JPS5835463A - Blood separating tube - Google Patents

Abstract

PURPOSE:To provide a blood separating tube being excellent in long storage stability, gamma-ray sterization and separating property, by a method wherein gel separating agent of thixotropy property including copolymer of alpha-olefin maleic diester and viscosity/specific gravity adjusting agent is arranged with a recess. CONSTITUTION:Gel separating agent 2 of thixotropy property with specific gravity 1.035-1.055 including copolymer of 100pts. in weight represented by formula (R1: H or alkyl of C1-20 being the same of different in one molecule; R2, R3: straight chain alkyl of C1-15, branched chain alkyl of C16-20. If R1 is H, R2 and R3 are straight chain alkyl of C2-15 and branched chain alkyl of C16-20. If R1 is alkyl of C1-20, total number of C in R1 and R2 and in R1 and R3 is 5-25. n: 5-30), gelling agent such as dimethyl polysiloxane of 0.4-0.6pts. in weight, aliphatic amine derivative of C8-24 of smectite clay as viscosity/specific gravity adjusting agent and inorganic fine powder such as sintered silica, is entered in a separating tube 1 of serum phase and cruor phase in blood. The separating agent 2 is entered in the separating tube 1 so as to form a recess 3. In this constitution, serum 4 and cruor 5 are separated well without using strong centrifugal force.

Description

DETAILED DESCRIPTION OF THE INVENTION 1. BACKGROUND OF THE INVENTION Technical Field The present invention relates to a blood separation tube for separating a blood sample into a supernatant phase and a blood clot layer by centrifugation.

PRIOR ART Blood separation tubes are known in the past in which a thixotropic gelatinous separating agent, such as a mixture of silicone, silica and a caking agent, is housed at the bottom of the tube (U.S. Pat. No. 3,780, No. 935). After collecting blood in this blood separation tube and allowing it to stand still for an appropriate time, when the centrifugal force is applied to the centrifugal force, this glue-like separation agent becomes fluid9. Since it has a specific gravity intermediate between the two, it gradually rises from the bottom of the tube and comes to be located between the serum layer and the blood clot layer, allowing the serum layer and the blood clot layer to be separated. However, when trying to separate serum from a small amount of blood using this method, a fairly strong centrifugal force (for example, 1500 G) is required, and therefore,
This strong centrifugal force damages red blood cells and causes hemolysis, which poses a problem in that accurate biochemical test values may not be obtained. This problem is especially serious when the cell material is made of a material that tends to harden over time due to hydrogen bonding and other factors, and whose floating properties tend to deteriorate.

In order to overcome these drawbacks, a blood separation tube is known in which the upper surface of the separation agent is slanted so that the separation agent can be easily fluidized during centrifugation (US Pat. No. 3.9).
No. 97.442).

However, in this conventional blood separation tube, in order to obtain sufficient fluidization of the glue separation agent, the angle of inclination of the upper surface of the separation agent must be made considerably large, and the larger the angle of inclination, the more difficult it is to transport the product. However, there was a drawback that the sloped surface could collapse due to handling or the like. In addition, to form such an inclined surface, operations such as centrifugation are required, but since this operation is performed patch by patch rather than assembly line work, the manufacturing line is complicated and costly. It has the disadvantage of being expensive.

In addition, the separation agent consisting of silicone oil, silica, and chelating agent mechanically mixes components that are poorly compatible with each other, and the chelating agent forms hydrogen bonds between silica particles (specific gravity adjusting agent). In order to achieve this goal, as time passes, these hydrogen bonds become stronger and agglomeration occurs, phase separation occurs, and centrifugal separation occurs. There were problems such as poor fluidity during operation. Therefore, it has been proposed to add a surfactant to prevent phase separation, but if a large amount of ionic surfactant is added, hemolysis becomes a problem.

If saliva with the above composition is placed in an appropriate amount in a blood collection tube and then subjected to gamma ray sterilization, it will be significantly denatured due to cross-linking reactions, impair its function as a separating agent, and reduce the formation of shell-like substances. Problems include that the molecular substances volatilize and make the inner surface of the tube water repellent, resulting in delayed blood coagulation and blood clot adhesion, and that the raw materials are relatively expensive.

In addition, separation agents made of gel-like substances based on polyester are also known. However, like the above-mentioned well-known shell-like substances, since they make the inner surface of the tube water repellent, they have problems such as delayed blood coagulation and adhesion of blood clots, as well as giving off an unpleasant odor, so they are not necessarily satisfactory. I can't say that.

10 OBJECTS OF THE INVENTION It is therefore an object of the present invention to provide a new and improved blood separation tube which does not have the disadvantages mentioned above.

That is, firstly, when blood is separated using a chicken-tropic shell-like separating agent, the blood separation operation can be performed with a smaller centrifugal force than conventionally, and problems such as hemolysis can be avoided. The aim is to provide a blood separation tube that can be avoided.

