CA2203908A1

CA2203908A1 - Process for filling and sealing a fluid-containing disposable syringe that is to be sterilized

Info

Publication number: CA2203908A1
Application number: CA002203908A
Authority: CA
Inventors: Ulrich Speck
Original assignee: Individual
Current assignee: Bayer Pharma AG
Priority date: 1994-10-28
Filing date: 1995-10-27
Publication date: 1996-05-09
Also published as: DE59502539D1; US6129711A; KR970706858A; NO971948L; WO1996013289A3; EP0788385B1; WO1996013289A2; FI971710A; JPH10507670A; MX9703085A; ATE167064T1; FI971710A0; EP0788385A1; NO971948D0

Abstract

A process is disclosed for filling with a fluid and closing disposable plastic syringes that are to be sterilised. The disposable syringes have an injection cylinder (11) with a shaped front nozzle part (20), a piston or piston plug (30) in at least one piece and a piston stop element (40) arranged in the area of the cylinder gripping plate (12). After inserting the piston (30) into the empty injection cylinder (11), together or not with its own piston rod, the piston is fully pushed up to the front end of the cylinder. The fluid medium is then fed under pressure into the injection cylinder (11) through the nozzle part (20) and pushes the piston (30) in the direction of the piston rod up to the piston stop element (40). After the syringe is filled, the front area (25) of the nozzle part (20) is closed by plastic deformation. This process allows a previously filled disposable syringe to be sterilised in a standard autoclave without any risk of the syringe inner pressure plastically deforming parts of the syringe.

Description

Process for Filling and Sealing a Fluid-Containing Disposable Syringe That Is To Be Sterilized DESCRIPTION
This invention relates to a process for filling and sealing a f luid-containing plastic disposable syringe that is to be sterilized, whereby the disposable syringe comprises a barrel with a nozzle part that is molded at the front, an at least one-piece plunger or plunger plug, and a plunger stop element that is placed in the area of the cylinder gripping plate.
To date, ampoules and injection vials have primarily been used for parenteral administration of liquid pharmaceutical agents. In addition, a hypodermic syringe with a matching injection cannula is required to administer the liquid or free-f lowing substances that are decanted in these containers . This means, however, that the pharmaceutical agent must be transferred to such a hypodermic syringe before f inal use . This is not only time-consuming but also creates considerable opportunities for contamination .
To keep the liquid pharmaceutical agent from being contaminated, therefore, prefilled disposable syringes are already available on the market. Such a disposable syringe is known from EP-B 0 227 401. There, a process for the production of filled, sterile plastic syringes is described. The disposable syringe, whose design corresponds to DIN 13 098 Part 2, is sterilized in a special process to preserve its geometric shape.
To prevent the plastic disposable syringe from being deformed in an autoclave under the action of high internal syringe pressure, the pressure is increased in the autoclave by adding compressed air until the internal syringe pressure is reached.
In addition to a pneumatic pump, this process required a steam generator with low inertia since although the compressed air that is introduced into the autoclave raises the internal autoclave pressure, it considerably lowers the temperature that is n~c~ccAry for sterilization. It is also disadvantageous that heat transfer is reduced by the presence of air in the air/vapor mixture, which leads to a prolonged retention time in the autoclave .
Another drawback arises from the design of the disposable syringe that is used. It must be f illed with the preparation through the opening on its plunger rod side. With this method of filling, a gas bubble is included in the barrel under the plunger plug that is to be used which further increases the internal syringe pressure during sterilization and thus forces the plunger plug to be pushed out and/or the syringe body to deform.
This drawbacis also exists for a subcutaneous syringe with a partial glass structure that is known from US PS 5,069.670. The syringe has a glass barrel, a mounted cylinder gripping plate with an internal collar, a mounted head element with a standard connecting part for attaching medical cannulae, a plunger plug, and a sealing part. It cannot be sterilized in the filled state, however, since its glass cylinder cannot withstand high internal pressure during a sterilization process in the autoclave.

