JPH0241141A - Vacuum blood collecting tube - Google Patents

Abstract

PURPOSE:To easily grasp a vacuum state and to easily and rapidly separate serum and clot, or plasma and a blood corpuscle by receiving a vacuum display jig composed of a flexible material having gas barrier properties and a serum or plasma separating agent substantially having thixotropicity in a tubular container. CONSTITUTION:A vacuum blood collecting tube 1 has an almost spherical display jig 3 provided therein in a vacuum state. Said vacuum display jig 3 is composed of hollow body formed by welding the peripheral edge parts of two disc-shape sheets having gas barrier properties by heat sealing and containing a small amount gas and expanded in a vacuum state before blood-collecting to be formed into an almost spherical shape and contracted under almost atmospheric pressure after blood-collecting to become a flat shape. When a serum or plasma separating agent 4 is received in the blood collecting tube 1, the coagulated lump or blood corpuscle layer of collected blood 5 is penetrated into the serum or plasma separating agent from a protruding part 51 by centrifugal separation operation to push up said separating agent and, therefore, the flowability of the separating agent 4 is enhanced to make it possible to easily and rapidly perform separation work of serum and clot, or plasma and blood corpuscle.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a blood test container, particularly a vacuum sample container used to collect a whole blood sample from a subject and separate serum or plasma by centrifugation. Concerning blood vessels.

(Prior Art) In recent years, vacuum blood collection tubes have been used to collect blood from a blood sample recipient.

When collecting blood, the blood collection needle inserted into the blood vessel of the blood sample is
When connected to a vacuum blood collection tube, blood is automatically sucked into the vacuum blood collection tube due to the pressure difference between the inside of the blood collection tube and the blood.
A predetermined amount of blood is collected.

The collected blood is separated into serum and blood clots or plasma and blood cells by centrifugation, and the serum, plasma components, or blood cells necessary for the blood test are taken out and subjected to the blood test.

In addition, some vacuum blood collection tubes contain various drugs depending on the purpose of the test.

Some of these containers contain a serum or plasma separation agent that has been adjusted in advance to have a specific gravity between that of serum and blood clots, or between plasma and blood cells. In that case, the serum or plasma separation agent is centrifuged,
Since it moves between the separated serum and blood clot or plasma and blood cells to form a partition wall, it enhances the effect of centrifugation and prevents the two separated components from mixing during storage.

(Problem to be Solved by the Invention) However, although the conventional vacuum blood collection tube described above needs to maintain a reduced pressure state until blood is collected, for example, during storage, the reduced pressure state may be lost for some reason. Something happened. (This is called a dead tube.) However, because there was no way to easily identify the reduced pressure state of a vacuum blood collection tube, the dead tube could not be discovered until it was actually used for blood collection. The problem was that the blood collection had to be repeated.

Furthermore, if the serum or plasma separating agent is a thixotropic fluid, the thixotropic coefficient will gradually increase during storage, and eventually under normal centrifugation conditions, the separating agent will separate serum and blood clots or plasma and blood cells. There was also the problem that it became impossible to move to the middle of the road, and the original purpose could not be achieved.

(Means for Solving the Problems) The vacuum blood collection tube of the present invention has been made in order to solve the above-mentioned problems of the conventional art. A second invention is a vacuum blood collection tube whose end is closed with an airtight stopper, in which a reduced pressure indicator made of a flexible material having gas barrier properties is housed inside the tubular container, and the second invention is based on the first invention. The tubular container of the invention stores a serum or plasma separating agent having a specific gravity between the light and heavy components of blood and having substantially thixotropic properties. The purpose is achieved.

The vacuum blood collection tube of the present invention has a reduced pressure indicator inside the blood collection tube that can identify a reduced pressure state.

The reduced pressure indicator is made of a flexible material having gas barrier properties, and is a hollow body containing a small amount of gas at atmospheric pressure.

The gas here may be, for example, a single gas such as nitrogen, oxygen, or chlorofluorocarbon, or a mixed gas such as air.

The reduced pressure indicator is required to be made of a material with gas barrier properties in order to retain the gas contained inside without escaping, and it also easily contracts and shrinks depending on the level of atmospheric pressure acting on the indicator. In order to be able to expand, the material must be flexible.Therefore, the material used for the reduced pressure indicator is metal foil, or a film or sheet made of plastic or elastomer with gas barrier properties. Preferably, said materials are used alone or as a laminate.

Examples of metal foil include aluminum foil, and examples of films or sheets made of plastic or elastomer having gas barrier properties include polyamide, saponified ethylene-vinyl acetate copolymer (EV), etc.
AL), polyethylene terephthalate (PET)
, polyvinylidene chloride (PVf)C), polyacrylonitrile (PAN), aluminum-deposited polyethylene terephthalate, isoprene/isobutylene rubber (abbreviation IIR)
, commonly known as butyl rubber).

