JPH08229026A - Decompression blood-collecting tube - Google Patents

Abstract

PURPOSE: To stabilize the coagulation activity of an inorganic material having blood coagulation activity for a long period and exert the coagulation activity of the inorganic material to the maximum extent by coating the inner face of a bottomed tube body made of a synthetic resin with a mixture of PVP and a water-soluble silicone oil, and granularly sticking the diatomaceous earth on the coating face. CONSTITUTION: The space formed with a bottomed tube body, which is made of a synthetic resin, closed at one end, and opened at the other end, and a sealing member, which closes the opened end and can be pierced, is kept at the decompressed state as a decompression blood-collecting tube. The inner face of the bottom tube made of a synthetic resin is coated with a mixture of polyvinyl pyrrolidone and a water-soluble silicone oil, and the diatomaceous earth is granularly stuck on the coating face. The wt.% of the mixture is set to silicone oil: 0.05-0.5 against polyvinyl pyrrolidone: 1. The diatomaceous earth quickly starts dispersion, contact, and coagulation when it is brought into contact with blood, and a high coagulating speed can be realized with a small amount of a coagulant.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a reduced-pressure blood collection tube. Decompression blood collection tubes are used for biochemical tests, serological tests, hematological tests, blood glucose measurements, blood coagulation tests, blood sediment tests, bacteriological tests, etc., and consist of a bottomed tube with an opening and a rubber stopper attached. . Before using the reduced pressure blood collection tube, the inside of the bottomed tube is in a reduced pressure state. The degree of pressure reduction is maintained at an appropriate reduced pressure so that a necessary amount of blood (2 to 20 ml) can be collected. Blood is allowed to coagulate in the blood collection tube, and the separated serum is subjected to a test.

[0002]

2. Description of the Related Art Conventionally, the material of the bottomed tube is glass. However, glass is liable to break during high-speed centrifugation during handling, and is recently being replaced by synthetic resins such as polyester, polyethylene, and polypropylene. As the polyester, polyethylene terephthalate is generally used, and a copolymer with polyethylene terephthalate is also used.

A synthetic resin vacuum blood collection tube typified by polyethylene terephthalate is inferior to a glass vacuum blood collection tube in that it takes more time to coagulate blood in the tube and is inferior in practical use. In order to solve this problem, an inorganic substance having a blood coagulation ability was attached to the inner surface of the blood collection tube, but the coagulated blood attaches to the inner surface of the blood collection tube, and serum separation becomes impossible. As a solution to this problem, a silicone-based material used for the same purpose in a vacuum blood collection tube made of glass is coated on the inner surface of a synthetic resin blood collection tube.

For example, Japanese Patent Publication No. Sho 59-6655 describes that
A blood collection tube for serum separation is described in which a dispersion mixture of a substance (silicone oil, etc.) that does not easily adhere to serum components and a substance that promotes serum coagulation (inorganic substance such as silica) is adhered to the inner surface of a synthetic resin blood collection tube. There is.

Further, according to US Pat. No. 4,153,739, the silicone gel present in a normal vacuum blood collection tube covers the surface of the inorganic substance present on the inner wall of the blood collection tube over time. When blood is collected underneath, the blood is prevented from coming into contact with the inorganic substance on the inner surface of the blood collection tube, and the blood coagulation activity of the inorganic material in the blood collection tube decreases with time. It describes that an inorganic substance dispersed in an alcohol solution of pyrrolidone (hereinafter, referred to as PVP) is adhered and dried on the inner surface of a blood collection tube. In this method, when blood comes into contact with the inner surface of the tube, PVP is dissolved, the inorganic substance is dispersed in the blood, the inorganic substance comes into contact with the blood, and the blood coagulates.

As described above, in the prior art, an inorganic substance having a blood coagulation ability for improving serum separation performance of a synthetic resin vacuum blood collection tube, a silicone oil for preventing blood adhesion,
And PVP for preventing a time-dependent decrease in blood coagulation performance caused by adhesion of the silicone oil to the surface of an inorganic substance
Is applied to the inner surface of the blood collection tube.

