradiation test (n = 50) A test was conducted in the same manner as in the test of the composition of Example 2.

4) Hemolysis test (n = 3) A serum layer was separated from the blood test container after subjected to the test of 2) above, and hemoglobin (Hb) in the serum was measured (analysis requesting destination: Fukuyama Clinical Laboratory Center).

Table 6 summarizes the above test results.

[0201]

[Table 6]

In Table 6, the evaluation criteria are the same as the criteria for Table 4.

Example 19 Dispersant A for organic gelling agent A 100 parts by weight Dibenzylidene sorbitol 25 parts by weight Titanium oxide 1.5 parts by weight The components were added, kneaded under reduced pressure for 1 hour, and homogeneously dispersed. A composition was prepared.

The specific gravity of this composition at 25 ° C. was 1.05,
The viscosity was about 250,000 centipoise.

Comparative Example 19 A composition was prepared in the same manner as in Example 19, except that the dispersant B of the organic gelling agent was used in place of the dispersant A of the organic gelling agent.

Comparative Example 20 Dicyclopentadiene oligomer A 100 parts by weight Viscosity reducing agent A 7.7 parts by weight Dibenzylidene sorbitol 0.1 part by weight DMSO 0.4 part by weight Fine powder silica B 2.3 parts by weight The mixture was kneaded under reduced pressure for 1 hour to prepare a composition.

Performance Evaluation The following items were evaluated for performance with respect to the serum or plasma separation compositions obtained in Example 19 and Comparative Examples 19 and 20.

A blood test container was prepared from the composition in the same manner as in the test of the composition of Example 1, and subjected to the following tests.

1) Phase separation test (n = 10) A test was conducted in the same manner as in the test of the composition of Example 4.

2) Inversion test and partition wall stability test (n =
10) The test was performed in the same manner as the test of the composition of Example 4.

3) Measurement of biochemical test values (n = 2) A test was performed in the same manner as in the test of the composition of Example 1.

Table 7 summarizes the above test results.

[0213]

[Table 7]

In Table 7, the standards for phase separation, reversibility, oil droplet and partition wall stability are the same as those for Table 3, and the standards for biochemical test values are the same as those for Table 1. .

The biochemical measurement values of the components in the serum obtained using the composition of Example 19 were equivalent to the measurement values of the control test in all items, and the composition had an adverse effect on the biochemical test. Was found to have no effect. The measured values of the components in the serum obtained using the compositions of Comparative Examples 19 and 20 were higher than the measured values of the control test in any of the items, and did not give correct measured values.

[0216]

Since the composition of the present invention is constituted as described above, the following effects are exhibited.

Effects of First to Sixth Compositions In the first to sixth compositions according to the present invention, since a specific polyoxyethylene polyoxypropylene block copolymer is used as a dispersant for an organic gelling agent, DMSO or DMA
No organic solvent such as is required, so that irradiation does not produce odorous substances. In addition, since the dispersant is a hydrophobic polymer compound, there is an advantage that a part of the dispersant is dissolved in blood, serum, and plasma to prevent hemolysis or the like.

The effect of the second composition In the second composition, the polyoxyethylene polyoxypropylene block copolymer and the tertiary amine act as a dispersant in a joint manner, so that the organic gelling agent can be used for a short time. In this case, the dispersion is uniformly dispersed in the cyclopentadiene oligomer, so that the occurrence of reversal failure due to an increase in thixotropy with time is prevented and the flow is also prevented.

Effects of Third to Sixth Compositions In the third to sixth compositions, an oligomer of cyclopentadiene having a specific softening point and a specific melt viscosity is used. The oligomer of cyclopentadiene is solid at room temperature, but becomes fluid at room temperature by adding a viscosity reducing agent thereto. To the oligomer of cyclopentadiene containing the viscosity reducing agent,
The third to sixth compositions obtained by adding the specific organic gelling agent, the specific dispersant, and the specific gravity adjusting agent as necessary, have a thixotropic property and a specific gravity of a composition for separating serum or plasma. And a phase separation does not substantially occur.

Effect of Fifth Composition In the fifth composition, by adding a compatibilizing agent, the compatibility between the oligomer and the viscosity reducing agent is increased, and the phase separation can be almost completely eliminated.

The effect of the sixth composition In the sixth composition, an oligomer of cyclopentadiene having a specific softening point and a specific melt viscosity and a viscosity reducing agent are used, and an organic gelling agent and a dispersion of the organic gelling agent are used. D as an agent
By adding MA and / or DMF, an equivalent dispersing effect can be obtained with a smaller amount of DMA and / or DMF than the conventional composition. As a result, hemolysis is not caused by a decrease in the concentration of the dispersant.

Effect of Seventh Composition In the seventh composition, the thixotropic property is expressed by a network structure formed by a single hydrogen bond of the organic gelling agent. There is no change over time, and phase separation is less likely to occur.

