JPH0245894B2 - - Google Patents

Description

[Detailed description of the invention]

I. BACKGROUND TECHNICAL FIELD OF THE INVENTION The present invention relates to a method for manufacturing a reduced pressure blood collection tube. More specifically, the present invention relates to a method for manufacturing a reduced pressure blood collection tube that has extremely high gas barrier properties and can maintain a high degree of reduced pressure for a long period of time. Prior Art The reduced-pressure blood sampling method is widely used because it produces samples with less hemolysis and coagulation, less contamination and water evaporation, and simplifies blood collection preparation and equipment management in terms of efficiency. Therefore, the vacuum blood collection tube used in such a vacuum blood collection system consists of a tubular container and a sealing rubber stopper that can be punctured. Blood is collected by puncturing the rubber stopper at the other rear end to communicate with the inside of the sealed container, and blood flows in due to the negative pressure inside the container. Conventionally, such vacuum blood collection tubes have been made of glass tubular containers, which have no gas permeability and good transparency, and butyl rubber stoppers, which have low gas permeability and can be punctured. More have been used. However, glass tubular containers have the disadvantage that they are easily damaged during storage, transportation, or use, and are heavy. For this reason, we investigated the use of a lightweight and transparent tubular container made of synthetic resin, but since synthetic resin is more or less gas-permeable, it may be difficult to prevent atmospheric gas from surrounding it during long-term storage. It has been found that air permeates into the reduced pressure blood collection tube, and as a result, the pressure inside the blood collection tube increases, making it impossible to perform blood collection under the specified reduced pressure. For this reason, if synthetic resin vacuum blood collection tubes were to be used, they had to be stored in vacuum packaging containers. However, storage in a reduced pressure packaging container has the drawback that, since the packaging container is a reduced pressure container, it is extremely expensive and also requires considerable time and effort to seal and open the can, resulting in high costs. OBJECT OF THE INVENTION Accordingly, an object of the present invention is to provide a novel method for manufacturing a vacuum blood collection tube. Another object of the present invention is to provide a method for manufacturing a vacuum blood collection tube that has extremely high gas barrier properties and can maintain a high degree of vacuum for a long period of time. Still another object of the present invention is to provide a method for manufacturing a vacuum blood collection tube that is free from breakage and has extremely high gas barrier properties. These objects consist of a tubular member made of synthetic resin with one end closed and the other end open, and a plug member that seals the open end of the tubular member and can be pierced; In the method for manufacturing a reduced pressure blood collection tube in which an internal space formed by the above is maintained in a reduced pressure state, a mixed gas consisting of a silane coupling agent and a carrier gas is applied to at least one of the inner and outer surfaces of the tubular member. This is achieved by a method for manufacturing a reduced pressure blood collection tube characterized by forming a transparent film by supplying and reacting by a plasma vapor phase growth method. Further, the present invention is a method for producing a reduced pressure blood collection tube in which the reaction is carried out under reduced pressure of 0.05 to 2 Torr. Furthermore, the present invention is a method for producing a vacuum blood collection tube in which the amount of carrier gas is ¹⁰⁴ moles or less per mole of silane coupling agent. Moreover, the present invention
This is a method for manufacturing a vacuum blood collection tube in which the reaction temperature is -20 to 150°C. The present invention also provides a method for producing a vacuum blood collection tube, in which the silane coupling agent is at least one silane compound selected from the group consisting of vinylsilane compounds, alkyldisiloxanes, and alkylcyclosiloxanes. Furthermore, the present invention provides a method for producing a vacuum blood collection tube, wherein the carrier gas is at least one selected from the group consisting of carbon dioxide, oxygen, argon, nitrogen, nitric oxide, air, carbon monoxide, and ammonia. . Also,
The present invention is a method for manufacturing a reduced pressure blood collection tube in which the carrier gas is carbon dioxide or oxygen. The present invention
The present invention also provides a method for manufacturing a vacuum blood collection tube in which the synthetic resin tubular member is made of transparent synthetic resin. Furthermore, the present invention
A method for producing a vacuum blood collection tube, in which the synthetic resin is at least one polymer selected from the group consisting of a styrene homopolymer or copolymer, a methyl methacrylate homopolymer or copolymer, and polycarbonate. In addition, these purposes consist of a synthetic resin tubular member with one end closed and the other end open, and a plug member that seals the open end of the tubular member and can be pierced. A method for manufacturing a reduced pressure blood collection tube in which an internal space formed by a plug member is maintained in a reduced pressure state, wherein a nitrogen-containing organic compound is supplied in gaseous form to at least one of the inner surface and outer surface of the tubular member. This is achieved by a method for producing a reduced pressure blood collection tube, which is characterized by forming a transparent film through reaction using a plasma vapor phase growth method. Further, the present invention is a method for producing a reduced pressure blood collection tube in which the reaction is carried out under reduced pressure of 0.05 to 2 Torr.
