Source: https://patents.justia.com/patent/6544233
Timestamp: 2020-07-05 05:59:47
Document Index: 592335499

Matched Legal Cases: ['art 22', 'art 22', 'art 22', 'art 22', 'art 22', 'art 22', 'art 22']

US Patent for Pre-filled syringe Patent (Patent # 6,544,233 issued April 8, 2003) - Justia Patents Search
Justia Patents Having Plural Material ReservoirsUS Patent for Pre-filled syringe Patent (Patent # 6,544,233)
Oct 18, 2000 - Terumo Kabushiki Kaisha
Method (1): Referring to FIG. 6, with the solution B sealed in a cylindrical member 22b that composes the cylindrical part 22 by using the gaskets 23 and 24 or the gasket 23 and other sealing means (not shown), the solution B is sterilized with high-pressure vapor. Then, the powder A prepared separately is filled into a cylindrical member 22a that also composes the cylindrical part 22. Thereafter, the cylindrical member 22a and the cylindrical member 22b are connected in an aseptic atmosphere to compose the cylindrical part 22.
Method (2): Referring to FIG. 7, the cylindrical part 22c whose both ends are open is prepared. With the solution B sealed in the cylindrical part 22 by using the gaskets 23 and 24 or the gasket 23 and other sealing means (not shown), the solution B is sterilized with high-t pressure vapor. Then, the powder A prepared separately in an aseptic atmosphere is introduced into the cylindrical part 22c from the opening at the front end thereof. Thereafter, a nozzle 30 of the syringe is installed on the cylindrical part 22 at the front end thereof.
However, the methods (1) and (2) are complicated in the producing process and much time and labor are required. In particular, the method (1) requires a high technique in connecting the cylindrical member 22b sealing the solution B therein and the cylindrical member 22a sealing the powder therein to each other accurately.
The inner cylinder 6 has the opening at its front and rear ends. The opening at its front end has a locking construction for keeping the first gasket 10 and the second gasket 11 inside the inner cylinder. The locking construction prevents the first gasket 10 and the second gasket 11 from slipping off from the front end of the inner cylinder. The locking construction has a flange 6a, facing radially inward, formed at the opening at the front end of the inner cylinder 6 to make the inner diameter of the opening at the front end thereof smaller than the outer diameter of the first gasket 10 and that of the second gasket 11.
In the case where a concave groove 15b is formed on the inner cylinder, as shown in FIG. 14, when the first gasket 10 moves forward to the position of the concave groove 15b, the concave groove 15b serves as a bypass duct 17 allowing communication between the first space 9 and the second space 12. The second medicine B flows into the first space 9 through the bypass duct 17.
The outer cylinder 1, the inner cylinder 6, and the plunger 13 of the pre-filled syringe of the present invention can be formed of materials that are not deformed by a pressure or an external force during use. For example, rigid synthetic resin, glass, ceramics, metal or the like can be used. It is preferable to use synthetic resins that are transparent and thus allow contents of the pre-filled syringe to be checked, are lightweight, resistant to fracture, moldable, and economical. Thus, the following rigid and tough synthetic resins are preferable: thermoplastic resin, for example, olyethylene; polyisoprene; polybutene; polymethylpentene-1; polybutadiene resin; polyolefin family resin such as cyclic polyolefin; olefin copolymer such as ethylene-&agr;-olefin copolymer; vinyl chloride resin; polyvinyl alcohol; polyvinyl acetal; polyvinyl acetate; ethylene-vinyl acetate copolymer; polyvinylidene chloride; polystyrene; acrylic resin; polyester resin such as polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate; polyamide, polysulfone, polycarbonate, polyether, and polyphenylene sulfide; and thermosetting resin, for example, epoxy resin, phenol resin, and polyurethane. The outer cylinder, the inner cylinder, and the plunger may be formed of one synthetic resin selected from the above ones respectively or a mixture of two or more kinds of the synthetic resins respectively. The outer cylinder, the inner cylinder, and the plunger may have a single layer formed of one kind of the synthetic resin respectively or a laminated structure formed of a plurality of resinous layers. The synthetic resin composing the outer cylinder and the inner cylinder should be selected in consideration of barrier property thereof and the like in correspondence to the kind of medicine sealed in the first space and the second space and chemical stability of the medicine against oxygen and the like. It is preferable to use polypropylene or cyclic polyolefin as the material of the outer cylinder, the inner cylinder, and the plunger, because the polypropylene or the cyclic polyolefin can be shaped into the outer cylinder, the inner cylinder, and the plunger easily and smoothly by injection molding and because the polypropylene and the cyclic polyolefin have favorable barrier properties to gas, are resistant to medicine, and are safe.
