Patent Application
20150148751
The present invention relates to piston members such as a gasket and a middle piston for a syringe used when administering a drug solution to the human body or an animal in fields of medicinal drugs and medicine.
An injection syringe prior to having an injection needle mounted thereto includes a syringe barrel (cylindrical tube) made from glass or plastic, a movable plunger rod (plunger), a gasket that is attached at a front end portion of the plunger rod and is a piston member for maintaining non-leakage and vapor impermeability and ensuring slidability of the plunger rod, and a top cap attached to a needle mount part of the syringe barrel. Vulcanized rubber has been conventionally used for gaskets, and silicone grease has been applied to the surface of the gaskets or the inner surface of syringe barrels in order to improve inferior slidability when the gaskets made from rubber slides on the inner surface of the syringe barrels.
However, there have been problems such as reduction in potency caused when an active ingredient in a drug solution is adsorbed in the silicone grease, and contamination of the drug solution by silicon particles in the silicone grease, and adverse effect thereof to the human body. In addition, there has been a fear of elution of soluble components contained in the rubber in the drug solution. In particular, since pre-filled syringes, which are used more frequently in recent years, are filled with a drug solution in advance and stored over a long period of time to be used; gaskets of the pre-filled syringes are required to have higher performance than those for ordinary injection syringes with regard to having a quality that does not change over a long period of time, being able to be used safely, ensuring scaling performance (non-leakage and vapor impermeability) with respect to highly permeable drug solutions, and also having slidability equivalent to that of ordinary injection syringes. With regard to this point, the same applies for gaskets mounted on a middle piston and the front end of a piston rod used in a dual syringe having a syringe barrel whose front end side is filled with a powder drug and whose piston rod side is filled with injection water via the middle piston.
In order to solve such a problem, a gasket that has been developed is obtained by affixing a medical-application plug covering film formed from a polytetrafluoroethylene (hereinafter, referred to as “PTFE”) film on an outer circumferential surface of a main body of the gasket where a slide-contact is made between a front end surface of a liquid contact side of the gasket main body made from rubber and an inner circumferential surface of a syringe barrel, and continuously and integrally forming a plurality of independent ring-shaped protruded rims on the outer circumferential surface adjacent to the front end surface of the liquid contact side (Patent Literature 1).
The gasket is formed by affixing, to a mold having multiple streaks of independent ring-shaped grooves formed on the inner circumference of the bottom of a cavity of the mold, a PTFE film that is formed piece by piece with a cast method, has a film thickness of about 20 to 60 μm, and whose adhesion surface to the gasket main body is surface-treated to have increased adhesive strength with rubber, press fitting the gasket main body made from rubber into the cavity to stretch the PTFE film and affix the PTFE film to the surface of the gasket main body, and lastly excising the PTFE film that has emerged out from a piston-rod mounting side end of the gasket main body. At the press fitting step, a plurality of independent ring-shaped protruded rims are formed on the front end portion of the PTFE film affixed to the surface thereof by ring-shaped grooves formed on the cavity of the mold.
The gasket can, because of having the PTFE film, largely improve slidability of the gasket with respect to the syringe when compared to a gasket made from rubber, and prevents, because of the plurality of independent ring-shaped protruded rims, leakage of drug solution loaded in the front end side of the syringe barrel in a direction from a slide-contact surface between the syringe barrel and the gasket toward the piston rod side. However, the gasket disclosed in Patent Literature 1 has problems described in the following.
[PTL 1] Japanese Laid-Open Patent Publication No. 2006-181027
(1) In the gasket obtained through such a PTFE film affixing method, at an attachment portion, depending on the length and diameter of the gasket, the PTFE film is stretched about three-fold with a gasket for a small-volume syringe of 5 ml or smaller, about two-fold with a gasket for a middle-volume syringe of larger than 5 ml but not larger than 100 ml, and about 1.5-fold with a gasket for a large-volume syringe of larger than 100 ml. Generally, when a resin film such as a PTFE film is stretched, the elongation direction of the molecules in the resin becomes uniform in accordance with the stretching. Therefore, orientation of the resin film becomes high, resulting in the resin film being unable to elongate with respect to a direction perpendicular to the elongation direction, and performance as a resin gradually deteriorates, and, when the deterioration is extensive, whitens to ultimately become torn. With the PTFE film, water repellency deteriorates as the film becomes oriented due to elongation, and tearing ultimately occurs in the film at the outer circumferential portion of the front end surface on the liquid contact side of the gasket main body that has been most rigorously stretched, resulting in reduced yield rate and quality degradation as a product.