Furthermore, the present invention is a method for producing a vacuum blood collection tube in which the reaction temperature is -20 to 150°C. The present invention also provides a vacuum blood collection tube in which the nitrogen-containing organic compound is at least one selected from the group consisting of a nitrogen-containing silane compound, an unsaturated aliphatic nitrile, preferably acrylonitrile, and a nitrogen-containing aromatic compound. It's a method. The present invention is a method for producing a vacuum blood collection tube in which the nitrogen-containing aromatic compound is pyridine. Further, the present invention is a method for manufacturing a vacuum blood collection tube in which the synthetic resin tubular member is made of transparent synthetic resin. Furthermore, the present invention provides a vacuum blood collection tube in which the synthetic resin is at least one polymer selected from the group consisting of a styrene homopolymer or copolymer, a methyl methacrylate homopolymer or copolymer, and polycarbonate. This is the manufacturing method. Specific Configuration of the Invention Next, the present invention will be described in detail with reference to the drawings. That is, as shown in FIG. 1, the reduced pressure blood collection tube 1 according to the present invention includes a transparent synthetic resin tubular member 2 with one end closed and the other end open, and a puncture tube with the open end 3 of the tubular member sealed. Possible plug member 4
The inner space 5 formed by the tubular member 2 and the plug member 4 is kept in a reduced pressure state. A transparent film is formed on at least one of the inner and outer surfaces of the transparent synthetic resin tubular member 2 by reacting a silane coupling agent or a nitrogen-containing organic compound. For example, as shown in FIG. 2A, a transparent coating 2 obtained by reacting a silane coupling agent or a nitrogen-containing organic compound on the entire outer surface of the tubular member 2
a is formed. Further, as shown in FIG. 2B, a transparent coating 2b obtained by reacting a silane coupling agent or a nitrogen-containing organic compound is formed on the entire inner surface of the tubular member 2. Further, as shown in FIG. 2C, the coating 2a is coated on the outer surface of the tubular member 2.
