JPH11253557A - Sliding valve for syringe, syringe and kit preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent a separation and a desorption, and improve the lubricity, the air-tightness, and the liquid-leakage preventing property by forming a sliding valve of a plastic wherein lubricant components are chemically combined. SOLUTION: To an ethylene vinyl acetate copolymerized resin, a low density polyethylene, and chlorinated polyethylene, a crosslinking agent, triallylisocyanulate and trimethylol propane trimethacrylate, which are assistants, a poly-4-ethylene fluoride powder as a lubricating material, and a silicone based grease which is a lubricant, are mixed. By using this uncrosslinked resin composition, a sliding valve 25 and a front stopper sliding valve 26 of a plunger, are injection-molded. By this constitution, the operatability of the sliding valve is improved, and a desorption is totally prevented from occurring.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sliding valve used for a syringe such as a disposable syringe.

[0002]

2. Description of the Related Art Injections to be introduced into the body by injection have long been supplied in ampoules or vials.
However, there is a problem that the glass fine powder generated at the time of opening the ampoule may enter the body, there is a possibility that various obstacles may occur due to the contact of the medicine with the air, and recently, a so-called disposable syringe in which the medicine is pre-filled is so-called. Increasingly supplied in kit formulations.

[0003] Since disposable syringes are literally disposable, they are now widely used because they are easy to use and have no risk of infection such as serum hepatitis.
This consists of a cylinder part made of resin or glass and a plunger part having a sliding valve made of rubber or rubber material (hereinafter, referred to as "rubber").

Two types of cylinders, glass and polypropylene, have been used. Here, a syringe having a glass cylinder portion is considered to be particularly suitable for kit preparations because of its excellent chemical resistance and gas barrier properties, but it is expensive and has a problem in treatment after use. on the other hand,
Although those made of polypropylene are inferior in chemical resistance and gas barrier properties, they have the advantage that they are inexpensive and can be incinerated after use. In both syringes, the inside of the syringe body and the sliding valve were coated with silicone in order to improve the sliding properties of the sliding valve.

[0005] In injection, the injection must be slowly introduced into the body in order to work safely and effectively, and therefore, the movement of the slide valve needs to be smooth.
In addition, in the case of a kit preparation in which a chemical solution is stored in a cylinder and a slide valve is provided as a front stopper in addition to the plunger portion, since there are two slide valves inside the cylinder, handleability due to deterioration of slidability is improved. The silicone coating treatment to improve this played an extremely important role.

[0006] Recently, however, the safety of silicone coating treatment has been questioned. For this reason, an amorphous polyolefin (copolymer of a cyclic olefin and an α-olefin) is used to solve the disadvantages of the glass and polypropylene cylinders while eliminating the need for silicone coating. was suggested. That is, unlike a glass syringe, the cylinder portion made of amorphous polyolefin can have a smooth mirror surface on the inner surface during manufacturing, and good sliding properties can be obtained while eliminating the need for silicone coating treatment. .

However, when actually examined, although a certain degree of slidability can be obtained without the silicone coating treatment, the slidability did not reach the level required for a syringe. The fact is that it is still being done.

On the other hand, as an alternative to the silicone coating treatment, measures such as providing a fluororesin layer inside the cylinder or on the surface of the sliding valve have been taken. However, in this case, adhesion of the contact portion between the sliding valve and the inside of the cylinder is likely to occur, so that the sliding valve is held for a long time other than at the tip inside the cylinder as in the case of a kit preparation, and injection from the position to the patient is performed. This was a particular problem when it was necessary to do so. In addition, fine cracks may occur at the adhesion portion between the inside of the cylinder and the sliding valve, and gas barrier properties,
This raises questions about drug stability and safety.

Although a method of forming a surface film on the rubber slide valve has been proposed, it is difficult to prevent the peeling of the slide valve and the reliability is poor. On the other hand, a sliding valve in which fine powder of a sliding material such as Teflon is mixed has been proposed, but there is also a concern that the fine powder may be detached.

[0010] As described above, the function of a syringe having good lubrication and becoming sophisticated and complicated can be fully exhibited.
In addition, there has been a demand for a safe sliding valve free from the possibility of peeling and detachment of foreign matter.

It is an object of the present invention to provide a syringe having a lubricating sliding valve which solves the above-mentioned problems of the prior art and which is free from peeling and detachment and has good lubricity. Thus, there has been a need for a safe sliding valve that can fully exhibit the function of a syringe with good lubricity and sophistication and complexity, and that is free from the possibility of peeling or detachment of foreign matter. .