Second, this invention has excellent stability over time due to the large dispersion power of the oil, and is also capable of being sterilized by γ-rays.
It exhibits almost no water repellency, has no unpleasant odor, and can be manufactured at a relatively low cost.As a result, there is no hemolysis, and even when stored in a blood collection tube in advance, there is no delay in coagulation or adhesion of blood clots to the tube wall. It is an object of the present invention to provide a blood separation tube containing a separation agent that does not cause such problems.

According to the present invention, a blood separation tube described in each of the following items is provided.

(1) A blood collection tube with a bottom and blood for serum and blood ωF phase contained in the bottom of the tube! = (7) A blood separation tube comprising a thixotropic shell-like separation agent having an intermediate specific gravity, wherein the separation agent is accommodated in the bottom of the tube with a depression formed on its upper surface, and The separating agent has a viscosity of 10.00
0 to 120,000 cp (25°C) (wherein R4 is the same or different in the same molecule and represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms, R
2 and R3 are each a linear or branched alkyl group having 1 to 15 carbon atoms or 16 carbon atoms.
to 20 branched alkyl groups. However, R1
is a hydrogen atom, R2 and R3 are each a linear or branched alkyl group having 12 to 15 carbon atoms or a branched alkyl group having 16 to 20 carbon atoms. When R1 is an alkyl group having 1 to 20 carbon atoms, the total number of carbon atoms of R1 and R2 and R4 and R3 is 5 to 25, respectively. Further, when R4 is an alkyl group having 2 to 20 carbon atoms, R2 and R3 are respectively a methyl group, an ethyl group,
Except when it is a butyl group or a 2-ethylhexyl group. n is an integer from 5 to 30. ) represented by α−
The main component is an olefin/maleic acid diester copolymer, and a viscosity/specific gravity regulator is added to this, resulting in a specific gravity of 1.0.
A blood separation tube characterized in that the blood separation tube is adjusted to 35 to 1.055.

(2) In the general formula of the above copolymer, R1 is a hydrogen atom, and R2 and R3 are each a linear or branched alkyl group having 12 to 15 carbon atoms or a branched chain having 16 to 20 carbon atoms. 2. The blood fraction 1 miscellaneous tube according to item 1, which is a chain alkyl group.

(3) In the general formula of the above copolymer, R, is a methyl group, and R2 and R3 are each a linear or branched alkyl group having 4 to 15 carbon atoms or a straight chain or branched alkyl group having 16 to 20 carbon atoms. 2. The blood separation tube according to item 1, which is a branched alkyl group.

(4) The blood separation tube according to item 1, wherein the gelling agent is contained in an amount of 0.04 to 0.06 parts per 100 parts of the α-olefin/maleic acid diester copolymer.

(5) Number of carbon atoms in α-olefin component: 30-6
2. The blood separation tube according to claim 1, further comprising 1 part by weight of 1.0 to 3.0 weight of the above-mentioned main component of a wax consisting of a copolymer of α-olefin and maleic acid diester having a weight of 1.0 to 3.0.

(6) The above viscosity/specific gravity regulator is C8 smectite clay.
2. The blood separation tube according to item 1, which is at least one selected from 24 aliphatic amine derivatives and inorganic fine powders.

(7) The aliphatic amine derivative of the smectite clay is a quaternary ammonium derivative of the smectite clay.
Blood separation tube as described in section.

(8) The blood separation tube according to item 6, wherein the viscosity/specific gravity regulator is an inorganic fine powder, such as calcined silica or precipitated silica.

(9) The size of the recess of the separation agent is such that the diameter of the upper surface is 0.15 times or more and 0.7 times or less the inner diameter of the pipe, and the depth is 0.13 times or more and 0.65 times or less the thickness of the separation agent. A blood separation tube according to item 1.

αQ The size of the recess of the separating agent is such that the diameter of the upper surface is 0.3 times or more and 0.5 times or less the inner diameter of the pipe, and the depth is 0.2 times or more and 0.55 times or less the thickness of the separating agent. The blood separation tube according to item 9.

0υ A blood separation tube according to any one of the above items 1 to 10, in which a carrier carrying a blood coagulation promoter is housed in the inner space of the tube above the separation agent housed in the bottom of the tube.

0.0 - A blood separation tube according to items 1 to 11 of paragraphs 1 to 11, in which the inside of the tube is maintained in a reduced pressure state.

In the general formula of the α-olefin/maleic acid diester copolymer, R1 is an alkyl group having 2 to 20 carbon atoms, and R2 and R3 are each a methyl group, an ethyl group, a butyl group, or a 2- A blood separation tube in which the ethylhexyl group is used was previously developed by the present inventors and a patent application has been filed (Japanese Patent Application No. 34634/1983).

111. Detailed description of the invention The present invention will be explained below with reference to illustrated embodiments.

