WO2010024326A1

WO2010024326A1 - Method of manufacturing blood testing container, blood testing container, and spray device

Info

Publication number: WO2010024326A1
Application number: PCT/JP2009/064948
Authority: WO
Inventors: 隆介岡本; 雄二瀬戸口; 勝也戸川; 智雅井上
Original assignee: 積水メディカル株式会社
Priority date: 2008-08-28
Filing date: 2009-08-27
Publication date: 2010-03-04

Abstract

A method of manufacturing a blood testing container which is less likely to allow a medication to disperse to the outside and which can cause the medication to highly accurately adhere to a specific region of the inner surface of the blood testing container. A method of manufacturing a blood testing container uses a spray device (2) to cause a medication to adhere to the inner surface of a tubular container body (1) having a closed bottom. The spray device (2) is provided with a valve device (3) capable of having both an open state in which a pressurized medication solution is allowed to pass through the valve device and a closed state in which passage of the medication solution is prohibited, and the spray device (2) is also provided with a spray nozzle (4) connected to the valve device (3) so that the pressurized medication solution can be supplied to the valve device (3) and having through holes (4a) formed in a side surface of the spray nozzle (4). In the method, the valve device (3) is opened and closed to cause drops of the pressurized medication solution to be ejected from the through holes (4a) toward the inner surface of the blood testing container, causing the medication solution to adhere to the inner surface.

Description

Blood test container manufacturing method, blood test container, and spray device

The present invention relates to a method for manufacturing a blood test container, and more specifically, a method for manufacturing a blood test container in which a drug solution is fixed to the inner surface of a bottomed tubular container body, and a method for manufacturing the blood test container. The present invention relates to a blood test container and a spray device used in the manufacturing method.

Conventionally, various methods have been proposed as a method for storing a predetermined amount of a drug solution in a container such as a blood test container. Patent Document 1 below discloses a method of spraying a drug solution on the inner surface of a blood collection tube with a spray nozzle in order to adhere the drug solution to almost the entire inner wall surface of the blood collection tube.

The spray nozzle has a double tube structure having an outer tube and an inner tube disposed in the outer tube. The drug solution is supplied into the inner tube by a pump, and the compressed gas is supplied to the space between the outer tube and the inner tube. With the tip of the spray nozzle inserted into the blood collection tube, the drug solution and the compressed gas are blown out simultaneously, whereby the drug solution is sprayed from the tip of the spray nozzle. That is, at the tip of the spray nozzle, a shearing force acts on the drug solution due to the pressure of the compressed gas, whereby the drug solution is divided into fine droplets, and aerosol is generated. This aerosol is scattered on the flow of the compressed gas and is attached to the inner surface of the blood collection tube.

Here, it is said that the drug solution can adhere to almost the entire inner wall surface of the blood collection tube by raising the spray nozzle in the blood collection tube after the start of spraying.

Japanese Patent Laid-Open No. 10-305024

In the spraying method using the spray nozzle having a double-tube structure as described in Patent Document 1, the drug solution is sprayed in all directions from the tip of the spray nozzle, but the aerosol that has lost its destination flows backward, and the tube Dissipate from the mouth. For this reason, it is difficult to accurately control the amount of drug contained in the blood collection tube, and when the drug solution is applied to a large number of blood collection tubes, the amount of the adhered drug may vary.

Also, the aerosol that dissipates to the surroundings may adhere to the worker or the aerosol may be inhaled by the worker.

Furthermore, there is a possibility that the drug solution adheres to the surrounding equipment and the microorganisms grow by using the drug solution as a nutrient source. In addition, it may be mixed in a test container other than the blood collection container, affecting the measurement value of clinical tests, or causing contamination due to the growth of microorganisms.

In addition, since this type of drug is generally expensive, the method described in Patent Document 1 in which aerosol is easily dissipated in the surrounding area has a problem in that the use efficiency of the drug is lowered due to the aerosol being scattered in the surrounding area and the cost is increased. is there.

On the other hand, depending on the type of drug, it may be desirable to fix it to a specific area on the inner surface of a container such as a blood collection tube. For example, in the case of a vacuum blood collection tube in which the inside of the blood test container is decompressed and then sealed with a stopper, blood flows in vigorously during blood collection. As a result, blood may foam. When the blood coagulation promoter acts in such a state, the blood coagulates while foaming. As a result, the specific gravity decreases as much as air is contained, and there is a possibility that serum and blood clots cannot be reliably separated even after centrifugation.

In order to prevent the above problems, it is desirable to store a blood coagulation promoter above the portion of the vacuum blood collection tube where blood is collected.