In the prior art, however, it takes time for PVP to dissolve in blood during blood collection, and since silicone oil also coexists on the surface of the inorganic substance, blood coagulation performance is not affected by the passage of time even during storage of the blood collection tube. It is necessary to increase the amount of the inorganic substance in order to maintain it for a long time and to make the inorganic substance into a fine particle diameter in order to increase the surface area that becomes the coagulation active point, and to obtain an industrially satisfactory decompressed blood collection tube. It was difficult.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to solve the drawbacks of the prior art, and to ensure that the coagulation activity of an inorganic substance showing blood coagulation activity is stable for a long period of time, and that the coagulation activity of the inorganic substance is maximized. Another object of the present invention is to provide a synthetic resin vacuum blood collection tube aiming to maximize its performance.

[0009]

SUMMARY OF THE INVENTION The present invention comprises a synthetic resin bottomed tube closed at one end and open at the other end, and a pierceable sealing member sealing the open end. In a reduced-pressure blood collection tube in which the space formed by the above is kept under reduced pressure, the inner surface of the synthetic resin bottomed tube is coated with a mixture of PVP and water-soluble silicone oil, and diatomaceous earth is coated on the coated surface. The present invention provides a reduced-pressure blood collection tube, which is characterized in that it is attached in a granular form.

In the present invention, the term "sealing member" refers to a member used for a reduced-pressure blood collection tube. For example, the term refers to a removable rubber plug or a sealing member including a gas barrier member and a sealing member.

In the present invention, the bottomed tube is used as a reduced-pressure blood collection tube. For example, when the pipe outer diameter is 10 to 1
It has a diameter of 6 mm and a pipe length of 60 to 170 mm.

In the present invention, the synthetic resin is a thermoplastic such as polyester, polyethylene and polypropylene. The synthetic resin may contain an antioxidant, an ultraviolet ray blocking agent, an extrusion aid, an additive for improving the polymer thereof, and the like.

For the blood collection tube, a polymer having excellent gas barrier properties is selected from synthetic resins, and polyester, ie,
Ethylene glycol and terephthalic acid or its ester
The use of polyethylene terephthalate obtained by reaction with (especially dimethyl terephthalate) is recommended.

When the molecular weight of the polyester polymer is 0.6 to 0.9 in terms of intrinsic viscosity [η], satisfactory bottomed tubular bodies can be obtained without any problem in molding. In this case, the intrinsic viscosity is 3 parts by weight of phenol and 1,1,2,2-
It is a value measured at 25 ° C. as a solution prepared by dissolving 0.25 g of a polymer in 100 ml of a mixture with 2 parts by weight of tetrachloroethane.

The PVP used in the present invention has excellent film-forming ability and is used in cosmetics and the like, and hardly adheres blood. However, PVP has a property that blood is more easily adhered than silicone oil or the like. However, PVP does not impair the blood coagulation performance of diatomaceous earth itself, and preferentially covers the contact surface with diatomaceous earth in the presence of silicone oil used to prevent blood adhesion, and the silicone oil adheres to the diatomite surface. Has the property of eliminating. In order to completely prevent blood adhesion to the inner surface of the blood collection tube while maximizing the blood coagulation performance of diatomaceous earth, a small amount of water-soluble silicone oil is added to PVP and the mixture is uniformly coated on the wall surface of the blood collection tube. Preferably.

The diatomaceous earth used in the present invention preferably does not contain impurities, and is baked at a high temperature of 1000 to 1200 ° C. to remove the burning loss. For that purpose, Celite (registered trademark of Celite) is most preferable.

Further, when the mixture layer of (PVP + water-soluble silicone oil) is dissolved in blood and the diatomaceous earth on the coating surface is dispersed in the blood and the blood is quickly coagulated, the water-soluble silicone oil is used. Preferably, the thinner the coating layer of the mixture, the better. In order to maximize the blood coagulation performance of diatomaceous earth, it is preferable that the diatomaceous earth on the blood collection tube wall be present as it is without being covered with PVP or silicone oil. However, it is impossible to adhere to the wall surface as it is, and a binder of water or alcohol is required. It is preferable that the binder does not affect the coagulation performance of the diatomaceous earth or the blood adhesion prevention ability on the wall of the blood collection tube.

The existence of diatomaceous earth in a state close to nature means that diatomaceous earth is present in a state where diatomaceous earth is placed on a blood adhesion preventing mixture layer on the inner surface of a blood collection tube.
It is important that the mixture layer of (+ water-soluble silicone oil) is thinner than the particle shape of the diatomaceous earth, and that even if the diatomaceous earth is strongly blown to the surface of the mixture layer, the diatomaceous earth is not buried in the mixture layer. The particle size must be 10 times or more, preferably 30 times or more the thickness of the mixture layer. In addition, it is important to spray a binder together with the diatomaceous earth so that the diatomaceous earth can adhere to the mixture layer.