[0012]

DISCLOSURE OF THE INVENTION The present invention has a sliding valve having good lubricating properties without fear of peeling and detachment, and
An object of the present invention is to provide a syringe excellent in airtightness and liquid leakage prevention.

[0013]

In order to solve the above-mentioned problems, a sliding valve for a syringe according to the present invention is a sliding valve for a syringe made of plastic in which a lubricating component is chemically bonded. .

According to the sixth aspect of the present invention, there is provided a syringe having a sliding valve made of plastic to which a lubricating component is chemically bonded. On the other hand, the kit preparation of the present invention is a kit preparation using a sliding valve made of plastic to which a lubricating component is chemically bonded, as described in claim 8.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Plastics used in the present invention include, among commonly used plastics, organic and inorganic substances, such as plasticizers, which may adversely affect living bodies.
Any substance that is suitable for pharmaceutical use that does not cause harmful metals or the like to be eluted or does not contain harmful metals and that has chemical resistance to the intended drug can be used. That is, polyester-based, polyamide-based, polypropylene-based, polyolefin-based, polyurethane-based, and the like. Here, it is not necessary that the plastic has rubber properties. That is, in the case of plastic having rubber, depending on the shape of the sliding valve, the sliding with the inner wall of the cylinder may be extremely deteriorated. Although an expensive fluororesin can be used as the plastic, it is unnecessary from the point of the present invention.

In the present invention, an inorganic lubricant such as molybdenum disulfide can be used as the lubricating component, but an organic lubricant is preferable. Such materials include, for example, hydrocarbon-based materials, polyglycol-based materials, and fluorine-based materials. These lubricating components are derivatized and chemically bonded to the plastic. Since the amount of the lubricating component chemically bonded has a great effect on the lubricity, it is necessary to determine the amount after various studies.

Incidentally, other silicone-based lubricants can also be used as the lubricating component. That is, in the present invention, since these lubricants and lubricants are chemically bonded to the base plastic, the problem of desorption, which has been a concern in conventional silicone lubricants, is solved.

As a chemical bonding method, a general chemical method such as an ordinary amide bond or ester bond may be used. However, a group which reacts with a crosslinking agent of the base plastic is introduced into the lubricating component in advance. In addition, a method that is performed simultaneously with the crosslinking of the plastic can be adopted. In this case, it is needless to say that the plastic used must be crosslinkable.

When the lubricating component is a poorly reactive lubricating material such as a fluororesin (polytetrafluoroethylene or a copolymer of tetrafluoroethylene and another comonomer), an electrophilic reagent (hindered) is used. Phenols and Grignard reagents) can be added together with these lubricants at the time of molding, and can be chemically bonded simultaneously with the granulation reaction.

The size of the lubricant is preferably 10 μm or more and 50 μm or less in diameter. When polytetrafluoroethylene is used as the lubricant, the amount is preferably 5 parts by weight or more and 60 parts by weight or less, particularly preferably 10 parts by weight or more and 50 parts by weight based on 100 parts by weight of the base plastic component.

When a silicone-based lubricant is used, it is preferably from 5 to 20 parts by weight, particularly preferably from 10 to 15 parts by weight, based on 100 parts by weight of the base plastic component. If the amount is excessive, a phenomenon similar to bloom may occur.

Hereinafter, an example in which a fluororesin and a silicone-based lubricant are used as a lubricating component will be described in detail. In other words, when a fluororesin or a silicone-based lubricant is used as the lubricating component, the movement of the slide valve is very smooth, and the start of the movement is smooth, so that injection into a predetermined place such as intravenous injection becomes easy. Of course, in addition, for example, in the case of a kit preparation, the injection volume may be adjusted according to the patient instead of injecting the entire injection solution in the cylinder. This has the effect of making injection extremely easy. Note that the fluororesin and the silicone-based lubricant, which are lubricants, can be used alone as a lubricating component, but by using both at the same time, better lubricity can be obtained. In addition, administration, which is difficult with a conventional syringe, such as application of high-viscosity, high-molecular-weight sodium hyaluronate to the knee joint cavity, can be easily performed.

In the above, it is necessary that the electrophile is compatible with the base plastic component and does not cause obstacles. Such compounds include hindered phenols such as pentaerythrityl-tetrakis [3- (3,5-t-butyl-4).
-Hydroxyphenyl) propionate], 2,2-thio-diethylenebis [3- (3,5-di-t-butyl-
4-hydroxyphenyl) propionate], 2,2-
Thiobis (4-methyl-6-t-butylphenol),
N, N'-bis [3- (3,5-di-t-butyl-4-
Hydroxyphenyl) propionyl] hydrazine and the like, and chlorine-containing compounds such as isopropylmagnesium chloride and isooctylmagnesium iodide as Grignard reagents.
Those containing iodine are exemplified. These electrophiles are usually based on 100 parts by weight of the base plastic component.
It is desirable to add 0.1 to 10 parts by weight, particularly 0.2 to 5 parts by weight.

