Pharmaceutical packaging container with lubricant layer for removal of a pressurizing member

Abstract

The present invention relates generally to a container for pharmaceutical packaging comprising a pressurizing element and having a lubricant layer. In particular, the present invention relates to a container, a method of preparing a treatment product and the use of a lubricant layer in the treatment.

Description

TECHNICAL FIELD

[0001] The present invention relates generally to a container for pharmaceutical packaging, the container comprising a charge and having a lubricant layer. In particular, the present invention relates to a container, a method of preparing a disposal product and the use of a lubricant layer in disposal. BACKGROUND

[0002] Pharmaceutical materials can be provided in a variety of forms and housed in a variety of different containers. In the case of liquid pharmaceutical materials, some common examples are ampoules, vials, cartridges and syringes. One widely used form is to employ a sliding plunger within the container to eject the liquid from the bore. One approach is to provide a lubricant layer on the inside of the container to facilitate sliding of the plunger.

[0003] US patent application document US 4767414 A describes plasma activation of the inner surface prior to application of a silicone lubricant layer.

[0004] European patent EP 0920879 B1 describes a formulation of a silicone-based mixture comprising a reactive component and a non-reactive component.

[0005] There is still a need for improvements to pharmaceutical containers. SUMMARY

[0006] It is an object of the present invention to at least partially address one or more of the above challenges.

[0007] It is an object of the present invention to provide an improved container for pharmaceutical packaging.

[0008] It is an object of the present invention to provide a container for pharmaceutical packaging which improves the fine control of the aspiration of fluid.

[0009] It is an object of the present invention to provide a container for pharmaceutical packaging which has improved transportability, in particular reduced likelihood of contamination.

[0010] It is an object of the present invention to provide a container for pharmaceutical packaging which simultaneously achieves two or more of the following secondary objects:

[0011] - improved fine control of infusion or aspiration or both;

[0012] - improved transportability, in particular reduced likelihood of contamination;

[0013] - improved disposability.

[0014] It is an object of the present invention to provide an improved method of disposing of a pharmaceutical packaging container.

[0015] It is an object of the present invention to provide a method for disposing of a pharmaceutical packaging container with fewer steps, preferably without a crushing step.

[0016] It is an object of the present invention to provide a method for disposing of a pharmaceutical packaging container that reduces the risk of contamination, in particular from pharmaceutical liquids and body fluids.

[0017] It is an object of the present invention to provide a method for disposing of a pharmaceutical packaging container that reduces the emission of halogens. Detailed description

[0018] In the following examples, the xth example is marked as |x|, representing a preferred arrangement to achieve the objects of the present invention.

[0019] |1| A container for pharmaceutical packaging, the container having an elongated barrel portion, wherein:

[0020] a. the container has a first end and a second end;

[0021] b. the elongated barrel portion has an elongated extension direction and has an axis in the elongated extension direction;

[0022] c. an axial position p is determined along the axis;

[0023] d. the elongated barrel portion extends from the axial position p A to the axial position p B ;

[0024] e. the length L B of the elongated barrel portion is the distance between p A and p B ;

[0025] f. the first end is closer to p A than to p B ;

[0026] g. the second end is closer to p B than to p A ;

[0027] h. the container has a first aperture at the first end and a second aperture at the second end;

[0028] i. the first aperture has a first aperture diameter and the second aperture has a second aperture diameter, the first aperture diameter being larger than the second aperture diameter, preferably at least 10% larger, more preferably at least 50% larger, even more preferably at least 100% larger, most preferably at least 500% larger;

[0029] j. the container has a side wall extending over the elongated barrel portion, the side wall having an inner surface delimiting an interior, the interior having a diameter;

[0030] k. the layer of lubricant is located on at least a portion of the inner surface;

[0031] l. at a given axial position p on the axis between p A and p B , the following are determined as the average values of the angles in a cross-sectional plane perpendicular to the axis at the axial position p, respectively:

[0032] i. the thickness of the side wall,

[0033] ii. the thickness of the layer, and

[0034] iii. the diameter of the interior;

[0035] m. the pressure booster is present in the interior and seals the cross-section of the interior between the inner surfaces of the side wall;

[0036] n. the axial position p + is the axial position of the pressure booster contacting the layer or the inner surface closest to p B ;

[0037] o. the axial position p - is the axial position of the pressure booster contacting the layer or the inner surface closest to p A ;

[0038] p. the value obtained by dividing the distance between p B and p + by the distance between p + and p A is in the range from 0 to 2, preferably in the range from 0.001 to 1, more preferably in the range from 0.01 to 0.7, more preferably in the range from 0.05 to 0.5, more preferably in the range from 0.1 to 0.4, most preferably in the range from 0.2 to 0.3;

[0039] q. the average thickness of the layer determined between p A and p - is at least 10 nm, preferably at least 20 nm, more preferably at least 30 nm, more preferably at least 40 nm, most preferably at least 50 nm;

[0040] r. one or more criteria selected from the following criteria are met:

[0041] i. the length L B is in the range from 3 cm to 20 cm;

[0042] ii. the average value of the diameter of the interior determined in the range from p A to p B is in the range from 0.4 cm to 4 cm;

[0043] iii. In p A to p B The average thickness of the sidewalls determined within the specified range is in the range of 0.3 mm to 4.5 mm;

[0044] iv. The internal volume is in the range of 0.1 ml to 150 ml.

