Barrier coat stopper and molding method

Abstract

The present invention provides a method for forming molded devices, such as stoppers, that require minimal post-molding processing. [Solution] The mold assembly (52) includes an upper plate (54), a sprue / vent plate (56) including a core portion (62), a main plate (58) including a recess (66) defining a mold cavity (68) having a contour surface (70), and a bottom plate (60). The core portion (62) fits into the recess (66) of the main plate (58), closing the mold assembly (52) to define a space (72) corresponding to the shape of the stopper (10,110) to be molded. Polymer material is introduced into the mold cavity (68), the stopper (10,110) is formed, a barrier layer (14,114) is inserted between the main plate (58) and the bottom plate and bonded to the molding device (10,110), the plates open, and the molding device is removed.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Provisional Application No. 63 / 116,533, filed on November 20, 2020, entitled "Barrier Coat Stopper and Molding Method", the entire disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a method of molding devices such as stoppers for use in a plunger rod within a syringe and stoppers for closing vials. More particularly, the present invention relates to a method of molding a stopper using a four - plate one - shot injection - molded device that requires minimal post - molding processing.

Background Art

[0003] Syringe syringe assemblies, particularly subcutaneous syringes, are well known in the medical field for dispensing fluids such as drugs. Conventional syringes typically include an elongated barrel having opposing proximal and distal ends and a chamber therebetween for receiving the fluid. A passage extends through the distal end of the syringe barrel and communicates with the chamber. The distal end of the syringe barrel is connected to a needle cannula for supplying fluid from the chamber and the passage. The proximal end of the syringe barrel slidably receives a plunger rod and stopper assembly, and a force applied to the plunger rod biases the stopper along the barrel to drive the liquid through the needle cannula from the chamber.

[0004] Some commercially available subcutaneous syringes have a problem with the amount of liquid remaining in the barrel (i.e., "dead volume") after the stopper has advanced to the full length of the barrel during injection. Therefore, there is a need to manufacture stoppers that can reduce the amount of dead space in the syringe barrel. Various stoppers have been designed to reduce or minimize the dead space in the syringe barrel and to properly seal against the inner wall of the syringe barrel. One example of a stopper is disclosed in U.S. Patent No. 5,795,337, which is incorporated in its entirety by reference. This design consists of a piston-shaped stopper body that engages liquid-tightly and slidably within the syringe barrel. The body includes a distal end, a proximal end, and a longitudinal axis passing through it. A conical projection oriented distally is positioned at the distal end of the stopper body. At least one elongated discontinuous surface is provided along the conical projection. The discontinuity prevents the stopper projection from unnecessarily sealing the passage extending from the syringe barrel to the needle cannula, allowing the fluid trapped in the barrel to flow into the passage along these discontinuity surfaces. Because the stopper is made of an elastic material, further distal pressure on the plunger rod causes the stopper to deform, squeezing the liquid out through the passage temporarily opened by the discontinuity. [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] Complex stoppers with a barrier film on the distal surface are typically molded using a two-shot molding / trimming process. Currently, this type of stopper is only used for small-volume production where cost is not a major concern. The two-shot process costs approximately twice as much as the conventional single-shot process. While some commercially available barrier-coated stoppers utilize a single-shot molding process, these stoppers often have undesirable characteristics. One such undesirable characteristic is that the first rib must be a trimmed edge rather than a molded feature, thus failing to guarantee fluid sealing and ensuring optimal lubrication. Adding two ribs to the stopper resolves the risk of container closure integrity (i.e., CCI), but such a design is undesirable for certain devices, such as precision syringes, where variable leakage through the first stopper rib can affect drug dispensing accuracy and system hysteresis. Stoppers that overcome these limitations have also been designed, but so far, they are only produced using manufacturing processes that require two steps: molding and trimming. This production process is not only very costly, but the more steps involved, the greater the opportunities for waste and scrap. Extending the production of this type of high-precision stopper using a single-shot molding process would offer significant economic benefits. [Means for solving the problem]

[0006] In one embodiment, the present disclosure relates to a method for molding a device such as a stopper using a one-shot injection molding apparatus that requires minimal post-molding processing. The method includes the steps of: providing a four-plate mold assembly having an upper plate, a sprue / vent plate including a core, a main plate including a recess defining a mold cavity having a contour surface, and a bottom plate; closing the mold assembly so that the core fits into the recess of the main plate and defines a space corresponding to the shape of the device to be molded; and introducing a polymer material into the mold cavity to fill the mold cavity and space to form the device to be molded. The device to be molded has a body and a molded surface corresponding to the contour surface of the mold cavity. The method further includes cooling the polymer material; separating the sprue / vent plate from the main plate and removing the core from the device to be molded; then separating the sprue / vent plate from the upper plate; then separating the bottom plate from the main plate; and finally removing the device to be molded or stopper from the main plate.

[0007] The step of separating the sprue / vent plate from the main plate causes the vent to break and the core to be pulled out of the molding apparatus and the main plate. It can be understood that the core can be designed to have several shapes depending on the desired internal shape of the apparatus or stopper. For example, the core can have a threaded design, a conical portion with a portion that expands toward the intersection of the core and the sprue / vent plate, or straight side walls. When the mold plate is opened, the molding apparatus can be removed from the main plate by pulling the molding apparatus through the bottom of the main plate.

[0008] The step of introducing the polymer material into the mold cavity consists of injecting the high-temperature polymer material into the cavity via an injection nozzle and runner associated with the upper plate, and the step of cooling the mold assembly consists of supplying a cooling material to the main plate.

[0009] The contour surface of the main cavity is the shape of a stopper having a main body that defines an open rear end, a closed front end, and a cylindrical side wall extending between the open rear end and the closed front end. According to one embodiment, the shape of the contour surface is configured to form a plurality of ribs that extend radially outward around the main body and are spaced axially along the main body. It can be understood that the main cavity may have other contour surfaces to make other products and / or stoppers with different shapes.