When forming a gasket with such a press fitting method in particular, depending on the shape of the gasket, since the PTFE film is greatly stretched at the outer circumferential portion of the front end surface on the liquid contact side of the gasket main body as described above when compared to other portions, degradation of resin performance at the portion is excessive. That effect, which is although thought to be alleviated to a certain degree due to the multiple independent ring-shaped protruded rims, may not be such a problem with middle and large volume syringes but causes a large problem for practical use with small-volume syringes of 5 ml or smaller due to having a small diameter of about 6 mm. The ring-shaped protruded rims formed on the film by the press fitting method are created through transcription from the cavity. However, since the gasket main body pushed in the cavity is made of rubber, the finished shape will inevitably have a certain degree of inaccuracy. In addition, the shape may become flawed since the ring-shaped protruded rims formed on the front end of the gasket have to be forcibly pulled out from the ring-shaped grooves when pulling out the gasket from the cavity on which the ring-shaped grooves are formed. Therefore, there is a limit to the degree of the alleviation effect.
(2) In addition, fine concavities and convexities exist on the surface of the used PTFE film obtained through the cast method, and these fine concavities and convexities are stretched through the elongation described above, leading to leakage of liquid along the film surface. In addition, the PTFE film including multiple applied layers has a large number of fine through-holes therein. Since the ring-shaped protruded rims in Patent Literature 1 have a width of 0.05 to 0.5 mm, a height of 0.01 to 0.2 mm, and the gasket main body is made from rubber, the ring-shaped protruded rims are barely compressed when the gasket main body is inserted in the syringe barrel. Therefore, the fine through-holes in the ring-shaped protruded rims remain without being crushed, leading to a problem of causing leakage of liquid through the fine through-holes. The leakage of liquid through the surface and inside the ring-shaped protruded rims is particularly significant in small-volume syringes, and this leakage has been an obstacle of practical use in small-volume syringes.
(3) When the PTFE film is manufactured through a cast method, a solution having PTFE suspended therein has to be applied multiple times and sintered every time, leading to a problem of a large manufacturing cost for the PTFE film itself.
(4) In addition, when affixing the PTFE film on the gasket main body with a press fitting method, the PTFE film can only be physically affixed to a front end portion on one side of the gasket main body. Therefore, the end of the gasket main body on the opposite side becomes inevitably uncovered. A middle piston of a dual syringe which uses a powder drug cannot be produced with this method, leading to a problem of limited use application.
(5) Furthermore, with such a method, because of temperature change during heat disinfection or the press fitting process, there have been problems such as weakened adhesion between rubber forming the gasket main body inside and the thin PTFE film affixed on the surface through thermal expansion difference, and wrinkles being generated on the surface of the PTFE film.
In view of such conventional examples, a main objective of the present invention is to provide a low cost piston member for a syringe, having sufficiently satisfying slidability and sealing performance such as non-leakage and vapor impermeability, without being limited to size, from small diameters to large diameters.
An invention disclosed in claim 1 is a piston member 10 that is a gasket 10a (
The piston member 10 formed by cut-processing a PTFE block and pressed and fitted in a syringe barrel 1 to be used in a slidable manner,
the piston member including protruded rims 13 formed at least in a circumferential direction of a whole circumference of a slide-contact surface 11a that is adjacent to a liquid contact surface 14 in contact with a drug solution 30, and that is a part of a slide-contact surface 11 of the piston member 10, slidingly making contact with an inner circumferential surface 2 of the syringe barrel 1, wherein
after the cut-processing, a pitch P of the protruded rims 13 is not larger than 50 μm, and a press-fit margin T of the piston member 10 with respect to the syringe barrel 1 is 10 to 150 μm.