[0045] |2|The container according to embodiment|1|, wherein, in p A and p - The average thickness of the layers determined between them is at most 300 nm, preferably at most 250 nm, more preferably at most 200 nm, even more preferably at most 150 nm, and most preferably at most 100 nm.

[0046] |3|The container according to embodiment|1| or|2|, wherein, in p A and p - The maximum thickness of the layer is at least 20 nm, preferably at least 30 nm, more preferably at least 40 nm, and most preferably at least 60 nm.

[0047] |4| Container according to any of the foregoing embodiments, wherein, in p A and p - The maximum thickness of the layer is at most 400 nm, preferably at most 350 nm, more preferably at most 300 nm, and most preferably at most 250 nm.

[0048] |5| A container according to any of the foregoing embodiments, wherein, in p A and p - The length between them is from p A to p - The minimum thickness of the continuous portion X, which is at least 50%, preferably at least 60%, more preferably at least 70% of the length, is at least 5 nm, preferably at least 10 nm, more preferably at least 20 nm, and most preferably at least 40 nm.

[0049] |6| A container according to any of the foregoing embodiments, wherein, in p A and p - The length between them is from p A to p - The minimum thickness of the continuous portion X, which is at least 50%, preferably at least 60%, more preferably at least 70% of the length, is at most 300 nm, preferably at most 250 nm, more preferably at most 200 nm, and most preferably at most 150 nm.

[0050] |7| A container according to any of the foregoing embodiments, wherein, in p A and p- The length between them is from p A to p - The difference between the minimum and maximum thickness of at least 50%, preferably at least 60%, more preferably at least 70% of the length of the continuous portion X is at least 5 nm, preferably at least 10 nm, more preferably at least 20 nm, and most preferably at least 30 nm.

[0051] |8| A container according to any of the foregoing embodiments, wherein, in p A and p - The length between them is from p A to p - The difference between the minimum and maximum thickness of the continuous portion X, which is at least 50%, preferably at least 60%, more preferably at least 70% of the length, is at most 300 nm, preferably at most 250 nm, more preferably at most 200 nm, and most preferably at most 150 nm.

[0052] |9| A container according to any of the foregoing embodiments, wherein, in p A and p - The maximum thickness of the layer determined between p - Comparison P A At a closer axial position.

[0053] |10| A container according to any of the foregoing embodiments, wherein, in p B and p + The average thickness of the layers determined between p A and p - The average thickness of the layers determined between them is at least 1.5 times, preferably at least 2 times, and more preferably at least 3 times.

[0054] |11| Container according to any of the foregoing embodiments, wherein, in p B and p + The maximum thickness of the layer determined between p is A The maximum thickness of the layer determined between p and p is at least 1.5 times, preferably at least 2 times, and more preferably at least 3 times.

[0055] |12| According to any of the foregoing embodiments, the diameter of the first hole is at least 80%, preferably at least 90%, more preferably at least 95%, and most preferably at least 99% of the average diameter of the interior.

[0056] |13| According to any of the foregoing embodiments, the diameter of the second hole is at most 70%, preferably at most 50%, more preferably at most 40%, and most preferably at most 30% of the average diameter of the interior.

[0057] |14| The container according to any of the preceding embodiments, wherein the booster comprises a halogen, preferably F, CI, Br or I, more preferably F, CI or Br, more preferably CI or Br, most preferably Br.

[0058] |15| The container according to embodiment |14|, wherein the halogen is present in the polymer.

[0059] |16| The container according to embodiment |14| or |15|, wherein the halogen is present in a coating of the booster.

[0060] |17| The container according to any of the preceding embodiments, wherein the maximum force required to remove the booster from the container through the first aperture is no more than 10 N, preferably no more than 8 N, more preferably no more than 7 N. The maximum force is preferably determined according to the removal process shown in the figure.

[0061] |18| The container according to any of the preceding embodiments, wherein the maximum force required to remove the booster from the container through the first aperture is at least 4 N, preferably at least 5 N, more preferably at least 6 N. The maximum force is preferably determined according to the removal process shown in the figure.

[0062] |19| The container according to any of the preceding embodiments, wherein the maximum force required to remove the booster from the container through the first aperture occurs when the front of the booster is closer to p A than to p B . The maximum force is preferably determined according to the removal process shown in the figure.

[0063] |20| The container according to any of the preceding embodiments, wherein:

[0064] a. the movement of the booster along the axis in the direction from p B to p A is resisted by a dynamic friction force g, g being a function of the axial position of the front of the booster;

[0065] b. g has a maximum value g MAX at the axial position p MAX ;

[0066] c. the minimum value of g between p + and p MAX is g MIN at the axial position p MIN ; and

[0067] d. one or more of the following criteria is satisfied:

[0068] i. F MAXin the range of 2N to 10N, preferably in the range of 3N to 8N, more preferably in the range of 3.5N to 7N;

[0069] ii. F MIN in the range of 0.5N to 5N, preferably in the range of IN to 4N, more preferably in the range of 2N to 3N;

[0070] iii. p MAX from p A than p B is closer to p

[0071] iv. p MIN from p B than p A is closer to p

[0072] v. g MAX / g MIN in the range of 1.1 to 4, preferably in the range of 1.2 to 3.5, more preferably in the range of 1.5 to 3.

[0073] The dynamic friction is preferably determined according to the removal method shown in the figure.