In the present invention, the inner surface of the blood collection tube is coated with PVP containing a small amount of water-soluble silicone oil. Therefore, when a dispersion of diatomaceous earth in water or isopropyl alcohol is sprayed onto the mixture layer on the inner surface of the blood collection tube. The PVP and silicone oil on the surface of the mixture layer also show the property of a binder, and the diatomaceous earth is suitably attached to the inner surface of the blood collection tube. Accordingly, the thickness of the mixture layer of (PVP + water-soluble silicone oil) needs to be as thick as possible as a binder with water or alcohol when spraying diatomaceous earth, but it is important that it is as thin as possible.

The synthetic resin vacuum blood collection tube of the present invention has a thin layer of PVP mixed with a small amount of water-soluble silicone oil formed on the inner surface of the tube, and the diatomaceous earth has an average particle size at least 10 times the thickness of the mixture layer. As described above, the diatomaceous earth not covered with the mixture layer is present on the inner surface of the blood collection tube, and as a result, excellent blood coagulation performance is exhibited. Due to such a constitution, the blood collection tube of the present invention does not deteriorate in blood coagulation performance even if it is stored for a long period of time. Specifically, after the blood collection tube is stored for about 8 months to 1 year, The blood coagulation time is less than 9 minutes even after the test. Further, since the configuration of the present invention is excellent, the amount of diatomaceous earth used in the blood collection tube can be reduced. As a result, according to the present invention, a blood collection tube having a good appearance can be provided.

The mixing ratio of PVP and water-soluble silicone oil is related to blood adhesion performance and coagulation time. PV by weight
If P is less than 0.05 and the water-soluble silicone oil is less than 0.05, blood adheres to the tube wall and it is difficult to observe the coagulation state of the blood from outside the blood collection tube. The oil adheres to the surface of the diatomaceous earth, causing changes during storage of the blood collection tube, resulting in a blood collection tube that takes a long time to coagulate. Therefore, this weight ratio is 0.05 to
It is in the range of 0.5, preferably in the range of 0.1 to 0.3.

Next, the weight ratio of diatomaceous earth to 1: (PV
P + water-soluble silicone oil) in the range of 0.2 to 1.
The setting of 0 will be described. A mixture of PVP and water-soluble silicone oil (indicated as CO in Table 1) was dissolved in isopropyl alcohol and sprayed on the blood contact part of a polyester blood collection tube having an effective blood contact area of about 39 cm 2 and 10 cc for blood collection. And evenly spread 5
It was dried with hot air at 0 ° C. By adjusting the mixing ratio and the spray amount, four types of blood collection tubes were prepared on the basis of the amount of the water-soluble silicone oil with respect to PVP. Celite Super Floss (fired diatomaceous earth manufactured by Celite), which is a blood coagulant, is dispersed in isopropyl alcohol on the inner surface of the blood collection tube, and then this is uniformly sprayed with a spray. It was created as shown in Table 1.

[0023]

[Table 1]

Using the blood collection tubes shown in Table 1, changes in blood coagulation performance during storage of the blood collection tubes were examined. However, by accelerating this change and performing a simulation at 50 ° C for up to 4 weeks,
The blood coagulation times from 10 healthy persons were investigated on average.

The present invention aims at keeping the blood coagulation time within 9 minutes even after storing the blood collection tube at room temperature for 8 months. Storage at room temperature for 8 months is considered to correspond to storage at 50 ° C. for 4 weeks in the simulation of the present invention. The criterion for determining the coagulability is that the coagulation time is 9 minutes or less,
9.5 minutes are indicated by Δ, and 10 minutes or more are indicated by ×. Further, a mixture of Celite / silicone oil / PVP was sprayed on the inner surface of the blood collection tube, and the one in which the surface of Celite was covered with PVP was compared as a blank.

Table 2 shows the relationship between the ratio of the mixture layer of PVP and water-soluble silicone oil (shown as CO in Table 2) to celite and the blood coagulability.