However, the transparent coating 2b is also formed on its inner surface. In addition, in FIGS. 2A to 2C, the transparent coatings 2a and 2b are exaggerated. Examples of the synthetic resin constituting the tubular member used in the present invention include styrene homopolymer or copolymer, methyl methacrylate homopolymer or copolymer, polycarbonate, and the like. Examples of polycarbonate include 4,4'-
In addition to bisphenol-type carbonates such as isopropylidene diphenol polycarbonate, other carbonates described in U.S. Pat. Examples include bisallyl carbonate. Monomers used for film formation include silane coupling agents, nitrogen-containing organic compounds, and the like. There are various types of silane coupling agents, but
For example, a vinylsilane compound having the general formula CH ₂ =CHSi(R) ₃ () (wherein R is a halogen atom such as chlorine or bromine, OCH ₃ , OC ₂ H ₅ , OC ₃ H ₇ , O-isoC ₃ alkoxy groups such as H ₇ , alkoxyalkoxy groups such as -OC ₂ H ₄ OCH ₃ , alkyl groups such as CH ₃ , C ₂ H ₅ , C ₃ H ₇ , isoC ₃ H ₇ ), alkyldisiloxanes,
Examples include alkylcyclosiloxanes and silane compounds having epoxy groups. Examples include vinyltriclosilane, vinyltris(β-methoxyethoxy)silane, vinyltriethoxysilane, vinyltrimethoxysilane, γ-methacryloxypropyltrimethoxysilane, β-(3,4
-epoxycyclohexyl)ethyltormethoxysilane, γ-glydoxypropyltrimethoxysilane, γ-glydoxypropylmethyldiethoxysilane, γ-mercaptopropyltrimethoxysilane, γ-chloropropyltrimethoxysilane,
Examples include hexamethyldisiloxane, tetramethylcyclosiloxane, γ-mercaptopropyltrimethoxysilane, and γ-mercaptopropyltrimethoxysilane. In addition, as nitrogen-containing organic compounds, hexamethylsilazane, 1,1,3,3-tetramethyldisilazane, N-β (aminoethyl)
γ-aminopropyltrimethoxysilane, N-β
(Aminoethyl) Nitrogen-containing silane compounds such as γ-aminopropylmethyldimethoxysilane, γ-aminopropyltriethoxysilane, N-phenyl-γ-aminopropyltrimethoxysilane, unsaturated nitriles such as acrylonitrile and methacrylonitrile, Preferred are nitrogen-containing aromatic compounds such as acrylonitrile, pyridine, cyanopyridines, and picolines, preferably picolidine. To form a transparent film on the surface of a tubular member, a plasma vapor growth method (Pazma Chemical Vapor Growth Method) is used.
Deposition method (hereinafter referred to as "plasma CVD method")
For example, use the following method. That is, as shown in FIG.
A dielectric base support stand 15 supported by the vacuum container main body holder 1 is provided on the dielectric base support stand 15.
6 is attached, and the reduced pressure container main body 2 to be subjected to plasma CVD treatment is held in the reduced pressure container main body holder 16.
Note that a ground 17 is connected to the dielectric base support 15. On the other hand, a high frequency electrode 17 connected to a power source (not shown) is provided on the opposite side of the dielectric base support 15. Then, the atmospheric gas in the reactor 13 is evacuated from the exhaust port 12 by a pressure reducing device 18 such as a vacuum pump, and while maintaining a predetermined degree of reduced pressure, the monomer is transported from the line 19 through the gas inlet 12 and again if necessary. Carbon dioxide from line 20 or line 1
While supplying oxygen or nitrogen gas from 9 into the reactor 13, the reduced pressure container main body 2 is rotated about the rotating shaft 14, and plasma is generated from the high frequency electrode to perform plasma CVD. Further, as another method, as shown in FIG. 4, there is a method in which the dielectric substrate support 15 is not rotatable but fixed. In this figure, the same reference numerals as in FIG. 3 represent the same members. When using a silane coupling agent as the monomer, a carrier gas is usually used in combination,
The silane coupling agent is fed to the reactor in gaseous form. The gas composition ratio of the silane coupling agent and carrier gas is 1 to ¹⁰⁴ moles of carrier gas per mole of silane coupling agent, preferably,
^10-102 moles. That is, if the carrier gas content is less than 1 mol, it is difficult to obtain a transparent coating film with high gas barrier properties, whereas if it exceeds 10 ⁴ mols, it is practically difficult to form a highly transparent coating film.
Examples of such carrier gas include carbon dioxide, oxygen, nitrogen, nitrogen monoxide, carbon monoxide, and ammonia, with carbon dioxide being preferred. On the other hand, when a nitrogen-containing organic compound is used as a monomer, a carrier gas is usually not required. The pressure during the plasma CVD reaction is 0.05 to 2 Torr, preferably 0.1 to 1.0 Torr. Also, the temperature of the substrate is -20 to 60℃ at the start of the reaction, preferably 20 to 50℃.
