RU2784650C2 - Low-force plug for use in injector - Google Patents

Abstract

FIELD: medical equipment.

SUBSTANCE: invention relates to medical equipment, namely to injectors for the injection of a pharmaceutical composition. The injector comprises cylinder (22) having inner wall (23), piston rod (10), and plug (1) having case (2), which has working surface (3) opposite to outlet surface (4), an axial length between working surface (3) and outlet surface (4), and a transverse diameter. Moreover, in the axial location from working surface (3), specified plug (1) contains deformable sealing element (5) made of thermoplastic elastomer (TPE), wherein deformable sealing element (5) surrounds case (2) of the plug and has an outer diameter exceeding the specified transverse diameter, while the axial extent of deformable sealing element (5) is from 5% to 95% of the axial length of case (2) of the plug, while deformable sealing element (5) provides sealing of an annular gap between case (2) of the plug and inner wall (23) of cylinder (22). Moreover, in the specified axial location of deformable sealing element (5), plug (1) has cavity (6), where an axial length of cavity (6) is from 5% to 50% of the axial length of case (2) of the plug. Moreover, case (2) of the plug has a tubular part for accommodation of piston rod (10) in an access diameter, and cavity (6) is formed at an interface between case (2) of the plug and piston rod (10) and/or at an interface between deformable sealing element (5) and piston rod (10), and a transverse length of specified cavity (6) is at least 50% of an outer diameter of deformable sealing element (5) and greater than the specified access diameter. Alternatively, in the specified axial location of deformable sealing element (5), plug (1) has cavity (6), where the axial length of cavity (6) is from 5% to 50% of the axial length of case (2) of the plug. Moreover, cavity (6) is a partial cavity, the transverse length of which is at least 50% of the outer diameter of deformable sealing element (5), and which has a hole facing working surface (3) of plug (1), or a hole facing outlet surface (4) of plug (1).

EFFECT: obtainment of an injector.

17 cl, 17 dwg, 6 tbl

Description

FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

The present invention relates to an injector plug as well as an injector having a reduced shear force (RS). The plug contains a deformable thermoplastic elastomer (TPE) sealing element, and the injector contains a cylinder extending along the longitudinal axis and having an inner wall, an outer wall and an outlet at the outlet end opposite the drive end. The injector of the present invention provides a reduced SOS and is particularly suitable for injectors pre-filled with long shelf life pharmaceutical compositions.

BACKGROUND OF THE INVENTION

Typically, a drug injector comprises a piston in a barrel such that the piston can be pushed from one end of the barrel to the other end, thereby expelling the liquid contained in the barrel. In this case, the piston in the cylinder is adjacent to the inner wall of the cylinder, and at the point of contact between the piston and the inner wall, static friction and dynamic friction will take place. To move the piston in the cylinder requires the application of a force sufficient to overcome first the static friction and then the dynamic friction. Static friction exceeds dynamic friction, and as a result, the force that provides the initial movement of the piston exceeds the force required to ensure stable movement of the piston. In the event that the piston movement stops, the force providing the initial movement must be overcome again. Typically, the inner wall of the barrel is lubricated to keep the dynamic friction low enough to allow sufficient sliding of the plunger and easy movement of the plunger in the barrel and thus easy administration of the drug formulation during injection. In the context of pharmaceutical injectors, said static friction is often referred to as "shear force" (S), while dynamic friction is commonly referred to as "sliding friction force". Dynamic friction may also be referred to as "extrusion force" or "average force". When creating injectors that are convenient and easy to use, it is necessary to strive to create injectors that have low SOS values. A low SV is especially important at the start of injections.

The SV depends on several factors, but is particularly sensitive to the increased duration of interaction between the sealing element(s) of the piston and the inner wall of the syringe. Unlike conventional syringes, which fill and empty in a few minutes, pre-filled syringes are stored for a longer time, which causes the sealing element(s) to tend to adhere to the inner wall of the syringe, also known as the “sticking effect”, which increases with time and further increases due to adverse environmental conditions such as high temperature, humidity, and other similar conditions.

DR is particularly important with pre-filled syringes, as these syringes have a shelf life of up to three years. Usually, the problem related to high SOS is solved by lubricating the plunger and/or the inner wall of the syringe. However, tests have shown that silicone lubricant often has the adverse effect of causing protein aggregation in liquid drug formulations for injection, rendering the formulations ineffective, spoiled, or even harmful to the patient being injected. For example, although silicone is a natural lubricant and has been used successfully for decades to lubricate conventional syringes, there are certain dosage forms in which silicone lubricant poses a serious threat to patient health, such as drugs used in the treatment of various forms of macular degeneration and diabetic macular edema, diabetic retinopathy and myopic choroidal neovascularization. These types of drugs are antibodies to vascular endothelial growth factor (vascular endothelial growth factor inhibitor). Moreover, these drugs are administered by injection into the eye and are delivered to the doctor in small ampoules, the solution having to be withdrawn from the ampule with a syringe (unless a pre-filled syringe is used). In this case, the needle is replaced with a thinner needle designed for injection into the eye. Due to the lubrication of the syringe component(s), silicone from the syringe may enter the solution, resulting in drops/particles of silicone being injected into the patient's eye. If this happens, the silicone particles can impair a person's vision and seriously impair the quality of daily life. In addition, in connection with ophthalmic injections, silicone lubricant tends to remain in the eye, which in itself is already undesirable.

Insulin, heparin, and other dosage forms requiring subcutaneous or intradermal injection represent another large area of injection practice in which the presence of silicone lubricant poses a health risk to the patient, since it is well known that frequent injections performed daily in the area of the same injection sites cause the patient to develop scar tissue at that site due to the presence of silicone in each injection.

US is even more critical with glass syringes, especially pre-filled syringes, because their containers, unlike precision molded plastic containers, are manufactured to much higher tolerances, which results in pistons either too tight or not tight enough. requiring the use of lubrication. With regard to the inner diameter of the most common glass syringes, the inner diameter of the container can vary by up to ±2/10 mm, depending on the size of the syringe container, resulting in a total variation of up to 0.4 mm from one container to another, which is has a significant effect on the friction between the piston and the inner wall of the container, and therefore on the CA, and since sealing is absolutely necessary to meet container seal integrity (CIT) standards, the outer diameter of existing pistons for glass containers must be significantly larger than the corresponding container diameter on the underside .

The best pistons known in the art typically have an SOS of 8 N to 14 N and average sliding friction forces of 6 N to 8 N when measured in unlubricated 1 ml borosilicate glass containers, obtained by testing with various liquid formulations. The indicated ranges can be attributed to the difference in tolerances for the inner diameter (ID) of the container, which for glass containers can vary within ± 0.1 mm.

There are several approaches in the prior art to address various issues related to overall user comfort in the use of syringes, or to address other more specific issues.

Some manufacturers in the industry have tried to avoid the addition of silicone lubricants and instead have implemented other solutions with various sintering surfaces or other similar features that are supposed to reduce the force required to initiate piston movement. Numerous proposals are known in the art to address the problem of reducing SOS, and typically these involve modifications to the lubricant, such as how the lubricant is applied, or changing the type of lubricant, such as in terms of viscosity. Alternatively, patent document WO 2014/194918 proposes the possibility of controlling the US using special piston designs. Another alternative solution is disclosed in WO 2017/157396.

EP 2703025 describes a syringe liner laminated with an inert resin film. This gasket is made of chlorobutyl rubber with a fluorine rubber film. It is assumed that the gasket has a cavity to reduce its resistance to slip.

Further improvements are likely to be possible, and it is an object of the present invention to provide an injector plug that provides a reduced SOS in the injector.

SUMMARY OF THE INVENTION

The present invention relates to a stopper for an injector intended for the administration of a pharmaceutical composition, said stopper having a body having a working surface opposite to the outlet surface, an axial length between the working surface and the outlet surface, and a transverse diameter, the body of the stopper forming an access diameter,

the plug at an axial location from the working surface contains a deformable sealing element that surrounds the body of the plug and has an outer diameter greater than the transverse diameter, and the deformable sealing element is made of thermoplastic elastomer (TPE) and has an axial extent in the range from 5% to 95% of the axial the length of the cork body, and

the plug in the axial location of the deformable sealing element has a cavity, the lateral extent of which is greater than the access diameter of the plug body.

The proposed plug has a cavity, and the location of the specified cavity partially coincides with the location of the deformable sealing element. Document EP 2703025 proposes a syringe liner which has a cavity formed at the top of a screw element located on the front circular rib of the liner. The cavity described in EP 2703025 is believed to provide a reduction in the slip resistance of the gasket. However, the present inventor has found that if the cavity proposed in EP 2703025 is made in a plug having a deformable seal made of TPE, this cavity has no effect on the shear force (SOS). The inventor of the present invention unexpectedly found that the presence of a cavity formed at the location of the deformable sealing element made according to the present invention, that is, when the axial location of the deformable sealing element and the cavity overlap, and when the diameter of the cavity is larger than the access diameter of the plug body, the SV required to move cork in the injector is reduced compared to a cork that does not have such a cavity. In particular, the SOS has been reduced to a level where the plug can be used without external lubrication, as well as without a resin-based coating, such as a fluorine rubber coating, applied to the surface of the deformable sealing element. Thus, an injector with a stopper according to the present invention will provide a smoother operating experience for the end user compared to a stopper without said cavity. The cork body has an access diameter. In the context of this invention, the term "access diameter" refers to the diameter of a piston rod suitable for use with a plug when inserted into an injector barrel.

Experiments carried out by the present inventor show that the external force exerted by the known stopper through its sealing element on the inner wall of the container is usually significantly greater than the force necessary to ensure sufficient tightness during storage and subsequent injection to the patient. Sealing capacity, also known as container seal integrity (CIT), is a parameter that must be especially considered when designing any injection system. However, the present invention shows that it is possible to eliminate excess force while maintaining the desired degree of CHA.

According to the present invention, the problem of reducing the excessive and undesirable forces exerted by the plug through the deformable sealing element towards the inner wall of the container can be solved by the design of the plug according to the present invention. Through the use of the proposed plug, static and unwanted forces applied to the inner wall of the container are significantly reduced, which significantly improves the performance of the entire injection system.

The plug has a body and a deformable sealing element. The diameter of the deformable sealing element is larger than the transverse diameter of the plug body. The stopper is intended for an injector providing the introduction of a pharmaceutical composition, and such an injector contains a cylinder having an inner wall and an inner diameter. The diameter of the deformable sealing element is greater than the inner diameter of the cylinder in which said plug is used. When the plug is inserted into the injector barrel, the deformable sealing member seals the annular gap formed between the plug body and the inner wall of the barrel. As a rule, the plug body is not in direct contact with the inner wall of the cylinder. Thus, the plug body and the deformable sealing element can be made from the same material or from different materials, or the plug body itself can be made from different materials. It can be considered that the cork sections that are not in contact with the inner wall of the cylinder are the cork body, and the cork sections that are in contact with the inner wall of the cylinder are a deformable sealing element. In a specific embodiment, the plug contains two or more deformable sealing elements, which may have cavities in their respective locations. For example, the plug may contain a first deformable sealing element located at a first axial location from the working surface, and a cavity located at the specified first axial location, as well as a second deformable sealing element located at a second axial location from the working surface, and a second cavity located at the specified second axial location. If the plug contains two or more deformable sealing elements, the distance between the deformable sealing elements is typically between 50% and 80% of the axial length of the plug, for example, said distance is from 1 mm to 6 mm, for example, about 5 mm. If the plug contains two or more deformable sealing elements made with cavities, the cavities may be separated, or the same cavity may extend from the first axial location to the second axial location, so that the deformable sealing elements can be said to "share" the cavity . Thus, the plug may include a first deformable sealing element located at a first axial location from the working surface, a second deformable sealing element located at a second axial location from the working surface, and a cavity extending between the first axial location and the second axial location. In a particular embodiment, the plug comprises a toroidal cavity extending between the first axial location of the first deformable sealing element and the second axial location of the second deformable sealing element. When several deformable sealing elements have a common cavity, the manufacture of a plug is simplified compared to a plug having several separate cavities. In addition, having two or more deformable sealing elements provides improved CHA control, while the plug also has a low SOS after insertion into the injector barrel, which is especially true for a pre-filled injector, since leakage is prevented over long periods of time, for example, over a week.