Fig. 1 shows an embodiment of the blood separation tube according to the present invention, in which a chicken tropic kale-like substance is added as a separation agent to the bottom of the separation tube 1 (IoTnI! tube) at a depth of about 15 + 71 m. 2 (alpha-olefin/maleic acid diester copolymer/filler) is accommodated, and a cylindrical depression 3 (opening diameter 2 mm, depth 2 mm) is formed at the center of the upper surface. Since this cylindrical depression 3 is formed by the thixotropic shell material itself, there is no substantial risk of it collapsing during normal transportation and handling.

In terms of shape, this separation tube is not particularly different from conventional ones except that it has the above-mentioned depression 3, and the opening is usually tightly plugged so that the inside is maintained at a reduced pressure. (not shown) is passed through one end of a blood collection needle (not shown) to collect blood. After blood is collected in this way, when a centrifugal separation operation is performed, the centrifugal force causes 1) the gel-like substance 2 to become fluidized, and as shown in FIG. It deforms so as to rise along the tube wall, further moves between the serum layer 4 and the blood clot layer 5 as shown in FIG. 3, and finally the serum layer 4 and blood clot shown in FIG. Two layers of separating agent having substantially uniform thickness are formed between layer 5 and layer 5.

Even in a conventional blood separation tube in which a glue-like separation agent is accommodated in the separation tube without such a recess 3, the first
Almost the same as shown in Figures 3 to 3, the flat upper surface of the glue-like separating agent becomes curved, distortion occurs and becomes exaggerated, the flow of the separating agent becomes noticeable, and finally the fourth A separation layer as shown in the figure is formed, but in the conventional case, a large stress was required until the first stage of distortion was formed. However, in the present invention, since centrifugation is performed in a state in which a strain (that is, a depression) is formed in the glue-like separating agent in advance, the glue-like separating agent can be easily fluidized by an extremely smaller stress than in the past. Become.

9 of the shell-like separating agent contained in the bottom of the
Any method can be used to form the depressions on the layer surface, taking into consideration the physical properties of the separating agent. For example, as shown in FIG. 5, it can be easily formed by ejecting a fluid such as air or water from a thin nozzle 6 toward the surface of the glue-like separating agent.

There are no particular restrictions on the position and shape of the depression formed on the upper surface of the gel-like separation agent.For example, in addition to the embodiment shown in FIG. 1, the position of depression 3 is at the center as shown in FIG. In this case, as shown in FIG. Various shapes can be selected as appropriate, such as cylindrical, conical, and prismatic shapes.

The point is that the stress during centrifugation concentrates in this type of depression, thereby causing distortion in the glue-like substance and causing shearing force to be observed.

There is no particular limit to the size of this depression, and even if it is quite small, fluidization of the glue-like substance will be promoted by the action described above, but in general, the preferred size of the depression is the size of the opening of the depression. The diameter of the part is 0.15 of the inner diameter of the pipe.
0.7 times or more, especially 0.3 layers or more and 0.5 times or less,
The depth is 0.13 times or more and 0.65 times or less, particularly 0.2 times or more and 0.55 times or less, the thickness of the gel-like substance. When the diameter of the recess opening is less than 0.15 times the inner diameter of the tube, and when the depth is less than 0.13 times the thickness of the glue-like substance, the glue state is close to a flat surface, and 0.65 If it exceeds the limit, it is difficult to form a depression and difficult to maintain the shape, which is not preferable. Also, the diameter of the recess opening is 0 of the pipe inner diameter.
, 71 sounds, and the depth is caused by a cable-like substance.
7) If it is less than 0.13 times 17, the result will be a nearly flat surface, and if it is 0.65, there will be hardly any parts to which stress is applied, which is inappropriate.

In this invention, the α-oleph, in-maleic acid diester copolymer used as the eliminative agent has a viscosity of 10.0.
00-120,000 cp (25°C), and has the general formula (wherein R1 is the same or different in the same molecule and represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms,
R2 and R3 are each a linear or branched alkyl group having 1 to 15 carbon atoms or 1 carbon atom;
It represents 6 to 20 branched alkyl groups. However, R1
is a hydrogen atom, R2 and R3 are each a linear or branched alkyl group having 12 to 15 carbon atoms or a branched alkyl group having 16 to 20 carbon atoms. When R4 is an alkyl group having 1 to 2 o carbon atoms, the total number of carbon atoms of R1 and R2 and R4 and R5 is 5 to 25, respectively.

Further, when R4 is an alkyl group having 2 to 2 o carbon atoms, the case where R2 and R3 are each a methyl group, ethyl group, butyl group or 2-ethylhexynyl group is excluded. n is an integer from 5 to 3 degrees. ) is a copolymer represented by

In the above formula, Rll R21R3 and 4n each represent a viscosity of the copolymer of 10,000 to 120,000 cp.
(25℃) Preferably 40,000 to 80,0OOcp
(25°C) and an integer.

In addition, in the above general formula, the number of carbon atoms is -30 to 6
The α-olefin/maleic acid diester copolymer consisting of the α-olefin component having 0 and the simaleic acid ester having R2 and R3 within a range that does not hinder the crystallization of the copolymer is a wax, and the separating agent of the present invention is Although they cannot be used as main ingredients, they can be used as additives to prevent the reduction of chicken tropism caused by phase separation of the separating agent.