The PTFE block is cut-processed (ordinarily, through lathing) by taking into consideration the press-fit margin T in accordance with an internal diameter S of the syringe barrel 1, and the protruded rims 13 are formed on the cut-processed surface (particularly on the slide-contact surface 11a in contact with the syringe barrel 1) such that, when being cut-processed, the pitch P is not larger than 50 μm (preferably 3 to 40 μm) and the diameter difference of the press-fit margin T of the piston member 10 with respect to the syringe barrel 1 is 10 to 150 μm. When the piston member 10 formed in such manner is inserted in the syringe barrel 1, the protruded rims 13 of the piston member 10, which has been pressed and fitted in, are crushed by the inner circumferential surface 2 of the syringe barrel 1 and cold-flow toward processed grooves 12, and the cold-flowing buries the processed grooves 12 (
In the invention according to claim 2 based on the piston member 10 in claim 1, a maximum height roughness Rz after the cut-processing is set to be not larger than 6 μm. When the maximum height roughness (in other words, groove depth or 10-point average roughness) Rz of the processed grooves 12 is not larger than 6 μm (preferably not larger than 3 μm), burial of the processed grooves 12 through the cold-flowing is performed with certainty.
In the invention according to claim 3 based on the piston member 10 of claim 1, the protruded rims 13 are helically formed. When the processed grooves 12 are helical grooves, although it may be thought in common sense that the drug solution 30 will flow out along the helical processed grooves 12; a high level of water tightness is achieved since the cold-flowing buries the processed grooves 12 as described above. When the processed grooves 12 are helical, the piston member 10 can be formed with ordinary lathing, and manufacturing can be performed rapidly at low cost.
In the invention according to claim 4 based on the piston member 10 of claim 1, the protruded rims 13 are formed in a ring shape. In this case, since the pitch P of the protruded rims 13 is very small as 50 μm and thereby the thicknesses of the protruded rims 13 themselves are very small, the placebo 30 leaks within the protruded rims 13 by passing through a grain boundary of a PTFE lump existing in the protruded rims 13. However, by setting the press-fit margin T as 10 to 150 μm, the grain boundary of the PTFE lump is resolved when the protruded rims 13 are pressed and crushed by being press-fitted to the syringe barrel 1 as described above, and not only leakage of liquid from the grain boundary is blocked but also passing of vapor is blocked. This also applies to the case with a helical shape. It should be noted that the slide resistance here is also 12 N or less, similarly.
In the invention (cf.
In the invention (cf.
In the invention (cf.
In the invention (cf
In the invention (cf.
In the invention (cf.
By adopting such a configuration, contact pressure by the syringe barrel 1 on the inner circumferential surface 2 is increased on the liquid contact surface 14 side to enhance reliability against leakage of liquid, and the contact pressure is reduced on the syringe barrel 1 at the narrow portion or the portion narrowed into a concaved arc shape to allow pressing of a piston rod 5 with lesser force.
In the invention (cf.
In this case, water tightness is ensured by the protruded rims 13 (at least 3 rims up to 5 rims) formed along the narrow processed grooves 12 on the liquid contact surface 14 side, and processing speed can be significantly improved by forming the processed grooves 12 that do not contribute to ensure water tightness on the liquid non-contact surface 14a side to be helical.
In the invention (cf.
In the invention (cf.
In the invention (cf.
With the present invention, it is possible to provide a low cost piston member for a dual syringe or a pre-filled syringe, having sufficiently satisfying slidability and water tightness such as vapor impermeability and leakage-less property, without being limited to size, from small diameters to large diameters, and without using a medical-application plug covering film or silicone oil.
In the following, the present invention will be described in accordance with illustrated examples.
The syringe barrel 1 is a cylindrical container. A mount part 1b on which an injection needle that is not shown is mounted is disposed at the front end of a barrel main body 1a in a protruding manner, and a flange 1c for finger placement is formed on the back end of the barrel main body 1a. For the material of the syringe barrel 1, glass, hard resin (e.g., cycloolefin resin which is hereinafter referred to as “COP”), or flexible resin (e.g., polypropylene which is hereinafter referred to as “PP”) is used.
Two types exist for the piston member 10 including the gasket 10a shown in
As the PTFE used in the present invention, pure PTFE, the modified objects of PTFE described above, or a block (round bar material) closed-celled by a hot isostatic pressing method that is called HIP treatment is used. The PTFE before the HIP treatment is powder PTFE or one that is obtained by forming the modified PTFE into a block shape (e.g., columnar) with high pressure and sintering thereof. Therefore, the PTFE before the HIP treatment is an aggregate of fine PTFE lumps and is an open cell type block in which fine gaps are continuously connected at grain boundaries of the PTFE lump.