[0074] In some aspects of this embodiment, the following combinations of features are met: i., ii., i.+ii., iii., i.+iii., ii.+iii., i.+ii.+iii., iv., i.+iv., ii.+iv., i.+ii.+iv., iii.+iv., i.+iii.+iv., ii.+iii.+iv., i.+ii.+iii.+iv., v., i.+v., ii.+v., i.+ii.+v., iii.+v., i.+iii.+v., ii.+iii.+v., i.+ii.+iii.+v., iv.+v., i.+iv.+v., ii.+iv.+v., i.+ii.+iv.+v., iii.+iv.+v., i.+iii.+iv.+v., ii.+iii.+iv.+v., i.+ii.+iii.+iv.+v.

[0075] |21| The container according to any of the preceding embodiments, wherein the side wall comprises plastic or glass or both.

[0076] |22| The container according to any of the preceding embodiments, wherein the lubricant comprises one or more silicone oils. Preferably, the lubricant comprises a total of at least 5 wt.%, more preferably at least 15 wt.%, most preferably at least 25 wt.% of one or more silicone oils, based on the total weight of the lubricant of the layer.

[0077] |23| The container according to embodiment |22|, wherein the one or more silicone oils are at least partially contained in a matrix, wherein the matrix is bound to the inner surface.

[0078] |24| The container according to embodiment |23|, wherein the matrix is a polymer, preferably a cross-linked polymer.

[0079] |25| The container according to embodiment |24|, wherein the polymer comprises a repeat unit comprising SiO. Preferred polymers are polysiloxanes, more preferred cross-linked polysiloxanes.

[0080] |26| The container according to any one of the preceding embodiments, wherein the interior is cylindrical or frustoconical over the elongated barrel portion. Preferred frustocones have a conical aperture in the range of 0.04° to 0.4°, preferably in the range of 0.08° to 0.25°, more preferred in the range of 0.1° to 0.2°.

[0081] |27| The container according to any one of the preceding embodiments, comprising an attachment means at the aperture. Preferably, the attachment means is at the end portion, more preferred at the second end. Preferred attachment means are adapted and arranged to attach one or both of the group consisting of a needle and a tube. Some preferred attachment means are threads, latches, luer fittings and bayonet fittings.

[0082] |28| The container according to any one of the preceding embodiments, comprising a liquid pharmaceutical composition present in a portion of the interior between p + and p B .

[0083] |29| A method for preparing a disposal product, comprising the steps of:

[0084] a. providing a container according to any one of the preceding embodiments;

[0085] b. converting the container into a disposal product.

[0086] |30| The method according to embodiment |29|, comprising the steps of:

[0087] - removing the pressurizing means from the container through the first aperture.

[0088] |31 | The method according to embodiment |29| or |30|, comprising a heating step.

[0089] |32| The method according to any one of embodiments |29| to |31 |, comprising an oxidizing step.

[0090] |33| The method according to any one of embodiments |29| to |32|, wherein the disposal product comprises less than 50 ppm of halogen by mass, preferably less than 40 ppm, more preferably less than 30 ppm, more preferably less than 10 ppm, most preferably less than 5 ppm.

[0091] |34| Use of a lubricant layer having an average thickness of at least 10 nm for improving disposal of a used drug container.

[0092] |35| The use according to embodiment |34|, wherein a disposal product with reduced halogen content is obtainable from the disposal.

[0093] Diameter, layer thickness and roughness

[0094] The axis of the container is used to determine axial positions. At a given axial position, the side wall is a periphery, the thickness of which lies in a cross-sectional plane perpendicular to the axis, the same as the lubricant layer. The inner diameter of the lubricant layer, the thickness, the thickness of the side wall and the surface roughness at a given point along the axis are preferably determined as an average value around the periphery. The average value around the periphery is an angular average. The angular average is preferably determined by measuring at 8 points on the periphery, the 8 points being equally angularly separated.

[0095] Container

[0096] Preferred containers are adapted and arranged to contain a liquid pharmaceutical composition. Some preferred containers are syringes, syringe barrels, cartridges and vials.

[0097] In one embodiment, the container can be provided by the following steps:

[0098] a. providing a container having a first end and a second end, the container containing a liquid pharmaceutical composition and a pressurizing means, the pressurizing means being located closer to the first end than to the second end;

[0099] b. moving the pressurizing means to a position closer to the second end than to the first end, thereby ejecting the liquid pharmaceutical composition from the second end.

[0100] The container is preferably a used drug container.

[0101] The preferred container has an attachment device, preferably at an end, more preferably at the second end. The preferred attachment device is adapted and arranged for attaching a needle or a tube. The needle or the tube can be attached to the assembled container.

[0102] Elongate barrel

[0103] The container has an elongated barrel. Elongated barrel is the name of a part of the container. The container can have other parts outside the elongated barrel. Another term for elongated barrel is tube. The preferred elongated barrel is tubular.

[0104] Possible examples of elongated barrel and axis are described in mathematical terms herein, such as axis of symmetry, axis of rotation or revolution, surface and solid of revolution, and shapes such as cylinder and truncated cone. These embodiments are to be understood as allowing for some variation from these precise mathematical concepts. Suitable variations of the mathematical concepts are those that do not prevent the elongated barrel from cooperating with the pressure booster as a plunger system.

[0105] The elongated barrel has an axis. The axis can be an axis of rotation of the elongated barrel. The axis can be an axis of revolution of the elongated barrel. The side wall can be a solid of revolution around the axis. The inner surface can be a surface of revolution around the axis. The layer can be a solid of revolution around the axis.

[0106] The axis defines an axial position p. The axial position p is an axial position along the axis. In this text, the symbol p generally denotes an axial position, and a specific axial position is denoted by the letter p with a subscript.