[0010] According to one embodiment, the bottom plate may have a flat surface configured to form a stopper having a flat surface at its distal end. According to another embodiment, the bottom plate may include a contoured surface configured to form a stopper extending inward from the outer edge of the closed front end or the distal end of the stopper, wherein the contoured surface is formed to form a projection extending from the closed front end, the projection intersecting with the distal end of the stopper and defining the base, extending from the flat surface at the top of the closed front end, and the projection is configured to cooperate within the syringe barrel to reduce dead space during injection. It can be understood that the bottom plate may have other designs for creating stoppers of various shapes at its distal end.

[0011] The method may further include the step of providing a film, such as a barrier film, between the bottom plate and the main plate, so that when the mold is closed, the film is sandwiched between the bottom plate and the main plate, and when the device is removed from the mold, the film is fixed to the device being formed. It can be understood that the barrier film may be a known film that provides a low-friction barrier between the stopper and the pharmaceutical composition (e.g., drug, medicine, or other therapeutic material) in the syringe barrel, thereby preventing the material from leaching out of the stopper or the stopper from extracting compounds from the pharmaceutical composition. The method further includes the step of trimming and removing any excess film from the device being formed.

[0012] In another aspect, the present disclosure relates to a system for molding devices such as stoppers, comprising a mold assembly having an upper plate, a sprue / vent plate, a main plate, and a bottom plate. The sprue / vent plate includes a core portion extending from its surface. It can be understood that the core portion may have any shape depending on the desired internal shape of the device or stopper to be molded. For example, the core portion may have a threaded design, a conical portion with a portion that expands toward the intersection of the core portion and the sprue / vent plate, or straight side walls. The main plate of the mold includes a recess that defines a mold cavity having a contoured surface. This mold cavity is configured to receive the core portion from the sprue / vent plate and defines a space corresponding to the shape of the device to be molded. An injection nozzle and runner are fitted into the upper plate. The injection nozzle and runner are configured to supply polymer material into the mold cavity to fill the space and form a device to be molded having a body and a molded surface corresponding to this contoured surface. At least one cooling element is provided to cool the polymer material inside the mold cavity.

[0013] The system further includes a first mechanism for separating the sprue / vent plate from the main plate and pulling the core out of the molding apparatus; a second mechanism for separating the sprue / vent plate from the upper plate; and a third mechanism for separating the bottom plate from the main plate so that the molding apparatus can be removed from the main plate. According to one embodiment, the first, second, and third mechanisms for separating the upper plate, sprue / vent plate, main plate, and bottom plate of the mold assembly consist of a series of spring mechanisms or a series of core lifters with different forces for sequentially separating the sprue / vent plate from the main plate, the sprue / vent plate from the upper plate, and the bottom plate from the main plate, the spring mechanism including guide pins for limiting the opening of each plate.

[0014] According to one embodiment, the film can be inserted between the bottom plate and the main plate, and the film can be sandwiched between the bottom plate and the main plate by closing the mold, thereby fixing the film to the device on which it is formed. The system may further include a trim mold for removing excess film from the device on which it is formed. According to one design, the trim mold may consist of a flat punch for removing excess film, but it can be understood that other types of molds having other types of cutting surfaces such as razor edges, and / or other types of trimming devices with or without air blasting, can be used to remove excess film.

[0015] In yet another embodiment, the disclosure relates to a stopper adapted for attachment to a plunger rod for use in a syringe barrel. The stopper comprises a main body defining an open rear end, a closed front end, and a cylindrical side wall extending between the open rear end and the closed front end. The open rear end is adapted to receive the attachment portion of the front end of the plunger rod. The stopper further includes at least one rib extending radially outward around the outer circumference of the main body. At least one rib is configured to form an active seal with the syringe barrel. Adjacent to at least one rib, a flat portion is provided on the upper outer edge surface of the closed front end of the stopper. The flat portion extends inward from the outer edge of the stopper. The stopper further includes a projection extending from the closed front end, the projection defining a base to intersect with the distal end of the stopper and extending from the flat portion to the top of the closed front end. The base has a base diameter smaller than the outer diameter of the distal end of the stopper, and the projection has a profile configured to cooperate with the inner surface of the syringe barrel, reducing dead space during injection.

[0016] Further embodiments of this disclosure are described in the following numbered clauses.

[0017] Clause 1: A method for molding an apparatus, comprising the steps of: providing a mold assembly having an upper plate, a sprue / vent plate including a core, a main plate including a recess defining a mold cavity having a contour surface, and a bottom plate; closing the mold assembly so that the core fits into the recess of the main plate and defines a space corresponding to the shape of the apparatus; introducing a polymer material into the mold cavity to fill the mold cavity and space, forming an apparatus to be molded having a body and a molded surface corresponding to a contour surface; separating the sprue / vent plate from the main plate and withdrawing the core from the apparatus to be molded; then separating the sprue / vent plate from the upper plate; then separating the bottom plate from the main plate; and removing the apparatus to be molded from the main plate.

[0018] Clause 2: The method according to Clause 1, wherein the sprue / vent plate is separated from the main plate in a step that causes the vent to be detached and withdrawn from the apparatus and main plate in which the core is formed.

[0019] Clause 3: The method according to Clause 1 or 2, wherein the step of removing the device to be molded from the main plate comprises removing the device to be molded through the bottom of the main plate.

[0020] Clause 4: The method according to any one of Clauses 1 to 3, wherein the step of introducing a polymer material into a mold cavity comprises injecting the polymer material into the mold cavity via an injection nozzle and runner associated with an upper plate.