[0027]

[Table 2]

As is apparent from Table 2, (P
If the ratio of the mixture of VP + water-soluble silicone oil) exceeds 1, the coagulation time becomes long and is the same as the blank. If this value is smaller than 0.2, the amount of diatomaceous earth increases, and a uniform surface cannot be obtained on the inner wall of the blood collection tube, which impairs the commercial value of the reduced-pressure blood collection tube. From this, the weight ratio of the mixture of (PVP + water-soluble silicone oil) to diatomaceous earth was 0.2-1.
A range of 0 is appropriate.

Next, “(PVP) is formed on the inner surface of the reduced-pressure blood collection tube.
The coating thickness of the mixture of water-soluble silicone oil) and the average particle diameter of diatomaceous earth will be described. Diatomaceous earth particle size is the distance between the diatomaceous earth maximum apex and the bottom when the portion in contact with the coating surface is the bottom, with diatomaceous earth adhered to the coating layer, and the average particle size is the diameter of the diatomite particle used Is the average of

A mixture of 1% by weight of PVP and 0.2% by weight of water-soluble silicone oil in isopropanol was sprayed evenly to various extents on the inner surface of a 10 cc polyester vacuum blood collection tube using a spray. After that, 50 ℃
And dried with hot air of an average thickness of about 0.03, 0.05, 0.
A mixture layer of 1, 0.2, 0.4, 0.6, 0.8, 1.0 μm was formed. 1% by weight of Celite Super Floss having an average particle size of about 1, 2, 3, 5, 6, 8, 10, and 12 μm was added to isopropyl alcohol, and a dispersion sufficiently mixed with a homogenizer was sprayed onto the inner surface of the blood collection tube. It was sprayed on the mixture layer, dried with hot air at 50 ° C., and aimed at a diatomaceous earth adhesion amount of about 0.015 mg / cm 2. The effective blood contact area of the 10 cc blood collection tube used was 39 square centimeters, so the amount of diatomaceous earth involved in blood coagulation was approximately 0.60 m.
It becomes g.

Immediately after fabrication, the state of adhesion of diatomaceous earth to the inner surface of the blood collection tube was observed with a microscope magnified 5000 times. The amount of diatomaceous earth attached was 0.02-0.1 per 1 cc of blood collected.
0 mg is sufficient, and excessive diatomaceous earth shortens the coagulation time, but causes hemolysis, so it is important to avoid excess in determining the amount of diatomaceous earth used. Table 3 shows the observation results of the effects of the coating layer thickness and the diatomaceous earth particle size on the diatomaceous earth particle adhesion status.

[0032]

[Table 3]

Criteria for judging adhesion condition I: The coating layer partially covers the surface of the diatomaceous earth particles,
Insufficient coagulation activity II: The surface of the diatomaceous earth particles is exposed on the coating layer, and the coagulation activity is good. III: Some diatomaceous earth particles are not retained in the coating layer. Diatomaceous earth particles cannot be uniformly dispersed on the coating layer.

From the results shown in Table 3, the average diameter of the diatomaceous earth particles is 10 times or more and 100 times or less the average coating layer thickness.
The thickness is preferably 10 μm or less, and the thickness of the coating layer is 0.1 μm.
The range of from 0.05 to 1.00 μm is preferred.

Hereinafter, the effects of the present invention will be described more specifically with reference to examples. Example 1 1% by weight of PVP in isopropanol and 0.1, 0.2, 0.3, 0.1% of water-soluble silicone oil.
4 and 0.5% by weight, respectively, as a comparative example.
The mixed solution in which the weight percent was dissolved was sprayed uniformly on the inner surface of a polyester bottomed blood tube (for collecting 10 cc blood) using a spray, dried with hot air at 50 ° C., and dried to an average thickness of about 0.1 mm. A 1 μm mixture layer was formed. Celite SuperFlos having an average particle size of about 4 μm in isopropanol
was added to the mixture layer on the inner surface of the blood collection tube using a spray, sprayed with hot air at 50 ° C., and dried with Celite Supe.
A blood collection tube having an r Floss adhesion amount of about 0.015 mg / cm 2 was obtained. Since the effective blood contact area of the blood collection tube for 10 cc blood collection is about 39 square centimeters, the amount of Celite Super Floss involved in blood coagulation is 0.60 mg.