In addition, polyethylene (PR) is used to impart heat sealability to these metal foils, films, sheets, etc.
), polypropylene (PP), etc. may be laminated.

As for gas barrier property, oxygen permeability is 300cc/
It is preferable to use a material that has a resistance of rn''·24 hr-atm or less.

If the oxygen permeability exceeds this value, it is not preferable because it will adversely affect the degree of vacuum in the blood collection tube.

In the present invention, the shape of the reduced pressure indicator in the reduced pressure state is not particularly limited, and for example, those having shapes such as cylindrical, cubic, and spherical can be suitably used.

Furthermore, the display device may have a bellows structure in order to quickly deform in response to changes in external pressure.

When the vacuum blood collection tube is in a reduced pressure state, the volume of the vacuum blood collection tube expands due to the expansion of the gas contained therein, whereas under approximately atmospheric pressure, the volume contracts. Due to the expansion and contraction of the volume, the reduced pressure state of the vacuum blood collection tube can be easily identified with the naked eye.

The serum or plasma separating agent of the present invention, which has a specific gravity intermediate between light and heavy blood components and is substantially thixotropic, will be described below.

Thixotropy refers to the property of serum that is difficult to flow under hydrostatic pressure, acting as if it were a solid, but regains fluidity and behaves like a liquid when subjected to shearing force, and has essentially thixotropic properties. Alternatively, a plasma separating agent is a plasma separating agent that, during centrifugation after blood collection, has a shearing force generated when the coagulated clot or blood cell layer (described below) falls into the separating agent due to centrifugal force, making the fluidity lower than before centrifugation. The separating agent is a fluid with a relatively high specific gravity of 1.03 or more and less than 1.08, and when centrifugation is completed, the separating agent is located between serum and blood clots or plasma and blood cells. A substance that serves to form a barrier layer that blocks the two.

To produce such a separating agent, Japanese Patent Publication No. 59-234
5, Special Publication No. 59-11863, Special Publication No. 57-59495
, Japanese Patent Publication No. 58-7187, Japanese Patent Publication No. 57-30542, etc. may be followed.

A common manufacturing method is to mix an appropriate amount of a fine powder filler such as silicon dioxide or bentonite into a viscous liquid such as silicone oil, acrylic oligomer, or olefin oligomer.

In such mixtures, the fine powder filler has an interaction based on attraction between the fine powders or the viscous liquid, e.g. In the case of a magnetic substance, it is believed that the hydrogen bonds formed by the hydroxyl groups present on the surface are the cause of attraction.

Furthermore, the covalent bonds in this network of hydrogen bonds are not very strong, and can only be broken apart by shearing force, and it is this network of subtle attraction that is the main body of thixotropy. It is believed that there is.

By the way, the separation agent produced as described above and dispensed into blood collection tubes easily recovers its fluidity under the normal centrifugation conditions of 1500G for 10 minutes for a while after production; As days pass, it gradually becomes less fluid, and eventually, if centrifugation is performed under normal conditions, the separation agent moves between the serum and blood clots or plasma and blood cells. However, the original purpose of forming a partition wall for separating the two components cannot be achieved.

This phenomenon is thought to be because the formation of the hydrogen bond network described above does not reach a certain level immediately after the separation agent is produced, but progresses over time.

(Function) The vacuum blood collection tube of the present invention has a flexible reduced pressure indicator having gas barrier properties, and the reduced pressure indicator contracts in volume under atmospheric pressure due to a small amount of gas present inside. Under reduced pressure, the volume expands.

When a serum or plasma separation agent is stored in the vacuum blood collection tube of the present invention, the vacuum indicator is either partially invaginated inside the separation agent or completely invaginated inside the separation agent. It exists in a state of

In such a state, when the pressure inside the blood collection tube increases after blood collection and the reduced pressure indicator contracts, the inner surface of the serum or plasma separation agent collapses to form a depression.

Since the collected blood takes on a pile shape along the recess, the coagulated mass formed by the blood coagulation also takes on a pile shape. Furthermore, when an anticoagulant is used during blood collection, the blood cell layer that settles in the serum when the blood is allowed to stand still also takes on a pile-like shape.

During centrifugation, the clot or blood cell layer falls into the serum or plasma separating agent through the depressions and pushes the serum or plasma separating agent upward, thereby increasing the fluidity of the separating agent. do.

(Example) Examples of the vacuum blood collection tube of the present invention will be described below with reference to the drawings.