The plug, namely the plug body and the deformable sealing element, can be made from any suitable material. In particular, the deformable sealing element must have adequate elasticity in order to seal the annulus when inserted into the injector barrel. For example, the cork, such as the cork body, or the cork body and deformable sealing member can be made from a flexible polymer such as TPE. In a particular embodiment, the plug is injection molded from TPE, for example, a styrenic block copolymer (SBC) such as SBC selected from the group consisting of hydrogenated SBC or non-hydrogenated SBS, or alloys thereof. It is particularly preferred if the plug, including the body and the deformable sealing element, is injection molded from TPE in one piece. A particularly preferred material for the deformable sealing element, and in particular for the deformable sealing element and the body of the plug, molded in one piece, is TPE having a Shore A hardness of 30 to 90, and even more preferred is the hardness Shore A in the range of 50 to 90, e.g. 60 to 80. If the deformable sealing element is a TPE with a hardness of Shore A corresponding to the range of 30 to 90, then the effect of the cavity on the decrease in SOS is so pronounced that a plug can be used without external lubrication. In this context, an external lubricant includes a lubricant of any kind, in particular silicone oils, silicone thermally applied to the inside surface of the injector barrel, perfluoropolymers or other layered polymers applied either to the surface of the plug or to the inside of the injector barrel. Thus, the TPE material of the deformable sealing member will be in direct contact with the inner surface of the injector barrel after insertion of the plug into the barrel. In particular, the inventor of the present invention noted that an injector with a stopper made according to the present invention with a deformable sealing element made of TPE can be used with a pharmaceutical composition that does not contain lubricating ingredients. However, the SOS will be reduced regardless of the presence of lubrication, and in particular if the deformable seal is made of materials other than TPE, such as butyl rubber, the plugged injector may also contain lubrication.

Any TPE can be used for the proposed stopper, for example for the deformable sealing element as well as for the body of the stopper. Suitable TPE materials include various SBCs, for example, hydrogenated - H-SBC - (SEBS - styrene-ethylene-butadiene-styrene block copolymer or the like) or non-hydrogenated (SBS - styrene-butadiene-styrene block copolymer) or alloys of these and other compatible polymers, such as SOC (cycloolefin copolymer) elastomers, or styrene-butadiene block copolymer (SB), styrene-isoprene-styrene (SIS) block copolymer, styrene-isoprene-butadiene-styrene (SIBS) block copolymer, styrene-ethylene-ethylene/propylene-styrene (SEEPS) ) block copolymer or alloys based on any of these compounds. Preferred SBCs are those known under the trademark "Evoprene" sold by AlphaGary Corporation (USA, Massachusetts, City of Leominster) and from Mexichem Specialty Compound Ltd. Evoprene materials are described in the brochure "EVOPRENE™ Thermoplastic Elastomer (TPE) Compounds - GENERAL INFORMATION") (published by AlphaGary Corporation in July 2007), and preferred Euorgepe™ polymers are Evoprene™ Super G, Evoprene™ G, Evoprene™ GC and Evoprene™ HP, which are described in their respective EVOPRENE™ SUPER G Thermoplastic Elastomer (TPE) Compounds brochures. ™ SUPER G), EVOPRENE™ G Thermoplastic Elastomer (TPE) Compounds)) (EVOPRENE™ G Thermoplastic Elastomer (TPE) Compounds), (EVOPRENE™ GC))), and EVOPRENE™ HP Thermoplastic Elastomer (TPE) Compounds)) (published by AlphaGary Corporation in July 2007) . The contents of all referenced brochures from AlphaGary are incorporated herein by reference. Other suitable elastomers include COS elastomers such as TOPAS® Elastomer E-140. The TPE can be selected based on gas permeability properties, for example with respect to oxygen, and it is generally preferred (especially for a stopper used in a pre-filled syringe) that the gas permeability is as low as possible. SIBS thermoplastic elastomers generally have very low gas permeability and are therefore suitable for making pre-filled syringe stoppers.

When injection molded, the cork can be made to tighter tolerances than technologies such as vulcanization, which are typically used to make traditional rubber pistons, such as bromobutyl or chlorobutyl rubber pistons, allow. However, the manufacture of cork is not limited to thermoplastic elastomers, and other suitable materials include elastomers such as rubbers, such as natural rubber, synthetic rubber (polyisoprene rubber, butyl rubber), silicone rubber, and the like, which can be evaluated, for example, by a Shore durometer indicating the elasticity of the elastomeric material and measuring its hardness, and the higher the durometer reading, the harder the connection. For example, in one embodiment of the invention, a plug, for example, containing a deformable sealing element, has a Shore hardness (A scale) in the range from 30 to 90, for example, from 50 to 90, preferably from 60 to 80, more preferably from 70 to 76. The terms "Shore hardness" and "Shore durometer" may be used interchangeably. As a rule, a deformable sealing element is homogeneous and throughout its volume consists of the same material, which has a Shore hardness (A scale) in given ranges. By using a material having a Shore A hardness corresponding to the above range, a relatively hard elastomeric material is provided. It should be noted that the Shore durometer (A scale) refers to only one of the many ways to determine the properties of the selected material, and that other studies can be used to determine the properties of the material. The measurement of Shore hardness (A scale) is well known to those skilled in the art and, in particular, Shore hardness (A scale) is usually recorded in accordance with ISO 868.

Table 1 lists exemplary thermoplastic elastomers (TPEs) and their Shore A hardness.

TPE can also be characterized by the value of compression set, which corresponds to the deformation remaining after removal of the force applied to the elastomer (and is usually expressed in %). The compressive set value is usually recorded over a certain period of time, for example, from 18 to 96 hours or from 22 to 72 hours, and at a certain temperature, for example, in accordance with ISO 815. In the context of the present invention, compressive set is usually recorded at "ambient temperature", for example, in the range from 10°C to 40°C. However, the temperature range can also be outside the ambient temperature, for example, ranging from 23°C to 100°C. As a rule, the higher the temperature, the shorter the time required to register the compression set. The compression set should be as low as possible, but for a cork or cork part according to the present invention, the compression set may be in the range of 15% to 40%, for example at ambient temperature. At higher temperatures, eg 100° C., the compression set will typically be higher, eg up to 50%. However, at ambient temperature, the compression set is preferably in the range of 10% to 40%. The amount of compression set is generally of concern for pre-filled injectors in which the plug is inserted into the barrel and therefore compressed when the pre-filled injector is stored for an extended period of time. If the cork, for example the cork body as well as the deformable sealing element, has a Shore A hardness in the range of 30 to 90 units, for example 50 to 90, and a compression set value of at least 25%, for example, from 25% to 35%, then the SV of a pre-filled injector made according to this invention will decrease during storage, for example, for at least 5 days, so that the stopper according to the invention is particularly suitable for a pre-filled injector. As long as the compression set is less than 40% at ambient temperature, the integrity of the container seal (CSH) is assured.

If the deformable sealing element is not deformed, for example, when the stopper is not inserted into the injector, said element is considered to be in a "non-stressed state", for example, in a state without deformation. The cork body material need not be elastic, and any material can be chosen for the cork body. In one embodiment, the material of the plug body is different from the material of the deformable sealing element. In another embodiment, the material of the plug body is the same as the material of the deformable sealing element. For example, the stopper, ie the body of the stopper and the deformable sealing element, may be injection molded as a single unit.

In the context of the present invention, the expression "deformable sealing element" can describe any section of the cork, the diameter of which is greater than the transverse diameter of the body of the cork. In the context of this invention, the term "diameter" does not imply that the corresponding element, for example, the cork body or deformable sealing element, must have a circular cross section, that is, a cross section in the diametral plane of the plug, and for the cork body and / or deformable seal may cross section of any desired shape can be used. For example, the cross section may be polygonal, such as triangular, square, pentagonal, hexagonal, etc., and in this case, the term "diameter" refers to the size of the cross section, for example, the largest cross-sectional dimension for the corresponding cross-sectional shape. The polygonal cross section is not limited to polygons having equal angles and side lengths, that is, regular polygons, and likewise the cross section can also be elliptical. The cross-sectional shape of the injector cylinder corresponds to the cross-sectional shape of the deformable sealing element. The plug body does not interact with the inner wall of the cylinder, and the cross-sectional shape of the plug body can be chosen arbitrarily, regardless of the cross-sectional shape of the deformable sealing element.

The proposed plug has a deformable sealing element, which, when the plug is inserted into the cylinder, abuts against the inner wall of the cylinder along the boundary surface of the abutment and seals the annular gap between the cork body and the inner wall of the container, and the axial dimensions of the boundary surface of the abutment and the deformable sealing element are parallel to the longitudinal axis. The deformable sealing element is located at an axial location from the working surface, and the cavity is also located at the specified axial location. Therefore, it can be considered that the cavity is located in the same place as the deformable sealing element, and it can also be called "the cavity of the sealing element", and it can be said that the location of the cavity is opposite to the deformable sealing element. Thus, at this location, the cavity reduces the force between the deformable sealing element and the inner wall of the container, providing a significant reduction in the force required to move the stopper, and allowing the complete elimination of any lubricants, including, but not limited to, any coating, any liquid lubricant and/ or thermally applied silicone between the sealing element and the inner wall of the container.

