JPH07104340B2 - Sealant composition for blood separation - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel blood separation used for separating a serum or plasma portion in blood from a blood clot portion composed of red blood cells, fibrin and the like. Sealant composition for use.

[Prior Art] Chemical analysis of blood is indispensable in current medical diagnosis and treatment, and whole blood and blood clots are not suitable as samples for this blood analysis, and serum and plasma are usually used. For serum or plasma used for such purposes, blood collected from a patient is placed in a blood collection test tube, centrifuged to separate the serum or plasma portion and the clot portion, and the serum or plasma portion is separated by pipette work. It is being taken out as a sample.

However, the work of removing the serum or plasma portion with a pipette work after centrifugation requires considerable skill and labor because the contamination of the blood clot portion may adversely affect blood analysis. There has been a problem that a large number of pipettes need to be handled and washed according to the number, which requires a great deal of labor.

Therefore, conventionally, a sealant (sealant) having an intermediate density between the serum or plasma portion and the blood clot portion has been used, and a partition wall of the sealant is formed between the serum or plasma portion and the blood clot portion during centrifugation. Attempts have been made to remove the serum or plasma portion by a simple operation such as decantation.

And as such a sealant, for example, those composed of hydrophobic spherical particles inert to blood and a viscous fluid which is a mixture of liquid polybutadiene and a specific gravity adjusting agent (Japanese Patent Publication No. 25-25438). ), Consisting of a silicone fluid and an inert filler (Japanese Patent Publication No. 59-2345, Japanese Patent Publication No. 5345)
9,11,863, JP-A-52-74,657, JP-A-57-106,622
Nos. Etc.), those composed of alkyl acrylate and / or alkyl methacrylate and silica fine powder (Japanese Patent Publication No. 59-17385), those composed of liquid polybutene and powdered silica (Japanese Patent Publication No. 52-78167). ), A thixotropic agent, an acid-modified product of a liquid polymer, a liquid polymer, a styrene oligomer and a chloride thereof (JP-A-57-37,260), an acrylic acid ester-based polymer or copolymer. Acrylic pressure-sensitive adhesive fine particles (JP-A-57-159,561), a thixotropic agent, a viscous liquid and a water-insoluble amine compound (JP-A-57-197,470), Those composed of polyether polyurethane and inert filler (JP-A-58-17366), those composed of polyether ester and inert filler (JP-A-58-366) 137,757), an α-olefin / fumaric acid diester copolymer and a viscosity / specific gravity adjusting agent such as an aliphatic amine derivative of smectite clay (JP-A-58,206,964) and the like,
Many things are known.

[Problems to be Solved by the Invention] However, although the above-mentioned conventional sealants each have excellent characteristics, various performances required as a sealant for blood separation, particularly in serum or plasma part are required. On the other hand, it is inert and does not dissolve, and does not affect blood analysis. It quickly forms a septum between the serum or plasma part separated during centrifugation and the clot part. , The formed partition wall has excellent sealing property, the formed partition wall is stable and does not break even when tilted, it has excellent stability over time and is easy to handle, etc. There is a demand for the development of a sealant composition for blood separation, which does not have the performance to be obtained but has more excellent performance.

Therefore, an object of the present invention is to provide a novel blood separation sealant composition, and to provide a blood separation sealant composition having excellent performance in that all the required performances are sufficiently satisfied. To provide.

[Means for Solving the Problems] That is, the present invention relates to a trifluorochloroethylene low polymer having an average molecular weight of 400 to 1,500 (0.1 to 60% by weight), an inert filler (0.1 to 60% by weight).
Semi-solid composition containing 30% by weight and a viscous liquid material which is compatible with the above low polymerized trifluoroethylene chloride and has a viscosity at 100 ° C of 1 cSt or more and is inert to blood It has a specific gravity of 1.015 to 1.070 and a consistency of 25.
It is a sealant composition for blood separation which is 0-450.

The trifluorochloroethylene low polymer used in the present invention exhibits various appearances ranging from colorless transparent to colorless translucent, from light oil to waxy, depending on the degree of polymerization, and has excellent hydrophobicity, It has heat resistance and chemical resistance. In the present invention, those having an average molecular weight of 400 to 1,500, preferably 500 to 1,300, more preferably 700 to 1,100 are used. Such a trifluoroethylene chloride low polymer has a pour point of about -70 ° C to about 65 ° C,
Liquids with a specific gravity of 1.850 to 1.975 (25 ° C)
For waxy products, 1.945 to 1.995 (10
0 ° C), and those with a liquid viscosity of 5 to 1,5
20 for waxy ones at 00cSt (25 ℃)
It is ~ 420cSt (100 ℃).