℃, but during the reaction -20 to 150℃, preferably
The temperature is 30-80℃. High frequency power amount is 0.01~1W/ ^cm2 ,
Preferably it is 0.04 to 0.5 W/cm ² . The thickness of the transparent film formed under such reaction conditions is 0.2 to 2.0 μm or less, preferably 0.5 to 1.0 μm. In addition to butyl rubber, the material constituting the plug member 4 may be one with sufficient elasticity to allow the blood collection needle to be inserted during use and to prevent the gap between the blood collection needle and the plug member from loosening due to the puncture of the blood collection needle, as will be described later. It is desirable that the gas permeability is low. Typical examples thereof include, for example, a blend of a thermoplastic elastomer, polyisobutylene, and partially crosslinked butyl rubber, and preferably a blend of a thermoplastic elastomer, polyisobutylene, and partially crosslinked butyl rubber. The composition of each component in the formulation ranges from 100 to 100 parts by weight of polyisobutylene per 100 parts by weight of thermoplastic elastomer.
200 parts by weight, preferably 120-150 parts by weight,
100 to 200 parts by weight of partially crosslinked butyl rubber, preferably
It is 120-150 parts by weight. Examples of thermoplastic elastomers include ethylene-propylene rubber, polyester elastomer, nylon elastomer, styrene-isoprene block copolymer, styrene-butadiene block copolymer, polybutadiene, thermoplastic polyurethane, and hydrogenated styrene-butadiene block copolymer. etc. Polyisobutylene has a molecular weight
15,000 to 200,000, preferably 80,000 to 150,000. Partially crosslinked butyl rubber is obtained by partially crosslinking butyl rubber obtained by copolymerizing isobutylene and a small amount (for example, 0.3 to 3.0 mol%) of isoprene. Specific Functions The reduced pressure blood collection tube having the above configuration is used in the following manner. That is, as shown in FIG. 6, one end is closed and the other end is open, and the blood collection tube holder 9 has a blood collection needle 8 screwed into the screw hole 7 of the closed end 6, and is inserted into the blood collection tube holder 9 through the opening. This blood collection needle 8
For example, it consists of a blood vessel piercing part 8a and a plug puncturing part 8b, and the plug puncturing part 8b is covered with a rubber sac or sheath 10 made of rubber. Next, when the blood vessel piercing portion 8a of the blood collection needle 8 is pierced into a blood vessel, for example, a vein, and the reduced pressure blood collection tube 1 is further pressed and inserted into the closed end 6 of the blood collection tube holder 9, the blood collection needle 8 is inserted as shown in FIG. The plug puncture part 8b is the luer adapter 1
0 and the plug member 4 and the tip reaches the internal space 5 of the blood collection tube 1, so that the tube and the internal space 5
The negative pressure in the internal space 5 causes blood within the blood vessel to flow into the internal space 5 of the blood collection tube 1 in an amount corresponding to the degree of reduced pressure. Then, blood collection is completed by removing the blood vessel piercing portion 8a of the blood collection needle 8 from the blood vessel. Next, the present invention will be explained in more detail with reference to Examples. Examples 1 to 6 As shown in FIG. 1, a tubular container 2 with a wall thickness of 1.2 mm and an inner diameter of 20 mm, closed at one end and open at the other end, was made of polystyrene. This tubular container 2 was placed in a reactor 13 as shown in FIG. 3, and the electrode area was 74 cm ² .