[0021] Clause 5: The method according to any one of claims 1 to 4, wherein, after the step of introducing a polymer material into a mold cavity, the mold assembly is heated to cure the polymer material, or the mold assembly is cooled by supplying a cooling material to the main plate.

[0022] Clause 6: The method according to any one of Clauses 1 to 5, wherein the contour surface of the main cavity has the shape of a stopper having a main body that defines an open rear end, a closed front end, and a cylindrical side wall extending between the open rear end and the closed front end.

[0023] Clause 7: The method according to Clause 6, wherein the shape of the contour surface is configured to form a plurality of ribs that extend radially outward around the outer circumference of the main body and are axially spaced along the main body.

[0024] Clause 8: The bottom plate has a flat surface configured to form a stopper having a flat surface, or the bottom plate includes a contour surface configured to form a stopper having a flat portion at the outer edge of the closed front end of the stopper and extending inward from the outer edge of the stopper, the contour surface being formed to form a protrusion extending from the closed front end, the protrusion defining a base so as to intersect the distal end of the stopper and extending from the flat portion at the top of the closed front end, and the protrusions being configured to cooperate within the syringe barrel to reduce the dead space during injection, the method according to Clause 6 or Clause 7.

[0025] Clause 9: The method according to any one of Clauses 1 to 8, including the step of providing a film between the bottom plate and the main plate, wherein the film is sandwiched between the bottom plate and the main plate when the mold assembly is closed, and the film is fixed to the device being molded when the device is removed from the mold assembly.

[0026] Clause 10: The method according to any one of Clauses 1 to 9, including the step of trimming excess film from the device being molded.

[0027] Clause 11: A system for molding a device, comprising a mold assembly having an upper plate, a sprue / vent plate, a main plate, and a bottom plate, wherein the sprue / vent plate includes a core portion extending from its surface, the main plate includes a recess defining a mold cavity having a contour surface, and the mold cavity is configured to receive the core portion from the sprue / vent plate and define a space corresponding to the shape of the device to be molded; an injection nozzle fitted to the upper plate and a runner, wherein the injection nozzle and the runner are configured to supply a polymer material to the mold cavity to fill the space and form a molded device having a body and a molding surface corresponding to the contour surface; at least one cooling member for cooling the polymer material in the mold cavity; a first mechanism for separating the sprue / vent plate from the main plate to withdraw the core portion from the molded device; a second mechanism for separating the sprue / vent plate from the upper plate; and a third mechanism for separating the bottom plate from the main plate to enable removal of the molded device from the main plate.

[0028] Clause 12: The system according to Clause 11, wherein the first, second, and third mechanisms for separating the upper plate, the sprue / vent plate, the main plate, and the bottom plate of the mold assembly comprise a series of spring mechanisms with different forces or a series of core lifters for sequentially separating the sprue / vent plate from the main plate, the sprue / vent plate from the upper plate, and the bottom plate from the main plate, and the spring mechanisms include guide pins for restricting the opening of each plate.

[0029] Clause 13: The system according to Clause 11 or Clause 12, wherein a film can be inserted between the bottom plate and the main plate, and when the mold is closed, the film is sandwiched between the bottom plate and the main plate so that the film is fixed to the molded device.

[0030] Clause 14: The system according to any one of Clauses 11 to 13, comprising a trim die having a flat punch for removing excess film from a molding device, wherein the trim die optionally includes a central part having an opening through which a clean air vent can move in order to remove a trimmed part from the trim die or mold block.

[0031] Clause 15: A stopper adapted for mounting with a plunger rod for use in a syringe barrel, the stopper comprising: a main body defining an open rear end, a closed front end, and a cylindrical side wall extending between the open rear end and the closed front end; a barrier film covering at least the closed front end of the main body, the open rear end of which is adapted to receive the mounting portion of the front end of the plunger rod; and at least one rib extending radially outward around the outer circumference of the main body, which is an active stopper for mounting with the syringe barrel. A stopper comprising at least one rib configured to form a barrel, and a flat portion adjacent to at least one rib on the upper outer edge surface of the closed front end, the flat portion extending inward from the outer edge of the stopper, the projection extending from the closed front end, the projection defining a base so as to intersect the closed front end of the stopper, the base having a base diameter smaller than the outer diameter of the distal end of the stopper, and the projection having a profile configured to cooperate with the inner surface of the syringe barrel to reduce dead space during injection.

[0032] Clause 16: The stopper as described in Clause 15, wherein the flat portion has a width of approximately 0.75 to 1 mm to the starting point of the upward slope that forms the projection.

[0033] Clause 17: The stopper according to Clause 15 or 16, wherein at least one rib comprises a first rib, a second rib, and a third rib, the second rib having a smaller diameter than the first rib and the third rib.

[0034] Clause 18: A stopper according to any one of Clauses 15 to 17, wherein the open rear end of the stopper includes a cavity configured to receive a mounting portion of the front end of a plunger rod, and the inner surface of the cavity includes a plunger rod cavity projection extending from the bottom surface of the closed front end of the stopper.

[0035] Clause 19: The stopper according to Clause 18, wherein the plunger rod cavity projection is configured to lightly engage with the mounting portion of the front end of the plunger rod in order to increase the force transmitted to the front of the stopper, and the plunger rod cavity projection has an inclined side wall.

[0036] Clause 20: The stopper according to any one of Clauses 15 to 19, wherein the open rear end of the stopper includes a cavity having a series of threads for threaded mounting to the mounting end of a plunger rod, the threads having a pitch that decreases slightly toward the bottom of the plunger rod cavity.

[0037] Clause 21: A stopper as described in any one of Clauses 15 to 20, wherein the thickness between the roof profile spline AA-BB and the internal roof projection LL is monotonically decreasing and protrudes upward to point XX.