On the other hand, when the blood anticoagulant is accommodated in the vacuum blood collection tube, it is desirable to accommodate the blood anticoagulant in the bottom of the vacuum blood collection tube. By the blood flow at the time of blood collection, the anticoagulant contained in the bottom is effectively washed away, and can be uniformly dissolved in the blood in a short time to prevent partial coagulation of the blood.

As described above, depending on the type of drug, it is desirable to store the drug in a specific area on the inner surface of a blood test container such as a blood collection tube. However, when a spray nozzle as described in Patent Document 1 is used, an aerosol is used. Since it diffuses, it is difficult to apply a medicine limited to a specific region.

In view of the current state of the prior art described above, the object of the present invention is that it is difficult to dissipate expensive drugs to the outside, the drug solution can be stored in the blood test container with high accuracy, and the inner surface of the blood test container is specified. An object of the present invention is to provide a blood test container manufacturing method, a blood test container obtained by the manufacturing method, and a spray device used in the manufacturing method, which can attach a drug to a region with high accuracy.

A production method according to the present invention is a method for producing a blood test container comprising a step of attaching a drug to the inner surface of a bottomed tubular container body, wherein the drug and a solvent that dissolves the drug are pressurized. A valve device configured to be able to be in an open state in which the drug solution is supplied and the drug solution is allowed to pass, and a closed state in which the drug solution is not allowed to pass, and a drug pressurized from the valve device A spray device is connected to the valve device so that the solution is supplied, the tip is closed, and a cylindrical spray nozzle having a plurality of through holes on the side surface. The pressed droplet of the drug solution is ejected from the through hole of the spray nozzle toward the inner surface of the container body, and the drug solution is adhered to the inner surface.

In a specific aspect of the manufacturing method according to the present invention, the valve device includes a needle valve as a valve body, a valve seat that is combined with the needle valve to open or close the valve device, and a closed state. Therefore, the needle is urged toward the valve seat, and the needle valve is moved so as to compress the spring against the urging force of the spring to open the valve device. A needle valve device is used in which a compressed gas supply port to which compressed gas for moving the valve is supplied is formed. In this case, since the valve body is a needle valve, a small amount of drug solution can be easily and reliably ejected from the through hole of the spray nozzle by reliably opening and closing the valve device.

In the production method of the present invention, preferably, a plurality of through holes provided in the spray nozzle are uniformly distributed in the circumferential direction of the cylindrical spray nozzle. In this case, the drug solution can be reliably applied uniformly in the circumferential direction of the spray nozzle.

In the production method of the present invention, preferably, at least one of the time in which the valve device is opened, the number and diameter of the through-holes, and the pressure for pressurizing the drug solution is adjusted. The amount of ejection is controlled. Thereby, the ejection amount of the drug solution can be controlled with high accuracy, and a desired amount of drug can be reliably fixed to the inner surface of the blood test solution.

In the manufacturing method according to the present invention, preferably, the solvent used in the drug solution is a solvent that volatilizes at room temperature, whereby the solvent volatilizes from the drug solution attached to the inner surface of the container body, and the solid drug Is fixed to the inner surface of the container body. In this case, the solid medicine can be reliably fixed to the inner surface of the test container by leaving it to evaporate the solvent.

In the production method of the present invention, preferably, when the drug solution is applied to the inner surface of the blood test container, the drug solution adheres to the inner surface of the container body above the blood surface after blood collection of the container body. Therefore, for example, if a blood coagulation promoter is attached to the inner surface of the container main body above the blood surface, even if bubbles are generated during the inflow of blood, the blood is not easily coagulated immediately while the bubbles are generated. Therefore, by mixing the blood test container by overturning after the bubbles disappear by leaving, blood without bubbles can be solidified reliably.

A blood test container according to the present invention is a blood test container obtained by the method for producing a blood test container of the present invention, and is a bottomed tubular container body, and a portion where blood is scheduled to be collected from the container body And a medicine fixed to the inner surface of the container main body above the container body.

A spray device according to the present invention is a spray device used in the method for manufacturing a blood test container of the present invention, and is stored in a state where a drug solution containing a drug and a solvent for dissolving the drug is pressurized. A chemical solution storage tank, a chemical solution supply port connected to the tank and supplied with a pressurized chemical solution, and a pressurized gas supply port supplied with a pressurized gas. Is closed, and is normally in a closed state that prohibits the discharge of the pressurized drug solution, and is in an open state in which the drug solution is discharged when pressurized gas is supplied. A cylindrical sprayer that is connected to the chemical solution discharge port of the valve device, has a closed end, and has a plurality of through holes on the side surface. And a nozzle. .

In the method for producing a blood test container according to the present invention, the pressurized drug solution can be discharged as fine droplets from the through-hole of the spray nozzle by opening and closing the valve device. Therefore, by discharging droplets from the through hole toward the inner surface of the container body, the drug solution can be reliably attached to a specific region on the inner surface of the blood test container.