As the inert filler used in the present invention, conventionally known ones, for example, precipitated silica, evaporated silica, hydrophobic silica treated with silane or polysiloxane, titanium oxide,
Alumina, talc, silylate, bentonite, mineral clay, glass powder, zirconium, asbestos, fine powder of carbon black and the like can be mentioned, but particularly preferred is an average particle size of 5 to 30 mμ, more preferably 12 to 20 m.
μ is a hydrophobic fine silica.

Further, the viscous liquid used together with the low molecular weight trifluoromethylene chloride polymer and the inert filler has a compatibility with the low molecular weight trifluorochloroethylene chloride and is 100 ° C.
It is essential that the viscosity is 1 cSt or more and is inactive to blood, and those satisfying such conditions include, for example, an average molecular weight of 200 to 4,000, preferably 2,000.
~ 3,000 water-insoluble polyoxyalkylene glycol-based oil, average molecular weight 300-6,000, preferably 1,000-5,000 polyolefins, average molecular weight 200-5,000, preferably
500-3,000 poly α-oleins, average molecular weight 200-15
There may be mentioned olefin / α-olein copolymers of 0,000, preferably 500 to 100,000, highly refined mineral oil, etc. These may be used alone or as a mixture of two or more kinds.

The water-insoluble polyoxyalkylene glycol-based oil specifically has an average molecular weight of 200 to 4,000, a 100 ° C viscosity of 2 to 100 cSt, and a specific gravity of 0.960 to 1.
Examples of the polyolefins include polyoxyalkylene glycols having an average molecular weight of 300 to 5,000, 100 ° C. viscosity of 4 to 6,000 cSt, and specific gravity of 0.820 to 0.920. Examples of the poly α-oleins include synthetic oil PAO having an average molecular weight of 200 to 5,000, a 100 ° C. viscosity of 1 to 200 cSt, and a specific gravity of 0.790 to 0.870. The above olefin / α-olein copolymers have an average molecular weight of 200 to 150,000 and 100
Examples include ethylene / α-olefin copolymers having a viscosity of 5 to 10,000 cSt and a specific gravity of 0.820 to 0.950. Further, as the highly refined mineral oil, 100 ° C.
Examples thereof include those having a viscosity of 1.5 to 60 cSt and a specific gravity of 0.875 to 0.975. 2% or less of poly (oxyethylene / oxypropylene) glycols may be used as a stabilizer for the sealant composition.

In the present invention, the compounding ratio of the trifluoroethylene chloride low polymer, the inert filler and the viscous liquid is such that the trifluoroethylene chloride low polymer is 0.1 to 60% by weight, preferably 5 to 50% by weight, It is more preferably in the range of 9 to 40% by weight, and depending on its type, the inert filler is 0.1 to 30% by weight, preferably 0.5 to 20% by weight, and the viscous liquid also varies depending on its type. It is 10 to 95% by weight, preferably 50 to 90% by weight. When the amount of low-polymerized trifluoroethylene chloride is less than 0.1% by weight, the specific gravity becomes too small, and when it is more than 60% by weight, the specific gravity becomes too large and the price becomes high. Occurs.

Regarding the blood separation sealant composition of the present invention, the trifluorochloroethylene low polymer, the inert filler and the viscous liquid are blended within a predetermined range, and the specific gravity thereof is 1.015 to 1.07.
It is necessary to adjust it so that it is in the range of 0, preferably 1.035 to 1.065, and its consistency is in the range of 250 to 450, preferably 270 to 400. The specific gravity needs to be an intermediate value between the blood serum or plasma and the blood clot. Regarding the consistency, the sealant composition of the present invention shows a semi-solid state property in forming a stable partition wall between the serum or plasma portion and the blood clot portion promptly during centrifugation of blood. It is necessary to be within the above range, and if it is lower than 250, it is too hard and it is difficult to quickly form a partition wall between the blood serum clot part and the separated serum or plasma part during centrifugation. There is a problem that the sealing performance is poor even if formed, and if it is higher than 450, it is too soft and the partition wall is not stable, and if it is inclined, there is a problem that it is easily broken.

[Operation] In the present invention, the trifluoroethylene chloride low polymer is chemically very stable to air (oxygen), moisture, heat, acid, alkali and other chemicals, and to the blood. In addition to being inert, it has a semi-solid sealant composition, so it can be used by putting it in the bottom of a blood sampling tube, or by putting it in a special container and covering the blood sampling tube with the lid. In any of these methods, the sealant composition does not flow out, and a septum can be easily formed between the serum or plasma portion and the blood clot portion by adding blood and centrifuging.

[Examples] Hereinafter, the sealant composition for blood separation of the present invention will be specifically described based on Examples and Test Examples.