A mixed gas of vinylmethoxysilane and carbon dioxide was supplied while maintaining a constant exhaust volume with an electrode spacing of 4.5 cm, and a reaction was carried out by plasma CVD under the conditions shown in Table 1. The results are shown in Figure 2A. A transparent film 2a like this was formed. The tubular container 2
Thermoplastic elastomer (1,2-polybutadiene)
25 parts by weight, polyisobutylene (molecular weight 100000) 35
A stopper member was made from a mixture consisting of 25 parts by weight of partially cross-linked butyl rubber and 15 parts by weight of liquid paraffin, and the stopper member 4 was tightly plugged into the open end of the tubular container 2 which had been reduced in pressure to 110 mmHg to obtain a reduced pressure blood collection tube. Ta. When the oxygen permeability coefficient of this vacuum blood collection tube was measured, it was as shown in Table 1. Examples 7-8 In the same method as in Example 1, the electrode area was
A vacuum blood collection tube was prepared by forming a transparent film using the same method except that the tube was 201 cm ² and the electrode spacing was 5.0 cm. When the oxygen permeability coefficient of this vacuum blood collection tube was measured, it was as shown in Table 1. Examples 9 to 15 In the same method as in Example 1, a film was formed by plasma CVD under the conditions shown in Table 1,
A vacuum blood collection tube was prepared. When the oxygen permeability coefficient of this vacuum blood collection tube was measured, it was as shown in Table 1. Example 16 Using the tubular member described in Example 1, the electrode area was 50 cm and the ^2- electrode spacing was 4.5 cm,
A transparent film was formed using the same method except that a water-cooled reactor was used, and then a vacuum blood collection tube was prepared. When the oxygen permeability coefficient of this vacuum blood collection tube was measured, it was as shown in Table 1. Examples 17-18 In the same method as in Example 1, a film was formed by plasma CVD under the conditions shown in Table 1,
Next, the change in water absorption of the vacuum blood collection tube in a 60°C oven was measured, and the results were as shown in Figure 8. Comparative Example 1 In the same method as in Example 1, plasma
We created vacuum blood collection tubes for those that do not form a CVD film. The oxygen permeability coefficient and changes in water absorption in a 60°C oven were measured for this vacuum blood collection tube, and the results were as shown in Table 1 and Figure 8. Examples 19 to 21 As shown in Fig. 1, a tubular container 2, which is a vacuum container body with a wall thickness of 1.2 mm and an inner diameter of 14 mm, which is closed at one end and open at the other end, is made of polystyrene (weight average molecular weight
100000). This tubular container 2 was placed in a reactor as shown in Figure 3, with an electrode area of 74 cm ² and an electrode spacing.
When the nitrogen-containing organic compounds shown in Table 2 were supplied in gaseous form while keeping the displacement constant at 4.5 cm, and the reaction was carried out by plasma CVD under the conditions shown in Table 2, the results shown in Figure 2A were obtained. Transparent film 2a as shown
was formed. In the tubular container 2, a plug member is made of a mixture consisting of 25 parts by weight of a thermoplastic elastomer (1.2-polybutadiene), 35 parts by weight of polyisobutylene (molecular weight 100,000), 25 parts by weight of partially cross-linked butyl rubber, and 15 parts by weight of liquid paraffin; The plug member 4
The open end of the tubular container 2, which had been evacuated to 150 mmHg, was sealed to obtain a vacuum blood collection tube. The oxygen permeability coefficient and changes in water absorption in this vacuum blood collection tube in a 60°C oven were measured, and the results were as shown in Table 2 and Figure 9. Comparative Example 2 In the same method as in Example 19, plasma
We created vacuum blood collection tubes for those that do not form a CVD film. The oxygen permeability coefficient and changes in water absorption in a 60°C oven were measured for this vacuum blood collection tube, and the results were as shown in Table 2 and Figure 7. Figure 8 shows a certain amount of pressure reduction (enough to absorb approximately 10 c.c. water) using the vacuum vessels of Examples 17 and 18 and Comparative Example 1.
Multiple blood collection tubes were prepared and the changes in water absorption over time were investigated in an oven at 60°C. 9th
The figure shows a plurality of blood collection tubes prepared using vacuum vessels according to Examples 19, 20, 21 and Comparative Example 2, which were depressurized by a certain amount (approximately 10 c.c. to the extent that water can be absorbed), and then placed in a 60°C oven for a certain amount of time. This study investigated changes in water absorption.