In the prior art as described in Patent Document 1 in which an aerosol using compressed gas is sprayed, the droplets are sprayed on the compressed gas, so that the aerosol is easily dissipated around. On the other hand, in the present invention, since it is not a method of spraying aerosol, the drug solution is difficult to dissipate around. Accordingly, it is possible to increase the use efficiency of expensive drugs and reduce the cost. In addition, there is little risk that the medicine adheres to the worker or the worker accidentally sucks the medicine. Furthermore, it is possible to reliably attach the medicine only to a specific region on the inner surface of the container body.

(A) is a perspective view for demonstrating the manufacturing method of the blood test container of one Embodiment of this invention, (b), (c) is the partial notch front view which shows the principal part of the spray nozzle used, It is a partial notch front sectional drawing. It is sectional drawing which follows the II-II line | wire of FIG.1 (b). (A) is a partial notch front view for demonstrating the modification of a spray nozzle, (b) is the partial notch front sectional drawing, (c) is along the III-III line in (a). It is sectional drawing. (A), (b) is each typical front view which shows the example of the blood test container to which the chemical | medical solution was adhered, respectively.

Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.

Fig.1 (a) is a perspective view for demonstrating the manufacturing method of the blood test container based on one Embodiment of this invention, (b), (c) is a part which shows the principal part of the spray nozzle used. It is a notch front view and a partial notch front sectional view.

In the method for manufacturing a blood test container according to this embodiment, a drug solution is attached to the inner surface of the container body 1 using the spray device 2 on the bottomed tubular container body 1 shown in FIG.

The spray device 2 includes a valve device 3 and a cylindrical spray nozzle 4 connected to the valve device 3.

The valve device 3 has a drug solution supply port 3a and a compressed gas supply port 3b. A tank 5 is connected to the drug solution supply port 3 a via a pipe 6. The tank 5 stores a pressurized drug solution. The pressurized drug solution is supplied from the tank 5 to the drug solution supply port 3a through the pipe 6. The drug and solvent constituting the drug solution will be described in detail later.

The spray nozzle 4 is connected to the drug solution outlet 3c of the valve device 3. In order to supply the drug solution from the valve device 3 to the spray nozzle 4 and eject the droplet of the drug solution from the spray nozzle 4, the drug solution needs to be pressurized as described above. The degree of pressure is not particularly limited because it is appropriately adjusted according to the viscosity of the drug solution, but is about 0.002 to 1.0 MPa, preferably 0.05 to 0.5 MPa. If the gas pressure is too low, it may be difficult to discharge the drug solution, or the discharge amount may vary. If the gas pressure becomes too high, the amount of drug solution discharged becomes too large, and there is a risk that more drug will be discharged than desired.

On the other hand, a compressed gas supply control device 8 is connected to the compressed gas supply port 3b via a pipe 7. The compressed gas supply control device 8 is provided with a compressed gas supply port 8a, and a compressed gas supply source such as a gas cylinder (not shown) is connected to the compressed gas supply port 8a.

The compressed gas supply control device 8 has an electromagnetic valve inside, and the internal gas flow path is opened and closed by the electromagnetic valve. The compressed gas is supplied to the compressed gas supply port 3b of the valve device 3 through the pipe 7 in a state where the electromagnetic valve opens the gas flow path. When the internal flow path of the compressed gas supply control device 8 is closed by the electromagnetic valve, the compressed gas is not supplied to the compressed gas supply port 3b.

The pressure of the compressed gas applied from the compressed gas supply port 3b is set according to the spring strength of a spring of a needle valve described later, but is generally 0.1 to 5 MPa. If the gas pressure is too low, the valve device described later will not move. If the gas pressure becomes too large, a valve device described later may be damaged.

In addition, as gas, cheap air may be used or inert gas, such as nitrogen, may be used, and it is not specifically limited.

On the other hand, the valve device 3 is not particularly limited, but is a known needle valve device in the present embodiment. The needle valve device includes a needle valve as a valve body, a valve seat that is combined with the needle valve to open or close the needle valve device, and the needle valve toward the valve seat to close the needle valve device. And a spring for biasing. Normally, the needle valve is brought into contact with the valve seat by the biasing force of the spring, and the valve device 3 is closed. When compressed gas is supplied from the compressed gas supply port 3b and pressure is applied, the spring moves so as to compress against the urging force of the needle valve or the spring. Thereby, the valve device 3 is opened.

The valve device 3 has a flow path through which the drug solution flows. When the valve device 3 is closed, the flow of the drug solution supplied from the drug solution supply port 3a to the spray nozzle 4 is blocked. The pressurized drug solution is configured to be supplied to the spray nozzle 4.

In the present embodiment, the valve device 3 is formed by the needle valve device. However, any appropriate valve device can be used as long as the pressurized drug solution can be intermittently supplied to the spray nozzle 4. .