This invention therefore focuses on the problem of developing a process for filling and sealing a fluid-containing plastic disposable syringe that is to be sterilized, by which the disposable syringe can be sterilized in the filled state in a standard type of autoclave, without the danger arising of plastic deformation owing to the internal syringe pressure of the syringe parts. In this case, the disposable syringe is to be configured in such a way that largely gas-free f illing is made possible.
Further, the syringe components are to be simple to clean and to handle. Also, the drawbacks that are known from the area of prior art are to be avoided.
The problem is resolved, i. a., by virtue of the fact that the plunger or plunger plug, after insertion into the empty barrel, is inserted all the way up to its front end with or without the specif ic plunger rod and then the f luid medium is forced into the barrel under pressure via the nozzle part, whereby the f luid medium pushes the plunger or plunger plug in the direction of the plunger rod side up to the plunger stop element. After filling, the front area of the nozzle part is sealed by plastic deformation.
With this process, the disposable syringe can be filled almost gas-free. The filling device is connected to the front, open end of the sealing element to force the preparation that is subjected to pressure via the nozzle part into the interior of the syringe body. Because of the plunger plug that is attached in the nozzle area, the preparation cannot flow freely into the barrel, but has to push the plunger plug forward, optionally with the plunger rod. As a result, i.a., foaming of the preparation is prevented, so that after the filling device is detached, only a few gas bubbles are present in the barrel. For the most part, the gas comes from the cavity of the nozzle part. As the disposable syringe is being moved to the next processing station, the gas rises and collects in the upper area of the nozzle part.
Theoretically, the liquid level should then have to lie at the lower edge of the noz z le part when the disposable syringes are arranged vertically. Since the preparation was filled under pressure, however, on the one hand the syringe body has PYrAnflPd slightly, and, on the other hand the plunger plug has been minimally compressed. Both elastic deformations heal themselves, causing the liquid level in the nozzle part to rise almost to the upper edge. Optionally, the rising of the gas bubbles into the front or upper nozzle part is supported by an ultrasonic generator or the 1 ike .
The plunger plug can also partially project into the nozzle part, thereby reducing the residual gas volume there.
Within the scope of the process, the disposable syringe is sealed in such a way that the front area of the nozzle part, for example, is plastically deformed with partial heat input. In this case, welding and gluing processes can be used.
To complete the process, a protective cap is optionally put on over the nozzle part. The protective cap is attached to the nozzle part or the barrel by friction and/or clamping. It protects the relatively thin and thin-walled nozzle part against mechanical damage.

In its rear area, the nozzle part preferably has the shape of a connecting part with an outer cone according to DIN 13 090 with or without a locking part.
If the rear area of the nozzle part is only a conical connecting part according to DIN 13 090, Part 1, the above-mentioned protective cap is pushed on to attach it to the outer cone of the connecting part.
The front area of the nozzle part is approximately a tubul~r sealing element that projects over the standard connecting part.
The so-called sealing element is at least three times longer than the connecting part. It i8 used, on the one hand, for adapting the syringe body to the f illing device and collecting the residual gas that remains after filling in the syringe body and, on the other hand, for sealing the syringe body on the nozzle s ide .
The nozzle part has a throat in the area between the connecting part and the sealing element. In this throat is mounted the tool for separating the connecting part and sealing element before the preparation is administered. The throat is placed and configured in such a way that after the sealing element is separated, the standard connecting part for attaching the medical devices that are to be connected later is created.
Despite the throat, the inner wall of the sealing element merges without a seam and without a change in size into the inner wall of the connecting part, so that there no fluidic or bubble-forming obstacle is created.

The throat can also be designed as a predetermined point of break with high notching action, i.a., when brittle materials are used. In this case, the sealing element can be separated from the connecting part by being twisted off and/or broken off.
The plunger stop element is a separate component that projects with at least one plunger support element into the barrel or covers the barrel, and engages cylinder gripping plate from behind with at least one gripping element. With the aid of the plunger stop element, the plunger or the plunger plug is kept from being pushed out from the barrel during f illing and autoclaving of the disposable syringe. For this purpose, the plunger stop element can be mounted on, for example, the cylinder gripping plate, whereby locking elements secure the plunger stop element to the cylinder gripping plate or the barrel.
Another alternative consists in shaping in the rear end of the barrel knobs which project inward and on which the plunger can be supported. To do this, the plunger must have recesses in the bottom of the plunger or the plunger base that correspond to the knobs, whereby the recesses are arranged spaced around the periphery of the plunger like the knobs on the inner wall of the cylinder. After insertion into the barrel, the plunger is swung around a half spacing around its longitudinal axis, so that the plunger bottom areas without a recess coincide with the knobs.
The plunger stop element is equipped with recesses at least in the area o~ the barrel, so that there are no closed cavities between the plunger and the plunger stop element. Such cavities could partially produce heating that is inadequate for sterilization during autoclaving owing to their thermal insulating action.
The same problem also exists for the protective cap with the subjacent nozzle part. To ensure that the nozzle part is heated adequately, the protective cap has recesses outside of its attachment area.
The recesses and breaks also make it possible for the disposable syringe to dry completely after autoclaving.
Owing to the small volume flow due to factors related to the cross-section, f illing the disposable syringe via the nozzle part takes more time than f illing the barrel at the back. To ensure that the cycle time of the conventional f illing process is maintained, several filling devices are preferably charged in parallel .
other details of the invention emerge from the embodiment that is described and depicted diagrammatically below.
Figure 1: Partially cut-away side view of the mounted disposable syringe before filling;
Figure 2: top view of the partially cut-away, mounted disposable syringe;
Figure 3: partially cut-away side view of the nozzle part with a Luer lock connecting part before the disposable syringe is filled;
Figure 4: partially cut-away side view of the nozzle part after the disposable syringe is filled and sealed.

