JPH063356A - Composition for separating blood serum or blood plasma and container for blood test - Google Patents

Abstract

PURPOSE:To obtain a composition for separating blood serum or blood plasma which can yield an excellent separated image even when blood serum or blood plasma is separated by centrifugal separation under a set condition of 4 deg.C. CONSTITUTION:The title composition contains a cyclopentadiene resin, viscosity adjusting agent, and organic gelatinizer and the cyclopentadiene resin maintains a liquid state at 25 deg.C. The viscosity adjusting agent is a liquid ester obtained from propionic acid, butyric acid, benzoic acid, or phthalic acid and the organic gelatinizer is a condensation product of sorbitol and aromatic aldehyde. In addition, the mixing ratios of the viscosity adjusting agent and organic gelatinizer against 100 pts.wt. of the cyclopentadien resin are respectively set at 0.8-25 pts.wt. and 0.03-0.9 pt.wt.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for separating serum or plasma used for centrifugal separation by utilizing the difference in specific gravity of blood components, and a blood test container containing the composition in advance. It is about.

[0002]

2. Description of the Related Art Heretofore, there has been known a blood test container in which a mixture of, for example, silicone and silica is previously contained in the inner bottom portion of a blood collection tube as a composition for separating thixotropic serum or plasma (JP-A-51-83654). issue). When blood is collected in the blood test container and left standing for an appropriate period of time and then centrifuged, the gel-like composition for separating serum or plasma becomes fluid due to the centrifugal force. In addition, since the gel-like composition for separating serum or plasma has a specific gravity intermediate between that of the serum or plasma component and that of the blood clot or blood cell component, it gradually rises in the collected blood from the bottom of the tube, and serum or plasma is obtained. It comes to be located between the layer and the clot or blood cell layer, and can separate the serum or plasma component and the clot or blood cell component. The serum or plasma component thus separated from the blood clot or blood cell component can be easily taken out from the blood test container and subjected to various tests, or can be stored without being transferred to another container. .

As a main component of such a composition for separating thixotropic serum or plasma, in addition to the above-mentioned silicone, an α-olefin-maleic acid diester copolymer (JP-A-56-166956 and JP-A-2). -16815
No. 9), a polyester-based polymer (JP-A-61-2333).
68), an acrylic polymer (JP-A-53-42283).
No.), chlorinated polybutene (JP-A-57-9718),
Cyclopentadiene resin (Japanese Patent Laid-Open No. 1-295163)
No.), cyclopentadiene resin with hydroxyl group, ester group,
A modified product of a cyclopentadiene resin having an ether group, an epoxy group or the like introduced therein (Japanese Patent Application Laid-Open No. 2-95257) is known, and imparts thixotropic properties to such a main component while acting as a specific gravity adjusting agent like silica. Inorganic fillers that also function as gelling agents, substances having polar groups at both ends of the molecule such as propylene glycol and ethylenediamine (above JP-A-1-295163), condensates of sorbitol and aromatic aldehydes (special Kaihei 2-1681
No. 59), an organic gelling agent and the like are added as necessary.

[0004]

However, silicone is hardly used at present because the phase separation with the inorganic filler is remarkable and the curing reaction occurs by γ-ray sterilization, and α-olefin-maleic acid is used. Those having a polar group such as diester copolymers, polyester polymers, acrylic polymers, and modified products of cyclopentadiene resin have relatively little influence on the measurement of clinical test items in blood, It often affects measurement of blood drug concentration (for example, measurement of blood concentration of antiepileptic drugs such as phenobarbital, carbamazepine, and phenytoin).

On the other hand, in the case of using chlorinated polybutene, there is a problem that the incinerator is damaged because hydrochloric acid is generated when the product is incinerated and discarded after use.

Cyclopentadiene resin is excellent in that it does not have these drawbacks, but since the viscosity has a large temperature dependency, a composition for separating serum or plasma containing cyclopentadiene resin as a main component has, for example, a temperature of 4 ° C. Under the separation conditions of the centrifuge set to ° C, the fluidity may deteriorate, and the composition may not function as a serum or plasma separation composition. That is, the composition for separating serum or plasma containing cyclopentadiene resin as a main component is 20 to 2 when performing a centrifugation operation.
There is no problem as long as it is used near room temperature of 5 ° C, but recently, in order to eliminate the influence of heat generation from the motor of the centrifuge, the temperature of
Centrifugation has come to be performed under the setting condition of ° C. In this case, the composition for separating serum or plasma containing a cyclopentadiene resin as a main component may not form a good separation image.

In order to solve the above-mentioned problem of separation image failure, the present inventors have previously investigated a two-component composition comprising a diclopentadiene resin and a gelling agent (Japanese Patent Application No. Hei 10-135242). 2-335034). However, it was found that with this composition, sufficient fluidity was not obtained during centrifugation under the set conditions of a temperature of 4 ° C.