One example of how the hot isostatic pressing method is performed is shown next. The open cell type PTFE block or the open cell type modified PTFE block (e.g., rod-like body) is placed in a heating furnace, and the pressure in the heating furnace first is reduced to a degree of vacuum of 0.013 to 133 Pa (a commonly used degree of vacuum is 0.13 to 13.3 Pa) to remove gas from the pressure formed body. Then, the closed cell type PTFE block is obtained by performing thermal-fusion at 320 to 400° C. (more preferably at 350 to 370° C.) for several to less than twenty hours while maintaining the reduced pressure state, and cooling thereof. Alternatively, the closed cell type PTFE block is obtained similarly by increasing the temperature to the above described temperature under the pressure reduced to the degree of vacuum described above, maintaining the temperature for the above described time, returning the pressure to ordinary pressure, and cooling thereof under pressure.
When the hot isostatic pressing method is applied to an open cell type PTFE block, gas is pulled out from gaps (space) between grain lumps of the PTFE forming the PTFE block, and the gaps (space) are reduced through the rapid expansion, caused by the hot isostatic pressing, of the contact interfaces of the grain lumps softened by the heating. At this moment, gas does not exist in the gaps (space) to provide resistance and can be reduced to a minimum, and open cells that have existed before the heating dissipate.
Next, the shape of the gasket 10a in
On the other hand, the liquid contact-side sliding part 16 of the gasket 10a is a slide-contact portion that slidingly makes contact with an inner circumferential surface 2 of the syringe barrel 1, and is adjacent to a liquid contact surface 14 where a contact with the drug solution 30 is made, and the liquid contact-side sliding part 16 has a certain width D from the liquid contact surface 14 to the end part 17 on the mounting side of the piston rod 5. On the whole circumference of a slide-contact surface 11a thereof, processed grooves 12 are formed in the circumferential direction. The width D is 0.5 to 3 mm. The width D is preferably 1 to 2 mm. The width D is applied in examples with the helical shape, the independent ring shapes, and in modifications thereof. The processed grooves 12 may be helical or may have independent ring shapes as shown respectively in
As a processing method, ordinarily, cut-processing with a lathe is selected in consideration of the shape of the piston member 10. Examples of a cutting tool (bit) used in the cut-processing include high speed steel, cemented carbide, and polycrystal and monocrystal diamonds capable of smoothly shaving the surface of PTFE to a certain degree.
The cutting method is performed by projecting the PTFE block 50 or 60 (bar material, preferably a round bar) beyond a chuck of the lathe by a predetermined amount, shaving off the end surface of the projected portion flatly or in a predetermined required shape, shaving the outer circumferential surface of the projected portion in a predetermined shape described later depending on whether the piston member 10 is the gasket 10a or the middle piston 10b. In the case with the middle piston 10b, after cutting of the external outer shape is finished, the base of the projected portion is cut across to form the middle piston 10b. In the case with the gasket 10a, a tap drill hole of a female-screw hole 15 for screwing in a male-screw part 5a of the piston rod 5 is additionally bored at the center of the end surface of the projected portion, a female-screw thread is engraved on the tap drill hole through tapping, opening edges of the female-screw hole 15 are chamfered, and lastly the base of the projected portion is cut across in a predetermined dimension to form the gasket 10a. The feed width is indicated with the pitch P in
In the cut-processing described above for cutting the slide-contact surface 11a of the piston member 10, in the case with helical protruded rims 13a in
:14
[0] is increased at a portion adjacent to the liquid contact surface 14, but the diameter (peak diameter H) is reduced on the liquid non-contact surface 14a side. In the piston member 10 according to the present invention, at the portion adjacent to the liquid contact surface 14, a width of at least 3 rims, and about 5 rims when ensuring water tightness and vapor impermeability, of the helical protruded rims 13a are necessary. Although a single rim of the ring-shaped protruded rims 13b is theoretically sufficient, it is preferable to have 3 rims or more as insurance. In each of the
As described above, certain degree of concavities and convexities are formed on the cut-processed grooves 12 and the protruded rims 13. However, PTFE is highly deformable, and when the piston member 10 is inserted in the syringe barrel 1 with a press-fit margin T, the protruded rims 13 are strongly crushed on the inner circumferential surface 2 of the syringe barrel 1 and flow (cold flow) toward the processed grooves 12, not only in the case with the helical shape but also with the ring shape. The processed grooves 12 become completely buried at most portions when the protruded rims 13 are formed to have the pitch P of not larger than 50 μm, the maximum height roughness Rz of not larger than 6 μm, and a diameter of the press-fit margin T of not smaller than 10 μm, after the cut-processing. The buried portions are shown in
When the pitch P of the protruded rims 13 is not smaller than 50 μm, depending on its relationship with the maximum height roughness Rz, sometimes the processed grooves 12 are not sufficiently buried and leakage occurs through the remaining fine gaps. In particular, when the difference in temperature of the surrounding area is particularly large (e.g., when an injection kept in a refrigerator is taken out and restored to normal temperature to be used), leakage sometimes occurs due to the physical property (of causing large dimensional change around room temperature) of PTFE. When the pitch P is not larger than 40 μm, leakage does not occur even when the difference in temperature of the surrounding area is large. A range from 3 to 40 μm provides the highest reliability in terms of non-leakage.