The deformable sealing element is preferably convex. In this context, the term "convex" means that a straight line drawn between any two points inside the deformable sealing element does not intersect the surface of the specified element. Any convex shape is possible, but the deformable sealing element preferably has a point, for example a point in the axial plane of the plug, corresponding to the maximum extent from the central axis of the plug. If the deformable sealing element has a convex surface, the force exerted by said element on the inner wall of the container will be maximum since the deformation of the sealing element in the direction of the longitudinal axis of the cylinder is minimal. The contact can take place, for example, along the boundary surface of the abutment between the deformable sealing element and the inner wall of the cylinder. Preferably, the degree of contact between the deformable sealing member and the inner wall of the injector barrel into which the plug is inserted is as small as possible. For example, when the proposed plug is inserted into the injector cylinder, a boundary abutment surface is formed on the inner wall of the cylinder, and for this surface, the ratio between the largest axial dimension of this surface and the largest axial dimension of the deformable sealing element is preferably in the range from 0.01 to 0.4, for example, 0.01 to 0.2, 0.01 to 0.15, 0.01 to 0.1, 0.01 to 0.05. For example, a convex deformable sealing element, i.e. in a relaxed state, may have an axial extent in the range of 5% to 25% of the axial length of the plug body, for example, an axial extent in the range of 0.5 mm to 2 mm, and an outer diameter in the range from 105% to 120% of the transverse diameter of the cork body. The deformable sealing element may further be characterized by angles formed between the plug body and the deformable sealing element, wherein said angles may be in the range of 120° to 160° when the convex deformable sealing element has an axial extent in the range of 5% to 25% of the axial tube body length. For example, the outer diameter may be in the range of 4.75 mm to 5.15 mm for a 0.5 ml injector having a cylinder with an inner diameter of 4.65 mm, the outer diameter may be in the range of 6.5 mm to 7 mm for a 1 ml injector having a barrel with an inner diameter of 6.35 mm, or the outer diameter can be in the range from 8.8 mm to 9.35 mm for a 2.25 ml injector having a barrel with an inner diameter of 8.65 mm . When the plug is inserted into the injector barrel, contact angles are formed between the inner wall of the barrel and the deformable sealing member. Thus, there will be formed a contact angle facing the working surface of the plug and a contact angle facing the exit surface of the plug, which angles may be called "working contact angle" and "discharge contact angle" respectively. In one embodiment, the operating angle of the contact is approximately equal to the release angle of the contact, although the operating angle may also be different from the release angle. For example, contact angles may range from 5° to 60°, such as from 15° to 45°. If the contact angles are in the range from 5° to 60°, the deformable sealing element will be convex even after the plug is inserted into the cylinder. This allows you to maximize the sealing effect of the deformable sealing element, which is especially important when the outer diameter of the specified element is 1.5 - 10% larger, for example, 2 - 5% larger than the inner diameter of the cylinder, since the integrity of the container sealing (CGC) is ensured . In one embodiment, the plug, i.e. the plug containing the deformable sealing element, is injection molded from TPE, and the deformable sealing element is convex and has an outer diameter that is 1.5-5% greater than the inner diameter of the cylinder when the plug is in an unstressed state. condition, and when the plug is inserted into the injector barrel, the operating contact angle and the outlet contact angle are, independently of each other, in the range of 5° to 45°.

The cork body has a working surface opposite to the outlet surface. Thus, the working surface and the outlet surface are located at opposite ends, that is, at opposite ends in the axial dimension of the cork body. It can also be said that the working surface is at the drive end of the cork body and the outlet surface is at the outlet end of the cork body. When inserted into the injector barrel, the outlet end of the plug body faces the outlet of the injector.

The deformable sealing element has an axial extent. The axial extension may be formed by the distance between the points at which the diameter of the deformable sealing element is greater than the diameter of the plug body. The axial extent of the deformable sealing element can be from 5% to 95% of the axial length of the cork body, and the specified deformable sealing element can be located anywhere in the cork body. In a preferred embodiment, the axial extent of the deformable sealing element is in the range of 20% to 50% of the axial length of the plug body.

The deformable sealing element is located at an axial location from the working surface of the plug body. The term "axial location" refers to a point, such as a point in the axial plane of the plug, defined by the axial extent of the deformable sealing element. In general, the axial location is the midpoint between the points where the diameter of the deformable sealing element is greater than the diameter of the plug body. However, according to an embodiment, the deformable sealing element is convex and has a point corresponding to the maximum extension from the central axis of the plug, for example, the maximum diameter of the deformable sealing element. If the deformable sealing element is convex and has a point corresponding to the maximum extension from the central axis of the plug, the axial location may be determined by the axial distance from the working surface to the point of maximum extension. Thus, if the deformable sealing element has a maximum extension, namely one maximum extension, from the central axis of the plug, for example, when the deformable sealing element is convex, the location of the maximum extension from the working surface is the axial location.

The plug has a cavity at the axial location of the deformable sealing element. In the context of this invention, the "cavity" contains a compressible material, for example a compressible fluid, in particular air or gas, surrounded by a plug material, optionally also including piston rod material. Thus, for example, the cavity can be enclosed, for example, completely located, in a deformable sealing element, for example, in the material of the specified element, or in the cork body, for example, in the material of the cork body. For example, the cavity may be a gas contained in the material of the deformable sealing element or the material of the plug body. In addition, the cavity may be a gas trapped in the cork body material. In other embodiments, the cavity is formed at the interface between the cork body and the deformable sealing element, for example, between the material of the cork body and the material of the deformable sealing element. In another embodiment, the cavity is formed at the interface between the material of the deformable sealing element and the piston rod, for example, the piston rod may include a plug body. In a specific embodiment, the cork body and the deformable sealing element are integrally formed from the same material, i.e. "cork material". In this embodiment, the cavity may be enclosed in the plug material, or the cavity may be formed at the interface between the plug material and the piston rod.

The cavity may be of any size, such as volume, and any shape. The cavity may be a single cavity or a cavity containing any number of smaller sub-cavities, for example, the cavity may be "foam". If the cavity contains smaller sub-cavities, the collection of sub-cavities is referred to as a single cavity containing sub-cavities in terms of size, shape and volume. The cavity may be a volume of air enclosed in the material of the plug or deformable sealing element and thus surrounded by the material of the plug and the material of the deformable sealing element. For example, the plug may be injection molded as a single piece, that is, a single piece containing the cork body and deformable sealing member, and air bubbles may be introduced during the injection molding process to form a cavity. In particular, the air pressure can be adjusted to the temperature during the injection molding process so that cooling of the stopper produced by said process results in the formation of appropriately sized cavities in the finished stopper.

The cavity, such as the cavity enclosed in the cork material, may be of any desired shape. For example, the cavity may be spherical, ellipsoidal, ovoid, or cylindrical. In specific embodiments, the cavity is spherical, ellipsoidal, ovoid, or cylindrical in shape and has a lateral extent, such as a diameter or major axis, located in the diametral plane of the plug. The cavity has a lateral extent, such as a transverse diameter. The lateral extension is greater than the access diameter of the cork body. The access diameter of the plug body is sufficient to accommodate the piston rod to drive the plug after it has been inserted into the injector barrel. The inventor of the present invention found that if the cavity had an extent, in particular a diameter, less than the access diameter of the plug body, the presence of the cavity had no effect on the VS of the plug, regardless of the presence of lubrication. However, if the transverse extent of the deformable sealing element was greater than the access diameter, the SOS value decreased to such an extent that the plug could be used without any lubricant, including a fluororubber coating on the deformable sealing element. The effect was observed both in the formation of a cylindrical cavity between the piston rod and the surface of the plug material, and in the formation of a toroidal cavity between the piston rod and the surface of the plug material, for example, the piston rod was completely inserted into the plug. The transverse diameter is preferably in the range of 50% to 65%, for example in the range of 60% to 65%, of the outer diameter of the deformable sealing element.

In a particular embodiment, the cavity has a generally toroidal shape, and in the diametral plane of the plug, the toroidal shape can also be characterized by a lateral extension, such as a transverse diameter or a transverse major axis. If the cavity is toroidal, the lateral extent refers to the extent without the core of the toroid. For example, the toroid may surround the plug body such that the core of the toroid matches the axial extent, eg, diameter, of the plug body, eg, access diameter. Typically, the plug body has a diameter in the range of 50% to 90% of the outer diameter of the deformable sealing element. The depth of the toroid, for example from the surface of the plug body, is typically 10% to 30% of the outer diameter of the deformable sealing element. The cavity, for example, a spherical, ellipsoidal, ovoid or cylindrical cavity, also has an axial extent in the axial direction of the plug, for example, an axial length, while the axial length can be from 5% to 95%, for example, from 5% to 50% or from 10% to 20% of the axial length of the cork body, for example when the cork is in a relaxed state.

In another embodiment, the cavity contains a compressible material such as a sponge or similar material. For example, a material, such as an elastic material, may have a mesh structure of regular or irregular shape, while the material is from 10% to 40% of the total volume of the structure. A plug having such a structure containing different materials, such as two materials, can be obtained by molding two components.

In a preferred embodiment, the plug, i.e. its body and deformable sealing element, is in its final form made in the form of a single piece of material. Such a material can be obtained by TPE injection molding. It is particularly preferred that the stopper is injection molded as a single piece in finished form, and is molded from TPE having a Shore A hardness of 30 to 90, such as 50 to 90, such as 70 to 90. This plug is suitable for an injector that does not contain lubricant, such as silicone lubricant.

In other embodiments, the cavity is formed at the interface between the plug elements or the plug elements and the piston rod. For example, the plug body may comprise a hard and rigid material, for example, the plug body may be a piston rod, in particular, the diameter of the piston rod may determine the access diameter of the plug body, and the deformable sealing element may be an o-ring with a notch along its inner diameter, so that after installing said ring on a plug body, such as a piston rod, a cavity will be formed in a recess between said ring and the plug body, thereby forming a toroidal-shaped cavity. In a particular embodiment, the body of the plug according to the invention is part of the piston rod or is the piston rod, and the deformable sealing element is a sealing ring made of TPE having a Shore A hardness of 30 to 90, wherein said the sealing ring has a recess along its inner diameter. The diameter of the part of the body of the plug, which is the piston rod, can be from 10% to 90%, for example, from 30% to 70% of the inner diameter of the injector corresponding to the plug made with the piston rod. The inner diameter of the sealing ring is smaller than the outer diameter of the part of the plug body that is the piston rod, so that the sealing ring is securely installed on the specified part, and after installing the said ring on the plug body, a cavity is formed between the plug body and the inner surface of the sealing ring, that is, in the recess in the form of a toroid. The surface of the part of the plug body, which is the piston rod, may have a groove that allows the sealing ring to be stably installed on the plug body. The O-ring material diameter may be from 0.2 mm to 2 mm, and the recess may have a depth in the range of 20% to 80%) of the specified O-ring diameter. In another embodiment, the piston rod contains two or more of the above-described sealing rings.

In another embodiment, the cork body has a cylindrical shape, for example, a cylindrical shape that determines the access diameter, and for the possibility of installation on the cork body, the deformable sealing element is made on a cylindrical structure, for example, on a “sleeve”, so that when installing the specified cylindrical structure on the body of the plug between the surface of the body of the plug and the inner surface of the cylindrical structure, a cavity will be formed. The cylindrical structure has an inner surface that may contain a recess at the axial location of the deformable sealing element, and/or the surface of the plug body may contain a recess at the axial location of the deformable sealing element. Thus, a toroidal cavity is formed in the recess or recesses between the plug body and the cylindrical structure. The "depth" of the toroid, i.e. the distance from the surface of the cork body to the surface of the cylindrical structure when it is installed on the cork body, as a rule, will be in the range from 10% to 30% of the outer diameter of the deformable sealing element. The cylindrical structure preferably contains two, three or more deformable sealing elements. The plug body may be part of the piston rod, the plug body being preferably made of a hard material such as a thermoplastic polymer. The plug body may have a transverse diameter ranging from 10% to 90%, for example 30% to 70%, of the inner diameter of the injector corresponding to the plug. The cylindrical structure is preferably made of an elastic material, for example, it can be injection molded from TPE, in particular from TPE having a Shore hardness (A scale) in the range from 30 to 90, for example, from 50 to 80.