The object of the present invention is to provide a thixotropic serum or plasma separating composition, which is a mixture of a cyclopentadiene resin, a viscosity modifier and an organic gelling agent, and which is centrifuged at a temperature of 4 ° C. It is an object of the present invention to provide a composition for separating serum or plasma capable of obtaining a good separation image even in operation, and a blood test container containing the composition in advance.

By the way, as one of the methods for sterilizing a composition for separating serum or plasma, the composition has a required dose of γ
-A line may be irradiated.

The composition for separating serum or plasma containing the cyclopentadiene resin, the viscosity adjusting agent and the organic gelling agent suitable for the above purpose can obtain a good separation image even in the centrifugation operation at the setting condition of 4 ° C. In addition, it does not affect the measurement of the drug concentration in blood, and is superior to conventional compositions for separating serum or plasma.

However, the composition for separating serum or plasma may cause remarkable foaming by sterilization treatment by γ-ray irradiation. This is because the composition was decomposed by γ-ray irradiation and gasified. The composition for separating serum or plasma does not impair the original function of separating serum or plasma, even if it causes foaming and is partially decomposed, depending on the degree of decomposition. However, since the viscosity modifier easily causes phase separation from the composition over time, decomposition by γ-ray irradiation is not preferable.

Another object of the present invention is that a good separation image can be obtained even in a centrifugation operation under the setting condition of 4 ° C., and it does not affect the measurement of blood drug concentration, and A stable composition for separating serum or plasma that is unlikely to decompose and foam upon sterilization treatment by γ-ray irradiation,
And to provide a blood test container containing the composition in advance.

[0013]

Means for Solving the Problems As a result of repeated studies to achieve the above-mentioned first object, the inventors of the present invention have selected a specific cyclopentadiene resin, a specific viscosity modifier and a specific organic gelling agent. The present inventors have completed the present invention by discovering that a composition containing a large proportion can obtain a good separation image even in a centrifugation operation under the setting condition of a temperature of 4 ° C.

The inventors of the present invention also conducted extensive studies to achieve the second object, and as a result, as a γ-ray stabilizer, a phenol antioxidant, a light stabilizer and a phosphite antioxidant were selected. By adding a mixture containing an appropriate ratio to a composition for separating serum or plasma consisting of a cyclopentadiene resin, a viscosity modifier and an organic gelling agent, a good separation image is shown and the blood drug concentration is measured. Does not affect the
The present invention has been completed by finding that it is possible to obtain a composition for separating serum or plasma that is free from the risk of decomposition and foaming by irradiation with radiation.

That is, the composition for separating serum or plasma according to the present invention which can achieve the above first object is a composition for separating serum or plasma containing a cyclopentadiene resin, a viscosity modifier and an organic gelling agent. The cyclopentadiene resin is a liquid resin at a temperature of 25 ° C.,
The viscosity modifier is a liquid ester obtained from propionic acid, butyric acid, benzoic acid or phthalic acid, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and 100 weight% of the cyclopentadiene resin. To the department
The ratio of the viscosity modifier is 0.8 to 25 parts by weight, and the ratio of the organic gelling agent is 0.03 to 0.9 parts by weight.

The composition for separating serum or plasma according to the present invention, which can achieve the above second object, is a serum containing cyclopentadiene resin, a viscosity modifier, an organic gelling agent and a γ-ray stabilizer. A composition for plasma separation, wherein the cyclopentadiene resin is a liquid resin at a temperature of 25 ° C., the viscosity modifier is a liquid ester obtained from propionic acid, butyric acid, benzoic acid or phthalic acid, and the organic gel The agent is a condensate of sorbitol and an aromatic aldehyde, the γ-ray stabilizer is a mixture of a phenolic antioxidant, a light stabilizer and a phosphite antioxidant, and the cyclopentadiene resin 100 The ratio of the viscosity modifier is 0.8 to 25 parts by weight, the ratio of the organic gelling agent is 0.03 to 0.9 parts by weight, and the ratio of the γ-ray stabilizer is 1.32 with respect to parts by weight. ~ 7.7 layers It is characterized in that it is part.

In a preferred embodiment of the invention, the phenolic antioxidant is n-octadecyl-3- (4 '.
-Hydroxy-3 ', 5'-di-t-butylphenyl)
Propionate, the light stabilizer is bis (2,2,6,6-
Tetramethyl-4-piperidyl) sebacate, and the phosphite antioxidant is 4,4'-butylidene-bis (3-
Methyl-6-t-butylphenyl-di-tridecyl) phosphite, which is the above cyclopentadiene resin 100.
The ratio of the phenolic antioxidant to the weight part is 0.
12-0.7 parts by weight, the proportion of light stabilizer is 0.6-3.5
The weight ratio of the phosphite-based antioxidant is 0.6 to 3.
5 parts by weight.

According to the present invention, there is provided a blood test container containing the above-described composition for separating serum or plasma.

Hereinafter, the composition for separating serum or plasma and the container for blood test according to the present invention will be described in detail.