The compressed gas supply control device 8 can arbitrarily perform the discharge time of the compressed gas by the electromagnetic valve every 0.001 seconds in the range of 0.006 to 99.99 seconds. The supply state of the pressurized drug solution can be arbitrarily performed within this time range.

On the other hand, the spray nozzle 4 is formed of a cylindrical body with a closed end. Inside the spray nozzle 4, a flow path through which a pressurized drug solution is supplied extends in the axial direction. In the vicinity of the tip of the spray nozzle 4, a plurality of through holes 4 a are formed on the side surface of the spray nozzle 4. In the present embodiment, as shown in FIGS. 1B and 1C and FIG. 2, the four through holes are uniformly distributed in the circumferential direction in the vicinity of the tip of the spray nozzle 4.

Further, as in the modification shown in FIGS. 3A to 3C, eight through holes 4a may be dispersedly arranged.

That is, the number of the plurality of through holes 4a is not particularly limited. However, the diameter of the flow path 4b extending in the axial direction of the spray nozzle 4 is generally about 1 mm, and a drug solution of about 1 to 30 μL from the vicinity of the tip is formed as a plurality of droplets in a time of about 0.006 to 0.3 seconds. For discharging, about 3 to 30, preferably about 4 to 20 through holes 4a may be provided. If the number of through holes is too small, it may be difficult to apply the drug solution to the inner surface of the container body 1 in a fan shape. If the number of through-holes is too large, it is difficult to apply a predetermined amount of the drug solution unless the through-hole diameter is reduced, and foreign substances in the drug solution are clogged in the through-holes, or through-holes with a uniform diameter. May be difficult to form.

In addition, when many through-holes are formed, a plurality of through-hole rows including a plurality of through-holes arranged in the circumferential direction may be provided on the side surface of the spray nozzle 4. For example, when 20 through-holes are formed, 20 through-holes are formed by forming two rows of through-holes in which 10 through-holes are arranged in the circumferential direction so that the central angle is 36 °. May be provided.

Further, as described above, it is desirable that the plurality of through-holes are uniformly distributed in the circumferential direction of the spray nozzle 4, whereby the liquid of the drug solution that is uniformly pressurized in the circumferential direction of the spray nozzle 4. Drops can be ejected. However, the plurality of through holes do not necessarily have to be uniformly distributed along the outer peripheral surface of the spray nozzle 4.

The material constituting the valve device 3 and the spray nozzle 4 is not particularly limited, and an appropriate metal such as stainless steel or titanium alloy can be used.

The material constituting the pipes 6 and 7 is not particularly limited, and an appropriate metal or synthetic resin material such as stainless steel, silicone resin, or fluorinated ethylene resin can be used.

In manufacturing a blood test container, after applying a drug to the container body 1 as shown in FIG. 1, the opening 1a may be closed by a stopper depending on the application. As such a plug, one made of rubber or an appropriate elastomer can be used. Examples of rubber include various rubbers such as natural rubber, butyl rubber, chlorinated butyl rubber, brominated butyl rubber, and silicone rubber. As the elastomer, various elastomers such as styrene, vinyl chloride, olefin, urethane, polyester, or polyamide can be used.

Further, preferably, in order to prevent clots from adhering, it is preferable to coat at least the surface part of the plug that is in contact with blood with a clot adhesion preventing agent. As such a clot adhesion preventing agent, a clot adhesion preventing agent described later can be appropriately used.

When the container body 1 is closed by the plug body, for example, in order to form a vacuum blood collection tube, the plug body may be attached in a reduced pressure state. Thereby, a vacuum blood collection tube can be obtained according to the present invention.

In the method of manufacturing a blood test container using the spray device 2, a bottomed tubular container body 1 is first prepared. The material which comprises the container main body 1 is not specifically limited, Glass or a suitable synthetic resin can be used. The synthetic resin is not particularly limited, and examples thereof include polyethylene terephthalate, nylon, polypropylene, polyethylene, polystyrene, polycarbonate, hard vinyl chloride resin, and acrylic resin.

The container body 1 has a bottomed tubular shape with one end closed, and has an opening 1a at the top.

In addition, when the container main body 1 is formed of a material other than glass, in order to prevent the clot from adhering after blood coagulation, the surface portion that contacts the blood is coated with a clot adhesion preventing agent. It is preferable. Examples of the clot adhesion preventing agent include silicone oil, alcon modified silicone oil, polyethylene glycol, polypropylene glycol, polyoxyethylene-polyoxyalkylene condensate, polyoxyalkylene alkylene glycol, polyoxyalkylene glycol derivative and the like. it can.

Prepare the container body 1 and store the drug solution in the tank 5 of the valve device 3.