The α-olefin/maleic acid diester copolymer used as the separation agent of the present invention is pale yellow, transparent, and odorless, and is inert to blood and may cause phenomena such as blood adsorption and elution. It is stable over time and does not release water-repellent biological substances, so when it is stored in a blood collection tube as a separation agent (the inside of the cut blood vessel can be kept clean. Radiation sterilization by sterilization causes virtually no chemical or physical changes.

α-olefin in the separating agent used in this invention
Specific gravity of maleic acid noester co-combination (ζ1.00-1
,038, preferably from 1027 to 1035.0 The specific gravity/viscosity modifier used in this invention is preferably an aliphatic amine derivative of smectite clay, and the specific f+IJ is aliphatic primary amine of smectite clay, Aliphatic secondary amine, aliphatic, tertiary amine, aliphatic quaternary
Derivatives of amines can be used and these amine derivatives are known. Among these, aliphatic quaternary amine derivatives of smectite clay are particularly preferred, and specific examples thereof include Bentone 34, Bentone 38, Bentone 27, and Bentone 128 (a quaternary ammonium salt derivative of smectite clay manufactured by NL Industries). C,C24 aliphatic amine derivatives of smectite clays can be used.

Further, as other examples of the viscosity/specific gravity modifier in the present invention, inorganic fine powders such as calcined silica and precipitated silica can be selected as appropriate. These viscosity/specific gravity adjusting/controlling agents are used in amounts that will sufficiently gel and have a predetermined specific gravity depending on the specific gravity/viscosity of the main component.

The gelling agent used in this invention is used to gel the serum separating agent and to keep the gelated state stable. , are used in cases where gelation cannot be achieved with these alone. For example, dimethylpolysiloxane polyoxyalkylene copolymer (e.g., trade name 5) 1-377
1,5H-190,5)l-192, manufactured by Torenlicon Co., Ltd.) or calpitol (for example, ethyl diglycol), etc. may be used.

The amount to be used also needs to be an amount necessary for kelization and not liberated from other components, depending on the combination of the main component of the present invention and the viscosity/specific gravity modifier used.

In this invention, in addition to these α-olefin/maleic acid diester copolymers, viscosity/specific gravity modifiers, and gelling agents, nonionic surfactants (
For example, polyoxyethylene hydrogenated castor oil monolaurate, polyoxyethylene hydrogenated castor oil triisostearate, etc.) may be added.

By adding a small amount of this surfactant (for example, 0.47 to 27%), it is possible to prevent phase separation that may occur if left for a long time, and to prevent it from occurring. Since it is an ionic system, hemolysis does not occur.

It is particularly useful when only silica is used as the viscosity/specific gravity modifier.

Table 1 below shows a formulation example of the separating agent used in this invention.
Shown below. The α-olefin/maleic acid diester copolymers used in the formulation examples are as follows.

Copolymer A R4 is a hydrogen atom, R2 and R3 are both tridecyl groups, average molecular weight 3000-5000, viscosity 100.0
00-110,000 (25℃), specific gravity 1.01-1
．． 05 α-olefin/maleic acid noester copolymer O copolymer B R4 is a hydrogen atom, R2 and R6 are both 2-ethylhexadecyl groups, average molecular weight 3000-4000, viscosity 1
10,000-120,000, specific gravity 1.00-1.0
1 α-olefin/maleic acid diester copolymer.

Copolymer C R1 is a methyl group, R2 and R3 are both 2-ethyltetradecyl groups, average molecular weight 3000-5000°, viscosity 90,000-110,000 (25°C), specific gravity 1.
003 (25°C) α-olefin/maleic acid diester copolymer.

Copolymer D R4 is a combination of hexyl group and octyl group, R2 and R3 are both hexyl groups, average molecular weight 3500-45
00, viscosity go, ooo~100,000, specific gravity 1.0
25-1.030 α-olefin/maleic acid copolymer O copolymer E R, consisting of a combination of cabtyl group and hexyl group, R and R3 are both hexyl groups, average molecular weight 2500-40
00, viscosity 50,000-70,000, specific gravity 1.01
~1.02 α-olefin maleic acid copolymer.

Copolymer F R1 consists of a combination of a decyl group and a dodecyl group, R2 and R3 are both propyl groups, and the average molecular weight is 2500~
4000, viscosity 30,000-40,000. Specific gravity 1.
．． α-olefin/maleic acid diester copolymer of 020 to 1.025.

R is a tetracontyl CC4QH81) group, R2 and R
, AC and both have methyl groups, and are an α-olefin/maleic acid diester copolymer with a specific gravity of 0.90 to 0.95.

*Hydrophobic silica fine powder, average particle size approximately 16 mμ, apparent specific gravity approximately 60 VB, manufactured by Nippon Aeronol Co., Ltd.

**Hydrophilic silica fine powder, average particle size approximately 12mμ, apparent specific gravity approximately 60M! , manufactured by Nippon Aeronol Co., Ltd.