A) Cyclopentadiene resin Cyclopentadiene resin, which is also called DCPD resin or cyclopentadiene-based petroleum resin, contains 15 to 20% of cyclopentadiene (CPD) in the C ₅ fraction of naphtha cracked oil. Obtained by thermal dimerization. The dimerization product also contains a co-dimer of cyclopentadiene, isoprene and 1,3-pentadiene. Cyclopentadiene resin is purified to high purity by repeating this dimerization, dedimerization and distillation. The number average molecular weight of the cyclopentadiene resin is preferably 100 or more and 300 or less as measured by gel permeation chromatography (GPC) polystyrene calibration. The reason is that if the value of the average molecular weight is too small, the amount of volatile components increases, and conversely if the value is too large, the viscosity becomes high, and it becomes almost solid near room temperature of 20 to 25 ° C.

When the cyclopentadiene resin is used as the serum or plasma separating composition of the present invention, it is desirable that the double bond of the cyclopentadiene resin is saturated by hydrogenation. The reason is that the hydrogenated cyclopentadiene resin has excellent heat resistance and weather resistance. In this case, the bromine number of the hydrogenated product is 5.0 as measured by the method specified in JIS2453.
Is preferably (gBr ₂ / 100g) or less, bad smell is grossly the bromine number exceeds this.

Further, the cyclopentadiene resin can be relatively easily obtained with a specific gravity of 1.00 or more, unlike ordinary olefin or α-olefin polymers. This means that the polymer molecules are tightly packed, which is also in agreement with the fact that there is almost no evaporation loss at 100 ° C. Examples of preferable cyclopentadiene resins include the three types shown in Table A.

[0023]

[Table 1] Since the cyclopentadiene resin having a large specific gravity as described above can be easily prepared, the specific gravity between the serum or plasma and the blood clot or blood cell required for the composition for separating serum or plasma, that is, about 1.02 to 1.08. A cyclopentadiene resin having a specific gravity of can be easily obtained by selecting polymerization conditions and the like. Further, when the cyclopentadiene resin is used as a serum or plasma separating agent, a specific gravity adjusting agent may be added and mixed as necessary to adjust the specific gravity to a desired value. Examples of the modifier used for this purpose include silica, alumina, glass, talc, kaolin, bentonite, titania, zirconium, inorganic fine powder such as asbestos, or polystyrene, organic polymer fine powder such as polyurethane, and the like. The addition amount thereof is preferably 50 parts by weight or less, particularly preferably 1 part by weight or more and 10 parts by weight or less with respect to 100 parts by weight of the cyclopentadiene resin. If the amount added is too small, the function of adjusting the specific gravity is no longer fulfilled. On the contrary, if the amount added is too large, the difference in the specific gravity between the resin and the specific gravity adjusting agent becomes too wide, so that the mixture easily separates, which is not preferable. Furthermore, when the above-mentioned fine powder is added, thixotropic properties are often imparted to the mixture. In either case of using the inorganic fine powder or the organic polymer fine powder, the fine powder preferably has an average particle diameter of 500 μm or less in order to facilitate mixing and dispersion.

On the other hand, the cyclopentadiene resin has the property that the viscosity sharply increases as the temperature decreases. That is, no problem occurs as long as it is used at a temperature of about 20 to 25 ° C., but for example, serum or plasma containing cyclopentadiene resin as a main component under separation conditions using a centrifuge set at a temperature of 4 ° C. Separation compositions often do not exhibit good inversion. Therefore, in order to improve the inversion property at low temperature, it is necessary to reduce the viscosity of the serum or plasma separating agent at low temperature.

The term "reversible" means that after collecting blood in a blood collection tube having the composition for separating serum or plasma at the bottom, the separating composition is fluidized by a centrifugation operation.
It is the property of being located between the serum or plasma layer and the blood clot or blood cell layer.

B) Viscosity modifier The inventors of the present invention have made various studies and found that a blood test in which a composition for separating serum or plasma at a temperature of about 23 ° C. was contained in a centrifuge set at a temperature of 4 ° C. Set the container for 13
It has been found that when the centrifugation is performed under the centrifugation conditions of 00 G and 5 minutes, the temperature of the serum or plasma separation composition contained in the blood test container reaches only 15 ° C at the lowest. From this, it was revealed that if a composition for separating serum or plasma having a sufficient septum-forming ability at 15 ° C. is designed, good inversion property is exhibited under the centrifugation conditions set at a temperature of 4 ° C. As a result of further study, it was found that the separating agent should be adjusted so that the viscosity at 15 ° C. is 1 million centipoise (cP) or less.