As described above, the drug solution is pressurized to a pressure of about 0.002 to 1.0 MPa, preferably 0.005 to 0.5 MPa, and supplied to the valve device 3.

Next, the pressurized drug solution supplied to the valve device 3 is supplied to the spray nozzle 4 by opening and closing an electromagnetic valve in the compressed gas supply control device 8. When the valve device 3 is opened, the pressurized drug solution flows into the spray nozzle 4 side. By repeatedly opening and closing the valve device 3, the pressurized drug solution is gradually filled in the spray nozzle 4, and after the filling is completed, the pressure by the compressed gas is filled according to the opening and closing of the valve device 3. It will be added to the drug solution. Therefore, liquid droplets of the drug solution are ejected from the plurality of through holes 4a provided in the vicinity of the tip of the spray nozzle 4 to the side by the gas pressure while the valve device 3 is in the open state.

Accordingly, as shown in FIG. 1A, the tip of the spray nozzle 4 is inserted into the inside of the container body 1 from the opening 1a and thoroughly placed at an appropriate height position so that the drug solution is contained in the container. At a predetermined height position on the inner side surface of the main body 1, it can be uniformly attached in the circumferential direction of the inner side surface. That is, at a certain height position, the drug solution can be applied so as to form a belt-like pattern along the inner peripheral surface of the container body 1.

The timing for opening and closing the electromagnetic valve may be adjusted according to the amount of the applied drug solution, but is generally 0.006 to 0.3 seconds, preferably 0.01 to 0.2 seconds. It is said. If the time for the open state is too short, it is impossible to discharge a desired amount of the drug solution. If it is too long, the discharge amount becomes too large, and the attached drug solution hangs down on the inner surface of the container body 1. There is a fear.

As described above, the ejection amount of the drug solution varies depending on the opening / closing timing of the valve device, the number and diameter of the through holes of the spray nozzle, and the pressure for pressurizing the drug solution. Therefore, it is desirable to control the amount of the drug solution ejected by adjusting at least one of the time for which the valve device is opened, the number and diameter of the through holes, and the pressure for pressurizing the drug solution.

When the solvent is volatile as described above after adhering the drug solution to the inner surface of the container body 1, it may be left to dry under natural pressure. However, gas such as air may be blown in and forcedly dried, or left under reduced pressure and vacuum dried. Furthermore, in these drying methods, drying may be accelerated by using heating together.

When a drug solution containing a drug and a volatile solvent is used as the drug solution, the solvent volatilizes by simply leaving it at room temperature, and the drug, for example, a solid drug is placed at a certain height position of the container body 1. It can be fixed in a band shape. In this way, it is possible to obtain a blood test container in which a drug is fixed only at a predetermined position on the inner surface of the container body 1.

In addition, preferably, when the drug solution is attached to the inner surface of the container body 1, it is desirable that the drug solution is attached to the inner surface of the container body 1 above the blood surface after blood collection of the container body 1. In this case, the height of the blood surface after blood collection can be predicted from the blood volume scheduled in advance and the volume of the container body. Therefore, the drug solution may be attached above the predicted blood surface.

4 (a) and 4 (b) are schematic front views showing examples of blood test containers obtained in this manner.

In the blood test container 11 of FIG. 4 (a), the drug 13 is attached from a height position H1 on the inner surface of the container body 1 to a lower height position H2. On the other hand, in the blood test container 12 shown in FIG. 4B, the medicine 14 is attached in a dot shape in the circumferential direction at a height position H3 where the container body 1 is located.

When the amount of the solvent in the drug solution is increased and the viscosity of the drug solution is relatively low, as shown in FIG. 4 (a), a part of the attached drug solution flows down and the solvent volatilizes. Accordingly, the drug 13 can be fixed so that the amount of the drug 13 attached gradually decreases downward from the portion where the drug solution is attached. In addition, when the concentration of the drug solution is relatively high, or when the solvent is a solvent that readily evaporates, the drug 14 can be fixed in a dot shape as shown in FIG. Accordingly, the timing and period of the opening / closing operation of the valve device 3 by the compressed gas supply control device 8 is adjusted by selecting the concentration of the drug solution and the type of the solvent, or by adjusting the diameter of the through hole 4a described above. By doing so, it is possible to fix the drug partially or selectively on the inner surface of the container body 1 in various patterns.

In the method for manufacturing a blood test container according to this embodiment, as described above, the flow path 4b through which the drug solution is supplied is provided, and a spray nozzle that does not have a flow path through which the compressed gas passes is used. Therefore, since a spray nozzle through which only one kind of fluid to be applied passes is used, a droplet of the drug solution is ejected from the through hole 4a, and a desired position on the inner peripheral surface of the container body 1 It is possible to attach the droplets with high accuracy.