When the pitch P of the protruded rims 13 is not larger than 3 μm, the time required for the cut-processing becomes too long, the height of the protruded rims 13 between the processed grooves 12 becomes too low (i.e., the maximum height roughness Rz of the processed grooves 12 becomes too small), and elasticity of the protruded rims 13 becomes too small. Therefore, the pitch P of the protruded rims 13 is preferably, for practical use, not smaller than 3 μm but not larger than 40 μm.
Furthermore, when the maximum height roughness Rz of the processed grooves 12 after cutting is not smaller than 6 μm, there may be places where the PTFE that had cold-flowed does not sufficiently bury the groove bottom 12a of the processed grooves 12, and leakage may occur at those places. In terms of safety, the maximum height roughness Rz is preferably not larger than 3 μm. From a standpoint of burying the grooves with cold flow, a smaller maximum height roughness Rz is preferable. The groove bottom 12a is preferably formed in a circular arc shape for smoothly allowing the cold flow of PTFE. The pitch P and the maximum height roughness Rz of the grooves are basically independent of the thickness of the syringe barrel 1, and are applicable to the syringe barrel 1 with various thicknesses. When the pitch P and the maximum height roughness Rz of the grooves are in the above described range, high water tightness (non-leakage and vapor impermeability) is achieved even with the processed grooves 12 that are helical grooves.
Next, a relationship of the processed grooves 12, the diameter (peak diameter) H of the liquid contact-side sliding part 16 of the piston member 10, and an internal diameter S of the syringe barrel 1 will be described. With respect to the internal diameter S of the syringe barrel 1, the diameter of the liquid contact-side sliding part 16 is set to be larger by, as the press-fit margin T, at minimum 10 μm (5 μm in radius) and at maximum 150 μm (75 μm in radius) (cf.
In addition, PTFE not having the HIP treatment provided as described above has fine communicatively-connected gaps inside. By inserting the piston member 10 in the syringe barrel 1 and crushing the protruded rims 13 with the press-fit margin T, the fine communicatively-connected gaps are clogged during the cold flow described above, and not only leakage of liquid but also passage of vapor through the communicatively-connected gaps are stopped even with a PTFE not having the HIP treatment provided thereon.
When the relationship (press-fit margin T) between the internal diameter S of the syringe barrel 1 and the outer diameter of the liquid contact-side sliding part 16 of the piston member 10 is in the above range, and when the pitch P and the maximum height roughness Rz of the processed grooves 12 of the slide-contact surface 11a are in the above described ranges; the width D of the slide-contact surface 11a of the piston member 10 is set to 0.5 to 3 mm. When the width D is smaller than 0.5 mm, the liquid contact-side sliding part 16 may become damaged during handling because of being too narrow. When the width D is not smaller than 3 mm, the press-fit margin of the piston member 10 with respect to the syringe barrel 1 is larger than 50 μm, and when the syringe barrel 1 is made from COP; the surface pressure by the liquid contact-side sliding part 16 with respect to the syringe barrel 1 becomes too high, and the piston member 10 may expand larger than the syringe barrel 1 at normal temperature or during autoclaving at 121° C. for 20 minutes to cause the syringe barrel 1 to crack. For practical use, 1 to 2 mm is suitable.