In the present invention, in order to obtain a separating agent satisfying the above-mentioned viscosity condition, the above-mentioned cyclopentadiene resin is used as a viscosity adjusting agent and the viscosity at a temperature of 25 ° C. is 10
A liquid substance having a freezing point of 00 cP or less, preferably 100 cP or less, and a freezing point of 0 ° C or less, preferably -10 ° C or less,
It has been found that the separating agent may be added so that the viscosity of the separating agent becomes 1,000,000 cP or less at 15 ° C. As the viscosity modifier, more specifically, an ester obtained by reacting propionic acid, butyric acid, benzoic acid, or phthalic acid with an alcohol is used. The alcohol is not particularly limited, and examples thereof include alkyl alcohols having 1 to 12 carbon atoms, such as methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol,
Examples are isopentyl alcohol, hexyl alcohol, octyl alcohol, 2-ethylhexyl alcohol, nonyl alcohol, decyl alcohol, undecyl alcohol and dodecyl alcohol. These alkyl alcohols may be used alone or in combination of two or more. In the case of a phthalate ester, an ester obtained from an alcohol having 8 to 12 carbon atoms and having a high carbon number is preferable. In particular, an ester obtained from an alcohol mixture having 9 to 11 carbon atoms and a high linearity ratio is preferable because the compatibility between the ester and the cyclopentadiene resin is improved and phase separation hardly occurs. Examples of such esters include Mitsubishi Gas Chemical Co., Inc.
An example of the product is PL-200, manufactured by the company. PL-20
0 is alcohol manufactured by Ciel Chemical Co., Ltd., trade name: Lineball 911 (carbon distribution is C ₉ = 20% by weight,
It is a phthalic acid ester obtained by using C ₁₀ = 45% by weight and C ₁₁ = 35% by weight, and the linearity of all alcohols is 80 to 85%, and reacting this with phthalic anhydride.

The addition amount of the viscosity modifier is preferably 0.8 parts by weight or more and 25 parts by weight or less, particularly 3 parts by weight or more and 20 parts by weight or less, relative to 100 parts by weight of the cyclopentadiene resin. If this amount is too small, the effect of lowering the viscosity cannot be expected, and conversely, if it is too large, phase separation easily occurs, which is not preferable.

C) Organic Gelling Agent The organic gelling agent acts as an auxiliary agent that imparts thixotropic properties. As an organic gelling agent, JP-A-2-1681
Condensates of sorbitol and aromatic aldehydes as shown in No. 59 are used. Examples of such condensates include dibenzylidene sorbitol, tribenzylidene sorbitol, methyl-substituted dibenzylidene sorbitol, and the like, and dibenzylidene sorbitol is particularly preferable.

The organic gelling agent comprising a condensate of sorbitol and aromatic aldehyde has the following excellent points.

First, since the organic gelling agent comprising the above condensate has neither hygroscopicity nor water solubility, the separating agent does not become cloudy due to water absorption even if it is brought into contact with a blood sample for a long time, and the sample is concentrated. Does not happen. In addition, since the organic gelling agent has a benzyl group as a hydrophobic group and a hydroxyl group as a hydrophilic group, it is compatible with both hydrophobic substances and hydrophilic substances, and phase separation hardly occurs. In order to exhibit good thixotropy, this organic gelling agent preferably has no polar group or is dispersed in a hydrophobic medium having a small polar group content. Furthermore, this organic gelling agent is more effective in combination with a cyclopentadiene resin than in combination with the copolymer of α-olefin and maleic acid diester as shown in JP-A-2-168159. It develops thixotropic properties. As a result, the amount of the organic gelling agent added to the cyclopentadiene resin can be further reduced, so that the original advantage of the cyclopentadiene resin, which does not affect the measurement of the blood drug concentration, can be maintained. As organic gelling agents, substances having polar groups at both ends of the molecule such as propylene glycol and ethylenediamine as disclosed in JP-A-1-295163 are known, but these are water-soluble. However, there is a problem that the separating agent absorbs moisture when it is brought into contact with blood for a long time, and the sample is concentrated.

The organic gelling agent can be dispersed in the other components of the composition by heating and melting, or alternatively, in a suitable solvent such as dimethyl sulfoxide, N-methylpyrrolidone, N, N-dimethylacetamide, cyclohexanone, Polar solvent such as N, N-dimethylformamide, hexamethylphosphotriamide, cellosolve-based solvent 100
If, for example, an organic gelling agent solution in which 5 parts by weight or more and 30 parts by weight or less of the organic gelling agent is dissolved at a temperature of 25 ° C. is added to parts by weight, it is possible to add other components without heating. Can be dispersed in. By dispersing the organic gelling agent in the other components in this manner, compatibility with the other components is imparted, and thus phase separation hardly occurs.

The amount of the organic gelling agent added is 0.03 to 0.9 part by weight, particularly 0.04 to 0.4 part by weight, based on 100 parts by weight of the cyclopentadiene resin. It is preferable. If the amount added is too small, the thixotropy is insufficiently imparted, and fluidity is imparted by a slight force other than the centrifugal force in the centrifugal separation operation, which makes handling difficult. On the other hand, if the amount added is too large, the thixotropy becomes excessive, and the composition of the present invention cannot move to the middle of the serum or plasma layer and the blood clot or blood cell layer under normal centrifugation conditions.

D) γ-Ray Stabilizer The γ-ray stabilizer is a mixture of a phenolic antioxidant, a light stabilizer and a phosphite antioxidant.