The material to compose the first gasket 10, the second gasket 11, the following-described fourth gasket 301 and slidable gasket 401 the third gasket 14 is not limited to a specific one. Elastic materials having sealing property (in other words, gas-tight property) can be used. Thus the following elastomers can be used: natural rubber, isoprene rubber, butyl rubber, butadiene rubber, styrene-butadiene rubber, silicone rubber, styrene-butadiene-styrene block copolymer, hydrogenated styrene-butadiene copolymer, hydrogenated styrene-ethylene-butylene-styrene block copolymer, ethylene-&agr;-olefin copolymer rubber, elastomer of polyurethane family, elastomer of polyamide family, elastomer of polyester family, and mixtures of these substances. Butyl rubber, silicone rubber, and elastomer of styrene family can be preferably used because they are resistant to medicine. In the case where the medicine is sterilized with high-pressure vapor, vulcanized isoprene rubber, vulcanized butyl rubber, vulcanized styrene-butadiene-styrene block copolymer can be preferably used to compose the first gasket 10, the second gasket 11, and the third gasket 14. The rubber or the elastomer for sealing the nozzle can be composed of the above-described elastic materials that are used to form the gaskets.
In using the pre-filled syringe 100 of the present invention, the plunger 13 installed on the second gasket 11 is pressed forward (direction shown with the arrow of FIG. 1B) to slidably move the second gasket 11, the second medicine B (solution) sealed in the second space 12, and the first gasket 10 forward in the inner cylinder 6. When the first gasket 10 is moved to the front end of the inner cylinder 6, as shown in FIGS. 1B and 10, a convexity (rib) 15a formed on the inner surface of the front side of the inner cylinder 6 presses a part of the peripheral surface of the first gasket 10. As a result, the peripheral surface of the first gasket 10 is deformed to the gap 16 between the inner surface of the inner cylinder 6 and the peripheral surface of the first gasket 10, as shown in FIG. 2A (cross-sectional view) and FIG. 13. The second medicine B sealed in the second space 12 flows into the first space 9 through the gap 16 serving as a duct. In each of the pre-filled syringes of the embodiment shown in FIGS. 1 and 13 which is a sectional view taken along a line B—B of FIG. 10, four convexities (rib) 15a are formed at regular intervals on the inner peripheral surface of the inner cylinder at its front side. Thus, the second medicine B sealed in the second space 12 flows into the first space 9 through the four gaps 16. Therefore, the first medicine (powder) A and the second medicine (solution) B are mixed with each other in the first space 9 rapidly and sufficiently. In the embodiment shown in FIGS. 2A and 13, four convexities 15a are formed. But the number of the convexities 15a is not limited to four. Three or less or five or more convexities 15a may be formed. Favorably, the number of the convexities 15a is in the range of 2-12 and more favorably, 3-5.
FIGS. 2B and 14 show the case where concave grooves 15b are formed on the inner surface of the inner cylinder at its front side, instead of the convexity 15a. When the first gasket 10 is moved to the front end of the inner cylinder, as shown in FIGS. 2B (cross-sectional view) and 14, the concave groove 15b formed on the inner surface of the front side of the inner cylinder 6 serves as a duct (bypassing duct) 17 for flowing the second medicine B sealed in the second space 12 into the first space 9. The groove 15b has a predetermined length (longer than the first gasket 10) extends axially to the rear end surface of the small-diameter portion of the front end of the inner cylinder 6. The groove is preferably located between the front end of the inner cylinder 6 and the first gasket 10. In each of the pre-filled syringes of the embodiment shown in FIGS. 2B and 14, four concave grooves 15b are formed at regular intervals on the inner peripheral surface of the inner cylinder at its front side. Thus, the second medicine B sealed in the second space 12 flows into the first space 9 through the four ducts 17. Therefore, the first medicine (powder) A and the second medicine (solution) B are mixed with each other in the first space 9 rapidly and sufficiently. In the embodiment shown in FIGS. 2B and 14, four concave grooves 15b are formed. But the number of the concave grooves 15b is not limited to four. Three or less or five or more concave grooves 15b may be formed. Favorably; the number of the concave grooves 15b is in the range of 2-12 and more favorably, 3-5. If necessary, both the convexity and the concave groove serving as the duct of the second medicine B may be formed on the inner peripheral surface of the inner cylinder 6 at its front side.