FIG. 1 is a perspective view showing one embodiment of the vacuum blood collection tube of the present invention, FIG. 1(a) shows the state before blood collection, and FIG.
b) shows the state after blood collection.

In FIG. 1, 1 is a vacuum blood collection tube, and 2 is a stopper inserted into the open end of the blood collection tube.

The vacuum blood collection tube 1 has a substantially spherical reduced pressure indicator 3 inside thereof in a reduced pressure state.

The reduced pressure indicator 3 is a hollow body that contains a small amount of gas inside, with the peripheral edges of two disc-shaped sheets fused together by heat sealing or the like, and in the reduced pressure state before blood collection, it is as shown in Figure 1 (a). ), its shape expands and becomes approximately spherical.

Further, the reduced pressure indicator 3 contracts under substantially atmospheric pressure after blood collection, and assumes a flat shape as shown in FIG. 1(b).

The specific gravity of the reduced pressure indicator 3 is not particularly limited, but if the reduced pressure indicator 3 floats on the surface of serum or plasma after centrifugation and interferes with the handling of serum, plasma, or blood cells, It is preferable to set the bulk specific gravity under atmospheric pressure to 1.02 or more.

As shown in FIG. 2, when the vacuum blood collection tube 1 of the present invention has a serum or plasma separating agent 4 inside the blood collection tube 1, the vacuum indicator 3 indicates that the serum or plasma separating agent 4 is present during the centrifugation operation. This has the effect of increasing the fluidity of the separating agent 4.

That is, as shown in FIG. 2(a), the reduced pressure indicator of the present invention floats in the vacuum blood collection tube 1 under reduced pressure while being partially submerged inside the serum or plasma separation agent 4. If so, blood is drawn into the vacuum blood collection tube,
When the pressure inside the blood collection tube is increased to atmospheric pressure, the reduced pressure indicator contracts and assumes a flat shape as shown in FIG. 2(b), leaving a dent on the surface of the serum or plasma separating agent 4. 41 is formed.

As a result, blood clots formed by coagulation of the collected blood 5 and blood cells N precipitated in the serum by standing the blood 5 (if an anticoagulant is used) are treated with serum or plasma separating agent. 4 A protruding portion 51 corresponding to the recess 41 formed on the surface
will be formed.

In the centrifugation operation, the clot or blood cell layer of the collected blood 5 penetrates into the serum or plasma separating agent 4 from the protruding portion 51 and pushes the separating agent 4 upward, so that the separating agent The fluidity of 4 is improved, making it possible to easily and quickly separate serum and blood clots or plasma and blood cells.

In addition, when the reduced pressure indicator 3 is present in a settled state on the bottom surface of the vacuum blood collection tube 1 as shown in FIG. 3(a), the reduced pressure indicator 3 contracts and becomes flat due to blood collection. shape, and a depression 41 is formed on the surface of the serum or plasma separating agent 4, producing a similar effect.

The reduced pressure indicator 3 is subjected to various treatments, such as a blood coagulation promoter and an anticoagulant, as necessary.

Laminate materials of the types shown in Table 1 were used as films or sheets made of metal foil, plastic, or elastomer having gas barrier properties.

Two sheets of the same type of laminate material were stacked one on top of the other, the peripheral edges were heat-sealed, and then punched out into a disc shape with a diameter of 8 fl to produce a reduced pressure indicator 3 in which a small amount of air existed in the hollow interior.

Next, after putting the reduced pressure indicator 3 into a glass container 11 for a blood sampling amount of 1Qml, the glass container 11 is
The pressure was reduced to 10 atm and the tube was sealed with a butyl rubber stopper 2 to produce a vacuum blood collection tube 1 shown in FIG. 1(a).

In this reduced pressure state, the reduced pressure indicator 3 expanded into a substantially spherical shape.

Next, when the blood collection needle is inserted into the stopper 2 of the vacuum blood collection tube 1 to break the reduced pressure state, the reduced pressure indicator 3 is crushed into a flat shape, making it possible to see changes in the reduced pressure state of the vacuum blood collection tube 1 with the naked eye. could be easily identified.

Note) (): Thickness Oxygen permeability: cc/rt 24hr-atm Two laminated films made of over 1 m thick (2 m thick) are laminated together.
8) A reduced pressure indicator 3 was created, and as in Example-1, the amount of blood collected was 10 m! After putting the blood into a glass container 11 for use, the glass container 11 is depressurized to about 1/10 atmosphere and sealed with a butyl rubber stopper 2 to produce the vacuum blood collection tube 1 shown in FIG. 1(a). did.