In the case of using a conventional double-tube spray nozzle, the liquid was sheared by the gas pressure to form an aerosol, so the aerosol was scattered around and scattered outside the container body, and even inside the container body, It could not be applied to the desired place with high accuracy. In contrast, in the present embodiment, since the spray nozzle 4 is used, the drug solution is unlikely to be scattered outside the container body 1. Therefore, there is no possibility that the drug solution adheres to the worker, and there is no possibility that the worker accidentally sucks the drug solution. In addition, the drug solution can be attached to the desired portion of the inner surface of the container body 1 with high accuracy and the drug can be fixed.

Therefore, for example, when blood is collected during a serum test, a drug 14 such as a blood coagulation promoter may be applied to the inner surface of the container body 1 above the liquid level of the blood collected in the container body 1. Thus, contact between the blood coagulation promoter and blood from the beginning can be avoided. For example, as shown in FIGS. 4 (a) and 4 (b), the drug 14 is fixed so that the blood level is located below the portion where the drug 14 is fixed, and the opening 1a is further closed with a plug. It is desirable to close it. In this case, even if the collected blood is foamed, it is allowed to stand until the foam disappears, and then the blood test container may be mixed by inversion and brought into contact with the drug 14 and the blood. It is possible to reliably coagulate blood with no blood. Therefore, since there is no possibility of blood coagulating with foaming, clean serum can be reliably obtained.

Next, the drug solution applied to the container body in the present invention will be described. The drug solution used in the present invention is not particularly limited, and examples of the drug include blood coagulation promoters, blood anticoagulants, glycolysis inhibitors, blood anticoagulation inhibitors and the like as described above. A plurality of types of drugs may be included in the drug solution.

The blood coagulation promoter is preferably an enzyme that can hydrolyze the bond between arginine and any amino acid residue and / or the bond between lysine and any amino acid residue in the peptide chain, and more specifically, Serine proteases such as trypsin, thrombin and snake venom thrombin-like enzymes; thiol proteases such as cathepsin B and ficin; metal proteases such as kininase I and the like. It is done. The method for preparing thrombin is not particularly limited, and for example, those obtained by purification from animal (human, bovine, etc.) plasma can be used. Two or more enzymes may be used in combination.

If the amount of the enzyme used is too small, it will take too much time for blood clotting, and if it is too large, blood clotting will be too fast, resulting in uneven clotting or adversely affecting the test value. As a guideline, the activity value is preferably 0.1 to 100 IU (international unit: hereinafter referred to as “unit”). For example, when thrombin is used as an enzyme, the amount used is 0.5 to 50 units per mL of blood. And more preferably 1 to 20 units.

The blood coagulation promoter may contain at least one of an enzyme inactivated product obtained by inactivating the enzyme by irradiation and β-alanine as a stabilizer for the enzyme. Examples of radiation include gamma rays and electron beams. Two or more enzyme deactivators may be used in combination.

The amount of the enzyme deactivator added to the blood coagulation promoter is preferably 0.001 to 100 μg, more preferably 0.01 to 10 μg, most preferably 0.03 to 5 μg per unit of thrombin. If the added amount is large, the production cost is disadvantageous, and therefore it is preferable to set the minimum amount necessary to achieve the desired performance. As the enzyme inactivated substance, an enzyme inactivated substance deactivated by irradiation with radiation may be added, or a part of the added active enzyme may be deactivated by irradiation with radiation to form an enzyme inactivated substance.

The amount of β-alanine added to the blood coagulation promoter is preferably 0.01 to 1000 μg, more preferably 0.1 to 200 μg, most preferably 0.5 to 50 μg per unit of thrombin. If too much is added, it may be difficult to dissolve β-alanine in the blood coagulation promoter, resulting in a non-uniform blood coagulation promoter or a blood coagulation promoter that cannot be sprayed. It is preferable that the amount be added so that it can be uniformly dissolved.

The blood coagulation promoter is added with a binder composed of a water-soluble polymer in order to stably fix the above enzymes and enzyme stabilizers to the bottomed tubular container and to dissolve them effectively during inversion mixing. May be. The binder is not particularly limited as long as it is a compound that does not affect the inspection value. For example, polyvinylpyrrolidone is preferably used. The weight average molecular weight of polyvinylpyrrolidone is 1 to 600,000, preferably 3 to 500,000. If the molecular weight is too small, hemolysis may occur. If the molecular weight is too high, solubility in blood is insufficient, and the action of the enzyme is inhibited.

As the blood anticoagulant, at least one selected from heparin salt, ethylenediaminetetraacetate, citric acid and the like is preferably used.

As the glycolysis inhibitor, sodium fluoride or the like is preferably used.

As the blood anticoagulant inhibitor, mucopolysulfate and the like are preferably used.