＊＊＊Quaternary ammonium salt derivative of smectite clay (manufactured by NL Industries (USA))＊＊＊＊Polyoxyethylene hydrogenated castor oil monolaurate, manufactured by Nippon Emulsion Company＊＊＊＊＊SH-3771, Torre silicone Made by company,
Polymethylpolysiloxane-polyoxyalkylene copolymer, specific gravity 1.060-1.080 (20°C), viscosity 26
0-280 cp.

Next, a method for producing the separating agent used in the present invention will be explained.

This is a method for producing mass, α-olefin/maleic acid diester copolymer, and i-α-
Obtain olefin. By fractional distillation, for example, carbon atoms with 2 carbon atoms, 4 carbon atoms, 6'+ 8 carbon atoms, 10 carbon atoms, 12.14 carbon atoms, 16.18 carbon atoms, 30 to 6 carbon atoms, etc.
Divide into items up to 0. Depending on the type and specific gravity of the viscosity/specific gravity adjusting agent used, these agents can be used alone or in combination; however, when used for serum separation, from the viewpoint of viscosity and specific gravity, those with 12 and 14 carbon atoms are preferred. or 6
, 8 are particularly preferred. n with odd number of carbon atoms
-α-olefin is obtained by cracking the n-α-olefin obtained above. Next
get the object.

Next, this α-olefin/maleic acid diester copolymer with a viscosity of 10,000 to 120,000 cp (preferably 40,000 to 80,000 cp (at 25°C)) is used as a paste, and the aliphatic amine of the smectite clay is added to it. Add viscosity/specific gravity adjusters such as derivatives and fine silica powder,
Furthermore, if necessary, a celifying agent, a nonionic surfactant, a waxy α-olefin/maleic acid diester copolymer (for example, the above n-α-olefin has 30 to 60 carbon atoms) may be added. Add and add the ingredients up to
Appropriate shearing force is applied using a three-roll mill, a crusher, a zoranetary mixer, etc., and the mixture is kneaded until it becomes a keel.

The separating agent prepared in this way has a viscosity of 250.00
Specific gravity 1.035~ at 0~800,0OOcp (25℃)
A value of 1.055 is preferred. Each of the composition examples in the above table has thixotropic properties, shows fluidity when stress such as centrifugal force is applied, and forms a homogeneous and stable cell under normal conditions. As is clear from 1, even if it is stored in a separation tube in advance, the inside of the tube will not become water repellent, and as a result, it will not cause blood clot adhesion or delay in blood coagulation. This is because α-olefin/maleic acid diester copolymer is used as the main component, so low-molecular volatile substances are not generated. Therefore, when the separation agent of this invention is used in a blood separation tube, it is possible to stabilize the blood between the serum and blood clot layers by centrifuging it for about 10 minutes with a normal centrifugal force (700 to 1,000 OOG) using a centrifuge. As a result, serum can be easily collected with a decanter/can without contaminating fibrin, etc., and after centrifugation,
Since the serum and blood clot are located in a stable shell, the serum and blood clot layers do not mix together even when transported from a hospital to a testing center after separation.

Furthermore, the present invention provides a blood separation tube for promoting blood coagulation, in which a carrier carrying a blood coagulation promoter is housed in the inner space of the tube above the separation agent housed in the bottom of the blood separation chamber. .

As the carrier used in the separation tube, a hydrophilic carrier having a specific gravity higher than that of blood cells and carrying an appropriate amount of a powdered blood coagulation promoter via a serum-soluble binder can also be used.

In this case, the carrier may be cloth, filter paper, non-woven fabric, or wire ring in any form, but it must have a higher specific gravity than blood cells, be non-hemolytic, and have no effect on biochemical tests. , have a material (e.g., hydrophilicity) or structure (e.g., porous structure with continuous pores) that provides water retention, have rigidity or elasticity that can be maintained between tube walls, and can withstand stress during centrifugation. It is necessary to have flexibility so that it can move into the blood clot layer, and a size that allows it to sink into the blood clot layer.

There are no particular restrictions on the blood coagulation promoter, and any substance can be used as long as it has substantially no risk of hemolysis and is floatable in blood. For example, in addition to silica sand with a size of 0.4 to 20 microns, particles with a size of 5 microns or less with an average particle size of 1
1 micron crystalline silica (for example, product name MIN-U-8IL' manufactured by Pennsylvania Glass Sand Company),
Diatomaceous earth, fine glass powder, kaolin, bentonite, etc. can be used.

The amount of blood coagulation promoter supported is 10me of collected blood.
It is used at a ratio of 0.3 to io, om9 per portion. If this amount is too large, hemolysis will occur. On the other hand, if this amount is too small, a sufficient coagulation promoting effect will not be obtained.

The appropriate amount of the blood coagulation promoter to be added to the carrier can be easily adjusted by adjusting the binder solution described below and the amount of the blood coagulation promoter added to the binder solution.