In this reduced pressure state, the reduced pressure indicator 3 expanded into a substantially spherical shape. Next, when a blood collection needle is inserted into the stopper 2 of the vacuum blood collection tube 1 to break the reduced pressure state, the reduced pressure indicator 3 is crushed into a flat shape, making it possible to see changes in the reduced pressure state of the vacuum blood collection tube 1 with the naked eye. could be easily identified.

3 into a glass container 11 for blood collection N10ml,
Next, 100 parts by weight of cyclopentadiene oligomer (manufactured by Exxon Chemical, ECR-327) with a specific gravity of 1.05 was added with finely powdered silica (average particle size: 16 mμ) by a gas phase method.
) and kneaded for 1.5 hours under reduced pressure to prepare 1.5 g of serum separating agent 4 (specific gravity: 1.06) was injected into the glass container 11 under reduced pressure.

Thereafter, the pressure of the glass container 11 was reduced to about 1/10 atm, and the container was sealed with a butyl rubber stopper 2.

As a result, the reduced pressure indicator 3 settled at the bottom of the serum separating agent 4 and expanded to take on a substantially spherical shape, as shown in FIG. 3(a).

After heating the thus prepared vacuum blood collection tube 1 in an oven at 60°C for a predetermined period of time, about 8.5 ml of fresh rabbit blood was sucked into the blood collection tube 1. b
), the reduced pressure indicator 3 has a flat shape.

Next, after confirming that the coagulation of the fresh blood has been completed,
Centrifugation was performed at 1500 G for 10 minutes.

In the above operations, in order to examine changes over time in the functions of the vacuum blood collection tube 1 and the serum separating agent 4, changes in the shape of the reduced pressure indicator 3, the formation status of the depression 41 on the surface of the serum separating agent 4,
The performance of each item including the shape of the blood clot and the fluidity of the serum separating agent 4 during centrifugation was evaluated, and the results are shown in Table 2.

A serum separating agent (100 parts by weight of dimethylpolysiloxane (manufactured by Dow Conning, grade 360) with a specific gravity of 0.975 and 15 parts by weight of finely powdered silica (particle size 5 μm))
Example-3 except that specific gravity 1.05) 4 was used.
Vacuum blood collection tube 1 was prepared in the same manner as described above, and vacuum blood collection tube l
The performance of Serum Separator 4 was evaluated using the same items and methods as in Example-3. The results are shown in Table 2.

The performance of a vacuum blood collection tube manufactured in the same manner as in Example 3 was evaluated using the same items and methods as in Example 3, except that the decompression indicator was not used. The results are shown in Table 2.

The performance of the vacuum blood collection tube manufactured in the same manner as in Example 4 was evaluated using the same items and methods as in Example 4, except that the vacuum blood collection tube was not used. The results are shown in Table 2.

Table 2 (Effects of the Invention) As mentioned above, the vacuum blood collection tube of the present invention has a reduced pressure indicator inside, and the reduced pressure indicator expands under reduced pressure and contracts under atmospheric pressure. By visually identifying changes in the shape of the reduced pressure indicator, the reduced pressure state can be easily grasped.

In addition, in this vacuum blood collection tube, when serum or plasma separation agent is stored, the pressure reduction indicator contracts due to the increase in pressure after blood collection, forming a dent on the surface of the serum or plasma separation agent.
When the clot or blood cell layer invaginates the depression,
Since the fluidity of the serum or plasma separating agent is improved by pushing up the serum or plasma separating agent, the work of separating serum and blood clots or plasma and blood cells can be easily and quickly performed.

[Brief explanation of the drawing]

FIG. 1(a) is a perspective view showing the state of one embodiment of the vacuum blood collection tube of the present invention before blood collection, FIG. 1(b) is a perspective view showing the same state after blood collection, and FIG. 2(a) 2(b) is a sectional view showing the state of another embodiment of the vacuum blood collection tube of the present invention before blood collection, FIG. 2(b) is a sectional view showing the same state after blood collection, and FIG. FIG. 3(b) is a sectional view showing the state of still another embodiment of the vacuum blood collection tube before blood collection, and FIG. 3(b) is a sectional view showing the state after blood collection. 1- Vacuum blood collection tube, 11- Glass container, 2- Stopper. 3.--Reduced pressure indicator, 4.--Serum or plasma separation agent. 5...-Blood.

Claims (1)

[Scope of Claims] 1. In a vacuum blood collection tube in which the inside of a bottomed tubular container is evacuated and the open end is closed with an airtight stopper, a flexible material having gas barrier properties inside the tubular container A vacuum blood collection tube containing a reduced pressure indicator consisting of: 2. The vacuum according to claim 1, wherein the bottomed tubular container houses a serum or plasma separation agent having a specific gravity intermediate between light and heavy blood components and having substantially thixotropic properties. Blood collection tube.