These lubricants / lubricants are blended with an electrophile, a plastic component and a cross-linking agent. For example, injection molding is performed in a mold at a temperature of 140 ° C. or more and 200 ° C. or less for 30 minutes or less, if necessary. By performing a crosslinking treatment by applying a pressure of 200 kg / cm ² or less, a sliding valve for a syringe to which a lubricating component is chemically bonded can be obtained. The crosslinking can be performed by a method known as a method for crosslinking these base plastic components.

In addition to the above, if necessary, various modifiers (antiaging agent, crosslinking aid, processing aid, reinforcing agent, softener,
Coloring agent, extender, antioxidant or ultraviolet absorber)
Can be added, but of course they need to have safety as a raw material for a sliding valve for a syringe.

In the sliding valve for a syringe according to the present invention, the lubricating component is integrated with the plastic component by chemical bonding, so that there is no possibility that the lubricating component may be mixed into the medicine by elution or peeling. In addition, since the sliding valve itself has lubricity, it is not necessary to use a silicone coating treatment or a combination with a lubricating film or the like, so that the sliding valve is safe.

As the material of the cylinder portion forming the syringe in combination with the above-mentioned sliding valve, a commonly used material, that is, glass, a polyolefin polymer such as polypropylene or amorphous polyolefin, or the like can be adopted. In particular, those having a cyclic olefin copolymer as a unit satisfy safety, heat and cold resistance, transparency, high precision, gas barrier properties, chemical resistance, and other properties required for syringes, and are easy to incinerate after use. It is desirable because there is.

[0028]

EXAMPLES Example I (Example with a Normal Syringe, Comparative Example) First, the operability of the sliding valve for a syringe of the present invention was evaluated with a syringe having a normal shape. Here, a sliding valve chemically bonded with a lubricating component according to the present invention was produced as follows.

That is, three kinds of base plastics, ethylene vinyl acetate copolymer resin (Evaflex 150, manufactured by DuPont Mitsui Polychemicals), low-density polyethylene (Sumikacene E-209, manufactured by Sumitomo Chemical) and chlorinated polyethylene (Eraslen TR, manufactured by Showa Denko),
Parkmill D40 (manufactured by NOF Corporation) as a cross-linking agent, triallyl isocyanurate and trimethylolpropane trimethacrylate (Sunester TMP, manufactured by Sanshin Chemical) as auxiliaries, and polytetrafluoroethylene powder (P
TFE powder, particle diameter of 20 μm or more and 30 μm or less), and a non-crosslinked resin composition obtained by mixing with a silicone-based grease as a lubricant at a weight ratio shown in Composition 1 of Table 1 at 180 ° C. The slide valve was molded by injection molding under the conditions of 130 kg / cm ² for 3 minutes (Example 1).

In addition, compositions having compositions shown in Compositions 2 to 9 in Tables 1 and 2 were prepared and molded in the same manner to prepare sliding valves (Examples 2 to 9 and Comparative Examples 1 to 6 respectively). did. Sliding valves of these Examples and Comparative Examples, and conventional silicone-coated butyl rubber sliding valves (obtained from Maeda Sangyo. Hereinafter referred to as "silicone-coated butyl rubber sliding valves. Comparative Example 7") and before coating. (Hereinafter, referred to as “uncoated butyl rubber sliding valve”; Comparative Example 8) was evaluated as a sliding valve for a syringe.

[0031]

[Table 1]

[0032]

[Table 2]

[0033]

[Table 3]

A drug injection test was performed for evaluation. In this test, a monitor test was performed using 10 ml of an amorphous polyolefin cylinder (obtained from Maeda Sangyo) using 10 physicians as monitors. The silicone-coated cylinder was used only in the test using the silicone-coated butyl rubber sliding valve as a comparative example, and the cylinder without the silicone coating was used in other cases.

The test was performed assuming intravenous injection using physiological saline as an injection solution. The touch at the beginning of pushing the plunger (initial slidability) and the ease of interruption at the injection volume of 4 ml (ease of handling) were evaluated in 10 stages, and 10 was the best and 1 was the worst. Averaged and rounded to the nearest decimal. Table 4 shows the results. At this time, the details of the samples were not described for each monitor, and the samples were performed in any order.