The plug may have a tubular portion to accommodate the piston rod. The piston rod may include a plug body. The diameter of the tubular portion or the diameter of the piston rod generally forms the access diameter of the plug body. In this embodiment, the cavity may be formed, for example, in the form of a toroidal cavity, at the interface between the plug body, for example the piston rod, and the deformable sealing element. In a specific embodiment, the plug, including the deformable sealing element, is made as a single unit, for example, by injection molding, and the plug body has a tubular part to accommodate the piston rod. The cork material is preferably TPE, eg styrene block copolymer (SBC). The piston rod may be of any size and shape to enable said rod to be inserted into the tubular portion and actuated, for example, to push the plug. One end of the piston rod has an engagement section having an end platform and an outer surface forming an outer diameter. The tubular part has an inner surface forming an inner diameter, the size of which ensures the placement of the engagement area. The inner diameter of the tubular portion may be approximately equal to or less than the outer diameter of the engagement portion. In particular, if the inner diameter of the tubular portion is smaller than the outer diameter of the engagement portion, the plug material must be elastic, for example, the plug may be injection molded from TPE. Thus, insertion of the engagement portion into the tubular portion may form a cavity at the interface between the end platform of the engagement portion and the tubular portion and/or between the inner surface of the tubular portion and the outer surface of the engagement portion.

The tubular part extends from the working surface to the bottom of the tubular part, beyond the axial location of the deformable sealing element. Thus, when the piston rod is inserted into the tubular portion, a cavity can be formed in the axial position between the outer surface of the engagement portion and the inner surface of the tubular portion and/or between the end platform of the engagement portion and the bottom of the tubular portion. For example, the piston rod may be inserted into the tubular part such that the end pad is in contact with the bottom of the tubular part, and a toroidal cavity, for example enclosed, is formed between the outer surface of the engagement portion and the inner surface of the tubular part. In another embodiment, the piston rod is inserted into the tubular part in such a way that a cavity is formed between the end platform of the engagement section and the bottom of the tubular part, and this cavity may have a cylindrical or ellipsoidal shape. By adjusting the degree of insertion of the piston rod into the tubular portion, it is also possible to provide any combination of toroidal, cylindrical and ellipsoidal shapes.

In order to control the degree of insertion of the piston rod into the tubular portion, the piston rod may include a shoulder or the like. The shoulder may be of any desired shape, but typically the shoulder is adjacent to the engagement portion. Thus, it is possible to introduce the engagement section into the tubular part at a distance at which the cavity formed between the inner surface of the tubular part and the outer surface of the engagement section and/or between the end platform and the bottom of the tubular part has a predetermined size and shape. The shoulder may completely surround the piston rod, or the shoulder may comprise two, three or more elements extending from the central axis of the piston rod. Regardless of the shape of the ledge, its extent, for example the diameter, is less than the inner diameter of the injector barrel and greater than the inner diameter of the tubular part.

In particular embodiments, the tubular portion includes an engagement device designed to interact with the mating engagement device of the engagement area. The engagement device and the mating engagement device can be chosen arbitrarily, but the interaction of the engagement device with the associated engagement device allows the piston rod to both push and pull the plug, so that the injector having the plug and the piston rod can be filled and emptied by moving the piston into injector up and down respectively. In one embodiment, the engagement portion has an external thread, for example, a screwed external thread, and the tubular part, respectively, contains a mating internal thread, for example, a screwed internal thread; thus, said threads provide an engaging device and a mating engagement device, respectively. An internal screw thread has a larger and a smaller diameter, which together form a helix. The smaller diameter determines the access diameter of the plug body. If the engagement portion is externally threaded, the piston rod, especially the engagement portion, is preferably made of a non-elastic material, such as a thermoplastic polymer. The inner surface of the tubular part having a mating internal thread can also be made of a non-elastic material, such as a thermoplastic polymer. Here, since the external thread is made of a non-elastic material, the internal thread, in particular the tubular part or the tubular part and the deformable sealing element, can be made of an elastic material, in particular TPE.

If the cork body comprises a tubular part, the bottom of the tubular part may also contain additional structures, for example, to shape the cavity. For example, the bottom of the tubular portion may include a protrusion, the upper surface of which can be brought into contact with the end platform of the engagement portion, so that a cavity is formed between said protrusion surface and the inner surface of the tubular part. The protrusion can also be considered a hard part. The protrusion may be a cylindrical protrusion with a smaller diameter, for example the diameter that defines the access diameter, compared to the internal diameter of the tubular cavity, so that the resulting cavity has the form of a cylindrical shell. The protrusion may take other forms. For example, the protrusion may include additional structures positioned between said protrusion surface and the inner surface of the tubular part, so that when the engagement portion is inserted into the tubular part, several sub-cavities may be formed, for example, the cavity will be in the form of a discontinuous cylindrical shell. For example, the stopper may comprise a protrusion with two, three, four or more elements extending from the protrusion to the inner surface of the tubular portion, respectively forming two, three, four or more sub-cavities. If the bottom of the tubular part contains additional structures, the plug is preferably injection molded as a single piece containing a deformable element and a plug body having a tubular part, the bottom of which contains a protrusion.

The proposed plug has at least one deformable sealing element, while in the axial location of the specified at least one deformable sealing element, the plug has a cavity. However, the plug may also contain additional deformable sealing elements. If the plug has more than one sealing element, for example, two or three deformable sealing elements, each specified element is located in an axial location from the working surface. The plug may have one or more cavities, with at least one cavity located at the axial location of the deformable sealing element. For example, the plug may have a first deformable sealing element located at a first axial location from the working surface and a second deformable sealing element located at a second axial location from the working surface. The plug may have a first cavity located at a first axial location from the work surface, and optionally also a second cavity located at a second axial location from the work surface. In the context of this invention, the first axial location is, unless otherwise indicated, the axial location closest to the outlet surface of the cork body. Any embodiment of the cavity described above refers to the first axial location if the plug contains additional deformable sealing elements.

In one embodiment, the plug has a second deformable sealing element located at a second axial location from the working surface of the plug body and a second cavity located at the second axial location. The cork body may be solid and both cavities may be surrounded by cork body material. In a specific embodiment, the plug, in particular the plug, injection molded in one piece from TPE, contains a tubular portion extending from the working surface to the bottom of the tubular portion beyond the first and second axial locations of the deformable sealing elements. In this embodiment, the plug must be used with a piston rod having the engagement area described above. The first cavity, located at the first axial location, that is, at the axial location closest to the outlet surface of the plug body, may be of any size and shape as described above, and the second cavity is formed at the interface between the outer surface of the engagement portion and the inner surface of the tubular parts. Thus, the second cavity has a generally toroidal shape, while the first cavity may be toroidal, ellipsoidal, cylindrical, or a combination of these shapes. For this embodiment, the piston rod preferably has a shoulder, as described above.

In another embodiment, the plug body contains a working element and an outlet element, which are connected to each other by an elastic contour element. The elastic contour element may be of any design, but in a particular embodiment, the elastic contour element is shaped as a whole in the form of a ring. When a plug having a resilient contour element is inserted into the injector barrel and the plug operating element is ejected, the resilient contour element ejects the plug outlet, and when the plug operating element is pulled out, the resilient contour element pulls the plug outlet. Each of the plug elements, outlet and working, has a deformable sealing element, as described above, and the outlet element and the working element of the plug are located respectively in the first and second axial locations from the working surface of the plug body, and the plug has a first and, optionally, also a second cavity located respectively in the specified first and second axial locations. The diameters of the cavities, as a rule, independently of each other, are in the range from 50% to 65% of the outer diameter of the deformable sealing elements. The plug, including the outlet element and the working element, as well as the elastic contour element, is preferably injection molded as a single unit, for example, from TPE. Preferred materials for the plug operating element, the plug outlet and the resilient contouring element are TPE, eg SBC, eg SBC selected from the group consisting of hydrogenated SBC or non-hydrogenated SBS, or alloys thereof. In addition, the plug operating element, the plug outlet and the elastic contour element are preferably integrally injection molded from TPE. In one embodiment, the plug operating element, the plug outlet, the resilient contour or plug operating element, the plug outlet, and the elastic contour have a Shore A hardness in the range of 30 to 90, such as 50 to 90. the contour element has a Shore A hardness in the range of 50 to 90, in particular 70 to 90.

When a plug having an elastic contour element is introduced into the injector barrel, the deformable sealing elements of both the plug working element and the plug outlet element abut against the inner wall of the cylinder and seal the gap between the inner wall of the cylinder and the plug body, thereby creating a compressible area between said elements. . Typically, the elastic contour element has a volume fraction of 10% to 90%, e.g. unstressed) and the remainder of the volume may be occupied by a compressible fluid, such as air, or air together with liquid droplets, such as water droplets, resulting from the presence of moisture in the air. The axial length of the compressible portion is typically between 10% and 90% of the total axial length of the plug in an unstressed state, such as at least 20%, such as at least 25% or at least 30% of the total axial length of the plug . For example, the elastic contour element may have a length in the range of 30% to 70%, such as 30%, 40%, 50%, 60% or 70% of the unstressed length of the plug. As a result of connecting the working element of the plug with the outlet element of the plug by means of an elastic contour element, the total US can be matched with the sliding friction force of the plug and has a value comparable to the specified force. This provides an even smoother experience for the end user of the stoppered injector compared to using the stopper of the present invention having two deformable sealing members provided with the cavities of the present invention. More detailed information about stoppers with an elastic contour element is presented in the document WO 2017/157396, the contents of which are incorporated into this description by reference.

In a specific embodiment, the elastic contour element has a cylindrical shape. For example, a plug can be injection-molded as a single piece, for example, from TPE, with the creation of a working element and an outlet element of the plug, as well as a tubular part, and at least a section of this tubular part, located between the specified working and outlet elements, has a wall of reduced thickness so that contact with the engagement portion of the piston rod introduced into the tubular portion is not possible. For example, the wall thickness is such that the tubular part, ie the elastic contour element, has a volume fraction in the range of 10% to 25% of the volume of the compressible part. In the absence of contact between the engagement area and the walls of the tubular part, these walls are flexible and allow the working element of the plug to start moving before the outlet element of the plug when pushing the working element, for example, using a piston rod. Thus, the cylindrical tubular part is an elastic contour element. In this embodiment, between the surface of the engagement area and the material of the working element of the plug, a cavity of a toroidal shape is preferably formed. Another cavity is located at the location of the plug outlet. Both cavities will have a reduced SOS compared to non-cavated piston elements, and the resilient contouring element, in this case the tubular portion, also levels out the SOS so that the end user of the plugged injector will experience little difference between the SOS and the friction force. slip. In this embodiment, the piston rod preferably has a shoulder, as described above.

In another embodiment, a plug with a tubular part, which is also an elastic contour element, is used with a piston rod that does not have an engagement area. For example, a plug may be used in conjunction with a piston rod configured to push said plug. In this embodiment, the wall thickness of the tubular part is such that the volume fraction of the tubular part, that is, the elastic contour element, is from 20% to 50%, for example, from 25% to 40%, of the volume of the compressible part.