Examples 1 to 6 Average molecular weight 900, pour point −20 ° C., specific gravity (25 ° C.) 1.950, viscosity (25 ° C.) 200 cSt, colorless transparent heavy oil trifluorinated ethylene chloride oligomer (FClEO, product of Daikin Industries, Ltd.) Name:
Daifloyl # 10), hydrophobic fine silica with an average particle size of 16 mμ (HPFSi, Nippon Aerosil Co., Ltd. product name: Hydrophobic Aerosil R972), average molecular weight 2,400, pour point 15
℃, specific gravity (15/4 ℃) 0.905, viscosity (100 ℃) 4,500cSt, viscous liquid polybutene (PBTEN, Idemitsu Kosan Co., Ltd. product name: Polybutene 2000H), average molecular weight 3,800, pour point 0
℃, specific gravity (20/4 ℃) 0.850, viscosity (100 ℃) 2,000cSt, viscous liquid ethylene / α-olefin copolymer (EAOC
O, Mitsui Petrochemical Industry Co., Ltd. product name: Lucant 200
0), pour point -20 ℃, specific gravity (15/4 ℃) 0.880, viscosity (10
(0 ℃) 9.5cSt highly refined mineral oil (HPMO, Kyodo Oil Co., Ltd. trade name: 500 Neutral oil), average molecular weight 560, pour point -67.5 ℃, specific gravity (15/4 ℃) 0.826), viscosity (100 ℃) 6c
Poly α-olefin, a synthetic oil of St (SYPAO, manufactured by Gulf Oil Corporation, trade name: Shinflude 601)
And average molecular weight 2,400, pour point −22.5 ℃, specific gravity (20/4
℃) 1.008, viscosity (100 ℃) 55cSt polyoxyalkylene glycol (POAG, Sanyo Kasei Co., Ltd. trade name: Newpol 1800X) and poly (oxyethylene / oxypropylene) glycol (POEPG) as stabilizer Then
The sealant compositions of Examples 1 to 6 were prepared by blending in the proportions shown in Table 1.

Regarding the obtained sealant compositions of Examples 1 to 6,
Its specific gravity and consistency were measured. The results are shown in Table 1. The specific gravity is calculated from the specific gravity of each raw material and its usage rate, and the consistency is measured according to JIS K2220 (5.3).
It was determined by mixing 60 times at 25 ° C.

Test Example The sealant composition obtained in each of the above Examples 1 to 6 was heated to a temperature of 10 ml and dispensed in 1.5 ml aliquots into blood collection tubes for blood separation. After defoaming, the tubes were sealed in a vacuum to remove these blood collection tubes. After blood collection, the cells were centrifuged (2,500 rpm × 10 min, arm length 12 cm).

As a result, in any case, a septum was formed between the serum or plasma portion and the blood clot portion, and the serum or plasma portion could be easily separated by decantation. In addition, when a clinical test was performed, the same result as when the serum or plasma part was fractionated by pipette out without using the sealant composition for blood separation of the present invention could be obtained.

[Effect of the Invention] The sealant composition for blood separation of the present invention has an average molecular weight of 40
Containing 0 to 1,500 trifluoroethylene chloride low polymer, it is a semi-solid state and is an extremely stable composition, which is inert to serum or plasma parts and does not dissolve,
In addition to not affecting blood analysis, a partition is formed quickly between the serum or plasma part and the clot part separated during centrifugation, and the formed partition has excellent sealing properties, In addition, the partition wall is stable and is not broken even when tilted, and it is excellent in temporal stability and easy to handle.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Yoshinori Nagachi 721-8 Isshiki, Shizuoka Prefecture (72) Inventor Kiyoshi Ishibashi 4-9-6 Doetsu, Shimada City, Shizuoka Prefecture (72) Hiroyuki Yamamoto Yokohama, Kanagawa Prefecture 6-31-102 Konandai, Konan-ku, Yokohama-shi (72) Inventor Kunio Yamada 111-12 Ootsuka Nitta, Kawagoe City, Saitama Prefecture

Claims (3)

[Claims] 1. A low polymer of trifluoroethylene chloride having an average molecular weight of 400 to 1,500, 0.1 to 60% by weight, and an inert filler, 0.1 to 30% by weight.
And a semi-solid composition containing a viscous liquid material which is compatible with the above low-polymerized trifluoroethylene chloride and has a viscosity at 100 ° C. of 1 cSt or more and is inert to blood. A sealant composition for blood separation, which has a specific gravity of 1.015 to 1.070 and a consistency of 250 to 450. 2. The sealant composition for blood separation according to claim 1, wherein the inert filler is hydrophobic fine silica. 3. A water-insoluble polyoxyalkylene glycol-based oil whose viscous liquid has an average molecular weight of 200 to 4,000, and an average molecular weight.
300-5,000 polyolefins, average molecular weight 200-5,000
The poly-α-oleins, the olefin / α-olein copolymers having an average molecular weight of 200 to 150,000, and highly refined mineral oil, or a mixture of two or more thereof. A sealant composition for separating blood according to the item.