[0036]

[Table 4]

As can be seen from Table 4, the operability of the sliding valves according to the present invention, which are the sliding valves to which the lubricating components are chemically bonded, compositions 1-4, compositions 7-10 and compositions 13-16 are remarkably good. You can see that.

The sliding valves of Compositions 2 to 5, Compositions 8 to 11 and Compositions 14 to 17 all have polytetrafluoroethylene powder having a particle diameter of 20 μm or more and 30 μm or less. In particular, when introduced into a blood vessel, the blood flow may be obstructed. Here, the presence or absence of detachment from the sliding valve was investigated.

Each of these three slide valves was placed in a test tube, and 10 ml of physiological saline which had been filtered through a 0.45 μm filter was added thereto.
Autoclave treatment was performed at 0 minutes. After cooling to room temperature, the slide valve was taken out, and the physiological saline was filtered through a filter having a pore size of 0.45 ml, and the filter surface was observed with a scanning electron microscope. As a result, when three types of sliding valves having compositions 5, 11, and 17 were used, some particles (diameter: 10 to 20 μm) were observed, and the presence of fluorine in these particles was determined by an electron probe X-ray microanalyzer. Although confirmed, other compositions 2 to 4,
When the sliding valves according to compositions 8 to 10 and compositions 14 to 16 were used, no particles were observed on the filter. As a result, these compositions 2 to 4, compositions 8 to 10, and composition 1 which are sliding valves to which the lubricating component according to the present invention is chemically bonded are attached.
It was confirmed that the slide valves of Nos. 4 to 16 completely prevented the desorption of the polytetrafluoroethylene powder.

On the other hand, with respect to the desorption of silicone-based grease, three sliding valves each consisting of composition 1 to 3, composition 5, composition 7 to 9, composition 11, composition 13 to 15, and composition 17 were each diluted with diethyl ether. Soxhlet extraction was carried out for 8 hours, and the extract was dropped on KBr tablets. After removing ether, FT-IR observation was carried out. As a result, silicone-based grease was observed in sliding valves of composition 5, composition 11 and composition 17. , But no such absorption was observed with the sliding valves of Compositions 2 and 3. This confirmed that the silicone-based grease was immobilized on the sliding valve of the present invention by chemical bonding.

Example II (Example with Kit-Type Syringe, Comparative Example) Next, an example with a kit-type syringe will be described.
1 (a) to 1 (d) show a kit-type syringe having a sliding valve for a syringe according to the present invention, which is made of plastic to which a lubricating component is chemically bonded.

FIG. 1 (a) shows a state before use, (b) shows a state during injection, (c) shows a state after injection, and (d) shows a cross-sectional shape of the cylinder (I- in FIG. 1 (a)). I sectional view). In the figure, reference numeral 21 denotes an amorphous polyolefin cylinder having openings 44 and 45 at both ends.
The tip on one opening 44 side is a hook-shaped tip 22 whose cross section is bent in a hook shape. Reference numeral 23 denotes the rear end of the cylinder,
Reference numeral 24 denotes a bulging portion, and 25 denotes a plunger sliding valve. The bulging portion 24 bulges in a part of the circumference of the cylinder 21 as shown in FIG. 1D, and forms a communication passage 24 'inside.

A front stopper sliding valve 26 is fitted near the center of the inside of the cylinder 21. The plunger slide valve 25 and the front stopper slide valve 26 are made of the composition 1 according to the present invention, and have a lip formed on the outer peripheral surface. The left end of the drawing of the cylinder 21 is closed water-tight by an end partition 27, whereby an empty space 28 between the plunger slide valve 25 and the front stopper slide valve 26 and an end part are formed in the cylinder. An empty space 29 is formed between the partition 27 and the front stopper sliding valve 26. Edge partition 2
7, the injection connection needle 30 is fitted, and the injection needle connection 3
0 is fitted with a cap 31 and a seal is provided to shut off the inside from the outside air.

Next, the operation of this syringe will be described. FIG.
2A, an empty space 28 of a cylinder 21 is filled with an injection, and the empty space 29 is stored in a state in which nothing is filled. Since the vacant space 29 is isolated from the outside air by the cap 31, there is no possibility that germs and the like enter. Before use, first remove the cap 31,
The injection needle 32 is fitted in a luer lock system. Next, injection needle 3
When the plunger is pushed upward as shown in FIG. 1 (b), the front stopper sliding valve 26 is located in the communication passage 24 'of the bulging portion 24, and the injection in the empty chamber 28 is released. Vacancy 29
Go to After all the air in the empty room 29 is exhausted, the injection needle 32 is pierced into the patient. The injection passes through the injection needle 32 and reaches the inside of the patient.