In yet another embodiment, the plug has a tubular part, which is also an elastic contour element, as described above, and in the injector this plug is used together with a piston rod having an engagement section with an engagement device associated with the tubular part engagement device. Thus, the piston rod can provide both filling and emptying of the injector using the specified stopper. For example, the tubular part may have a first inner diameter passing through the material of the working element of the plug from the working surface, and a larger, second, inner diameter in the area of the tubular part, which is an elastic contour element, and the zone of change in size from the first inner diameter to a larger, second, inner diameter is the hooking device of the tubular part. The piston rod has a section of engagement, the diameter of which is approximately equal to the first inner diameter, and an end platform having a larger cross section compared to the first inner diameter. Thus, the end platform serves as a hook that can pull the piston towards the drive end of the plug injector. Thus, said end platform is an engaging device associated with the engaging device of the tubular portion. The end platform may have any desired shape. For example, the end platform may be in the form of a disc whose diameter is larger than the first inner diameter but smaller than the second inner diameter, or the end platform may have two or more parts extending from the central axis of the piston rod to create a cross section that is larger than the first inner diameter. .

In another embodiment, the plug has a cavity at the axial location of the deformable sealing element closest to the outlet end of the plug, this cavity being open towards the outlet end, i.e. at the outlet surface. The plug may have a tubular portion as described above, in particular a tubular portion having an engaging device designed to engage with the mating engagement device of the engagement portion of the piston rod. Said engagement device and mating engagement device may be an internal screw thread and an external screw thread, respectively. The plug according to this embodiment can be used in the injector without any modifications, because the cavity will reduce the SOS of the plug, compared to a plug without such a cavity. However, the stopper according to this embodiment has an appropriate base point for creating a cavity enclosed in the body of the stopper. For example, a tip may be attached to the cork body such that the cavity is enclosed between the material of the tip and the cork body. Optionally, the tip can be attached to the cork body material. For example, the tip and body of the stopper may be glued or welded to each other. The tip and body of the plug can be made from the same or different materials. In a specific embodiment, the stopper, thus comprising the body of the stopper and the deformable sealing element, and the tip are preferably injection molded from TPE, for example from the same TPE, the tip being ultrasonic or laser welded to the stopper.

In yet another embodiment, the plug, thus including the body and the deformable sealing element, is injection molded from TPE to form a tubular portion extending from the face to the bottom, located behind the axial location of the deformable sealing element. Then, a cavity is formed in the tubular part by fixing the plug in the tubular part, so that the cavity is enclosed in the body material of the plug and the plug. If desired, the plug and stopper can be fixed. The plug may fill the tubular part completely or partially. For example, when the tubular portion is completely filled with a plug, a plug may be formed that cannot engage with the piston rod, thereby preventing the plug from being pulled out by said rod. The plug may also partially fill the tubular portion. As a result, the tubular portion may include an engagement device for engaging with the mating engagement device of the engagement portion of the piston rod, such as internal and external screw threads, respectively. The cork and plug can be made from the same or different materials. Preferably, however, the plug is made of TPE, in particular the same TPE as the stopper. This allows the plug and plug to be welded together, for example by ultrasonic or laser welding. In a particular embodiment, the body of the plug, for example on the work surface, includes a recess to facilitate orientation in a vibratory feeder, for example a feed hopper. The orientation aid recess in the vibrating feeder generally does not contain an internal screw thread. In another embodiment, the working surface is symmetrical with respect to the outlet surface. If the working surface is symmetrical with respect to the outlet surface, said surfaces preferably do not contain any engaging device for engaging the piston rod. In a specific embodiment, the plug contains two or more deformable sealing elements and at least two cavities formed at the location of two of said deformable sealing elements, and the working surface is symmetrical with respect to the outlet surface. However, in another embodiment, the working surface includes an engagement device for engagement with a mating engagement device of the piston rod. Any engaging device and associated engaging device can be used in the present invention. In one embodiment, the engagement device comprises an internal screw thread and the mating engagement device comprises an external screw thread.

The proposed plug can be built into the piston rod in such a way that the working surface is the drive end of the piston rod, for example, the plane for the thumb. Thus, another aspect of the present invention relates to a piston rod for an injector designed to administer a drug mixture. The piston rod is an integrated plug design according to any embodiment of the plug according to the invention.

The cavity or "seal cavity" may be surrounded by the solid material of the plug in a region towards the outlet end of the plug and therefore closest to the drug. As a general rule, the larger the size of the cavity perpendicular to the longitudinal axis of the container and stopper and/or the vertical size, the smaller the force acting through the deformable sealing element on the inner wall, and, consequently, the less static and dynamic friction between the deformable sealing element and the inner wall. container and, for example, on the boundary surface of the abutment.

In the known cork, the lowest deformable sealing element closest to the outlet end of the cork is responsible for the bulk of the sealing ability of the cork, since the cork is solid in the region opposite the lowest deformable sealing element and in the area facing and in contact with the drug. contact. However, the hard part of the elastomeric material opposite the deformable sealing element, in combination with the increased diameter of this element compared to the inner diameter of the container, leads to a significant clamping force at the time of insertion of the plug and beyond. The use of lubricating agents is required to eliminate the significant forces typically encountered in prior art plugs.

According to the present invention, the significant clamping force directed from the deformable sealing element to the inner wall of the container, in stoppers of the prior art is significantly reduced due to the implementation of a cavity in the solid part of the stopper, respectively, with a decrease in the amount of elastomeric material behind the deformable sealing element, and, ultimately , with a reduction in static and dynamic forces arising between the sealing element and the container. The plug according to the present invention contains a cavity in the sealing element, which can be considered as a replacement for the hard part of the plug, opposite the deformable sealing element. In an unstressed state, prior to insertion into the container, the diameter of the deformable sealing member is larger than the inside diameter of the container so that a proper seal can be provided to properly seal the container after insertion. According to the invention, the replacement of elastomeric material by a cavity can take place outside of any deformable sealing element of the cork, regardless of its position on the cork, and therefore, the deformable sealing element with the opposite cavity can be the upper, as well as the lowest deformable sealing element, or the middle sealing element. element or sealing element located anywhere between the upper and lower deformable sealing elements, or between the working and outlet ends of the plug, without limiting the present invention.

The cavity according to the invention may be a continuous or partial cavity located opposite the sealing element. According to the present invention, the solid cavity has no holes and is therefore completely enclosed in the cork body. According to the present invention, the partial cavity may have an opening opening said cavity in any direction. The opening of the cavity may be oriented towards the drive end of the plug, towards the internally threaded cavity, or towards the connecting means for the piston rod. According to the present invention, the cavity of the sealing element is located opposite the deformable sealing element, and in the preferred embodiment, in the direction of the outlet end of the plug, the elastomeric material is adjacent to the cavity.

In one embodiment, the opening of the cavity of the sealing element is oriented towards the outlet end of the plug, while the closed end and the elastomeric material adjacent to the cavity are oriented towards the working part of the stopper.

Initially, the diameter of the deformable sealing element is larger than the inner diameter of the container, and therefore, when introduced into the container, the specified element will exert a circumferential force directed into the container, for example, "main force". Said main force is the force due to the fact that the diameter of the sealing element is larger than the inner diameter of the container. The main force may be relatively small or relatively large, depending on how the deformable sealing element is supported by the elastomeric material located opposite the specified element. The more elastomeric material is placed against the deformable sealing element to support it, the greater the total force directed towards the inner wall of the container.

Conversely, the less elastomeric material is behind the deformable sealing element, the less force is exerted towards the inner wall of the container. The total force exerted by the deformable sealing element towards the container wall is a combination of a main force depending on the diameter of the deformable sealing element and a force causing a decrease or increase in force depending on the amount of elastomeric material located opposite the deformable sealing element. Ultimately, the overall force is positively or negatively affected by the amount of elastomeric material pressed by the sealing element against the inner wall of the container, which as a result will depend on the size and dimension of the cavity of the sealing element.

The cavity of the sealing element extends in such a way that its width is limited along the axis of the deformable sealing element inside the cork, and its height is limited along the longitudinal axis of the container inside the cork. Although the height of the cavity of the sealing element may influence the force directed towards the inner wall of the container, it is the width along the axis, coinciding with the deformable sealing element, that will have the greatest influence on the force directed towards the inner wall of the container. The greater the width and height, the less elastomeric material that causes a decrease in the pressing force of the sealing element. Conversely, the smaller the width and height, the more elastomeric material that causes an increase in the clamping force of the sealing element.

In one embodiment, the cavity of the sealing element is completely surrounded by the plug material, and according to this embodiment, the cavity of the sealing element contains a gas, but may contain any deformable material.

According to any embodiment of the invention, the cavity of the sealing element may have any geometric shape in any dimension of the plug and may be rectangular, oval, round, square, or any shape in between. The diameter of the cavity of the sealing element can be up to 95% of the diameter of the cork body along the axis of the deformable sealing element. However, the preferred cavity diameter is preferably in the range of 50% to 65% of the size along the axis of the deformable sealing element. The cavity of the sealing element may have a diameter of up to 80% of the diameter of the cork body along the longitudinal axis of the cork.

In a fourth embodiment, the cork body can be made of a material that expands and contracts depending on the surrounding material with which it interacts, thereby providing, like the cavity of the sealing element according to this invention, the same result, but by different means. Some plastic compositions, such as polystyrene in combination with, for example, butadiene or acrylonitrile, can be designed and used to form the cork body and thus replace the known elastomeric material opposed to the deformable sealing element. By replacing the prior art elastomeric material located in the solid portion of the cork with a material providing greater compressibility against the deformable sealing element, excess force towards the inner wall of the container is reduced. In this embodiment, the plug may be rigid against a deformable sealing element and therefore, depending on the specific force requirements for a given application of the injection system, may not have a cavity in the sealing element.

In any embodiment or combination of embodiments, the stopper may have the ability to absorb excess forces exerted towards the deformable sealing member and further against the container wall during injection, which the prior art stopper cannot, due to the presence of a solid portion of the elastomeric material. in the area opposite to the deformable sealing element.

Cork can be made from any material. In particular, the cork body does not come into contact with the inner wall of the container, and the material of the cork body generally has only one requirement, namely that it must be inert to any pharmaceutical composition present in the injector. The deformable sealing element must also be inert with respect to the pharmaceutical composition in the injector.

In one embodiment of the invention, the stopper is colored or pigmented, for example, the stopper is black, to create a contrast between the stopper and the syringe container. This contrast will allow more accurate dose measurement if the container contains volume indication lines. For example, in a container marked with black lines indicating volume, a black stopper may make reading easier to better control the volume drawn into or out of the injector. However, pigments and dyes can leak from the stopper into the pharmaceutical composition in the injector. This is especially true for injectors pre-filled with a pharmaceutical composition, since in this case the pharmaceutical composition may be in contact with the stopper for an extended period of time. In a preferred embodiment, the cork according to the invention does not contain any pigments or dyes, eg is "clear". This is particularly advantageous if the plug is used in an injector containing a pharmaceutical composition, such as a pre-filled injector, since there is no danger of leakage of dyes or pigments, and there is no obvious need for the aforementioned contrast, since the filling of the syringe is done on an automated filling equipment in a pharmaceutical company.

In a specific embodiment of the invention, the plug and the deformable sealing element are made of the same material, for example, the plug body and the deformable sealing element are made of the same material and are manufactured as one component. In one embodiment, the plug and deformable sealing element are made as a single component from any material appropriate to the purpose of the deformable sealing element. By making the plug, such as the plug body, and the deformable sealing element, as well as any optional support sealing elements, from the same material, more economical and simpler production can be achieved, thereby largely avoiding various process steps, such as labor-intensive assembly . In a preferred embodiment, the plug and/or deformable sealing element is made of TPE. A particularly suitable formulation is Evoprene G970 from Mexichem Specialty Compounds, which is a styrene-ethylene-butadiene-styrene (SEBS) block copolymer and has the right combination of Shore A hardness combined with a relatively low compression set.