Immediately after the preparation of the blood collection tube and after storage at 50 ° C. for 1, 3, and 6 weeks, 10 cc of blood was collected from each blood collection tube by a conventional method, and the blood coagulation time was measured. At the same time, the blood adhesion state of the blood collection tube wall and the Celite SuperFloss adhesion state of the blood collection tube inner surface are 50
Observation was performed with a microscope magnified to 00 times. Table 4 shows the result. In this example, it was assumed that 6 weeks at 50 ° C. was a simulation at room temperature for about 1 year.

[0037]

[Table 4]

The diatomaceous earth adhesion state is indicated by Δ when the effective area of diatomaceous earth is slightly small due to the ability of PVP to form a film, and it takes time to dissolve the tube wall coating layer after blood contact. Indicated. When the water-soluble silicone oil is not contained, blood adheres to the wall surface of the blood collection tube during blood coagulation after blood collection, which is an obstacle to confirming the coagulation state. Furthermore, the amount of silicone oil increases, which is 6% of the amount of PVP.
At 0%, the blood coagulation performance decreases during storage of the vacuum blood collection tube. Thus, the mixture layer on the inner surface of the blood collection tube gives a good result at a weight ratio of water-soluble silicone oil / PVP of 0.1 to 0.5. The overall judgment was poor when there was no silicone oil or when 0.6% by weight.

Example 2 A mixture of 1% by weight of PVP and 0.1% by weight of a water-soluble silicone oil dissolved in isopropanol was applied to the inner surface of a vacuum tube (for collecting 10 cc blood) of a bottomed tube made of polyester. After spraying uniformly using a spray, the mixture was dried with hot air at 50 ° C. to form a mixture layer having an average thickness of about 0.1 μm. Celite Super Fl with an average particle size of about 4 µm (up to 7 µm) in isopropyl alcohol
was added to the mixture layer on the inner surface of the blood collection tube using a spray, sprayed with hot air at 50 ° C., and Celite Sup was added.
A blood collection tube having an er Floss attachment amount of about 0.30 mg was prepared.

Immediately after the production of the blood collection tube, the adhesion state of Celite Super Floss on the inner surface of the blood collection tube was observed with a microscope magnified 5000 times. The diatomaceous earth was present on the mixture, and no mixture layer was found on the surface of the diatomaceous earth opposite to the surface in contact with the mixture layer. 50 to accelerate changes over time
In a simulation test at 4 ° C. for 4 weeks, the blood had a coagulation time of 9.0 minutes, and the appearance of the blood collection tube was extremely good due to the small amount of diatomaceous earth.

[0041]

As described above, according to the present invention, when diatomaceous earth having blood coagulation activity in a reduced-pressure blood collection tube comes into contact with blood, dispersion / contact / coagulation starts immediately, and a high coagulation rate can be achieved with a small amount of coagulant. And a reduced-pressure blood collection tube capable of preventing a decrease in coagulation activity during storage of the reduced-pressure blood collection tube and maintaining a good appearance forever.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yukinori Enohara 3-9-3 Honjo Nishi, Kita-ku, Osaka City

Claims (5)

[Claims] 1. A bottomed tube made of synthetic resin, one end of which is closed and the other end of which is open, and a pierceable sealing member which seals the open end, and a space formed by both members is decompressed. In the reduced-pressure blood collection tube, the inner surface of the synthetic resin bottomed tube is coated with a mixture of polyvinylpyrrolidone and water-soluble silicone oil, and diatomaceous earth is adhered in a granular form on the coated surface. Characterized vacuum blood collection tube. 2. The weight ratio of the mixture of polyvinylpyrrolidone and water-soluble silicone oil is such that the ratio of the water-soluble silicone oil to the polyvinylpyrrolidone is 0.05 to 0.5.
The reduced pressure blood collection tube according to claim 1, wherein 3. The average thickness of a mixture of polyvinylpyrrolidone and a water-soluble silicone oil is 0.05 to 1.0 μm.
The reduced pressure blood collection tube according to claim 1, wherein the reduced pressure blood collection tube is m. 4. The average particle size of diatomaceous earth is 10 μm or less,
The reduced pressure blood collection tube according to claim 1, wherein the thickness is 10 to 100 times the thickness of the coating layer of the mixture of polyvinylpyrrolidone and water-soluble silicone oil. 5. The reduced-pressure blood collection tube according to claim 1, wherein the weight ratio of diatomaceous earth to 1, and the mixture of polyvinylpyrrolidone and water-soluble silicone oil are 0.2 to 1.0.