Typical examples of phenolic antioxidants include:
n-octadecyl-3- (4'-hydroxy-3 ',
5'-di-t-butylphenyl) propionate, and a typical example of the light stabilizer is bis (2,2,6,6).
6-tetramethyl-4-piperidyl) sebacate, and typical examples of the phosphite-based antioxidant include 4,
4'-butylidene-bis (3-methyl-6-t-butylphenyl-di-tridecyl) phosphite.

The substances used as γ-ray stabilizers are listed in Table B.
-1, B-2, and B-3 are illustrated.

[0037]

[Table 2]

[Table 3]

[Table 4]

[Table 5]

[Table 6] When a γ-ray stabilizer is added to a serum or plasma separating composition comprising a cyclopentadiene resin, a viscosity modifier and an organic gelling agent, the cyclopentadiene resin, the viscosity modifier and the organic gelling agent are blended together. The γ-ray stabilizer may be added to the product as it is, but by previously dissolving it in a polar organic solvent such as N-methylpyrrolidone or dimertyl sulfoxide and adding it in a solution state, A larger amount of γ-ray stabilizer can be added than that of the -ray stabilizer as it is, and a composition for separating serum or plasma having a good dispersion state can be easily obtained.

The amount of the phenolic antioxidant as the γ-ray stabilizer added is 0.12 to 0.7 part by weight, particularly 0.17 to 0.7 part by weight, based on 100 parts by weight of the cyclopentadiene resin. Preferably. The addition amount of the light stabilizer of the γ-ray stabilizer is preferably 0.6 to 3.5 parts by weight, particularly preferably 0.8 to 3.5 parts by weight. The addition amount of the phosphite-based antioxidant as the γ-ray stabilizer is preferably 0.6 to 3.5 parts by weight, particularly preferably 0.8 to 3.5 parts by weight.

If the amounts of the above-mentioned three components constituting the γ-ray stabilizer are too small, the composition may be foamed due to decomposition of the composition by γ-ray irradiation. On the contrary, if the addition amount of each is too large, the polar solvent used for the purpose of assisting the dispersion of the above three components absorbs the composition and concentrates the sample, which is not preferable.

The mechanism of action of the γ-ray stabilizer is as follows. That is, the γ-ray stabilizer captures decomposition intermediates such as radicals produced in the composition for separating serum or plasma by γ-irradiation, and prevents the intermediate from proceeding to further decomposition.

E) Container To use the composition for separating serum or plasma according to the present invention, the composition is previously contained in a bottomed tubular container used as a blood collection tube of a vacuum type or a non-vacuum type, and the same container is used. It is generally used as a blood test container. By a predetermined method in this container, the collected blood is injected, and after centrifugation for a suitable time, centrifugation is performed, and the blood component is separated into serum or plasma and clot or blood cell component due to the difference in specific gravity,
When the specific gravity of the composition is set between 1.02 and 1.08, the composition of the present invention is provided between the upper serum or plasma layer and the lower blood clot or blood cell layer. The substance acts as a separating agent by intervening as a diaphragm or partition that separates the two. The material of the blood test container used may be glass, plastic or the like, and is not particularly limited.

The amount of the composition of the present invention contained in this glass or plastic blood test container varies depending on the volume and shape of the test container, but is generally 0.3 to 3. It is about 0 g.

In the present invention, the material of the blood test container may be thermoplastic resin, thermosetting resin, modified natural resin, glass or the like. Examples of the thermoplastic resin include polyethylene, polypropylene and poly-4-methylpentene-
1. Polystyrene, polymethylmethacrylate, polyvinyl chloride, polyethylene terephthalate, polybutylene terephthalate, acrylonitrile polymer, acrylonitrile copolymer obtained by copolymerizing styrene or butadiene, styrene-butadiene copolymer, styrene-isoprene copolymer Polymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-methyl methacrylate copolymer, ethylene-propylene copolymer, ethylene-acrylic acid copolymer, ethylene-acrylate copolymer, Polyvinyl alcohol acetalized products, polyvinyl alcohol butyralized products, etc. are used, and as the thermosetting resin, for example, unsaturated polyester resins, epoxy resins, epoxy-acrylate resins, etc. are used, and modified The natural resins, cellulose acetate, cellulose propionate, cellulose acetate butyrate,
Ethyl cellulose, ethyl chitin and the like are used.

As the glass, for example, silicate glass such as soda lime glass, phosphosilicate glass, borosilicate glass, and quartz glass are preferably used.

[0045]

EXAMPLES Next, some examples for specifically explaining the present invention and some comparative examples for showing a comparison with the examples are given, and the performance of the obtained compositions was evaluated.