In one embodiment of the invention, the stopper is specifically designed for use with a disposable syringe or the plunger rod of a pre-filled syringe through a means of connecting it together with a plunger shaft connecting means. According to this embodiment, the plug and piston rod can be produced separately and the piston rod can then be installed in the plug. According to this embodiment, the alternative manufacturing of the plug and piston rod is characterized by a double molding procedure, in which the plug and piston rod are produced in a sequential double molding, ensuring that the cavity of the sealing element is created after the final molding cycle, while the expensive assembly step through a manual or automated operation is saved. This principle of double or triple molding can be equally relevant for an embodiment containing a solid material with good expansion and contraction. Any of these embodiments, including a piston rod, is characterized in that when installed in a plug, the total width or diameter of the extreme end of the piston rod that can pass into the cavity of the sealing element is 5-90% less than the width of the cavity of the sealing element.

In the sixth embodiment, the cavity of the sealing element is formed by a discontinuous or continuous circular cylindrical free area of material between the sealing element and the solid part of the cork towards the center of the cork. The free area of the material forms a vertical cone of a given size on the longitudinal axis of the cork.

In any of the embodiments of the invention, the stopper may further comprise a reduction in the thickness of the material of the body of the stopper between the upper and lower sealing elements, also referred to as an elastic contour element. This elastic contour element is sufficient to provide adequate elasticity. The elastic contour element can be made, for example, from an elastic polymer, such as TPE, or from a flexible metal. In a specific embodiment, material thickness reduction is performed by injection molding a TPE, eg, a styrenic block copolymer (SBC) such as SBC selected from the group consisting of hydrogenated SBC or non-hydrogenated SBS, or alloys thereof. In a particularly preferred case, the plug and resilient contour are injection molded as a single unit in their final form from TPE having a Shore A hardness in the range of 50 to 90, for example 70 to 90.

Unlike existing plugs, the plug according to the invention reduces the static force, also known as SV, required to move the plug, to much lower values, by shearing the sealing elements, with a uniform division of the total SV into smaller increments due to the stepwise movement of the sealing elements. When the seal closest to the open end of the container, called the working seal, starts to move, its movement will push the seal closest to the needle end of the container, called the passive seal, but the present inventor surprisingly found that the static the friction of the passive sealing element contributes only a small amount to the force required to move the plug and push the fluid out of the cylinder, so that the smooth movement of the plug is achieved with static friction of only the working sealing element, which contributes to the static friction of the plug.

Thus, the maximum SOS experienced by the user will never exceed the SOS for a single sealing element. The following values illustrate the SOS obtained according to an embodiment of the invention: SOS of the working sealing element of 7 N reduced to an average sliding friction force of 4 N increased to SOS of the passive sealing element of 7 N reduced to an average sliding friction force of 4 N to complete the injection is equal to about 50% of the SOS value of a conventional plug, which is about 14 N. Thus, the plug made in accordance with the present invention is able to achieve a reduction in the SOS to half the value or lower compared to any known stopper.

The elastic contour element has a thickness dimension that provides differential movement of the plug sealing elements, thereby reducing the US. Unlike conventional plugs, which move all the sealing elements at the same time, the elastic contouring element ensures that the sealing element closest to the container opening and activated by the piston rod first begins to move before the sealing element closest to the end of the container, on which the needle is located, moves. . As a result of the differential movement, the overall SOS is significantly reduced, providing a significantly better sliding characteristic, ultimately improving the stability of the injection, handling and comfort for the patient, where a sharp and sudden movement of the piston rod can lead to very unpleasant sensations for the patient.

The size of the elastic contour element can vary in length and thickness along the longitudinal and horizontal axes of the plug. The elastic contour element can additionally vary in thickness for one given plug.

The deformable sealing element is made of a material having adequate hardness and elasticity to seal the annular gap between the stopper and the inner wall of the container. Any TPE material can be chosen for the deformable sealing element. In a preferred embodiment, the plug and deformable sealing element of this invention are injection molded in one piece from a suitable thermoplastic polymer such as Evoprene available from Mexichem, which is a chemically inert SEBS composition. The plug is preferably injection molded and thus the deformable sealing element can be manufactured to tighter tolerances than conventional rubber plugs made by conventional vulcanization techniques. Suitable cork materials include elastomers such as halobutyl rubber, such as butyl chlorine, bromobutyl, natural rubber, synthetic rubber (polyisoprene rubber, butyl rubber), silicone rubber, thermoplastic elastomers such as TPE, and similar materials that can be evaluated, for example, with a Shore durometer. , showing the elasticity of the elastomeric material and measuring its hardness, and the higher the durometer reading, the harder the connection. For example, in one embodiment of the invention, the deformable sealing element or plug and the deformable sealing element have a Shore A hardness in the range of about 30 to 90, preferably 60 to 80, more preferably 70 to 76. ” and “Shore Durometer” can be used interchangeably. As a rule, a deformable sealing element is homogeneous and throughout its volume consists of the same material, which has a Shore hardness (A scale) in given ranges. By using a material having a Shore A hardness corresponding to the above range, a relatively hard elastomeric material is provided. A harder material than prior art closures is particularly advantageous in terms of reducing the boundary surface abutment against the inner wall of the container while maintaining an adequate container seal, since the harder material reduces the common tendency of butyl rubber and other known materials to be substantially softer. expands along the inner wall of the cylinder upon insertion, thereby providing a significant boundary abutment and hence an adhesion area that increases the forces acting between the deformable sealing member and the inner wall of the container.

The plug may have one or more deformable sealing elements as described above, although the plug may also have additional sealing elements having other shapes and functions. For example, the plug may have a support seal configured to guide or control the orientation of the plug in the cylinder. Moreover, the stopper may have support elements that are not capable of sealing, but are physically capable of maintaining the correct position of the stopper within the container.

Testing has shown that a deformable seal that is 1.5% larger than the inside diameter of the container is sufficient to achieve complete container sealing for a given material, although most deformable cork seals have a diameter that is at least 3% larger than the inside diameter. container. Ultimately, the selection of the diameter of the deformable sealing element is influenced by the hardness of the initial material of the sealing element and/or its design.

Other tests have shown that two plugs having the same starting material, profiles and diameters of the deformable sealing elements differ significantly in terms of static and dynamic forces depending on whether they are solid or contain a sealing element cavity behind the deformable sealing element.

Other tests confirm that the cavity according to the invention can provide a 35.26% reduction in SOS for Tween solution and 56% for WFI. In addition, the cavity according to the invention provides a reduction in the dynamic force of the plug, also known as "mean sliding friction force", by 73.68%) for Tween solution and by 62.5%) for water of injection.

The proposed stopper is intended for an injector, and according to another aspect, the present invention relates to an injector containing the specified stopper. Deformable sealing elements seal the annular gap between the inner wall and the plug body when the plug is inserted into the cylinder. In the injector according to this invention, a stopper according to any embodiment can be used. The injector contains a cylinder, and in the context of this invention, the term "cylinder" means any kind of tube or similar element that allows the plug to move from one position in the cylinder to another position. The cylinder has a "drive end" and an "exhaust end" located opposite each other. The drive end of the cylinder allows access to the plug to move it, that is, to "drive" the plug in the cylinder through the working surface. The outlet end of the cylinder contains an opening for the release of the fluid contained in the cylinder.

As a rule, the outer diameter of the deformable sealing element is 1.5-10% larger than the inner diameter of the cylinder, for example, 2-5% larger. If the injector according to the invention is used with a plug having a deformable sealing element whose outer diameter is 1.5-10% larger than the inner diameter of the cylinder, and if the deformable sealing element has a Shore A hardness in the range of 30 to 90, for example , ranging from 50 to 90 or 70 to 90, the injector does not require external lubrication. Thus, in one embodiment of the invention, the injector contains no external lubricant.

The cylinder may be made from any suitable material, and typical materials include polymeric materials such as cyclic olefin copolymer (COC), e.g. TOPAS polymers (available from TOPAS Advanced Polymers GmbH), cyclic olefin polymer (COP), e.g. Zeonor, or polystyrene, or glasses, such as borosilicate glasses. Borosilicate glass generally has superior barrier performance compared to plastics. COC polymers are preferred because of their excellent barrier performance and thus these polymers meet the long shelf life requirement of pharmaceutical agents. In another embodiment, the cylinder is made of glass, such as borosilicate glass. It is also contemplated that the cylinder may be made of metal or may contain any combination of polymeric materials, glasses or metals. There is no restriction on the shape of the cross section of the cylinder, although it is preferred that the cylinder has a circular cross section. It is also contemplated that the cross section may be oval, elliptical, polygonal, etc. If the barrel has a circular cross section, the diameter, such as the inside diameter, may be any value commonly used for syringes. For example, in a preferred embodiment, the inside diameter of the cylinder is between 2 mm and 12 mm, such as 4.65 mm, 6.35 mm, 8.65 mm, or 11.85 mm, although larger values may be used in accordance with this invention.

If the deformable sealing element is a TPE with a Shore A hardness in the range of 30 to 90, then the effect of the cavity in reducing SOS is so pronounced that the plug can be used without external lubrication. In this context, the external lubricant includes silicone oils, silicone thermally applied to the inside surface of the injector barrel, perfluoropolymers applied either to the surface of the plug or to the inside surface of the injector barrel. In particular, the present invention notes that an injector with a stopper according to the invention with a deformable sealing member made of TPE can be used with a pharmaceutical composition that does not contain lubricant ingredients.

In one embodiment, the plug contains a deformable sealing element made of TPE, and the injector contains no lubricant, in particular, the injector does not contain silicone lubricant. Lubricants, such as silicone lubricants, are not inert to certain pharmaceutical formulations, such as protein-based pharmaceuticals such as vaccines, and lubricants should be avoided when storing injectors pre-filled with pharmaceutical formulation for long periods of time. Thus, this embodiment preferably allows long-term storage of the proposed injector, pre-filled with a pharmaceutical composition, for example, a pharmaceutical compound based on a protein, without adversely affecting the pharmaceutical composition. If the deformable sealing elements in contact with the inner surface of the cylinder are made of TPE having a Shore hardness (A-scale) in the range of 30 to 90, the sticking effect is eliminated even in the absence of lubrication, such as silicone grease, and in particular when residual compression strain at ambient temperature is in the range of 15% to 40%. Thus, any embodiment in which the deformable sealing element is made of TPE having a Shore A hardness in the range of 30 to 90 and in which there is no lubrication is particularly suitable for long-term storage of injectors, since no sticking effect occurs, provides a long-term seal and eliminates the negative impact on the pharmaceutical agent from the lubricant, while maintaining a smooth feeling for the end user due to the reduction of the SOS created by the proposed stopper. This result is observed for injectors having both polymer and glass cylinders. These results are especially relevant when the plug contains a working element and an outlet element connected to each other by an elastic contour element. Thus, in one embodiment, the injector comprises a plug having a working and outlet elements that are connected to each other by an elastic contour element, as described above.

Lubrication-free engagement is particularly suitable for glass barrel injectors, wherein in one embodiment the injector comprises a glass barrel and the plug has a deformable sealing element made of TPE with a Shore A hardness ranging from 30 to 90, with the injector not contains lubricants, for example, external lubricant relative to the cork. In a specific embodiment, the injector comprises a glass cylinder, for example, a borosilicate glass cylinder, and a plug having a working and outlet elements connected to each other by an elastic contour element, as described above, while the injector is not lubricated.