In the seventh composition, an organic gelling agent is mainly involved in imparting thixotropy. Therefore, when a small amount of silica is used as a specific gravity adjusting agent, even if re-aggregation of silica occurs, phase separation occurs. Is not encouraged.

Further, the polyoxyethylene polyoxypropylene block copolymer is a nonionic surfactant, and uniformly disperses the organic gelling agent to exhibit good thixotropy. In addition, its HLB value is 1.0-
Since it is 9.0 and is extremely hydrophobic compared to common nonionic surfactants, it is hardly compatible with blood,
Therefore, it does not adversely affect the biochemical test values of blood.

Furthermore, the polyoxyethylene polyoxypropylene block copolymer has a lower temperature dependence of viscosity than the prior art oligomer of cyclopentadiene. Therefore, the temperature dependency of the seventh composition is sufficiently smaller than that of the conventional art, and the conventional problem of poor separation of serum or plasma during low-temperature centrifugation hardly occurs.

 ──────────────────────────────────────────────────続 き Continued on the front page (31) Priority claim number Japanese Patent Application No. 8-108086 (32) Priority date Hei 8 (1996) April 26 (33) Priority claim country Japan (JP)

Claims (8)

[Claims] 1. An organic gelling agent comprising an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde. A composition for separating serum or plasma, which is a polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0. 2. An organic gelling agent comprising an oligomer of cyclopentadiene, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and the dispersant of the organic gelling agent is A polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0, and a tertiary amine compound having two methyl groups and an alkyl group having 10 or more carbon atoms; A composition for separating serum or plasma, wherein the amount of a secondary amine compound is in the range of 0.03 to 0.5 part by weight based on 100 parts by weight of cyclopentadiene oligomer. 3. An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the oligomer of cyclopentadiene has a softening point of 70 to 140.
And a melt viscosity at 180 ° C. and 30 to 500 centipoise, the viscosity reducing agent is a phthalate ester, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and a dispersing agent of the organic gelling agent. Is selected from the group consisting of polyoxyethylene polyoxypropylene block copolymers having an HLB value of 1.0 to 9.0, 1-methyl-2-pyrrolidone and mixtures thereof. Serum or plasma separation Composition. 4. The composition according to claim 3, wherein the amount of the viscosity reducing agent is in the range of 30 to 130 parts by weight per 100 parts by weight of the cyclopentadiene oligomer. 5. An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, a dispersant of an organic gelling agent, and a specific gravity adjusting agent, wherein the oligomer of cyclopentadiene has a softening point of 70 to 140.
And a melt viscosity at 180 ° C. and 30 to 500 centipoise, the viscosity reducing agent is a phthalate ester, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and a dispersing agent of the organic gelling agent. Is selected from the group consisting of polyoxyethylene polyoxypropylene block copolymers having an HLB value of 1.0 to 9.0, 1-methyl-2-pyrrolidone and mixtures thereof, wherein the specific gravity adjusting agent is A composition for separating serum or plasma, which is a chlorinated paraffin, wherein the ratio of a viscosity reducing agent is in the range of 30 to 130 parts by weight and the ratio of the specific gravity adjusting agent is in the range of 1 to 100 parts by weight based on 100 parts by weight of cyclopentadiene oligomer. 6. An oligomer of cyclopentadiene, a compatibilizer, a viscosity reducing agent, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the oligomer of cyclopentadiene has a softening point of 70 to 140.
And a melt viscosity at 180 ° C. of 30 to 500 centipoise, the compatibilizer is a low molecular weight styrene-based thermoplastic resin, the viscosity reducer is a phthalate ester, and the organic gelling agent is sorbitol and aromatic. A condensate of an aldehyde, wherein the dispersant of the organic gelling agent is a polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0, 1-methyl-2-pyrrolidone, and a mixture thereof. A composition for separating serum or plasma, wherein the amount of the compatibilizer is in the range of 0.1 to 15 parts by weight based on 100 parts by weight of cyclopentadiene oligomer. 7. An oligomer of cyclopentadiene, a viscosity reducing agent, an organic gelling agent, and a dispersant of an organic gelling agent, wherein the oligomer of cyclopentadiene has a softening point of 70 to 140.
And a melt viscosity at 180 ° C. and 30 to 500 centipoise, the viscosity reducing agent is a phthalate ester, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and a dispersing agent of the organic gelling agent. Is selected from the group consisting of N, N-dimethylacetamide, N, N-dimethylformamide and mixtures thereof, wherein the amount of the dispersant of the organic gelling agent is 0.1 to 100 parts by weight of cyclopentadiene oligomer. A composition for separating serum or plasma, which is in the range of 0.01 to 0.4 parts by weight. 8. A polyoxyethylene polyoxypropylene block copolymer having an HLB value of 1.0 to 9.0, comprising a main agent and an organic gelling agent, wherein the organic gelling agent is sorbitol and an aromatic gelling agent. A composition for separating serum or plasma, which is a condensate of an aldehyde.