Examples 1-1 to 1-14, 2-1 to 2-1
4, 3-1 to 3-14, 4-1 to 4-14, 5-1 to 5
-5, 6-1 to 6-2, 7-1 to 7-8 and Comparative Example 1-
1-1-4, 2-1-2-4, 3-1-3-4, 4-1
.About.4-4, 8-1 to 8-4, 9-1 to 9-4 ECR-327 manufactured by Exxon Chemical Co., Ltd. having properties as shown in Table A as hydrogenated products of cyclopentadiene resin.
(Trade name), Quinton hydrogenated product-1 and Quinton hydrogenated product-2 (trade name) manufactured by Nippon Zeon Co., Ltd., and phthalate ester A (di (2-ethylhexyl phthalate)) as a viscosity modifier. ), Phthalate ester B (PL-200 (trade name) manufactured by Mitsubishi Gas Chemical Co., Inc.), isopentyl propionate, isopentyl butyrate, and butyl benzoate, manufactured by Shin Nippon Rika Co., Ltd. as an organic gelling agent. Gelol D, which is dibenzylidene sorbitol (however, Gelol D is dissolved in dimethyl sulfoxide and is 20% by weight).
Aerosil (a primary particle size of 5 to 20 nm, an average primary particle size of about 5 to 20 nm), which is fine powder silica manufactured by Nippon Aerosil Co., Ltd. 7 nm) was used.

Then, these are shown in Tables C-1, -2, -3,
-4, -5, -6, -7, -8 and -9 were mixed and the mixture was kneaded under reduced pressure for 80 minutes to prepare a serum or plasma separating composition.

Specific gravity and viscosity were measured as properties of the obtained composition, and reversibility and white turbidity due to water absorption were observed as performances of the composition, and evaluation was performed after lying down.

These results are shown in Tables D-1, -2, -3,-.
4, -5, -6, -7, -8 and -9.

The specific gravity is measured by a float-sink method using a copper sulfate specific gravity liquid in a constant temperature room at about 23 ° C., and the viscosity is measured by connecting a circulating constant temperature water tank to an E-type viscometer manufactured by Tokyo Keiki Co. A rotor (3.0 °, diameter 14.0 mm) was used to rotate at a rotational speed of 0.
The measurement was carried out at a measurement temperature of 15 ° C. and 25 ° C. at 5 rpm.

Performance evaluation was performed as follows.

The reversibility and the appearance of water turbidity due to water absorption were examined by the following operations. That is, 1.2 g of the above composition was stored in a commercially available 10 ml hard glass plain tube, and the tube was used as a blood test container. 8 ml of human fresh blood was dispensed into this tube and allowed to stand at room temperature around 23 ° C. After confirming the completion of coagulation, the container was allowed to stand at 15 ° C. for 30 minutes, and a centrifugal separator with a refrigerator set at 15 ° C. was centrifuged at 1300 G for 5 minutes. After that, the contents are observed, and the degree of formation of the separation image is indicated by ⊚, ○, × (⊚ = good separation image is formed, ◯ = partition of the composition in which some of the composition remains on the tube wall. Is formed, x = no partition is formed)
It was judged by. Moreover, the presence or absence of water turbidity was visually examined.

For evaluation after laying over, 1.2 g of the above composition was similarly put in a commercially available 10 ml hard glass plain tube, and the tube was used as a blood test container, which was laid down at 60 ° C. for 24 hours. Observing the flow of the composition in this state, "phase separation" means that the viscosity modifier has separated from the composition, and "phase separation" means that the composition has flowed to the tube mouth. It was judged as "overflow".

[0054]

[Table 7]

[Table 8]

[Table 9]

[Table 10]

[Table 11]

[Table 12]

[Table 13]

[Table 14]

[Table 15]

[Table 16]

[Table 17]

[Table 18]

[Table 19]

[Table 20]

[Table 21]

[Table 22]

[Table 23]

[Table 24] As is clear from the above tables, Examples 1-1 to 1-1
4, 2-1 to 2-14, 3-1 to 3-14, 4-1 to 4
-14, 5-1 to 5-5, 6-1 to 6-2, 7-1 to 7
With the composition for separation of No. -8, a good separation image was formed, and there was no clouding due to water absorption of the composition, and the evaluation after lying over was also good.

On the other hand, as is clear from Tables C-1 and D-1, in the separating compositions of Comparative Examples 1-1 and 1-3, the reversibility was poor because the amount of the viscosity modifier was small. Comparative Example 1
In the separation compositions of Nos. 2, 1-4, the amount of the viscosity modifier was too large, and thus the phase separation occurred in the evaluation after overturning.

Further, as is clear from Table C-2 and Table D-2, the separation compositions of Comparative Examples 2-1 and 2-3 contained a small amount of the organic gelling agent, and thus were evaluated after being laid down. Overflow occurred, and in the separating compositions of Comparative Examples 2-2 and 2-4, the amount of the organic gelling agent was too large and the increase in viscosity was too large, resulting in poor reversibility.

As is clear from Tables C-3 and D-3, in the separating compositions of Comparative Examples 3-1 and 3-3, the reversibility was poor because the amount of the viscosity modifier was small, and the comparison Example 3-2,
In the composition for separation of 3-4, since the amount of the viscosity modifier was too large, phase separation occurred in the evaluation after overturning.