Figure 1 shows a large-volume disposable syringe, which, apart from a special nozzle part (20) and a plunger stop element (40) of DIN 13 098, Part 1, corresponds to a plastic disposable syringe. Accordingly, its syringe body (10) consists of a barrel (11) with a cylinder gripping plate (12) that is molded at the rear end and a lockable connecting part (21) that is placed at the front end with an outer cone according to DIN 13 090, Part 2.
Connecting part (21), however, within the framework of the invention, i.a., is designed extended. A plunger plug (30) is located in barrel (11). This plunger plug (30) consists of a plunger seal (33) that is put on plunger base (31) and has inner threading (32). Inner threading (32) is used to attach the plunger rod, not shown. Plunger base (31) projects at its rear end in the longitudinal direction of the syringe over plunger seal (33) to form a defined support for resting on plunger stop element ( 4 0 ) .
In Figure 3, nozzle part (20) of the unfilled disposable syringe is presented in enlarged form. In addition to standard locking part (22) and conical connecting part (21), it has, i.a., an extension that is provided for filling. The extension, which is about 3 times as long as connecting part (21), is a so-called sealing element (25). A throat (26) separates sealing element (25) and connecting part (21). Behind connecting part (21), the side of throat (26) is an outer radius that is adapted to the shape of connecting part (21). The base of the throat is cylindrical. There, the wall thickness is less than a half millimeter. Behind sealing element (25), the side of the throat is a 45~ bevel.
At its front end, sealing element (25) has an outer cone with a 1:4 slope. The inner wall of entire nozzle part (20) is approximately cylindrical.
Plunger stop element (40) is located at the other end of the disposable syringe in barrel (11), cf. Figures 1 and 2. It comprises a base plate (41), on which, on the one hand, four plunger support elements (46) that project into barrel (11) are located, and, on the other hand, there are two gripping elements (43), which at least partially engage cylinder gripping plate (12) on the outside. Plunger support elements (46) are molded at equidistant intervals around a central hole (42) of base plate (41). Each of plunger support elements (46) has, over its entire length, a cross-section that largely corresponds to the shape of a circular ring section. The outer contour of the circular ring cross-section has about the length of 1/8 the circumference. The uncurved lateral surfaces of plunger support elements (46) form planes that run parallel around half the width of plunger support elements (46), offset to the assumed center line of the disposable syringe . Plunger support elements ( 4 6 ) that are aligned parallel to the wall of barrel (11) do not touch the wall itself. This has, i.a., the advantage that after sterilization, these zones dry quickly.
Centering elements (47) are located between plunger support elements (46) and the wall of barrel (11). The centering elements are located on the outer contour of plunger support elements (46) in the area of cylinder gripping plate (12). They are aligned parallel to the center line of the syringe and midway to respective plunger support element (46). Their cross-section is approximately semi-circular.
Base plate (41), whose center hole (42) is also used to guide the plunger rods, not shown, completely covers cylinder gripping plate (12) from the outside. In this case, it projects slightly over the edge of cylinder gripping plate (12). The projecting edge is designed to be circular in sections in the area that is the farthest from the center line of the syringe.
I.a., in this edge area, gripping elements (43) are molded-on.
In both halves of cylinder gripping plate ( 12 ), the shapings also extend, as Figure 2 shows, in the direction of barrel (11).
Corresponding to Figure 2, this is on the right half in the lower area and in the left half in the upper area. Gripping elements (43) partially engage the lower side of cylinder gripping plate (12) from the outside, so that the lower side on both halves is obliquely covered in each case. The shape of the plunger stop element is partially determined by the type of assembly. Plunger stop element (40) is, like a bayonet catch, first inserted into the barrel and then brought into the gripping position, relative to the direction of insertion, by a clockwise rotation by 90~.
To this end, plunger stop element (40) is used in barrel (11) rotated by 90~ relative to the center line of the syringe in the assembly compared to the illustrations in Figures 1 and 2.
Plunger stop element (40) reaches the position shown only by clockwise rotation. For attaching in this gripping position, in each case two safety knobs (44) are placed on the edge of two gripping elements (43 ) . They prevent any unintentional reversal of plunger stop element (40).
Before the disposable syringe is filled and after the sterilization of the individual parts and the application of lubricant on the inner wall of the barrel, plunger plugs (30) are inserted into syringe body (10) and pushed up to the front end of the barrel. Then, plunger stop element (40) is inserted and swiveled to secure it. When plunger plug (30) and/or plunger stop element (40) is inserted, ~l~r~n-l;n~ on design, the original plunger rod can also be mounted. When plunger plug (30) is inserted, plunger stop element (40) can even sit loosely on the plunger rod.
For filling the disposable syringe, for example, the filling nozzle of the decanting machine that is equipped with an inner cone is mounted on the outer cone o~ sealing element (25).
During the filling process, plunger plug (30) is pushed by the liquid preparation that is pressed into barrel (11) in the direction of plunger stop element (40). As soon as plunger plug (30) rests on plunger stop element (40), the filling process is completed, and the filling nozzle rises from sealing element (25). As the disposable syringe is being moved to the next processing position, gas bubbles that are included in the preparation by shaking during shipment or by any additional vibration rise and collect in the front area of sealing element (25). As heat is input, the front part is crushed, twisted off, or similarly tightly sealed with plastic deformation.