In each of the pre-filled syringes 100 of the embodiment shown in FIGS. 1, 8, and 10, the third gasket 14 has an annular construction having an annular lip portion 14a that contacts the inner peripheral surface of the outer cylinder 1, as shown in FIGS. 3 and 15. Thereby, it is possible to sufficiently seal the gap between the peripheral surface of the front side of the inner cylinder and the portion of the inner peripheral surface of the outer cylinder located on the peripheral surface of the front side of the inner cylinder. It is also possible to accomplish the slidable movement of the third gasket in the outer cylinder. Accordingly, owing to the rise of the pressure inside the first space 9 caused by the movement (inflow) of the second medicine B into the first space 9, the inner cylinder 6 and the third gasket 14 move rearward automatically, as shown in FIG. 1C. That is, the resistance to the third gasket 14 in its sliding movement is lower than a resilient force generated against the compression of the first space 9 caused by the movement (inflow) of the second medicine B into the first space 9. The third gasket 14 is unremovably installed on the front end of the inner cylinder 6 by fitting a flange 18 formed on the opening at the front end of the inner cylinder in a flange 19 formed on the annular opening of the third gasket 14.
As shown in FIG. 20 showing a pre-filled syringe 300a of another embodiment, the desiccant 201 may be accommodated in the space 302 formed between the fourth gasket 301 and the first gasket 10. The desiccant 201 reliably prevents the first medicine A from absorbing water of the second medicine B that has moved to the first space. As the desiccant 201, the above-described ones can be preferably used. The desiccant having a form or size which does not block and pass the medicine duct is used.
In the pre-filled syringe 600 of the embodiment, as the inner cylinder movement prevention portion 406, an engaging portion 406a which engages a flange formed at the rear end of the outer cylinder is formed at the front end thereof, and a rear-end portion 406b which can contact a flange formed at the rear end of the inner cylinder 6 is formed at the rear end thereof. The inner cylinder movement prevention portion 406 is removable from the outer cylinder 1. The inner cylinder movement prevention portion 406 is not limited to this construction so long as the inner cylinder movement prevention portion 406 can prevent the inner cylinder 6 from moving toward the front side of the outer cylinder 1. In the pre-filled syringe 600, the inner cylinder movement prevention portion 406 is removed from the outer cylinder 1 after the first medicine and the second medicine are mixed with each other by operating the plunger 13. The inner cylinder movement prevention portion 406 does not prevent the inner cylinder 6 from moving toward the rear end of the outer cylinder 1. Thus, the inner cylinder 6 can move to the rear end of the outer cylinder 1, when the plunger mounted or mountable at the rear end of the second gasket 11 is pressed.
As in the case of a pre-filled syringe 400a of an embodiment shown in FIG. 24, the desiccant 201 may be accommodated in any of the pre-filled syringes 400, 500, and 600.
The construction of the pre-filled syringe 400a is fundamentally the same as that of the above-described pre-filled syringe 400, except that the pre-filled syringe 400a has a desiccant 201 accommodated between the front end of the inner cylinder 6 and the first gasket 10 and has an interception portion 202, disposed at its front end, for preventing the desiccant 201 from flowing into the outer cylinder 1 (in other words, first space 9). According to the pre-filled syringe 400a, owing to the provision of the desiccant 201, it is possible to prevent the first medicine A from absorbing moisture. In particular, it is possible to prevent the first medicine A from absorbing water of the second medicine B that has moved to the first space. As the desiccant 201 and the interception portion 202, those used for the pre-filled syringe 200 can be preferably utilized.
3678931 July 1972 Cohen
5501673 March 26, 1996 Hjertman et al.
5785682 July 28, 1998 Grabenkort
0 737 485 October 1996 EP
52-41273 September 1977 JP
11-169460 June 1999 JP
Patent number: 6544233
Inventors: Hideo Fukui (Nakakoma-gun), Masato Nishimura (Nakakoma-gun)
Application Number: 09/690,892
Current U.S. Class: Having Plural Material Reservoirs (604/191); Means For Preventing Accidental Displacement Of Piston (604/220); Closure Or Barrier Between Compartments Moved To Permit Mixing (604/89)