[0107] The axial position p along the axis is used as a parameter to describe the position of a point or cross section along the elongated barrel, for example on the side wall. The axial position of a point not on the axis can be found by projecting the point onto the axis with a displacement vector perpendicular to the axis. A cross section is a plane perpendicular to the axis. The axial position of a cross section is at the intersection of the cross section and the axis.

[0108] The elongated barrel extends from an axial position p A to an axial position p B . The boundary of the elongated barrel is the cross section at p A and the cross section at p B .

[0109] The container has a side wall extending over the elongated barrel. The side wall has an inner surface. The inner surface delimits the boundary of the interior. The preferred shape of the side wall is a hollow cylinder, a hollow prism, and a hollow truncated cone. The preferred hollow truncated cone has a diameter that decreases from p A to p B . The preferred shape of the interior is a cylinder, a prism, and a truncated cone. The preferred truncated cone has a diameter that decreases from p A to p B .

[0110] The inner surface is preferably smooth, but can have some roughness.

[0111] The thickness of the side wall is preferably measured as the difference between the radial distance from the axis of the inner surface to the outer surface of the side wall.

[0112] Preferred materials for the side wall are polymers and glass.

[0113] In one embodiment, the side wall comprises a polymer, preferably is made of a polymer. The polymer is preferably one or both of the materials selected from the group consisting of one or more cyclic olefin copolymers and one or more cyclic olefin polymers. In an aspect of this embodiment, the polymer is preferably at least 30 wt.%, more preferably at least 50 wt.%, more preferably at least 80 wt.%, most preferably about 100 wt.% of the side wall.

[0114] In one embodiment, the side wall comprises glass, preferably is made of glass. In this context, preferred glass comprises one or more materials selected from the group consisting of silicon, boron and aluminum. One preferred glass comprises boron and silicon. One preferred glass is borosilicate glass. One preferred glass comprises aluminum and silicon. One preferred glass is aluminosilicate glass. In an aspect of this embodiment, the glass is preferably at least 30 wt.%, more preferably at least 50 wt.%, more preferably at least 80 wt.%, most preferably about 100 wt.% of the side wall.

[0115] Lubricant layer

[0116] The lubricant layer is located on the inner surface of the side wall. The lubricant layer can extend over the entire elongated barrel or only over a portion thereof.

[0117] A preferred lubricant is a silicone-based lubricant.

[0118] A preferred lubricant comprises one or more polysiloxanes.

[0119] A preferred lubricant comprises one or more silicone oils, preferably the total content of silicone oils is in the range of 10 to 50 wt.%, more preferably in the range of 20 to 40 wt.%, most preferably in the range of 25 to 35 wt.%, based on the total weight of the lubricant. A preferred silicone oil is polydimethylsilicone oil.

[0120] A preferred lubricant comprises a cross-linked polysiloxane matrix, preferably the total content of cross-linked polysiloxane matrix is in the range of 50 to 90 wt.%, more preferably in the range of 60 to 80 wt.%, most preferably in the range of 65 to 75 wt.%, based on the total weight of the lubricant.

[0121] A preferred lubricant can be prepared with a mixture comprising one or more, preferably all, of the following materials:

[0122] - a reactive polysiloxane;

[0123] - a non-reactive polysiloxane;

[0124] - a catalyst;

[0125] - diluent.

[0126] The preferred reactive polysiloxane is adapted and arranged to undergo a cross-linking reaction to obtain a cross-linked network. The cross-linking can be catalyzed by a catalyst.

[0127] The preferred non-reactive polysiloxane does not undergo a cross-linking reaction. The preferred non-reactive polysiloxane includes one or more alkyl groups. Another preferred non-reactive polysiloxane is completely substituted with alkyl groups.

[0128] The preferred catalyst catalyzes the reaction to cross-link the polysiloxane.

[0129] The preferred diluent is soluble with one or more other ingredients in the mixture. The preferred diluent is silicon-based. The preferred diluent is a short chain polysiloxane, preferably with 6 or fewer repeat units. The preferred diluent is hexamethyldisiloxane.

[0130] The preferred lubricant includes no more than 10 wt% water, preferably no more than 5 wt%, more preferably no more than 1 wt%, based on the total weight of the lubricant.

[0131] In one embodiment, the layer extends over at least 70% of the length of the elongated barrel, more preferably at least 80%, more preferably at least 90%, most preferably about 100%. In another embodiment, the lubricant extends over 20% to 60% of the length L of the elongated barrel. B

[0132] The preferred method of applying the layer is coating and wiping, preferably using a suitable tool to apply.

[0133] The thickness of the layer is preferably measured as the difference between the radial distance from the inner surface of the layer to the inner surface of the sidewall to the axis.

[0134] The lubricant layer can be cured after application. The preferred curing can be heat-induced or radiation-induced or a combination of both. Some preferred ways of curing are applying ultraviolet radiation and applying infrared radiation.

[0135] Liquid pharmaceutical composition

[0136] The container is for a pharmaceutical package. The preferred container is adapted and arranged to contain a liquid.

[0137] The liquid pharmaceutical composition preferably includes an active compound.

[0138] The liquid pharmaceutical composition is a fluid.

[0139] ​The preferred amount of the liquid pharmaceutical composition is in the range of 0.001 ml to 10 ml, preferably in the range of 0.01 ml to 5 ml, more preferably in the range of 0.05 ml to 1 ml, most preferably in the range of 0.1 ml to 0.8 ml, most preferably in the range of 0.2 ml to 0.5 ml.