【table】

[Table] Silane inside the reactor High-frequency electricity

Claims (1)

[Scope of Claims] 1. Consists of a tubular member made of synthetic resin with one end closed and the other end open, and a plug member that seals the open end of the tubular member and can be pierced, further comprising the tubular member and the plug. In the method for manufacturing a reduced pressure blood collection tube in which an internal space formed by a member is maintained in a reduced pressure state, a mixed gas consisting of a silane coupling agent and a carrier gas is applied to at least one of the inner and outer surfaces of the tubular member. 1. A method for manufacturing a reduced pressure blood collection tube, which comprises supplying a liquid and causing a reaction using a plasma vapor phase growth method to form a transparent film. 2. The method for manufacturing a reduced pressure blood collection tube according to claim 1, wherein the reaction is carried out under reduced pressure of 0.05 to 2 Torr. 3. The method for producing a reduced pressure blood collection tube according to claim 1 or 2, wherein the amount of carrier gas per mole of silane coupling agent is ¹⁰⁴ moles or less. 4. The method for manufacturing a vacuum blood collection tube according to any one of claims 1 to 3, wherein the reaction temperature is -20 to 150°C. 5. The method for producing a vacuum blood collection tube according to claim 1, wherein the silane coupling agent is at least one silane compound selected from the group consisting of vinylsilane compounds, alkyldisiloxanes, and alkylcyclosiloxanes. . 6. The carrier gas is at least one selected from the group consisting of carbon dioxide, oxygen, argon, nitrogen, nitric oxide, air, carbon monoxide, and ammonia.
The method for manufacturing a vacuum blood collection tube according to claim 1, which is a seed. 7. The method for manufacturing a vacuum blood collection tube according to claim 6, wherein the carrier gas is carbon dioxide or oxygen. 8. The method for manufacturing a vacuum blood collection tube according to item 1, wherein the synthetic resin tubular member is made of transparent synthetic resin. 9. Claims 1 to 8, wherein the synthetic resin is at least one polymer selected from the group consisting of a styrene homopolymer or copolymer, a methyl methacrylate homopolymer or copolymer, and polycarbonate. A method for manufacturing a vacuum blood collection tube according to any one of paragraphs. 10 Consists of a synthetic resin tubular member with one end closed and the other end open, and a plug member that seals the open end of the tubular member and can be pierced, and is further formed by the tubular member and the plug member. In a method for manufacturing a reduced pressure blood collection tube whose internal space is maintained in a reduced pressure state,
A reduced pressure blood collection tube, characterized in that a nitrogen-containing organic compound is supplied in gaseous form to at least one of the inner and outer surfaces of the tubular member and is reacted with the nitrogen-containing organic compound by a plasma vapor phase growth method to form a transparent film. Production method. 11. The method for producing a reduced pressure blood collection tube according to claim 10, wherein the reaction is carried out under reduced pressure of 0.05 to 2 Torr. 12. The method for manufacturing a vacuum blood collection tube according to claim 10 or 11, wherein the reaction temperature is -20 to 150°C. 13 The nitrogen-containing organic compound is a nitrogen-containing silane compound,
The method for producing a vacuum blood collection tube according to any one of claims 10 to 12, which is at least one selected from the group consisting of unsaturated aliphatic nitriles and nitrogen-containing aromatic compounds. . 14. The method for producing a vacuum blood collection tube according to claim 13, wherein the nitrogen-containing aromatic compound is pyridine. 15. The method for manufacturing a vacuum blood collection tube according to claim 10, wherein the synthetic resin tubular member is made of transparent synthetic resin. 16. Claims 10 to 16, wherein the synthetic resin is at least one polymer selected from the group consisting of a styrene homopolymer or copolymer, a methyl methacrylate homopolymer or copolymer, and polycarbonate. 16. The method for manufacturing a reduced pressure blood collection tube according to any one of Item 15.