[0038] Clause 22: The stopper described in Clause 21, wherein point XX is within the range of 0.25 to 0.75 mm within the thickness of the stopper wall defined by YY. [Brief explanation of the drawing]

[0039] The features and other advantages of this disclosure, as well as the methods for achieving them, will become clearer and the disclosure itself will be better understood by referring to the following description of embodiments of this disclosure taken in conjunction with the accompanying drawings. [Figure 1A] Figure 1A is a top perspective view of a stopper for use in a syringe according to one embodiment of the present invention. [Figure 1B] Figure 1B is a side perspective view of the stopper shown in Figure 1A according to an embodiment of the present invention. [Figure 2A] Figure 2A is a top perspective view of a stopper for use in a syringe according to an embodiment of the present invention. [Figure 2B] Figure 2B is a cross-sectional side view of the stopper shown in Figure 2A according to an embodiment of the present invention. [Figure 3] Figure 3 is a cross-sectional side view of a four-plate one-shot injection-molded apparatus that can be used to form a molded device such as the stopper shown in Figures 1A to 1B and Figures 2A to 2B, according to one embodiment of the present invention. [Figure 4] Figure 4 is a perspective view of the mold of Figure 3 in an open state, including the removal of the molding stopper according to an embodiment of the present invention. [Figure 5A] Figure 5A shows the steps for molding the device using the mold shown in Figure 3 according to an embodiment of the present invention. [Figure 5B] Figure 5B shows the steps for molding the device using the mold shown in Figure 3 according to an embodiment of the present invention. [Figure 5C] Figure 5C shows the steps for molding the device using the mold shown in Figure 3 according to an embodiment of the present invention. [Figure 5D] Figure 5D shows the steps for molding the device using the mold shown in Figure 3 according to an embodiment of the present invention. [Figure 5E] Figure 5E shows the steps for molding the device using the mold shown in Figure 3 according to an embodiment of the present invention. [Figure 6A] Figure 6A is a side view of a die punch for cutting off excess barrier film after molding the stopper shown in Figures 1A and 1B, according to an embodiment of the present invention. [Figure 6B] Figure 6B is a side view of the die punch of Figure 6A, including an air passage for removing excess film according to an embodiment of the present invention. [Figure 7A] Figure 7A is a side view of the stopper shown in Figures 1A and 1B according to an embodiment of the present invention. [Figure 7B] Figure 7B is a cross-sectional view of the stopper in Figure 7A along line BB according to an embodiment of the present invention. [Figure 7C]Figure 7C is a top view of the stopper shown in Figure 7A according to an embodiment of the present invention. [Figure 7D] Figure 7D is a bottom view of the stopper shown in Figure 7A according to an embodiment of the present invention. [Figure 7E] Figure 7E is a side view of the stopper in Figure 7A, with a portion of the stopper cut off to show the interaction between the plunger rod core and the inner portion of the distal end of the stopper, according to an embodiment of the present invention. [Figure 7F] Figure 7F is a partial cross-sectional perspective view of the stopper shown in Figure 7A, and shows the inner thread and inner portion of the distal end of the stopper according to an embodiment of the present invention. [Figure 7G] Figure 7G is a cross-sectional view of the stopper in Figure 7A, showing that the pitch of the internal threads of the stopper increases towards the bottom of the plunger rod cavity according to the embodiment of the present invention. [Figure 8] Figure 8 is a cross-sectional view of a stopper fixed to the mounting end of a plunger rod being molded by the molding apparatus shown in Figure 3, according to an embodiment of the present invention. [Figure 9A] Figure 9A shows the stopper design of Figure 8 assembled inside a syringe barrel before and after a distal force is applied to the plunger rod and stopper according to an embodiment of the present invention. [Figure 9B] Figure 9B shows the stopper design of Figure 8 assembled inside a syringe barrel before and after a distal force is applied to the plunger rod and stopper according to an embodiment of the present invention. [Figure 10A] Figure 10A is a representative diagram showing the amount of dead space generated in the syringe barrel after a distal force is applied to the plunger rod using the stopper design shown in Figures 1A to 1B according to an embodiment of the present invention. [Figure 10B] Figure 10B is a representative diagram showing the amount of dead space generated in the syringe barrel after a distal force is applied to the plunger rod using the stopper design shown in Figures 2A to 2B according to an embodiment of the present invention. [Figure 11] Figure 11 is a perspective cross-sectional view of a stopper according to an embodiment of the present invention.

[0040] Corresponding reference numerals indicate corresponding parts in some of the figures. The examples described herein illustrate exemplary embodiments of the disclosure and should not be construed as limiting the scope of the disclosure in any way. [Modes for carrying out the invention]

[0041] The following description is provided to enable those skilled in the art to create and use the described embodiments intended for carrying out the invention. However, various modifications, equivalents, variations, and substitutes will be readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and substitutes are intended to fall within the spirit and scope of the invention.

[0042] Hereinafter, for explanatory purposes, “top,” “bottom,” “right,” “left,” “vertical,” “horizontal,” “top,” “bottom,” “horizontal,” “vertical,” and their derivatives shall be used in relation to the present invention as oriented in the drawings. However, it will be understood that the present invention may presuppose various alternative modifications unless explicitly specified otherwise. It should also be understood that the specific devices shown in the accompanying drawings and described below are merely exemplary embodiments of the present invention. Therefore, specific dimensions and other physical features relating to the embodiments disclosed herein should not be considered limiting.

[0043] Furthermore, in the description of the present invention, the term "distal end" is intended to refer to the end of the syringe from which the injection needle protrudes and the end of the stopper closest to the injection needle, while the term "proximal end" is intended to refer to the end of the syringe closest to the syringe holder and furthest from the tip of the injection needle and the end of the stopper furthest from the tip of the needle.