[0140] Pressure booster

[0141] The elongated barrel is adapted and arranged to accommodate a plunger. The preferred plunger is adapted and arranged to be accommodated in the elongated barrel. The elongated barrel and the plunger are preferably complementary such that the plunger can be moved inside in a direction parallel to the axis.

[0142] The preferred plunger is made of an elastic material or comprises a component made of an elastic material. The plunger is preferably adapted and arranged to seal the cross section of the interior. The plunger is preferably adapted and arranged to move inside the container preferably along the axis defined by the elongated extension of the container. The movement of the plunger when moving inside the container is preferably subject to a resistance which is the friction between the plunger and the inner surface of the container.

[0143] The plunger can be attached to an elongated rod which is adapted and arranged to push or pull the plunger in a direction parallel to the axis.

[0144] The preferred plunger is a plunger.

[0145] The preferred plunger comprises a halogen, preferably F, CI, Br or I, more preferably F, CI or Br, more preferably CI or Br, most preferably Br. The preferred plunger can comprise two or more of the above mentioned halogens. The halogen can be present in a polymer compound, for example in a brominated or chlorinated polymer. The preferred polymer can comprise one or more isobutylene structural units which are halogenated or non-halogenated, preferably halogenated. The preferred polymer can comprise one or more isoprene structural units which are halogenated or non-halogenated, preferably halogenated. The preferred polymer is a chlorinated or brominated isobutylene isoprene copolymer, preferably a brominated isobutylene isoprene copolymer. In this context, the isobutylene isoprene copolymer preferably comprises 95 to 99.5 wt.-%, preferably 96 to 99 wt.-%, most preferably 97.5 to 98.5 wt.-% isobutylene structural units and 0.5 to 5 wt.-%, preferably 1 to 4 wt.-%, most preferably 1.5 to 2.5 wt.-% isoprene structural units.

[0146] In one embodiment, the halogen content can be present in a coating of the plunger, preferably the coating is adapted and arranged to be in contact with the inner surface of the side wall.

[0147] Axial position of the pressure booster

[0148] When positioned in the container, the pressurizing element contacts the layer or inner surface, or both. The front end of the pressurizing element is the point of first contact with that layer or inner surface. The rear end of the pressurizing element is the point of last contact with that layer or inner surface. The front end is closer to p than the rear end. B The front end is farther from the back end than p. A Further. The axial position of the booster is the axial position of the front end.

[0149] The distance between the front and rear ends of the booster unit is the length L of the booster unit. C .

[0150] Friction force

[0151] The movement of the pressurizing component within the container is accompanied by frictional forces between the pressurizing component and the inner surfaces of the sidewalls and / or layers. These frictional forces include both static frictional forces resisting the base as the pressurizing component moves relative to the container and dynamic frictional forces acting during the movement of the pressurizing component.

[0152] The dynamic friction force depends on the axial position of the supercharger. Preferably, it is achieved by controlling the axial position p of the supercharger. + The pressurizing component begins to move and is moved from point p at a constant speed of 100 mm / min. + To p A The dynamic friction force at a given axial position p of the booster is determined by movement. The value of the dynamic friction force at the axial position p of the booster is the force required to maintain the speed of the booster at 100 mm / min when the booster is at the axial position p. The method for determining the dynamic friction force is shown in the attached figure.

[0153] Luer fitting

[0154] The preferred container preferably has a Luer fitting at the second end. The preferred Luer fitting is compatible with ISO 80369. The preferred Luer fitting is a Luer lock fitting and a sliding tip fitting, preferably a Luer lock fitting. In one embodiment, the container has a Luer lock fitting. In another embodiment, the container has a sliding tip fitting. The preferred Luer fitting is a male Luer fitting. The preferred Luer lock fittings are one-piece and two-piece Luer lock fittings. In one embodiment, the container has a one-piece Luer lock fitting. In another embodiment, the container has a two-piece Luer lock fitting.

[0155] Disposal

[0156] The method for preparing the treatment product contributes to achieving the objectives of this invention, and the method includes the following steps:

[0157] a. Provide a container;

[0158] b. converting the container into a disposal product.

[0159] In one embodiment, the pressurizing member is removed from the container, preferably through the first aperture.

[0160] In one embodiment, the method comprises one or more operations selected from the group consisting of: oxidizing, heating, burning, incinerating. Preferably, at least one of those operations is performed on the container once the pressurizing member has been removed from the container.

[0161] A preferred disposal product is a combustion product. A preferred product is a gas, preferably with suspended solid particles. A preferred disposal product comprises less than 5 ppm, preferably less than 4 ppm, more preferably less than 3 ppm of halogen by mass.

[0162] In one embodiment, converting the container into a disposal product comprises the steps of:

[0163] c. removing the pressurizing member from the container;

[0164] d. burning the container without the pressurizing member. BRIEF DESCRIPTION OF DRAWINGS

[0165] The application is now further illustrated by the accompanying drawings. The drawings are exemplary and do not limit the scope of the application. Some features of the drawings are shown.

[0166] Summary of drawings

[0167] Figure 1 A cross-sectional view of a cartridge embodiment of a container according to the application is shown.

[0168] Figure 2 A cross-sectional view of a syringe embodiment of a container according to the application is shown.

[0169] Figure 3 A cross-sectional view through the container at an axial position p along the axis is shown.

[0170] Figures 4a to 4f A process of removing the pressurizing member from the container is shown.