The points described above also apply to the middle piston 10b. In the middle piston 10b, as shown in
The syringe barrel 1 has the needle mount part 1b at the front end, the finger placement part 1c at the back end, and a cylindrical drug solution loading part 4c formed therebetween; and is formed from cyclic polyolefin in the present example. It is needless to say that the shape of the syringe barrel 1 is not limited to those that are diagrammatically represented, and the material of the syringe barrel 1 may be polypropylene, glass, or the like.
The piston rod 5 is a rod shaped member having the male-screw part 5a formed at the front end part and a finger rest part 5b formed at the back end. On the outer circumferential surface of the male-screw part 5a of the piston rod 5, male-screw threads to be screwed in the female-screw hole 15 of the gasket 10a are engraved. The material of the piston rod 5 includes resins such as cyclic polyolefin, polycarbonate, and polypropylene.
The top cap 8 is attached to the needle mount part 1b of the syringe barrel 1, and is a sealing member to prevent leakage of the drug solution 30 loaded in the syringe barrel 1 and contamination of the drug solution 30 by unwanted germs drifting in air. The top cap 8 includes a cap main body 8a having a circular truncated cone shape, and an engagement protrusion 8c extending in an opening direction from a top surface of the cap main body 8a and having formed thereon a concaved portion 8b in which the needle mount part 1b is fitted. The top cap 8 is formed from an elastomer. Examples of the elastomer include both “thermoplastic elastomers” and “thermosetting elastomers” such as vulcanized rubbers and thermosetting resin based elastomers.
The pre-filled syringe A as shown in
In the gasket 10a in
In the gasket 10a in
In the piston member 10 manufactured as described above, although the resin material 61 is exposed on the liquid contact surface 14, the drug solution 30 in contact thereto is not adversely effected since the resin material 61 has excellent drug solution-resistant property, such as COP and ultrahigh molecular weight polyethylene. Since the slide-contact surface 11a is formed from PTFE, excellent slidability is obtained without having leakages. It should be noted that when a resin harder than PTFE is selected as the drug solution-resistant resin material 61, PTFE at the outer circumference is reinforced from inside, and, since the drug solution-resistant resin material 61 ordinarily has a thermal expansion coefficient smaller than PTFE in a temperature range from around 0° C. to near room temperature, the piston member 10 is not likely to be subjected to the influence of change in outside air temperature, and becomes superior than PTFE in terms of dimensional change associated with temperature.
For usage, the top cap 8 is taken off and an injection needle is mounted on the needle mount part 1b, allowing immediate usage. When being used, the piston rod 5 is pressed, and the middle piston 10b advances via the loaded injection water 32. When the back end of the middle piston 10b passes the opening portion 1e of the bypass 1d on the flange 1c side, the injection water 32 passes through the bypass 1d and flows into the closed space filled with the drug 31 from an opening portion 1f on the front end side, and dissolves the drug 31 to be injected. In this case, the slide resistance is almost the same as that of the pro-filled syringe A in
In the following, the present invention will be described more specifically using Examples and Comparative Examples.
As shown in
(1) Liquid Sealing Performance (Leakage of Liquid) Test
An interface portion between the slide-contact surface of the gasket and the inner circumferential surface of the syringe barrel was enlarged by 100 times to observe the presence of leakage of the placebo to the sliding portion. Those having a protruded rim with the pitch P of not larger than 50 μm and the maximum height roughness Rz of not larger than 6 μm did not generate leakage of liquid at room temperature even when the syringe barrel was made from PP, COP, or glass.
With all the internal diameters of the syringe barrel, leakage of liquid was observed when the pitches P of the protruded rims were 80 μm and 100 μm. Although a gasket whose protruded rims had the pitch P of 50 μm did not have any problems at room temperature, slight leakage of liquid was observed therein when a pre-filled syringe filled with placebo was kept overnight in a refrigerator at 5° C., and then returned to room temperature. Leakage of liquid was not observed with a gasket whose protruded rims had the pitch P of not larger than 40 μm. Although leakage of liquid was observed when the maximum height roughness Rz (groove depth) was 6.6 μm or 10 μm, leakage of liquid was not observed when the maximum height roughness Rz was not larger than 6 μm. The upper limits were a groove pitch of 50 μm and a maximum height roughness Rz (groove depth) of 6 μm. To be safe, the groove pitch is not larger than 40 μm and the maximum height roughness Rz (groove depth) is 3 μm.