CA 02203908 l997-04-28 Deformed sealing element (25') is shown in Figure 4. A
frustum-like protective cap (50) is put over sealing element (25') and screwed tight with the aid of the threading that is integrated in locking part (22). To this end, two short threaded sections (51) are located on the lower edge of protective cap (50), as indicated by, for example, DIN 13 090, Part 2, cf.
connecting part LLS with shape A or B. Protective cap (50) has four recesses (53) that are arranged symmetrically to the center line of the syringe and extend over 3/4 of the length of the protective cap.
To prepare the disposable syringe for use, protective cap (50) is screwed off, and sealing element (25') is separated from conical connecting part (21). The separation in the area of throat (26) can be done with the aid of shears, a knife, a scalpel, or the like. After sealing element (25') is separated, nozzle part (20) corresponds with respect to its geometrical shape to DIN 13 090.

CA 02203908 l997-04-28 wo 96/13289 PCT/DE95/01523 LIST OF REFERENCE SY~BOLS
10 Syringe body 11 barrel 12 cylinder gripping plate 20 nozzle part 21 conical connecting part 22 locking part 25 sealing element, undeformed 25' sealing element, deformed 2 6 throat 30 plunger plug, plunger 31 plunger base 32 thread for plunger rods 33 plunger seal 40 plunger stop element 41 base plate 42 hole, central 43 gripping elements 44 safety knobs CA 02203908 l997-04-28 46 plunger support elements 47 centering elements 50 protective cap 51 threaded section 52 webs 53 recesses

Claims

Title:
Fluid-Containing Plastic Disposable Syringe That Is To Be Sterilized

1. Fluid-containing plastic disposable syringe that is to be sterilized, which comprises a barrel (11) with a nozzle part (20) that is molded at the front, an at least one-piece plunger or plunger plug (30), and a plunger stop element (40) that is placed in the area of cylinder gripping plate (12), characterized in that -- nozzle part (20) in its rear area has the shape of a connecting part (21) with an outer cone according to DIN 13 090, Parts 1 and 2, with or without locking part (22), -- nozzle part (20) in its front area is an approximately tubular sealing element (25, 25'), which is plastically deformable in the area of its free, outer end with partial heat input and -- nozzle part (20) has a throat (26) in the area between connecting part (21) and sealing element (25, 25').

2. Disposable syringe according to claim 1, wherein a protective cap (50) can be put on over nozzle part (20), whereby protective cap (50) can be attached to nozzle part (20) or to barrel (11) by friction and/or clamping.

3. Disposable syringe according to claim 1, wherein plunger stop element (40) is a separate component that projects with at least one plunger protective element (46) into barrel (11) or covers barrel (11) and engages cylinder gripping plate (12) from behind with at least one gripping element (43).

4. Disposable syringe according to claim 1, wherein outside of its attachment area protective cap (50) has recesses (53).