[0171] Figure 5 A schematic view of a disposal process is shown.

[0172] Figure 6 A dynamic force curve of Example 1 in the example section is shown.

[0173] Figures 7a to 7f A process for preparing an example container is shown. Detailed description

[0175] Figure 1A cross-sectional view of a cartridge embodiment of the container 100 according to the present invention is shown. The container 100 has a first end 119 and a second end 120. A first hole 102 is provided at the first end 119. A second hole 103 is provided at the second end 120. An attachment device 104 (not shown) may be present at the second end 120, preferably a Luer Lock type attachment device for attaching needle accessories. The container 100 has a cross-sectional view from an axial position p. A Extending to axial position p B The slender cylindrical section 501. p A and p B The distance between them is the length L of the slender cylindrical section 501. B For simplicity, the elongated cylindrical portion 501 is shown as a hollow cylinder. As a preferred alternative, the elongated cylindrical portion 501 can also be a hollow truncated cone, which, in p... A The diameter at point p is larger than that at point p. B The diameter at the point. Axis 101 extends in the elongated direction of container 100, serving as the axis of rotation for the elongated cylindrical portion 501. Sidewall 107 has an inner surface 118 on which a lubricant layer 106 is present. Sidewall 107 defines the boundary of interior 121. Layer 106 extends on some portions, but not all, of sidewall 107, not reaching end p. A and p B The axial position along axis 101 along container 100 is measured. The reference point p can be used as the zero point. + The axial position is given. The overall axial position p and the inner diameter d between the inner surfaces 118 of the sidewall 107 at that axial position are shown. The thickness t for the general position is shown. A pressure booster 203 (here, a brominated butyl rubber stopper) is present inside 121, with its front end at the axial position p. + At the point where its rear end is at the axial position p - The location. Existing internally in p + and p B The layer 106 in the middle part is more than the one that exists inside p. - and p A Layer 106 is thicker in the middle section. Layer 106 in p - and p A The thickness in the portion between them meets the requirements of the claims. In p + and p B Some liquid drug composition (not shown) may be present in the middle portion.

[0176] Figure 2A cross-sectional view of a syringe embodiment of a container 100 according to the present invention is shown. The container 100 has a first end 119 and a second end 120. At the first end 119 there is a first bore 102 and an outwardly protruding flange 105. At the second end 120 there is a second bore 103. At the second end 120 there can be an attachment means 104 (not shown), preferably a luer lock type attachment means 104 for attaching a needle fitting. The container 100 has an elongated barrel 501 extending from an axial position p A to an axial position p B . The distance between p A and p B is the length L B of the elongated barrel 501. For simplicity, the elongated barrel 501 is shown as a hollow cylinder. As a preferred alternative, the elongated barrel 501 can also be a hollow truncated cone, having a larger diameter at p A than at p B . The axis 101 is in the direction of the elongated extension of the container 100, which is the axis of rotation of the elongated barrel 501. The side wall 107 has an inner surface 118, on which there is a lubricant layer 106. The side wall 107 delimits the boundary of the interior 121. The layer 106 extends over some, but not all, of the side wall 107, not reaching the ends p A and p B . Axial positions along the container 100 are measured along the axis 101. Axial positions can be given with reference to p + as a reference zero point. The overall axial position p is shown, as well as the inner diameter d between the inner surface 118 of the side wall 107 at that axial position. The thickness t is shown for a general position. A booster 203 (here a bromobutyl rubber stopper) is present in the interior 121, with its front end at axial position p + and its back end at axial position p - . The booster 203 has an attached elongated rod 202 for pushing or pulling the booster 203 along the axis 101. The layer 106 present in the interior between p + and p B is thicker than the layer 106 present in the interior between p - and p A . The thickness of the layer 106 in the portion between p - and p A satisfies the requirements in the claims. In the portion between p + and p B there can be some liquid pharmaceutical composition (not shown).

[0177] Figure 3A cross-sectional view of the container 100 at an axial position p along axis 101 is shown. The sidewall 107 and lubricant layer 106 are shown as concentric circular bands. The thickness 301 of the sidewall 107 and the thickness 302 of the lubricant layer 106 are shown at eight equidistant points around this circle. The thickness of the sidewall 107 or layer 106 at axial position p is the average thickness around the circle. This average value is measured as the average of multiple (eight in this example) sampling points evenly distributed around the circle.

[0178] Figures 4a to 4f The process of removing the booster 203 from container 100 is illustrated. This series of figures shows how the booster 203 is pulled along the axis 101 of container 100 in a single motion at a constant speed of 100 mm / min. The illustrated process can also be used to construct a dynamic friction curve between the booster 203 and the sidewall 107 / lubricant layer 106, which is a function of the axial position along axis 101. Since the movement occurs in a single push, the static friction is only related to the starting point. Throughout the series of figures, the axial position of the booster is the position of its front end.

[0179] Figure 4a The diagram illustrates the preparation for removing the pressurizing element 203 from the container 100 according to the invention. Container 100 as... Figure 2 As shown. The booster 203 is at the axial position p + At the location, facing the second end 120 of the container.

[0180] Figure 4b It shows Figure 2 The container 100 contains a tension force 207 applied to an elongated rod 202 in a direction along axis 101 toward the first end 119. The force 207 is transmitted to the pressure booster 203. In this figure, the force 207 is less than the initial axial position p. + The static friction at the location is such that the booster 203 is stationary, and the force 207 is offset by the static friction between the booster 203 and the sidewall 207 / lubricant layer 106. The static friction at the axial position 201 is defined as the force 207 at which the booster 203 begins to move along the axis 101.