FIG. 1C shows a state where the injection is completed. When the plunger is pushed in, the end partition 27, the front stopper sliding valve 26, and the plunger sliding valve 25 come into close contact with each other. At this time, the tip of the plunger sliding valve 25 (injection needle) Side) reaches the communication path 24 ′, and all the injections in the empty space 28 can be injected. Further, the passage 27b of the end partition 27 is also connected to the communication passage 24 '.
, The axial thickness of the end partition 27, the front stopper slide valve 26 and the plunger slide valve 25, and the length and position of the bulge 24 are determined.

In such a syringe, two slide valves are simultaneously moved at the time of injection, so that a syringe not coated with a lubricant requires force, and it is difficult to perform a delicate operation such as intravenous injection. . However, by using the sliding valve according to the present invention, a lubricating property having a good lubricating property can be obtained without using a lubricant, so that the injection operation can be performed extremely smoothly, and the injection liquid can be slowly discharged. It is introduced into the body.

Compositions 1 to 18 for this kit type syringe
Among them, slide valves of compositions 1-4, compositions 6-10, compositions 12-16 and composition 18 were prepared, and these and silicone-coated butyl rubber slide valves and non-coated butyl rubber slide valves were used. Using sodium hyaluronate having a molecular weight of 900,000, a monitor test was performed on the assumption that sodium hyaluronate was injected into the knee joint cavity.

Assuming a kit preparation, a syringe in which 2.5 ml of a 1% sodium hyaluronate solution (having a viscous liquid) was previously injected into a 5 ml amorphous polyolefin cylinder using a slide valve of the above type was prepared. Each of the kit-type syringes shown in FIG. 1 was prototyped by a usual manufacturing method, and left in a room at room temperature for 3 months. Using these syringes, 1 ml of lidocaine hydrochloride in a vial was aspirated into each syringe, and the evaluation was made on the assumption that the entire amount was administered. Only in the test using the silicone-coated butyl rubber sliding valve, a cylinder coated with silicone was used. In other cases, a cylinder not coated with silicone was used.

The sliding properties of these sliding valves were evaluated in 10 steps by 10 monitors of an orthopedic surgeon, and 10 was the best.
1 was determined to be the worst, and the results were averaged and rounded to the nearest whole number. Table 5 shows the results.

[0050]

[Table 5]

According to Table 5, when the sliding valves according to the present invention, the sliding valves of Compositions 1 to 4, 7 to 10 and 13 to 16 were used, the operability as a kit preparation was excellent. It turns out that it is.

[0052]

EFFECTS OF THE INVENTION By using the sliding valve for a syringe of the present invention, a lubricating oil having a good slidability, which may adversely affect the living body, or a sliding material having a danger of peeling or detaching. And an excellent syringe that does not require a surface coating.

[Brief description of the drawings]

FIG. 1 is a view showing a syringe having a sliding valve of the present invention. (A) State before use (b) State during injection (c) State after injection (d) Cross-sectional shape of cylinder

[Explanation of symbols]

 Reference Signs List 21 cylinder 24 bulging portion 27 end partition 25 plunger sliding valve 26 front stopper sliding valve 27b passage 28 chamber 30 injection needle connection portion 32 injection needle

Claims (9)

[Claims] 1. A sliding valve for a syringe, wherein the lubricating component is made of a chemically bonded plastic. 2. The sliding valve for a syringe according to claim 1, wherein the lubricating component is at least one of polytetrafluoroethylene and a silicone-based lubricant. 3. The sliding valve for a syringe according to claim 1, wherein the plastic is crosslinkable. 4. The sliding valve for a syringe according to claim 3, wherein the lubricating component is chemically bonded by an electrophilic reagent. 5. The slide valve for a syringe according to claim 4, wherein the electrophilic reagent is at least one selected from hindered phenols and Grignard reagents. 6. A syringe having a sliding valve made of plastic to which a lubricating component is chemically bonded. 7. The syringe according to claim 6, wherein the cylinder portion is made of a material selected from amorphous polyolefin, glass, and polypropylene. 8. A kit preparation using a sliding valve made of plastic to which a lubricating component is chemically bonded. 9. The kit preparation according to claim 8, wherein the kit preparation has a detachable cap for covering the injection needle connection part, and a seal for shielding the inside from outside air.