As the solvent, an appropriate solvent that dissolves the above-mentioned drug can be used, but a volatile solvent at room temperature, for example, water is preferable. The reason is that there is no environmental pollution due to volatilization of the solvent. When water is used, it is preferable to forcibly dry it by introducing dry air after application. Other examples include alcohols such as ethyl alcohol and isopropyl alcohol, chlorofluorocarbons, and freons. When these organic solvents are used, the solvent can be volatilized naturally at room temperature and dried.

Next, a specific experimental example will be described.

Example 1
As the spray nozzle 4, a spray nozzle having an outer diameter of 4 mm, an inner diameter of 2 mm, and a length of 150 mm and having four through-holes formed at intervals of central angles of 90 ° in the circumferential direction is used. The diameter of the through hole 4a was 0.045 mm.

Thrombin as a drug solution, concentration of 12500 units / mL, β-alanine as a stabilizer, 5.8% by weight, PVP having a weight average molecular weight of 45,000 as a binder (K30 manufactured by BASF) at a concentration of 0.8% by weight Thus, a blood coagulation promoter solution dissolved in distilled water as a solvent was prepared.

The blood coagulation promoter solution was added to the tank 5 and pressurized with air so that the pressure was 0.05 MPa. The spray nozzle 4 is inserted into the container body 1 so that the through hole 4a of the spray nozzle 4 is located at a depth of 7 mm from the opening end of the glass container body 1 having an inner diameter of 10 mm and a length of 100 mm. Using the apparatus shown, the blood coagulation promoter solution was discharged and adhered to the inner surface of the container body 1. In this case, the electromagnetic valve in the compressed gas supply control device 8 was opened for 0.015 seconds to eject 4 μL of the blood coagulation promoter solution.

After discharging for 0.015 seconds, the blood coagulation promoter solution was adhered to the inner surface of the container body 1, and then the weight of the container body 1 was measured immediately. As a result, the increase in weight was 4 mg. Therefore, it was confirmed that the entire amount of the blood coagulation promoter solution ejected from the spray nozzle 4 was adhered and was not dissipated outside the container body 1.

Further, when the inner surface of the container body 1 was observed, the drug solution was adhered in an annular region having a width of 3 mm centering on a position corresponding to a depth of 7 mm from the opening end.

(Example 2)
The concentration of thrombin was 6250 units / mL, the concentration of β-alanine was 2.9% by weight, the time for opening the solenoid valve was 0.06 seconds, and 8 μL of the blood coagulation promoter solution was ejected. Except for this, the blood coagulation promoter solution was adhered to the inner surface of the container body 1 in the same manner as in Example 1.

As a result, immediately after the blood coagulation promoter solution was discharged, the weight of the container body 1 was measured immediately. As a result, the increase in weight was 8 mg, and the entire amount of the blood coagulation promoter solution discharged from the spray nozzle 4 adhered. It was confirmed that That is, it was confirmed that the blood coagulation promoter solution was not dissipated outside the container body 1.

Moreover, when the inner surface of the container main body 1 was observed, it was recognized that the blood coagulation promoter solution was adhered in an annular region having a width of 5 mm, centering on a portion at a height of 7 mm from the opening end. .

(Example 3)
Ten through holes in the spray nozzle are arranged in the circumferential direction with a central angle of 36 °, the diameter of each through hole is 0.025 mm, and the time for opening the solenoid valve is 0.06 seconds. A blood test container was manufactured in the same manner as in Example 1 except that 5 μL of the blood coagulation promoter solution was discharged.

In Example 3, when the weight of the tubular container was measured immediately after discharge, the weight increase was 5 mg, and the whole amount of the blood coagulation promoter solution discharged from the spray nozzle 4 was adhered and dissipated to the outside. It was confirmed that it was not.

Also in Example 3, when the inner surface of the obtained blood test container was observed, the blood coagulation promoter solution was adhered in an annular region having a width of 4 mm centering on a portion corresponding to a depth of 7 mm from the opening end. It was confirmed.

Example 4
Except that the concentration of thrombin was 5000 units / mL, the concentration of β-alanine was 2.3% by weight, the time for opening the solenoid valve was 0.02 seconds, and 10 μL of the blood coagulation promoter solution was discharged. In the same manner as in Example 3, the blood coagulation promoter solution was adhered to the inner surface of the container body. When the weight of the container body 1 was measured immediately after the blood coagulation accelerator solution was discharged, the increase in weight was 10 mg, and the entire amount of the discharged blood coagulation accelerator solution was adhered, and the outside of the container body 1 was It was confirmed that it was not dissipated.

It was confirmed that the blood coagulation promoter solution was adhered in an annular region having a width of 6 mm centering on a portion corresponding to a depth of 7 mm from the opening end of the container body 1.