[0181] Figure 4c This shows that when force 207 exceeds the axial position p + The static friction force causes the pressurizing component 203 to move, resulting in the immediate state of the container 100. The pressurizing component 203 is still located at the axial position p+, but is in motion 208 along the axis 101. The force 207 is equal to the dynamic friction force at the axial position p+, and the pressurizing component 203 is in a constant speed state along the axis 101.

[0182] Figure 4d It shows the continuation Figure 4cThe container 100 following the container, wherein the pressurizing element 203 has traveled along axis 101 from p + The distance to p1. The booster 203 remains in constant velocity motion 208, where the tension 207 is equal to the dynamic friction force at the axial position p1. Therefore, the tension is measured based on the dynamic friction force at the axial position p1.

[0183] Figure 4e It shows Figure 4d Following the situation in container 100, the pressurizing member 203 has traveled a greater distance from p1 to p2 along axis 101. p2 is closer to the first hole 102 at the first end 119. The pressurizing member is still moving at a constant speed, and the force 207 and the kinetic friction force are equal. Therefore, the force 207 is measured based on the kinetic friction force at the axial position p2.

[0184] Figure 4f The image shows the container 100 after the pressurizing element 203 has exited through the first hole 102.

[0185] The dynamic friction at any point along axis 101 directly provides the force 207 required to maintain the constant speed (100 mm / min) of the booster 203 along axis 101 at that point. Point p + The kinetic friction forces at points p1 and p2 are respectively Figure 4c , 4d And the stage measurement of 4e.

[0186] Figure 5 A schematic diagram of the treatment process is shown. In the first step 2003, a container according to the invention is provided. In the second step 2004, the pressurizing element 203 is removed from the container. Then, in step 2005, the container 100 without the pressurizing element 203 is incinerated to obtain a treatment product 2001 as a gaseous combustion product. The pressurizing element 203, which contains butyl rubber, can be treated separately in step 2006 to obtain another treatment product 2002. Step 2006 is preferably not a combustion step. This method produces a gaseous combustion product 2001 that is halogen-free or has a reduced halogen content.

[0187] Figure 6 The dynamic force curves for 10 runs of Example 1 in the Example section are shown. The axial position of the booster 203 from p B to p A Presented in the direction of p, where p + The zero point is the starting point. The maximum value, approximately 4.5N to 6N, is displayed at a distance of about 50mm from the starting point. The minimum value, approximately 2.5N to 3N, is displayed at the start of operation.

[0188] Figures 7a to 7f The process for preparing the example container is shown. Figure 7aAn empty container with a plastic sidewall 107, a first hole 102 and a second hole 103 is shown. As Figure 7b indicated, a relatively thin lubricant layer 106 is applied to the inner surface of the sidewall 107, in this case with an average thickness of 20 nm. The 20 nm lubricant layer is applied by spraying. A booster 203 is provided. The booster 203 has a flexible bromobutyl rubber surface and has an elongated rod 202 attached by a thread. The booster 203 and the elongated rod 202 together act as a plunger. As Figure 7c indicated, the elongated rod 202 is used to push the booster 203 into the container via the first hole 102 and inside the container to near the second hole 103. The lubricant layer 106 facilitates the movement of the booster 203 inside the container by reducing friction with the sidewall 107. Some of the lubricant can be pushed forward by the booster 203 and accumulate in front of the booster 203. For ease of illustration, in Figure 7c the illustration, the thickness of the lubricant layer 106 in front of the booster 203 is exaggerated. As a result, the thickness of the lubricant layer 106 behind the booster is reduced to below the original value of 20 nm. As Figure 7d indicated, the elongated rod 202 is unscrewed from the booster 203 to facilitate access to the inside of the container, at which point the booster 203 is still located inside the container near the second hole 103, but the elongated rod 202 has been removed. The thickness of the lubricant layer 106 is then adjusted by adding or removing lubricant material. The lubricant material is added by spraying. The lubricant material is removed using a wiping tool, such as a sanitary tampon. The thickness profile of the lubricant layer 106 is adapted to the profile given in the example. Figure 7e A situation is shown in which the thickness of the lubricant layer 106 is increased by adding more lubricant. Once the desired thickness profile has been reached, the lubricant layer is cured by heating at 175 °C for 20 seconds. Figure 7f A container is shown with the elongated rod 202 screwed back onto the booster 203 to allow it to be used as a plunger.

[0189] Test method

[0190] Layer thickness

[0191] The thickness of the layer is determined by optical interferometry using a RapID Explorer available from rap.ID Particle Systems GmbH. The measurement is made from the outside of the container through the sidewall. The device uses proprietary software and is operated according to the 2014 proprietary instruction manual.

[0192] Resistance

[0193] The resistance was measured using a TesT 106.2kN device, available from TesT GmbH in Germany. The booster moved at a speed of 100 mm / min.

[0194] Examples

[0195] The following examples are provided to further illustrate the invention and do not limit the scope of the claimed invention.