The binder needs to be soluble in serum. This is because the inder dissolves at the same time as the blood is drawn.
In addition, the O binder is used to quickly disperse blood coagulation promoters into the blood and promote good clot formation.
It is desirable that the /<inder Examples include water-soluble silicone, polyethylene glycol, polyvinylpyrrolidone, dextran, carboxylmethylcellulose, hydroquinlopylcellulose, methylcellulose and nanocellulose derivatives. In particular, cellulose derivatives and polyvinylpyrrolidone are most preferred because they are excellent in solubility and hygroscopicity. Dextran has slightly lower solubility than others. Polyethylene glycol is hygroscopic and should not be left at room temperature for a long period of time after production.

Note that the method for producing a medium such as a nonwoven fabric containing a certain amount of this blood coagulation promoter can be easily carried out by a dipping method or the like.

Table 2 shows examples of carriers and bath compositions when the blood coagulation promoter is applied to the carrier by the dipping method.

Table 2 (Fuji) In this invention, a carrier carrying a blood coagulation promoter is housed in the inner space of the bottomed tube above the separation agent housed in the bottom of the blood separation tube to promote blood coagulation. A specific example of a blood separation tube is as follows.

As shown in FIG. 8, approximately 17 ml of each of the liquid separation agents 2 having composition numbers 1 to 12 above is dispensed into the bottom of each blood collection tube 1, and a depression 3 is provided on the top surface of the tube. Silica sand (e.g. Cape Flattery Sand, trade name WG)
-200, manufactured by Kyoritsu Ceramic Materials Co., Ltd.) 0.3 to 10.0
'n9 was carried. After storing the nonwoven fabric 7 made of 71J ester obliquely at a position midway between the tube bottom and the opening, a rubber stopper 8 made of butyl rubber was placed on the tube and the pressure inside the blood collection tube was reduced. Next, venous blood was collected into each blood collection tube, which was then allowed to stand for 7 to 8 minutes. As a result, diatomaceous earth was dispersed in the blood by the introduction of the blood, and together with the nonwoven fabric 7, promoted the coagulation of the blood, so that the blood coagulated sufficiently even in this time period. Furthermore, each separation tube was centrifuged for 10 minutes with a centrifugal force of 700 to 1,000 G, and as a result, all separation agent compositions were able to be stably interposed between the serum and blood clot layers. The state at this time is shown in FIG. 9. The separating agent has chicken tropism and has an intermediate specific gravity between serum 4 and blood clot 5, so it is located between serum 4 and blood clot 5, and it separates both. It was divided into sections to form 8 keels again. Since diatomaceous earth and nonwoven fabric 7 have a higher specific gravity than serum, they were not included in the serum 4 layer, and serum 4 was of high purity without any fibrin contamination. This serum 4 could be easily taken out from the blood collection tube by decantation or suction with a capillary nozzle.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Separating agent of composition number 2 in Table 1 above (α-olefin/maleic acid noester copolymer/Aerosil 200/Bentone 2) was added to the bottom of a cylindrical 7-separation tube with an inner diameter of 10.8 mm.
7. Surfactant, specific gravity 1.035, viscosity 680,000 cp/2
s℃) about 0.9; t+7! Dispensing (thickness at the center of the separating agent: 1.3 nm) L, using a nozzle tube with an inner diameter of about 2 mm, into a hollow cylindrical depression with an opening diameter of about 4 mm and a depth of about 5,711 mm. was formed.

Next, a nonwoven fabric coated with a blood coagulation promoter (with a diameter of 6 mm) obtained in exactly the same manner as in the above example was inserted to obtain a separation tube similar to the above.

After blood is collected using this separation tube, the rotation speed is set to 2200 rpm (approximately 920 G) after blood coagulation is completed.
Centrifugation was performed. The separating agent formed a barrier between the serum and the blood cell layer, making it easy to obtain serum free of blood cells and fibrin.

■0 Specific effects and effects of the invention As detailed above, the blood separation tube t according to the present invention has a chicken tropism for blood separation containing an α-olefin/maleic acid diester copolymer as a main component housed at the bottom of the tube. A depression is pre-formed on the top surface of the glue-like substance, and the stress during centrifugation is concentrated in this depression, and the shearing force makes the del-like substance easily and quickly fluidized. Force can move this glue-like material to a predetermined separation area. Therefore, when used for blood separation, the risk of damaging blood cells can be reduced and the time required for centrifugation can be shortened. Furthermore, the blood separation tube according to the present invention is easy to manufacture because the shape of the gel-like separation agent itself is changed, and no special parts are required for floating the gel-like separation agent. It is also advantageous in terms of manufacturing cost. Note that the diameter of the opening of the recess is 015 times or more the inner diameter of the pipe.
7 times or less, and if the thickness is 0.13 times or more and 0.65 times or less than the thickness of the shell material, even if a small volume of blood is collected or a blood collection tube with a small diameter is used, The gel-like substance flows sufficiently with the usual centrifugal force (100 OG), and there is no risk of hemolysis or the like. In addition, when a recess is formed, the width of the opening is 0.3 times or more and 0.55 times or less the inner diameter of the pipe, and the depth is 0.2 times or more and 0.55 times or less the thickness of the cell material, in particular, Even when blood from an anemic patient with a low blood cell count and low specific gravity is used, the fluidity of the gel-like substance can be ensured by the centrifugal force described above.