(Comparative Example 1)
Using a conventional spray nozzle in which an outer tube with an outer diameter of 1.5 mm, an inner diameter of 0.9 mm and a length of 160 mm is inserted into an outer tube with an outer diameter of 4 mm, an inner diameter of 2.0 mm and a length of 150 mm, a thrombin of 5000 units / blood coagulation promoted by dissolving PVP with 2.3% by weight of β-alanine as a stabilizer and PVP with a weight average molecular weight of 45,000 as a binder in distilled water to a concentration of 0.8% by weight According to a conventional method, the agent solution was sprayed by inserting a spray nozzle to a depth of 7 mm from the open end of a glass bottomed tubular container body having an inner diameter of 10 mm and a length of 100 mm. In spraying, while supplying 0.15 MPa of air to the outer tube, 10 μL of the blood coagulation promoter solution was ejected from the inner tube, and aerosol was generated and sprayed at the tip of the nozzle.

When the weight of the tubular container body was measured immediately after spraying, the weight increase was 7.5 mg, and it was found that 25% of the blood coagulation promoter solution ejected from the spray nozzle was dissipated outside the container body. It was.

Further, when the container body was observed after spraying, the blood coagulation promoter solution was adhered in an annular region having a vertical width of 50 mm with reference to a portion corresponding to a depth of 7 mm from the opening end.

DESCRIPTION OF SYMBOLS 1 ... Container main body 1a ... Opening 2 ... Spray apparatus 3 ... Valve apparatus 3a ... Chemical solution supply port 3b ... Compressed gas supply port 3c ... Chemical solution discharge port 4 ... Spray nozzle 4a ... Through-hole 4b ... Flow path 5 ... Tank 6 ... Piping 7 ... Piping 8 ... Compressed gas supply control device 8a ... Compressed gas supply port 11, 12 ...

Blood test container

13, 14 ... Drug

Claims

A method for producing a blood test container comprising a step of attaching a drug to the inner surface of a bottomed tubular container body,
A pressurized drug solution containing the drug and a solvent for dissolving the drug is supplied, and an open state in which the drug solution is allowed to pass and a closed state in which the drug solution is not allowed to pass can be taken. A cylindrical spray that is connected to the valve device so that a pressurized drug solution is supplied from the valve device, the tip is closed, and a plurality of through holes are provided on the side surface. Using a spray device having a nozzle, a droplet of a drug solution pressurized by opening and closing the valve device is ejected from the through hole of the spray nozzle toward the inner surface of the container body, and the drug solution is attached to the inner surface. A method for producing a blood test container, characterized by comprising:
The valve device includes a needle valve as a valve body, a valve seat that is combined with the needle valve to open or close the valve device, and the needle valve is urged toward the valve seat to close the valve device. And a compressed gas supply for supplying a compressed gas for moving the needle valve to open the valve device by moving the needle valve so as to compress the spring against the urging force of the spring. The method for producing a blood test container according to claim 1, which is a needle valve device in which a mouth is formed.
The method for producing a blood test container according to claim 1 or 2, wherein a plurality of through holes provided in the spray nozzle are uniformly distributed in the circumferential direction of the cylindrical spray nozzle.
The ejection amount of the drug solution is controlled by adjusting at least one of the time in which the valve device is opened, the number and diameter of the through holes, and the pressure for pressurizing the drug solution. The method for producing a blood test container according to any one of claims 1 to 3.
The solvent used for the drug solution is a solvent that volatilizes at room temperature, whereby the solvent volatilizes from the drug solution attached to the inner surface of the container body, and the solid drug is fixed to the inner surface of the container body. The method for producing a blood test container according to any one of claims 1 to 4.
6. The drug solution according to claim 1, wherein the drug solution is attached to the inner surface of the container body above the blood surface after blood collection of the container body when the drug solution is attached to the inner surface of the container body. Blood test container manufacturing method.
A blood test container obtained by the method for manufacturing a blood test container according to any one of claims 1 to 6, wherein a bottomed tubular container body and blood collection of the container body are scheduled A blood test container comprising: a medicine fixed on the inner surface of the container body above the portion being present.
A spray device used in the method for producing a blood test container according to any one of claims 1 to 6,
A drug solution storage tank storing a drug and a drug solution containing a solvent or the like for dissolving the drug in a pressurized state;
It is connected to the tank, and a drug solution supply port to which a pressurized drug solution is supplied from the tank and a pressurized gas supply port to which a pressurized gas is supplied are formed. A closed state for prohibiting the discharge of the pressurized drug solution, an open state for discharging the drug solution when the pressurized gas is supplied, and a discharge port for discharging the pressurized drug solution; A valve device comprising:
A spray device comprising: a tubular spray nozzle connected to a drug solution outlet of the valve device, closed at a tip, and provided with a plurality of through holes on a side surface.