Further, as is clear from Tables C-4 and D-4, in the separating compositions of Comparative Examples 4-1 and 4-3, since the amount of the organic gelling agent was small, the evaluation was made after lying over. Overflow was caused, and in the separating compositions of Comparative Examples 4-2 and 4-4, the amount of the organic gelling agent was too large and the increase in viscosity was too large, resulting in poor reversibility.

As is clear from Tables C-8 and D-8, since the separating composition of Comparative Example 8-1 uses propylene glycol as the organic gelling agent, the absorbing composition becomes cloudy due to water absorption. In the separation composition of Comparative Example 8-2, since the viscosity modifier was not added at all, the reversibility at 15 ° C. deteriorated, and the separation composition of Comparative Examples 8-3 to 8-4. However, since no organic gelling agent was added at all, overflow occurred in the evaluation after overturning.

As is clear from Table C-9 and Table D-9,
Since the separation composition of Comparative Example 9-1 uses propylene glycol as the organic gelling agent, water absorption turbidity of the separation composition occurs, and a viscosity modifier is added to the separation composition of Comparative Example 9-2 at all. Since the inversion property at 15 ° C. is deteriorated, the compositions for separation of Comparative Examples 9-3 to 9-4 do not contain an organic gelling agent at all, and thus overflow occurs in the evaluation after overturning. Oops.

Examples 10-1 to 10-6 and Comparative Example 11 Viscosity of 100 parts by weight of ECR-327 manufactured by Exxon Chemical Co., Ltd. having properties as shown in Table A as a hydrogenated product of cyclopentadiene resin. Phthalic acid ester B (manufactured by Mitsubishi Gas Chemical Co., Inc., trade name: PL-20)
0) was used at a ratio of 5 parts by weight, and as an organic gelling agent, gelol D, a dibenzylidene sorbitol manufactured by Shin Nippon Rika Co., Ltd., was used at a ratio of 0.2 parts by weight. 20% by weight dissolved
Used as a solution), as the specific gravity adjusting agent, Aerosil (primary particle size 5 to 20 nm, average primary particle size of about 7 nm), which is fine powder silica manufactured by Nippon Aerosil Co., Ltd., was used at a ratio of 3 parts by weight. Examples of the phenolic antioxidant of the γ-ray stabilizer include n-octadecyl-3- (4′-hydroxy-).
3 ', 5'-di-t-butylphenyl) propionate (Asahi Denka Kogyo KK, trade name: ADK STAB A
O-50) is used, and the light stabilizer is bis (2,2,2).
6,6-Tetramethyl-4-piperidyl) sebacate (manufactured by Asahi Denka Co., Ltd., trade name: ADK STAB L
A-77), as a phosphite antioxidant,
4,4'-butylidene-bis (3-methyl-6-t-butylphenyl-di-tridecyl) phosphite (Asahi Denka Kogyo KK, trade name: ADK STAB 260) was used.

As the γ-ray stabilizer, a mixture of the above three components was dissolved in N-methylpyrrolidone to form a 58% by weight solution.

Then, these γ-ray stabilizer components were added to 100 parts by weight of the above ECR-327 and phthalic acid ester B.
5 parts by weight of the above, 0.2 parts by weight of gelol D, and 3 parts by weight of aerosil were mixed in the proportions shown in Table E and kneaded under reduced pressure for 80 minutes to prepare a composition for separating serum or plasma. did.

As the performance of the obtained composition, the state of foaming after γ-ray irradiation, the reversal property, and the state of clouding due to water absorption were evaluated.

The results are shown in Table E.

The performance evaluation was performed as follows.

First, 1.2 g of the above composition was added to a commercially available 10 m
It was housed in a hard glass plain tube, and the obtained blood test container was used as a sample for performance evaluation.

Regarding the state of foaming after irradiation with γ-rays, γ-rays having cobalt-60 as a radiation source in the above blood test container were used for each evaluation sample at 2.5 Mrad (actually measured 2.6 to 2.8 Mr.
irradiation) and 5.0 Mrad (actual measurement: 5.2 to 5.6 Mrad). Then, the presence or absence of foaming was visually inspected, and the ratio of the number of non-foaming samples to the total number of samples (100 in each test) was calculated as a foaming suppression rate (γ of medical device).
Irradiation of 2.5 Mrad is usually sufficient for sterilization with − rays, but in consideration of variation in irradiation and resterilization.
The test was also performed at 0 Mrad irradiation).

Regarding the reversibility and the state of water turbidity due to water absorption, the operation was performed according to the method of the above-mentioned example. ◎, ○ in Table E
And x have the same meaning as described above.

[0070]

[Table 25] As is clear from the above table, the reversibility was quite good in both the separating compositions of Examples and Comparative Examples.

In the separating compositions of Examples 10-1, 10-2 and 10-3, white turbidity due to water absorption was not recognized. However, the phenomenon of foaming was observed for both γ-ray irradiation of 2.5 Mrad and 5.0 Mrad.

In the separating composition of Example 10-4, no white turbidity due to water absorption was observed, and no foaming phenomenon was observed upon irradiation with γ-ray of 2.5 Mrad. However, 5.0Mr
The phenomenon of foaming was observed for the γ-ray irradiation of ad.