(2) Vapor Permeability Test (
A syringe barrel made from glass (internal diameter: 6.34 mm, total volume: 2 ml) was filled with 1 ml of pure water that had been colored. On the syringe barrel, the PTFE gasket (the width D=2.5 mm, diameter (peak diameter H)=6.38 mm, press-fit margin=40 μm in slide-contact surface 11a) manufactured in a shape that does not lead to leakage was mounted. A top cap made from butyl rubber was mounted on the front end of the syringe barrel to measure weight change during the course of time. As a Comparative Example, a gasket made from butyl rubber commonly used for the syringe barrel was used.
A precision balance (manufactured by Shimadzu Corporation) used for measurement can measure a weight as small as 1/10,000 g.
Weight reduction of the syringe barrel having the gasket of the present invention used therein was almost 0 even after 1,500 hours, and the fluctuation range was within the error range of the precision balance. On the other hand, the conventional syringe barrel having used therein the gasket made from butyl rubber exhibited a weight reduction of 0.005 g.
(3) Measurement of Slide Resistance Value (
Conditions of Gasket of the Present Invention
Diameter (peak diameter h) of liquid contact-side sliding part=6.36 6.38 6.40 (unit: mm)
Width of slide-contact surface=2.3 mm
Internal diameter of syringe barrel (COP, glass)=6.34 mm
Testing rate=100 mm/min.
The average slide resistances were 4.2 N with 6.36 mm, 5.9 N with 6.38 mm, and 7.4 N with 6.40 mm, and the average slide resistances were all 12 N or less as required. In the case where PTFE is used for the gasket 10a, when these average values were connected with a straight line and an intersection point with a horizontal line drawn from point where the slide-movement average (N) is 12 N was obtained, a press-fit margin of 150 μm is derived. Thus, it can be said that slidability is not compromised even when the press-fit margin in the diameter with respect to the syringe barrel 1 is increased to 150 μm. However, in the case with a COP syringe barrel, when the press-fit margin in the diameter is not smaller than 150 μm and the width D of the slide-contact surface 11a is larger than 3 mm, cracks had sometimes occurred in the COP syringe barrel. Thus, the upper limit of the press-fit margin is 150 μm.
The lower limit is 10 μm when the relationships of cold flow of PTFE, groove depth, and pitch are considered. When the press-fit margin was not larger than 10 μm, the processed grooves could not be fully buried, and leakage had occurred.
A: pre-filled syringe, B: dual syringe, D: width, P: pitch, Rz: maximum height roughness, Ra: arithmetical mean roughness, H: peak diameter, S: internal diameter of syringe barrel, T: press-fit margin, W: closed range adjacent to liquid contact surface, 1: syringe barrel, 1a: barrel main body, 1b: needle mount part, 1c: flange, 1d: bypass, 1e: opening on flange side, 1f: opening on front end side, 2: inner circumferential surface, 5: piston rod, 5a: male-screw part, 5b: finger rest part, 8: top cap, 8a: cap main body, 8b: concaved portion, 8c: engagement protrusion, 10: piston member, 10a: gasket, 10b: middle piston, 11: slide-contact surface, 11a: slide-contact surface on liquid contact surface side, 12: processed groove, 12a: groove bottom, 13: protruded rim, 13a: helical protruded rim, 13b: ring-shaped protruded rim, 14: liquid contact surface, 14a: liquid non-contact surface, 15: female-screw hole, 16: liquid contact-side sliding part, 17: end part of piston rod on mounting side, 18: cavity, 20: main body portion, 21: liquid contact-side outer circumferential surface, 23: liquid contact side slide-contact ring, 26: main body portion, 27: liquid contact-side sliding part, 28: liquid contact side slide-contact cap, 30: drug solution, 31: drug, 32: injection water, 50: PTFE bar material, 60: composite block, 61: drug solution-resistant resin material, 62: PTFE cylindrical material.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2013/001314 | 3/4/2013 | WO | 00 |