[0044] Next, refer to Figures 1A to 1B and 2A to 2B, which show two different types of stoppers 10,110 that can be manufactured in a four-plate one-shot injection molding system, generally indicated as 50 in Figures 3 and 4 of this disclosure. The stoppers may include a plurality of annular ribs 12,112 configured to engage and seal liquid-tightly with the inner surface of the syringe barrel 16 shown in Figures 9A1 to 9E2.

[0045] A syringe barrel typically includes an open proximal end, a distal end 38, and a cylindrical body portion between them that defines a chamber for holding a liquid, such as a liquid drug, as shown in Figures 9A and 9B. The syringe barrel may be made of glass, plastic, or a combination thereof, and may include a flange at the proximal end. Examples of plastic materials that can be used to form a syringe barrel include, but are not limited to, substantially transparent thermoplastic materials such as polycarbonate, polypropylene, and polyethylene terephthalate (PET).

[0046] The stoppers 10,110 can be positioned so as to engage liquid-tightly within the barrel by the action of the annular ribs 12,112, with their distal ends 20,120 facing the distal end of the syringe barrel. The distal end 38 of the syringe barrel includes a passage 39 that fluidly communicates with the chamber. Although not shown, an elongated needle cannula having a lumen extending through it may be provided to connect to the distal end 38 of the barrel so that the lumen fluidly communicates with the chamber through the passage. It can be understood that the needle may be permanently attached to the syringe barrel, for example by using an adhesive, or it may be removablely attached to the syringe barrel, for example, by permanently attaching it to the needle cannula and then frictionally attaching the tip to the needle hub at the distal end of the syringe barrel. The stoppers 10,110 can slide within the chamber for initial positioning adjacent to the drug and thereafter to facilitate the drug through the lumen of the needle cannula or the passage at the distal end of the syringe barrel 38. Alternatively, the stoppers 10 and 110 can be slid within the syringe barrel for reconfiguration purposes.

[0047] Barrier films 14,114 can be provided at the distal ends 20,120 of the stoppers to reduce and / or eliminate direct contact between the material of the stoppers 10,110 and the contents of the syringe, thereby reducing friction between the contents of the syringe and the stoppers 10,110.

[0048] Continuing with Figures 3 and 4, a four-plate injection molding system 50 is shown. While this molding system is intended for molding stoppers used on syringe plunger rods, it will be understood that this molding system can also be used to mold other products, such as closures for medical vials or test tubes, or other known molded devices. The molding system 50 consists of a mold assembly 52 having an upper plate 54, a sprue / vent plate 56, a main plate 58, and a bottom plate 60. The sprue / vent plate 56 includes a core portion 62 extending from its bottom surface 64. It can be understood that the core portion 62 may have any shape depending on the desired internal shape of the device or stopper 10,110 to be molded. For example, the core portion 62 may have a threaded design, a conical portion with an expanded portion toward the intersection of the core portion and the sprue / vent plate, or straight side walls. The main plate 58 of the mold includes a recess 66 that defines a mold cavity 68 having a contour surface 70. This mold cavity 68 is configured to receive a core portion 62 from a sprue / vent plate 56 and defines a space 72 corresponding to the shape of the device to be molded. An injection nozzle 74 and a runner 76 are fitted into the upper plate 54. The injection nozzle 74 and runner 76 are configured to supply polymer material to the mold cavity 68 to fill the space 72 and form a device to be molded having a body and a molded surface corresponding to the contour surface 70. At least one cooling member 78 is provided to cool the polymer material in the mold cavity 58. The cooling member 78 may be a series of tubes containing a cooling medium flowing through it, or it may be any other known cooling member.

[0049] System 50 further includes a first mechanism 80 for separating the sprue / vent plate 56 from the main plate 58 in order to pull the core portion 62 out of the molding apparatus 10,110, a second mechanism 81 for separating the sprue / vent plate 56 from the upper plate 54, and a third mechanism 82 for separating the bottom plate 60 from the main plate 58 in order to allow the molding apparatus 10,110 to be removed from the main plate 58. According to one embodiment, the first, second, and third mechanisms 80, 81, 82 for separating the upper plate, sprue / vent plate, main plate, and bottom plate of the mold assembly consist of a series of spring mechanisms with different forces for sequentially separating the sprue / vent plate 56 from the main plate 58, the sprue / vent plate 56 from the upper plate 54, and the bottom plate 60 from the main plate 58. The spring mechanisms may include guide pins that limit the opening of each plate. It can also be understood that the first, second, and third mechanisms 80, 81, and 82 for separating the upper plate, sprue / vent plate, main plate, and bottom plate of the mold assembly can be composed of a series of core lifters.

[0050] According to one embodiment, barrier films 14,114 can be inserted between the bottom plate 60 and the main plate 58, and the films 14,114 can be sandwiched between the bottom plate 60 and the main plate 58 by closing the mold assembly 52, thereby fixing the films 14,114 to the molded bodies 10,110. By using these barrier films 14,114 as stoppers, the sliding properties of the stoppers within the syringe barrel are improved. It is desirable that the barrier films 14,114 do not exhibit harmful effects on pharmaceuticals and do not contain silicone-based materials such as silicone oil. An example of a usable barrier film 14,114 is a fluoropolymer resin laminate, which is known to have good biocompatibility, good mechanical integrity, inertness, and processability. Due to the excellent strength of the extended fluoropolymer structure, these materials can form a thin barrier that remains intact during the molding process and during the attachment of the stoppers to the syringe barrel. For example, the barrier film may be selected from the group consisting of polytetrafluoroethylene resin (PTFE), ethylenetetrafluoroethylene resin (ETFE), and expanded polytetrafluoroethylene (ePTFE). Further details are described below, and the trim mold 84 shown in Figures 6A and 6B may be provided to remove excess barrier films 14,114 from the molding apparatus.