In the separating compositions of Examples 10-5 and 10-6, no white turbidity due to water absorption was observed, and the phenomenon of foaming was recognized under irradiation with γ-rays of 2.5 Mrad and 5.0 Mrad. I couldn't do it.

Therefore, the separating compositions of Examples 10-1, 10-2 and 10-3 can achieve the above-mentioned first object, and Examples 10-4, 10-5 and 1
The separating composition 0-6 can achieve both the first and second objects described above.

On the other hand, in the separating composition of Comparative Example 11, the phenomenon of foaming was not observed when irradiated with γ-rays of 2.5 Mrad and 5.0 Mrad, but the composition of N-methylpyrrolidone Due to water absorption due to the increase in the amount, water turbidity due to water absorption of the separating composition occurred.

Examples 12-1 to 12-4 In Examples 2-5, 2-6, 2-7, and 2-8,
Instead of containing the serum or plasma separating composition in a rigid glass plain tube with a volume of 10 ml,
The sample was housed in a polyethylene terephthalate resin tube having a capacity of ml, and other points were the same as in the above-mentioned example.

As a result, the performance of the composition contained in the resin tube (reversal property, cloudiness due to water absorption, evaluation after lying over) was evaluated in Examples 2-5, 2-6, 2-7, and 2-8. The performance of the composition contained in the glass tube was exactly the same.

Examples 13-1 to 13-6 In Examples 10-1 to 10-6, instead of containing the serum or plasma separating composition in a hard glass plain tube having a volume of 10 ml, the composition was separated into a volume of 10 ml. The sample was housed in a polyethylene terephthalate resin tube (1), and the other points were the same as in the above-mentioned example.

As a result, the performance of the composition contained in the resin tube (foaming suppression rate, reversal property, cloudiness due to water absorption)
Was exactly the same as the performance of the compositions contained in the glass tubes in Examples 10-1 to 10-6.

[0080]

EFFECT OF THE INVENTION The composition for separating serum or plasma comprising the cyclopentadiene resin, the viscosity modifier and the organic gelling agent of the present invention is satisfactory even when using a centrifuge with a refrigerator. It is possible to form various separated images. Further, since the composition has almost no polarity, it does not show hygroscopicity after centrifugation, and has no adverse effect on not only measurement of clinical test items in blood but also measurement of drug concentration in blood.

Further, the composition for separating serum or plasma comprising the cyclopentadiene resin, the viscosity modifier, the organic gelling agent and the γ-ray stabilizer according to the present invention, in addition to the above effects,
The remarkable effect that there is no risk of decomposition and foaming due to the sterilization treatment by the irradiation of rays can be achieved.

Claims (4)

[Claims] 1. A serum or plasma separating composition comprising a cyclopentadiene resin, a viscosity modifier and an organic gelling agent, wherein the cyclopentadiene resin is a liquid resin at a temperature of 25 ° C. Is propionic acid, butyric acid,
Liquid ester obtained from benzoic acid or phthalic acid,
The organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and further the above cyclopentadiene resin 10
The proportion of the viscosity modifier is 0.8 to 25 parts by weight relative to 0 parts by weight.
The composition for separating serum or plasma, characterized in that the weight ratio of said organic gelling agent is 0.03 to 0.9 weight part. 2. A serum or plasma separating composition comprising a cyclopentadiene resin, a viscosity modifier, an organic gelling agent and a γ-ray stabilizer, wherein the cyclopentadiene resin is a liquid resin at a temperature of 25 ° C. The viscosity modifier is a liquid ester obtained from propionic acid, butyric acid, benzoic acid or phthalic acid, the organic gelling agent is a condensate of sorbitol and an aromatic aldehyde, and the γ-ray stabilizer is It is a mixture of a phenolic antioxidant, a light stabilizer, and a phosphite antioxidant, and further contains the above cyclopentadiene resin 100.
The ratio of the viscosity modifier is 0.8 to 25 parts by weight, the ratio of the organic gelling agent is 0.03 to 0.9 parts by weight, and the ratio of the γ-ray stabilizer is 1.32 with respect to parts by weight. ~ 7.7 parts by weight of the composition for separating serum or plasma. 3. The phenolic antioxidant of the γ-ray stabilizer is n-octadecyl-3- (4'-hydroxy-3 ',
5'-di-t-butylphenyl) propionate, the light stabilizer is bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate, and the phosphite antioxidant is 4,4'-butylidene. -Bis (3-methyl-6-t-butylphenyl-di-tridecyl) phosphite,
The ratio of the phenolic antioxidant is 0.12 to 0.7 parts by weight, the ratio of the light stabilizer is 0.6 to 3.5 parts by weight, and the phosphite antioxidant is based on 100 parts by weight of the cyclopentadiene resin. The composition for separating serum or plasma according to claim 2, wherein the ratio of the agent is 0.6 to 3.5 parts by weight. 4. A blood test container containing the composition for separating serum or plasma according to any one of claims 1 to 3.