As a rule, glass cylinders have too large inside diameter tolerances to work with conventional pistons without being lubricated, due to the SOS values being too high for a conventional piston. At small diameters, the CA will be too high, and at large diameters and the use of conventional pistons, the integrity of the container seal (CGC) will be degraded. In contrast, the plug used in the present invention is able to compensate for large tolerances by offsetting deformable sealing elements, allowing for a larger piston diameter while maintaining SOS within acceptable limits while avoiding the use of traditional lubrication.

In one embodiment, the barrel is made of glass, such as borosilicate glass, and the injector contains no lubricant, namely silicone-based lubricant. The combination of effective sealing achieved and reduced SOS is particularly advantageous for long term storage of the pre-filled injector since no sticking occurs and furthermore the pharmaceutical composition, e.g. a protein-based pharmaceutical composition, is not adversely affected by lubricants. It can be said that the invention provides an injector for long-term storage of a pharmaceutical composition, in which there are no sticking effects.

The injector may be any type of injector used to administer the pharmaceutical composition to a subject through their skin. For example, the injector may be a syringe fitted with an injection needle for administering the pharmaceutical composition, for example, by subcutaneous (SC), intramuscular (IM), intradermal (ID) or intravenous (IV) or other type of drug delivery.

For example, at the outlet end, the injector may have a fitting for attaching or receiving an injection needle. Thus, the cylinder may have a conical outlet, such as a tubular outlet, from the cylinder having an engagement device designed to engage with the mating engagement device of the injection needle, for example, the engagement device and the associated engagement device may include a male-to-female interaction type interaction, the tubular the outlet optionally comprises an external thread, eg an external screw thread, and said needle optionally comprises a mating internal thread, eg an internal screw thread. The injection needle may be mounted in a manner that can be easily removed and replaced, or may be mounted on the injector in a non-removable manner. In particular, the injection needle can be installed on the injector in such a way that its removal requires the destruction of the injector, thereby preventing reuse, which in the context of this invention is considered to be installed in a "non-removable manner". The injector preferably comprises an injection needle attached, for example in a non-removable manner, to the barrel outlet.

In one embodiment of the present invention, the injector, preferably pre-filled, is a syringe with an injection needle. The syringe may have an injection needle mounted, for example, in a non-removable manner, on an outlet having a tubular or other shape. If the injector is pre-filled, in particular when it also contains a needle cap for use as a piston rod, a gap may be formed between the drive end of the barrel and the working surface of the plug. This gap keeps the piston rod stable when it is inserted into the cylinder, resulting in a safer and easier operation of the injector. The gap value, eg measured in units of length, may be any value corresponding to the size, eg volume, of the injector and the dose of the pharmaceutical composition contained in the injector. Common clearance values are between 2 mm and 20 mm. However, the gap may exceed 20 mm in cases where the actual volume of the injected substance is significantly less than the useful volume of the cylinder, for example, when performing ophthalmic injections, when the injected volume is only 0.01 ml to 0.2 ml, for example, 0.05 ml, although the body of the injector and hence the barrel is considerably larger and especially longer in order to allow the user to handle and operate the injector.

The injector according to the invention is preferably a pre-filled injector. Tests have shown that the cork according to the present invention has different static and dynamic forces, obtained by comparing the forces from testing the same plugs with the same cylinders, depending on their contents. Tests show that when testing cylinders filled with WFI (Water for Injection) or Tween Solution (Tweel 80 Solution) and with the same components used, SOS and sliding friction are reduced. Conversely, the SOS and sliding friction force are higher when testing empty cylinders. This result indicates that the stopper and the sealing elements according to the invention have a lubricating effect when interacting with a liquid of this type, so that the injector is particularly suitable as an injector pre-filled with a pharmaceutical composition, in particular a pharmaceutical composition that does not contain any lubricating additives. . There is reason to believe that this interaction between the sealing element at the outlet end is further improved by pharmaceutical injectables, which typically contain a carrier medium in the form of plasticizers and/or oil additives that further reduce frictional forces.

Features of injectors made according to any aspect of the invention can be combined in an arbitrary manner, and any advantage obtained for a particular feature can be used for any aspect by including the corresponding feature in the design of the injector.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is further explained in more detail with examples and with reference to the schematic drawings, in which:

fig. 1 shows a stopper according to the prior art;

fig. 2 is a sectional view of the proposed plug;

fig. 3 is a sectional view of the proposed injector;

fig. 4 is a sectional view of the proposed plug, together with the piston rod;

fig. 5 is a sectional view of the proposed plug, together with the piston rod;

fig. 6 is a sectional view of the proposed plug;

fig. 7 is a sectional view of the proposed plug;

fig. 8 is a sectional and plan view of the proposed plug;

fig. 9 is a sectional and plan view of the proposed plug;

fig. 10 is a sectional and plan view of the proposed plug;

fig. 11 shows an embodiment of the proposed plug having an elastic contour element;

fig. 12 shows an embodiment of the proposed plug having an elastic contour element;

fig. 13 shows an embodiment of the proposed plug having an elastic contour element;

fig. 14 shows several embodiments of the proposed plugs;

fig. 15 depicts embodiments of the proposed plugs;

fig. 16 shows an embodiment of the proposed piston rod; and

fig. 17 shows an embodiment of the proposed plug.

It should be understood that combinations of features of the various embodiments are also possible, and that various features, characteristics, and embodiments may be combined into other embodiments.

Reference to the drawings serves to explain the invention and should not be construed as limiting the features to the particular embodiments shown in the drawings.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to injector stoppers for the administration of a pharmaceutical composition, as well as to injectors. Hereinafter, the present invention is described in more detail with reference to the accompanying drawings. In some drawings, the proposed injectors are shown "in section", and the injector "in section" is presented at an angle of 90° compared to another image of the injector. Some drawings show side views of the proposed injectors. These side views do not show the outlet of the injectors, but it should be understood that the injector according to the invention has an outlet, for example an outlet on which an injection needle is mounted.

In FIG. 1 shows an example of a stopper 1001 according to the prior art. The plug 1001 has a piston body 1002 with a drive end 1003 and an outlet end 1004, with the drive end 1003 comprising a tubular portion 1007 having an internal screw thread 1008. The plug 1001 includes two deformable sealing members 1005. The plug 1001 has a solid portion 1006. Thus, the stopper 1001 exerts a significant force from the hard elastomeric material 1006 through the deformable sealing member 1005 towards the inner wall of the container (not shown), which requires the use of lubricants for satisfactory injection and causes significant disadvantages.

In FIG. 2 shows an embodiment of the proposed plug 1, and shown in FIG. 3 the plug 1 is inserted into the injector 21 according to the invention. The plugs 1 shown in the drawings are injection molded in one piece from thermoplastic elastomer (TPE). In FIG. 4 and 5 show a plug 1 having a piston rod 10 according to various embodiments. The plug 1 has a body 2 containing a working surface 3 opposite to the outlet surface 4, while between these surfaces the axial length of the plug passes. The plug body 2 has a transverse diameter and forms an access diameter. At an axial location from the working surface 3, the plug 1 comprises a deformable sealing element 5 surrounding the plug body 2 and having an outer diameter greater than the said transverse diameter. The axial extent of the deformable sealing element 5 is from 5% to 95% of the axial length of the plug body 2. When injected into the barrel 22 of the syringe 21, the deformable sealing element 5 abuts against the inner wall 23 of the barrel 22, so that said element seals the annular gap formed between the inner wall 23 and the cork body 2. The plug 1 is shown with a support seal 51 which also abuts against the inner wall 23. If a support seal 51 is provided, its diameter is generally smaller than the diameter of the deformable seal 5 which has a lateral extension, and in the depicted embodiment this diameter is greater than than the body access diameter 2 plugs. The support seal 51 can prevent the plug 1 from tilting when it is installed in the cylinder 22. The deformable seal 5 is made of TPE, the TPE being non-lubricated Evoprene G970 (from Mexichem Specialty Compounds) in the illustrated embodiment.

The tubular part 7 extends from the working surface 3 and has an internal screw thread 71, which is an engaging device designed to interact with the mating engagement device of the engagement section 11 of the piston rod 10. Thus, when the piston rod 10 is inserted into the tubular part 7, a cavity 6 is formed at the interface between the end platform 13 of the engagement section 11 of the piston rod 10 and the deformable sealing element 5. In particular, the mating engagement device is an external screw thread 14. The internal screw thread 71 has a minimum diameter and a maximum diameter specified by the helix. In this embodiment, the minimum diameter of the helix is equal to the access diameter formed by the body 2 of the plug.

The piston rod 10 is typically made from a hard polymeric material. As shown in the drawing, the piston rods 10 have a ledge 12, the diameter of which is greater than the maximum diameter of the helix of the internal screw thread 71, but less than the inner diameter of the cylinder 22. part 7. When the engagement section 11 of the piston rod 10 is fully inserted into the tubular part 7, namely, in the illustrated embodiments, the engagement section 11 is screwed into the tubular part 7, a cavity 6 is formed between the end platform 13 of the piston rod 10. Accordingly, the cavity 6 may be cylindrical cavity 6, as shown in Fig. 4 or a toroidal cavity 6 as shown in FIG. H. In both cases, the cavity 6 has a lateral extent, for example, a diameter larger than the access diameter of the body 2 of the plug.

In FIG. 6 shows an embodiment of a plug 1, according to which said plug has a cavity 6 at the axial location of the deformable sealing element 5 closest to the outlet surface 4 of the plug 1, the cavity 6 being open towards the outlet surface 4.

In FIG. 7 shows an embodiment of a stopper 1 in which the stopper 1 has a cavity 6 which is contained within the TPE of the stopper. For example, the plug 1 may be injection molded in two parts, where one part is the plug body 2 having an open cavity 6 as shown in FIG. 6, and the other part is a tip that can be attached to the plug body 2 in such a way that, after welding, the cavity 6 is enclosed between the material of the tip and the plug body 2. Plug 1 shown in Fig. 7 does not have a tubular part 7, but the cork body 2 having a tubular part 7 can also be made with a closed cavity 6 as shown in FIG. 7.

In FIG. 8, 9 and 10 show variants of the plug 1, in which the cavity 6 has a toroidal shape. The top views of the plugs 1 are shown in section, and the bottom views of the plugs 1 are top views. In all three embodiments shown, the plugs 1 are preferably injection molded in one piece from TPE. In FIG. 8 and 9, the tubular part 7 has a protrusion 72 located in its lower part and extending into said tubular part 7. Thus, when the piston rod (not shown in FIGS. 8 and 9) is inserted into the tubular part 7, toroidal cavities 6 are formed, . Shown in FIG. 9, the protrusion 72 corresponds to the shape of the toroidal cavity 6, which has the form of two sub-cavities, so that the cavity 6 has the form of a broken cylindrical shell. Shown in FIG. 10, the tubular part 7 is separated from the cavity 6, which in this case extends from the outlet surface 4 into the body 2 of the plug.