[0051] Next, we will refer to Figures 5A to 5E illustrating the sequential steps for molding the apparatus 10,110 using the four-plate injection molding system 50 of the present invention. Referring to Figure 5A, the method includes providing a four-plate mold assembly 52 having an upper plate 54, a sprue / vent plate 56 including a core portion 62, a main plate 58 including a recess 66 defining a mold cavity 68 having a contour surface 70, and a bottom plate 60, by closing the mold assembly 52 so that the core portion 62 fits into the recess 66 of the main plate 58 in order to define a space 72 corresponding to the shape of the apparatus 10,110 to be molded, as shown in Figure 3; and introducing a polymer material into the mold cavity 68 to fill the mold cavity 68 and the space in order to form the apparatus 10,110 to be molded. The mold assembly 52 may include an optional part 53 including a pin-shaped member (not shown) that an operator can hold by hand to push a part out of the cavity plate 58.

[0052] The molding apparatus has a main body 18, 118 and a molding surface corresponding to the contour surface 70 of the mold cavity 68. Depending on the type of polymer material used, such as the use of a thermoplastic elastomer, this method may include a step of cooling the polymer material. If the polymer material consists of uncured rubber, after introducing the material into the mold cavity, the mold is heated to approximately 180°C or the like to cure the rubber. After the polymer material has cooled, or after the rubber has been heated to cure, the sprue / vent plate 56 is separated from the main plate 58, as shown in Figure 5B, and the core portion 62 is pulled out from the molding cavity 68, the recess 66, and the molding apparatus 10, 110. Next, as shown in Figure 5C, the sprue / vent plate 56 is separated from the upper plate 54. Next, as shown in Figure 5D, the bottom plate 60 is separated from the main plate 58. The molding apparatus or stopper 10, 110 can be removed from the bottom 59 of the main plate 58, etc., as shown in Figure 5E.

[0053] The step of separating the sprue / vent plate 56 from the main plate 58 causes the vent 57 to detach, as shown in Figure 4, and the core portion 62 is withdrawn from the molding apparatus 10,110 and the main plate 58. It can be understood that the core portion 62 may be designed to have several shapes depending on the desired internal shape of the apparatus or stopper 10,110. For example, the core portion may have a threaded design, a conical portion with a portion that expands toward the intersection of the core portion and the sprue / vent plate, or straight side walls. When the plates of the mold assembly 52 are opened, the molding apparatus 10,110 can be removed from the main plate 58 by withdrawing the molding apparatus from the bottom 59 of the main plate 58.

[0054] Returning to Figure 3, the step of introducing the polymer material into the mold cavity consists of injecting the polymer material into the mold cavity 68 through the injection nozzle 74 and runner 76 associated with the upper plate 54. The polymer material can be synthetic rubber, but it can be understood that other materials can be used, such as natural rubber, elastomers, and combinations thereof. Examples of elastomers that can be used for the polymer material include, but are not limited to, silicone rubber, natural rubber, styrene-butadiene rubber (SBR), ethylene-propylene-diene monomer (EPDM), and polychloroprene. If the polymer material consists of an elastomer, it is usually heated to about 225°C, although this varies depending on the material. Alternatively, if the material consists of, for example, thermosetting rubber, the material is only heated to a molten state (i.e., about 20°C to 50°C) so that it can be injected into the mold cavity. The step of cooling the mold assembly as needed includes supplying a cooling medium to the main plate 58, such as through a cooling tube 78.

[0055] Referring back to Figures 1A to 1B and 2A to 2B, the contour surface of the main cavity can have the shape of a stopper 10,110 having a main body 18,118 defining an open rear end 22,122 and a closed front or distal end 20,120, and cylindrical side walls 24,124 extending between the open rear end 22,122 and the closed front or distal end 20,120. According to one embodiment, the shape of the contour surface is configured to form a plurality of annular ribs 12,112 extending radially outward around the main body 18,118 and spaced apart axially along the main body 18,118. It can be understood that the main cavity may have other contour surfaces for manufacturing other products and / or for manufacturing stoppers 10,110 having different shapes.

[0056] According to one embodiment, the bottom plate 60 may have a flat surface configured to form a stopper 110 having a flat surface 121 at its distal end 120, as shown in Figures 2A and 2B. According to another embodiment, the bottom plate 60 may include a contoured surface configured to form a stopper 10 having a distal end 20, as shown in Figures 1A and 1B. The overall shape of the stopper in Figures 1A and 1B will be described later in the explanation of Figures 7A to 7G. However, the bottom plate 60 has a contour surface configured to manufacture a stopper having a distal end 20 having a shape that includes a flat portion 26 extending inward from the outer edge 28 of the closed front or distal end 20 of the stopper 10 and a projection 30 extending from the closed front or distal end 20, wherein the projection 30 defines the base 32 so as to intersect with the closed front or distal end 20 of the stopper and includes an inclined portion 34 extending upward from the flat portion 26 at the top of the closed front or distal end 20 to the projection 30. The inclined portion 34 will be described in more detail below in relation to Figure 7B. This projection is configured to cooperate within the syringe barrel 16 to reduce dead space during injection. It can be understood that the bottom plate 60 may have other designs to make stoppers with various shapes at its distal end.

[0057] The method may further include the step of providing a film such as a barrier film 14,114 between the bottom plate 60 and the main plate 58, so that when the mold assembly 52 is closed, the film 14,114 is sandwiched between the bottom plate 60 and the main plate 58, and when the device is removed from the mold assembly 52, the film 14,114 is fixed to the device in which it is molded. It can be understood that the barrier film 14,114 may be a known film that provides a low friction barrier between the stopper 10,110 and the pharmaceutical composition (e.g., drug, medicine, or other therapeutic material) in the syringe barrel 16, thereby preventing the material from leaching out of the stopper 10,110 or the extraction of compounds from the pharmaceutical composition by the stopper 10,110.