Next, the gel-like material that has formed the depressions will have a much larger stress applied to it than if the top surface of the cell-like material was simply made oblique, so the gel-like material can be reliably fluidized. can be done.

In addition, in the case where the depression is provided near the tube wall of the glue-like substance, compared to the case where the depression is provided in the center, the flow of the glue-like substance can be concentrated on the far side of the tube wall. The amount of glue-like substances adhering to the bottom and tube wall can be minimized, and hemolysis, which is thought to occur due to friction between the glue-like substances and blood cells, is reduced. Furthermore, the upper part of the glue-like substances after centrifugation The amount of floating blood cells remaining in the blood can be reduced.

Further, in the present invention, when an α-olefin/maleic acid diester copolymer is used as the main component as described above, the cost is about 1/3 that of a silicone fluid. Furthermore, since it is a stable copolymer, it does not release water-repellent substances to form a water-repellent coating inside the separation tube, thereby delaying blood coagulation. Since the separation tube is made of glass, its inner surface promotes coagulation when it comes into contact with blood, so it is necessary to keep the inner surface clean. Therefore, compared to the conventional method which had the disadvantage of forming a water-repellent film inside the separation tube, the serum collection time can be shortened, and this effect becomes remarkable when used in conjunction with diatomaceous earth and nonwoven fabric or the blood coagulation promoter mentioned above. . In this case, the time required for blood coagulation is reduced to about 30 minutes.

In addition, when used in a separate tube as described above, it is desirable to sterilize it, but even if sterilized with gamma rays (for example, at a dose of 25 megarads), it may have an adverse effect on clinical tests. No chemical or physical changes observed.

In addition, as shown in the above composition example (Table 1), since a C8 to C24 aliphatic amine derivative of smectite or an inorganic fine powder such as hydrophobic phosphoric acid fine powder is used as a viscosity/specific gravity adjuster, phase separation occurs. , it is possible to obtain a stable chicken-tropic separating agent with little deterioration in fluidity. Among these, in the separation agent using a C8-C24 aliphatic amine derivative of smectite clay, the smectite clay particles are opaque to light, so the dispersion state can be easily grasped by microscopy, etc. This is convenient for management.

In addition, as shown in Table 1 of composition examples, aliphatic amine derivatives of smectite clay, such as quaternary ammonium salt derivatives of smectite clay, and aliphatic amine derivatives of phtite clay have excellent thickening effects, so it is recommended to use a caking agent. It is possible to obtain a stable chicken-tropic separating agent.

In addition, among the composition examples shown in Table 1 above, α-olefin/maleic acid diester copolymer (α-olefin/maleic acid diester copolymer)
All of these are α-olefin/dimethyl maleate copolymers, and separation agents based on this copolymer have a specific gravity close to that between serum and coagulated parts, and an appropriate viscosity. The viscosity of the viscosity can be easily obtained.

A relatively small amount of specific gravity adjusting agent is required, and there is little change over time, and phase separation and fluidity decline are less likely to occur.

Further, the use of the above-mentioned wax is particularly effective in preventing a decrease in thixotropy caused by phase separation of the separating agent. .

[Brief explanation of the drawing]

Fig. 1 is a dust diagram showing one embodiment of the serum separation tube according to the present invention, and Figs. 2 to 4 show the cell-like portion t'1lffi when the serum separation tube shown in Fig. 1 is centrifuged. FIG. 5 is a cross-sectional view showing the flow operation of the agent step by step; FIG.
FIGS. 6 and 7 are cross-sectional views of serum separation tubes according to other embodiments of the present invention, and FIG. 81 is a partially cutaway view showing an embodiment of the serum separation tube provided with a blood coagulation promoting medium according to the present invention. 9 is a sectional view of the serum separation tube shown in FIG. 8 when it is centrifuged. In the figure, 1... blood collection tube, 2... shell-like substance, 3...
- Hollow, 4... Serum layer, 5... Blood cell layer, 6... Nozzle, 7... Blood coagulation promoting medium, 8... Rubber stopper.