In FIG. 11, 12 and 13 show embodiments of a plug 1 having a resilient contour element 83. These plugs are preferably made in separate pieces by injection molding from TPE. In FIG. 11a and 11b the plug 1 is shown in different views at different angles and at 90° relative to each other, respectively. In FIG. 12 and 13, views "a" depict plugs 1, and in views "b" plugs 1 are inserted into cylinders 22 of injectors 21. Thus, plug 1 has a working element 81 and an exhaust element 82, which are interconnected by an elastic contour element 83. The working element 81 and outlet element 82 of the plug rest against the inner wall 23 of the cylinder 22 and seal the gap between said wall and the body 2 of the plug, thereby forming a compressible part 84 between said elements 81 and 82. The presented embodiments have cavities 6 in both deformable sealing elements 5. In FIG. 12 and 13 in views "b" shows how the elastic contour element 83, having a cylindrical shape, can be deformed when the force indicated by the arrow is applied. Thus, the arrows represent the force generated when the piston rod 10 is pushed towards the outlet end of the cylinder 22. The plug 1 shown in FIG. 12 has a piston rod 10 with an engagement section 11 having an end platform 13 of a larger diameter than the tubular part 7, so that said platform acts as a hook that can pull the plug 1 back and thereby ensure the filling of the cylinder 22 of the injector 21.

In FIG. 14 shows several embodiments of a plug 1 having a cavity 6 enclosed in the plug body 2, and FIG. 15, respectively, on the left and right views, similar plugs 1 are shown with cavities 6 having different diameters, and the arrows indicate the force exerted on the inner wall 23 of the cylinder 22 through the deformable sealing element 5. Thus, the smaller the diameter of the cavity 6, the greater force on the inner wall 23 and the higher the shear force (SS). Therefore, the lateral extent of the cavity 6 must be at least 50% of the outer diameter of the deformable sealing element 5. If the lateral extent of the cavity 6 is less than 50% of the outer diameter of the deformable sealing element 5, then a sufficiently low SOS will not avoid the need to lubricate the plug.

In FIG. 16 shows how the cavity 6 can be enclosed in the piston rod 10. Thus, for example, the piston rod 10 may have a cylindrical part with a built-in plug 1. Alternatively, the piston rod 10 can have a cylindrical part corresponding to the engagement section 11, which is surrounded by an O-ring made of TPE, said O-ring having a recess, providing, thereby creating a cavity 6 when mounted on the piston rod 10. In another embodiment, the piston rod 10 may have a cylindrical part corresponding to the engagement section 11, which is surrounded by a sleeve made of TPE, the sleeve comprising one, two or more deformable sealing elements 5 having cavities 6 formed between the inner surface of the sleeve and the outer the surface of the engagement area of the piston rod 10.

Another embodiment of the stopper 1 according to the invention is shown in FIG. 17. In this embodiment, the plug comprises two deformable sealing elements 5 that have a common toroidal cavity 6 extending from the working surface 3 of the plug 1. Thus, the cavity 6 extends between the axial locations of the deformable sealing elements 5. The plug 1 has a supporting deformable sealing element 51.

EXAMPLES

Example 1

The tube shown in Fig. 2 was injection molded from TPE material Evoprene G970 (from Mexichem Specialty Compounds))). The plug had two deformable sealing elements. The stopper was mounted in a 1 ml cylinder of unlubricated borosilicate glass with an internal diameter of 6.35 mm and a non-removable 27G needle, was supplied to the test bench as part of pre-filled glass injectors with an integrated needle and stored at a temperature of 23 ° C, relative humidity (RH) of air constituting 50% prior to testing. The tests included analysis of SOS and sliding friction forces in water for injection (WFI) and an aqueous solution of Twill. Testing was based on ISO 7886-3:2005 Annex B "Single use sterile injectors") - Part 3: "Injectors with automatic disabling after use for fixed dose immunization, Method for checking the force required to operate the plunger". Specific conditions included emptying the injectors while measuring forces for an initial 5 mm at a test speed of 100 mm/min in an Instron mechanical testing machine equipped with a 100 N load cell. The test results are shown in Table 2.

For comparison, plugs having only one deformable sealing element were made and the tests were repeated. The results of these tests are presented in Table 3.

In tables 2 and 3, the numbers in parentheses indicate the standard deviations. The sliding friction force shows the average forces for displacements between 2 mm and 30 mm. The mean and standard deviation are calculated for all combined data plots.

Thus, the proposed plug provided stable low US values, as well as a low sliding friction force.

The same plugs and glass injectors, ie plugs having one deformable sealing element and plugs having two deformable sealing elements, were also tested for cylinder seal integrity (CIT). Specifically, the injectors were pre-filled with a blue dye solution prepared in accordance with ASTM F 1929 guidelines, and tests were based on Parenteral Drug Association Technical Report No. 27, 1998 "Pharmaceutical Packaging Integrity". The injectors were stacked on absorbent paper in a desiccator with the vacuum profile shown in Table 4 and Table 5.

plug with one deformable sealing element

The absence of leakage indicates that the injection system may contain dye during the vacuum test. Thus, plugs according to this invention provide injectors that meet the requirements of the CGC, even if the plug has only one deformable sealing element.

Example 2

Further experiments were carried out with 1 ml injectors containing plugs with one or two deformable sealing elements to test the CHA and US over a period of time up to 4 weeks. Unlike Example 1, the injectors had barrels made of cyclic olefin polymer (COP). Needle-injectors were pre-filled with solutions of 0.1% surfactant (Tween 80) in water and stored at 23° C. and 50% relative humidity (RH) until testing.

The area around the stopper was observed immediately after filling the injectors, as well as after 1 hour, 1 week, 2 weeks and 4 weeks. No leakage was observed for any of the samples, and it was concluded that the injectors met the requirements of the CGC.

To measure the SOS values, the injectors were tested at a stroke rate of 100 mm/min over a stroke length of 28 mm. The SV values are given in Table 6.

Thus, within 4 weeks there was no significant change in the SV values, which indicates that the proposed stopper is suitable for use in a pre-filled injector. In all cases, the SV values were within the acceptable range.

REFERENCE SYMBOLS

1001 Cork according to the state of the art

1002 Piston body of famous plug

1003 Drive end of known plug

1004 Exhaust end of known plug

1005 Sealing element of a famous cork

1006 Hard part of famous cork

1007 Tubular part of famous cork

1008 Female screw thread of famous plug

1 Stopper according to the invention

2 Plug body

3 Work surface

4 Release surface

5 Deformable sealing element

51 Support seal

6 cavity

7 Tubular part

71 Internal screw thread

72 ledge

81 Cork working element

82 outlet plug

83 Elastic contour element

84 Compressible part

10 piston rod

11 Engagement area

12 Ledge

13 Piston rod end

14 External screw thread

21 Injector

22 Cylinder

23 The inner wall of the cylinder.

Claims (24)

1. An injector (21) for the introduction of a pharmaceutical composition, containing a cylinder (22) having an inner wall (23), a piston rod (10) and a plug (1) having a body (2) that has a working surface (3) opposite surface (4) of the outlet, the axial length between the working surface (3) and the surface (4) of the outlet and the transverse diameter, moreover, in the axial location from the working surface (3), the specified plug (1) contains a deformable sealing element (5) made of thermoplastic elastomer (TPE), moreover, the deformable sealing element (5) surrounds the body (2) of the plug and has an outer diameter exceeding the specified transverse diameter, while the axial extent of the deformable sealing element (5) is from 5% to 95% of the axial length of the body (2) of the plug, while the deformable sealing element (5) seals the annular gap between the body (2) of the plug and the inner wall (23) of the cylinder (22), characterized in that in the specified axial location of the deformable sealing element (5), the plug (1) has a cavity (6), where the axial extent of the cavity (6) is from 5% to 50% of the axial length of the body (2) of the plug, and that the body (2) of the plug has a tubular part for accommodating the piston rod (10) in the access diameter, and the fact that the cavity (6) is formed at the interface between the body (2) of the plug and the piston rod (10) and/or at the interface between deformable sealing element (5) and piston rod (10), and the transverse extent of the specified cavity (6) is at least 50% of the outer diameter of the deformable sealing element (5) and more than the specified access diameter, or that in the specified axial location of the deformable sealing element (5), the plug (1) has a cavity (6), where the axial extent of the cavity (6) is from 5% to 50% of the axial length of the body (2) of the plug, and that cavity (6) is a partial cavity, the transverse extent of which is at least 50% of the outer diameter of the deformable sealing element (5), and which has an opening facing the working surface (3) of the plug (1), or a hole facing the surface (4) release plug (1). 2. An injector (21) according to claim 1, wherein said transverse extension is between 50% and 65% of the outer diameter of the deformable sealing element (5). 3. Injector (21) according to claim 1, wherein said cavity (6) has a cylindrical, ellipsoidal or toroidal shape. 4. The injector (21) according to claim 1, in which the body (2) of the plug contains a working element (81) and an exhaust element (82), each of which contains the specified deformable sealing element (5), while the specified working element (81 ) and said exhaust element (82) are connected to each other by an elastic contour element (83), with the exhaust element (82) located at the first axial location from the working surface (3), and the working element (81) located at the second axial location from the working surface (3), wherein said cavity (6) of plug (1) is located at said first axial location. 5. The injector (21) according to claim 4, wherein the plug (1) comprises a second cavity (6) located at said second axial location. 6. Injector (21) according to claim 5, in which the elastic contour element (83) has a cylindrical shape. 7. The injector (21) according to claim 1, in which the deformable sealing element (5) is a sealing ring with a recess located along the inner diameter of the specified sealing ring, so that when the sealing ring is installed on the body (2) of the plug, the specified cavity (6 ) is formed between said O-ring and housing (2) in the O-ring recess. 8. The injector (21) according to claim 1, in which the cork body (2) has a cylindrical shape, and the deformable sealing element (5) is located on the cylindrical structure for installation on the cork body (2), so that when installing the cylindrical structure on the body (2) of the plug, said cavity (6) is formed between said body (2) and the cylindrical structure. 9. The injector (21) according to claim 1, in which the deformable sealing element, or the body (2) of the plug and the deformable sealing element (5), has (have) a Shore hardness (scale A) in the range from 30 to 90. 10. The injector (21) according to claim 1, wherein the plug body (2) is made of thermoplastic elastomer (TPE). 11. The injector (21) according to claim 1, in which the plug (1) contains the first deformable sealing element (5) located at the first axial location from the working surface (3), and the cavity (6) located at the specified first axial location , as well as the second deformable sealing element (5) located at the second axial location from the working surface (3), and the second cavity (6) located at the specified second axial location. 12. The injector (21) according to claim 1, in which the plug (1) contains the first deformable sealing element (5) located in the first axial location from the working surface (3), and the second deformable sealing element (5) located in the second axial location from the working surface (3), while the cavity (6) passes between the specified first and second axial locations. 13. The injector (21) according to claim 1, in which the cylinder (22) has an inner diameter, and before inserting the plug (1) into the cylinder (22), the outer diameter of the deformable sealing element (5) is 1.5-10% larger than the inner cylinder diameter (22). 14. An injector (21) according to claim 1, wherein the deformable sealing element (5) has a Shore hardness (A scale) in the range of 30 to 90, wherein the injector (21) contains no external lubricant. 15. Injector (21) according to claim 1, in which the cylinder (22) is made of glass. 16. The injector (21) according to claim 1, wherein the inner diameter of the cylinder (22) is between 2 mm and 12 mm. 17. An injector (21) according to claim 1, wherein the barrel (22) is pre-filled with a pharmaceutical composition.

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