[0058] Referring to Figures 6A and 6B, this method further includes the step of trimming and removing excess film 14,114 from the molding apparatus 10,110. This trimming step can be performed in a trim mold 84. According to one design, the trim mold can consist of a flat punch 86 for removing the excess film 14,114. The trim mold 84 includes a punch center having an opening 88 through which clean air can pass to remove the trimmed part from the mold block 85. The flat punch 86 has a plane 87 for removing the excess film 14,114. The central part 90 of the punch 86 is deep enough to allow for repeated sharpening, and is more cost-effective than using a mold punch 86 with a razor edge (used when the stopper does not have a flat section and a conical slope begins from the edge of the stopper and the upper rib). The razor edge wears out quickly, requiring the punches to be sharpened individually, which is costly. However, it can be understood that other types of molds with other types of cutting edges, such as razor edges, and / or other types of trimming devices can be used to remove excess film.

[0059] Continuing with reference to Figures 1A and 1B, and further to Figures 7A through 7G, one type of stopper 10 that can be manufactured using the injection molding system 50 of the present disclosure is shown. The stopper 10 is adapted to be mounted on the mounting end 17 of a plunger rod used within a syringe barrel 16, as shown in Figures 9A through 9B.

[0060] As described above, the stopper 10 consists of an open rear end 22, a closed front or distal end 20, and a main body 18 defining a cylindrical side wall 24 extending between the open rear end and the closed front or distal end 20. A barrier film 14 (not shown in Figures 7A to 7G) may be provided at least adjacent to the closed front or distal end 20. The open rear end 22 is adapted to receive the mounting end 17 of the front end of the plunger rod. The stopper 10 further includes at least one rib 12 extending radially outward around the outer circumference of the main body. At least one rib 12 is configured to form an active seal with the syringe barrel 16. Ribs 12 extending in annular or circumferential direction are intended to provide a stable liquid-tight seal between the stopper body and the syringe barrel. It can be understood that one or more ribs may be provided. In the embodiments disclosed in Figures 7A to 7G, the main body 18 may include first, second, and third ribs 12a, 12b, and 12c that extend radially outward from the outer circumference of the main body and are spaced apart in the axial direction along the main body 18.

[0061] The ribs 12 include a recess 13 between them, and the ribs 12 have an outer diameter larger than the outer diameter of the recess 13. The ribs 12 can have a curved shape when viewed from the distal end of the stopper body 10. It can be understood that other embodiments of the stopper, including those having smooth cylindrical sides, can be formed using the molding system 50 of this disclosure.

[0062] A cavity 35 is formed at the open rear end 22 of the stopper 10, configured to receive the front mounting end 17 of the plunger rod. According to the embodiment shown in Figures 7A to 7G, the cavity 35 includes a thread 36 configured to cooperate with the thread 17a of the front mounting end 17 of the plunger rod, as shown in Figures 9A and 9B. There are many ways in which the plunger rod can be coupled to the stoppers 10, 110, and it can be understood that the thread arrangement is an example of many possibilities. For example, the cavity 35 of the stopper 10 may have a reduced diameter or neck at the proximal end of the cavity 35 and / or at the open rear end 22 of the stopper 10. According to one arrangement, the cavity 35 may be shaped to receive the tip or projection 30 of the distal end or front mounting end 17 of a plunger rod having an enlarged distal end, so that the parts can be assembled in a snap-fit ​​arrangement. In another embodiment, the stopper 10 is attached to the mounting end 17 of the plunger rod with adhesive, or molded together with it.

[0063] Continuing with reference to Figures 7A to 7G, a flat portion 26 is provided on the upper outer edge surface of the closed front or distal end 20 of the stopper 10 adjacent to at least one rib 12. The flat portion 26 extends inward from the outer edge 28 of the stopper 10. According to one embodiment, the flat portion 26 can be about 0.75 to 1 mm wide, extending to the starting point of an upward slope 34 that forms a conical projection 30 with its apex at the top of the closed front or distal end 20 of the stopper 10. The projection 30 defines a base 32 so as to intersect with the closed front or distal end 20 of the stopper 10 and extends from the flat portion 26 to the top of the closed front or distal end 20. The base 32 has a base diameter "BD" smaller than the outer diameter "OD" of the closed front or distal end 20 of the stopper 10, and the projection 30 has a profile configured to cooperate with the inner surface 40 of the syringe barrel, as shown in Figures 9A and 9B, thereby reducing dead space during injection.

[0064] In particular, referring to Figures 7B, 7E, and 7F, the stopper 10 of this disclosure can be designed such that the second rib 12b has a slightly smaller diameter (up to 4% to 15%) than the other ribs 12a and 12c, in order to reduce the sliding force of the stopper while maintaining a seal. The rib radius at the apex of the second rib 12b can be approximately 0.45 to 0.65 mm, depending on the diameter of the barrel, resulting in a lower sliding force. A plunger rod cavity projection 42 can be provided at the bottom of the cavity 35 of the stopper 10. This cavity projection 42 is designed to lightly engage with the front mounting end 17 of the plunger rod, first pulling the front rib 12a and quickly increasing the force transmitted to the front of the stopper (compared to transmitting axial load through the threads) in order to make it easier to remove the stopper 10 (reducing the initial removal force). The side wall 42a of the projection 42 is at a steep angle, such as approximately 60°, with respect to a vertical line extending through the tip of the stopper 10, so that the initial contact with the front mounting end 17 of the plunger rod is light, but the force quickly increases. Continuing to refer to Figure 7B, the thickness between the roof profile splines AA-BB and the internal roof projection LL can monotonically decrease and protrude upward to point XX. Point XX can be located between 0.25 and 0.75 mm within the thickness of the stopper wall defined by YY. This special design prevents the roof from buckling downward at the location of the stopper with a thin cross-section and prevents wrinkles in the barrier film 14.