Claims (1)

[Scope of Claims] (1) Blood comprising a bottomed blood collection tube, a chickentropic capsule-like component housed in the bottom of the tube and having a specific gravity intermediate between the serum phase and the blood clot phase, and a releasing agent. In the separation tube, the separation agent is housed in the bottom of the tube with a depression formed on its upper surface, and the separation agent has a viscosity of io, o o o to 12
0,000 cp (25°C) (wherein R1 is the same or different in the same molecule and represents a hydrogen atom or an alkyl group having 1 to 20.7 carbon atoms), and R2 and R3 each have 1 carbon atom. It represents a linear or branched alkyl group having 1 to 15 carbon atoms or a branched alkyl group having 16 to 20 carbon atoms. however,
When R1 is a hydrogen atom, R2 and R3 are each a linear or branched alkyl group having 12 to 15 carbon atoms or a branched alkyl group having 16 to 20 carbon atoms. R4 has 1 to 20 carbon atoms
R4 and R2 and R4 and R
The total number of carbon atoms in 3 (t is 5 to 25, respectively. In addition, when R2 is an alkyl group having 2 to 20 carbon atoms, R and R3 are each a methyl group, ethyl group, butyl group, or 2 - Except when it is an ethylhexyl group, n is an integer from 5 to 30. is 1.03
A blood separation tube characterized in that the blood separation tube is adjusted to 5 to 1.055. (2) In the general formula of the above copolymer, R4 is a hydrogen atom, and R2 and R3 are each a linear or branched alkyl group having 12 to 15 carbon atoms or a branched chain having 16 to 20 carbon atoms. The blood separation tube according to claim 1, which is a chain alkyl group. (3) - In the general formula of the above copolymer, R1 is a methyl group, and R and R5 are each a linear or branched alkyl group having 4 to 15 carbon atoms or 16 to 20 carbon atoms. The blood separation tube according to claim 1, which is a branched alkyl group. (4) Based on 100 parts by weight of the α-olefin/maleic acid diester copolymer, 0.04 to 0.6 of the dulling agent is added.
The blood separation tube according to claim 1, wherein the blood separation tube includes an amount of N. (5) Number of carbon atoms in α-olefin component: 30 to 60
2. The blood separation tube according to claim 1, further comprising a wax consisting of an α-olefin/maleic acid diester copolymer added thereto in an amount of 1.0 to 3.0 parts of the main component. (6) The above viscosity/specific gravity regulator is C8 smectite clay.
The blood separation tube according to claim 1, which is at least one selected from the group consisting of 24 aliphatic amine derivatives and inorganic fine powders. (7) The blood separation tube according to claim 6, wherein the aliphatic amine derivative of smectite clay is a quaternary ammonium derivative of smectite clay. (8) The blood separation tube according to claim 6, wherein the viscosity/specific gravity adjusting agent is an inorganic fine powder such as calcined silica or precipitated silica. (9) The size of the recess of the separation agent is such that the diameter of the upper surface is 0.15 times or more and 0.7 times or less the inner diameter of the pipe, and the depth is 0.13 times or more and 0.65 times or less the thickness of the separation agent. A blood separation tube according to claim 1 for moxibustion. 0Q The size of the recess of the separating agent is such that the diameter of the upper surface is 0.3 times or more and 0.5 times or less the inner diameter of the pipe, and the depth is 0.2 times or more and 0.55 times or less the thickness of the separating agent. A blood separation tube according to claim 9. (11) A blood collection tube with a bottom, a chickentropic glue-like separation agent housed in the bottom of the tube and having a specific gravity intermediate between the serum phase and the blood clot phase, and a chickentropic glu-like separating agent held in the middle of the bottom tube with a higher pH than blood cells. A blood separation tube comprising a blood coagulation promoting medium having powdered blood coagulation promoting particles supported on a carrier having a specific gravity, wherein the separating agent is housed in the bottom of the tube in a state in which a depression is formed on the upper surface thereof, and The separating agent has a viscosity of io, oo. ~120,000 cp (25°C) (wherein R4 is the same or different in the same molecule and represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms, and R2 and R3 each have 1 to 20 carbon atoms) The linear or branched alkyl group t7'c of 15 has 16 carbon atoms.
to 20 branched alkyl groups. However, R1
When is a hydrogen atom, R2 and R314 are each a linear or branched alkyl group having 12 to x6 carbon atoms or a branched alkyl group having 16 to 20 carbon atoms. When R1 is an alkyl group having 1 to 20 carbon atoms, R1 and R2 and R1 and R3
have a total number of carbon atoms of 5 to 25, respectively. Further, when R1 is an alkyl group having 2 to 20 carbon atoms, the case where R2 and R3 are each a methyl group, ethyl group, butyl group or 2-ethylhexyl group is excluded. n is an integer from 5 to 30. ) The main component is a copolymer of α-olefin and diester maleate, and a viscosity/specific gravity modifier is added to it.1. Specific gravity is 1.0
A blood separation tube characterized in that the blood separation tube is adjusted to 35 to 1.055. oNo The blood separation tube Go3 according to claim 11, wherein the blood coagulation promoting particles are at least one selected from silica sand, crystalline silica fine powder, diatomaceous earth, glass fine powder, kaori/bentonite. 13. The blood separation tube according to claim 11 or 12, wherein the promoting particles are blood 10-10,3-10.0111P. Q4: The blood separation tube according to claim 11, wherein the carrier is cloth, filter paper, nonwoven fabric, or cotton. 0→ The blood separation tube according to claim 11, wherein the inside of the blood separation tube is maintained in a reduced pressure state.