[0065] As shown in Figure 7G, the pitch of the stopper threads can be variable and not constant, increasing toward the rear end or proximal face 22 of the stopper and / or toward the bottom of the plunger rod cavity 35. This initially applies more pressure to the front of the stopper 10, concentrating the applied thumb force on the plunger rod and loosening the first rib 12a of the stopper. This also results in the stopper rib being pulled and sequentially detaching from the container wall, instead of a pusher acting on the rear end or proximal face 22 of the stopper 10. For example, as shown in Figure 7G, the first pitch L1 can be shorter in length than the second pitch L2. According to one embodiment, the pitch can advance from L2 to L1 in the range of 2.1 mm to 1.4 mm. For example, the pitch from L2 to L1 can be reduced by about 2 turns, with L2 being about 1.73 mm and L1 being about 1.57 mm.

[0066] Figure 8 shows a stopper 10 fixed to the mounting end 17 of a plunger rod, which can be manufactured using the 4-plate injection molding system 50 of the present invention. It can be understood that this stopper 10 can be formed with or without barrier films 14,114. Figures 9A and 9B show the interaction of the stopper design of Figure 8 in the syringe barrel 16 after assembly and after applying 10 lbf (pounds of force) or 44.5 N to the plunger rod. Figure 8 is a similar design to the stopper 10 in Figures 7A to 7G. As shown in Figure 9B, these stoppers minimize dead space in the syringe barrel 16 after applying 10 lbf (44.5 N) to the plunger rod.

[0067] Referring to Figures 10A and 10B, it was found that the stopper 10 in Figure 10A, which has a conical head or conical projection 30 at its distal end 20, significantly reduces the dead space at the end of injection compared to the stopper 110 in Figure 10B, which has a flat surface or flat head 121 at its distal end 120. The dead space is the space between the distal ends 20 and 120 of the stoppers 10 and 110 and the inner surfaces 40 and 140 of the distal ends of the syringe barrels 16 and 116, where the drug or medication is trapped. This trapped drug is often called dead volume, represented as 41 in Figure 10A and 141 in Figure 10B. This dead volume 41 and 141 remains in the syringe at the end of injection and cannot be injected, no matter how much force is applied to the plunger rod at the end of injection. The flat-headed stopper 110 shown in Figures 2A to 2B and Figure 10B is generally used in filled syringes with a size range of 1 ml to 3 ml. However, finite element analysis (FEA) was performed to compare the dead volume 41 of the cone-head stopper 10 in Figures 1A to 1B and 10A with the dead volume 141 of the flat-head stopper 110 in Figures 2A to 2B and 10B. The results of this analysis are shown in Table 1 below. Normally, the force acting on a stopper is between 10 and 25 N, but Table 1 also shows values ​​that exceed this typical range (44.5 N) and values ​​that fall below it (8.9 N).

[0068] [Table 1]

[0069] As can be seen from Table 1, the dead volume 41 of the conical stopper 10 is approximately 4.5 mm 3 Therefore, the dead volume of 141 is approximately 11.5 mm 3 From 18.2mm 3 It is considerably smaller than the flat-head stopper 110, which is within the same range.

[0070] Next, refer to Figure 11, which shows a design of the stopper including a fourth rib 12d provided on the base 23 of the stopper 10. This design includes a thicker front portion 46 than the designs in Figures 7A to 7G. This thicker front portion 46 helps to reduce buckling of the stopper 10. This particular design, similar to the designs in Figures 7A to 7G, includes a distal end 20 in the shape of a flat portion 26 extending inward from the outer edge 28 of the closed front or distal end 20 of the stopper 10, and a projection 30 extending from the closed front or distal end 20, the projection 30 defining the base 32 so as to intersect with the closed front or distal end 20 of the stopper, and including an inclined portion 34 extending upward from the flat portion 26 at the top of the closed front or distal end 20 to the projection 30. As described above in relation to Figure 10A, the projection 30 is configured to cooperate within the syringe barrel 16 to reduce dead space during injection.

[0071] While this disclosure has been described as having exemplary designs, it can be further modified within its spirit and scope. Therefore, this application is intended to encompass any variations, uses, or adaptations of this disclosure using its general principles. Furthermore, this application is intended to cover any deviations from this disclosure that fall within the scope of the appended claims, provided that such deviations are within the scope of known or customary practices in the relevant art.

Claims

1. A stopper suitable for mounting to a plunger rod for use inside a syringe barrel, A main body defining an open rear end, a closed front end, and a cylindrical side wall extending between the open rear end and the closed front end, wherein the open rear end is adapted to receive the mounting portion of the front end of the plunger rod, A barrier film positioned adjacent to the closed front end, At least one rib extending radially outward from the outer circumference of the main body, configured to form an active seal with the syringe barrel, On the upper outer edge surface of the closed front end, there is a flat portion adjacent to at least one rib, the flat portion extending inward from the outer edge of the stopper, A projection extending from the closed front end, wherein the projection defines a base that intersects the closed front end of the stopper, extends from the flat portion to the upper part of the closed front end, the base has a base diameter smaller than the outer diameter of the distal end of the stopper, and the projection has a profile configured to cooperate with the inner surface of the syringe barrel to reduce dead space during injection, A stopper equipped with this feature.

2. The stopper according to claim 1, wherein the thickness between the roof profile spline AA-BB and the internal roof projection LL is monotonically decreasing and protrudes upward to point XX.

3. The stopper according to claim 1, wherein point XX is within a range of 0.25 to 0.75 mm within the thickness of the stopper wall defined by YY.

4. The stopper according to claim 1, wherein the open rear end of the stopper includes a mounting end for the plunger rod and a cavity having a series of threads for screw mounting, the threads having a pitch that decreases toward the bottom of the plunger rod cavity.

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