[0196] The lubricant was prepared as follows: First, 10 g of vinyl-functionalized polydimethylsiloxane was loaded into a reaction vessel and mixed with 65 g of decamethylcyclopentasiloxane. Under constant stirring at 800 rpm, 0.5 g of methylhydrosiloxane / dimethylsiloxane copolymer, 6.25 g of liquid polydimethylsiloxane, 0.01 g of isopropanol containing 10% hexachloroplatinic acid as a catalyst, and 0.05 g of 2,4,7,9-tetramethyl-5-decyn-4,7-diol as an inhibitor were added to the reaction mixture. The reaction solution was used after stirring for 60 seconds. Figures 7a to 7f The method shown is based on Figure 2 A container was provided. The container was a 1 ml lg TopPac available from Schott AG, Germany. The thickness distribution of the applied layer is shown in Table 1. The pressurizing element was a brominated butyl rubber stopper FM257 / 2 available from Dedecke GmbH, Germany. Similar to... Figures 4a to 4f The process shown was used to determine the dynamic friction along the cylinder. A TesT 106.2kN device, available from TesT GmbH, Germany, was used. Values ​​at 10mm, 20mm, 50mm, and 60mm along the cylinder are shown in Table 2. During the measurement, the pressurizing element was kept at a constant speed of 100mm / min. The axial position within the cylinder is shown from p... B to p A The direction, where p + The value is zero. For each of Examples 1 through 5, a batch of 50 syringes was tested.

[0197] Table 1

[0198]

[0199] Table 2

[0200]

[0201] A small amount of liquid is drawn into the container and released using the container. The booster is then removed from the container, ready for the container to be incinerated. The force profile in Example 1 provides useful haptic feedback that allows fine control of the syringe, even without looking at the syringe while drawing up fluid. This is particularly useful when introducing a medicament into a patient, to combine the medicament with bodily fluids. The booster can be easily removed from the syringe of Example 1 before incineration. The empty container can then be incinerated, leaving no halogens in the disposal gas.

[0202] The syringe of Example 2 provides too much resistance for controlled drawing of liquid into the syringe. The booster is difficult to remove from the container, and sometimes gets stuck. The container, with the booster still inside it, has to be crushed and manually sorted to remove the booster before incineration, to avoid halogens in the disposal gas.

[0203] The syringes of Examples 3 and 4 do allow liquid to be drawn into the syringe. In both cases, it is more difficult to control the draw of liquid than in Example 1, due to the lack of haptic feedback. Controlled draw is not possible when looking away from the syringe. The booster can be easily removed in both Examples 3 and 4. However, during storage of the syringes of Examples 2 and 3, some boosters fall out of the container, spilling the remaining medicament.

[0204] List of reference signs

[0205] 100 container

[0206] 101 axis

[0207] 102 first aperture

[0208] 103 second aperture

[0209] 104 attachment means at the front end of the container

[0210] 105 outwardly projecting flange of the container

[0211] 106 lubricant layer

[0212] 107 side wall of the container

[0213] 118 inner surface of the side wall

[0214] 119 first end of the container

[0215] 120 second end of the container

[0216] 121 interior of the container

[0217] 202 elongate rod for pushing the booster

[0218] 203 booster

[0219] 207 tension

[0220] 208 movement of the pressurizing member along the axis

[0221] 501 elongated barrel portion

[0222] 2001 disposal product (combustion product)

[0223] 2002 additional disposal product (non-combustion product)

[0224] 2003 providing a container

[0225] 2004 removing the pressurizing member from the container

[0226] 2005 burning the empty container

[0227] 2006 disposing of the pressurizing member separately.

Claims

1. A container (100) for packaging medicines, having an elongated cylindrical portion (501), wherein: a. The container (100) has a first end (119) and a second end (120); b. The elongated cylindrical portion (501) has an elongated extension direction and an axis (101) in the elongated extension direction. c. Determine the axial position p along the axis (101); d. The elongated cylindrical portion (501) is located from the axial position p A Extending to axial position p B ; e. Length L of the cylinder B It is p A With p B The distance between them; f. The distance from the first end (119) to p A Comparison distance p B Closer; g. The second end (120) is at a distance from p B Comparison distance p A Closer; h. The container (100) has a first hole (102) at the first end (119) and a second hole (103) at the second end (120). i. The first hole (102) has a first hole diameter (601), and the second hole (103) has a second hole diameter (602), wherein the first hole diameter (601) is larger than the second hole diameter (602); j. The container (100) has a sidewall (107) extending on the elongated cylindrical portion (501), the sidewall (107) having an inner surface (118) defining the boundary of an interior (121), the interior (121) having a diameter (113). k. A layer (106) of lubricant is located on at least a portion of the inner surface (118); l. In p A and p B At a given axial position p on the axis (101) between the two axes, the following values ​​are determined as the average angles in the cross-sectional plane perpendicular to the axis (101) at the axial position p: i. The thickness of the sidewall (107), ii. The thickness of the layer (106), and iii. The diameter of the interior (113); m. A pressure booster (203) is present in the interior (121) and seals the cross section of the interior (121) between the inner surfaces (118) of the sidewall (107); n. Axial position p + The closest point of contact between the pressurizing element (203) and the layer (106) or the inner surface (118) is... B axial position; o. Axial position p - The closest point of contact between the pressurizing element (203) and the layer (106) or the inner surface (118) is... A axial position; p. p B and p + Distance between them divided by p + and p A The distance between them is in the range of 0 to 2; q. In p A and p - The average thickness of the layers determined between them is at least 10 nm; r. Meets one or more of the following criteria: i. Length L B Within the range of 3cm to 20cm; ii. In p A to p B The average value of the diameter (113) of the interior (121) determined within the range is in the range of 0.4 cm to 4 cm; iii. In p A to p B The average thickness of the sidewall (107) determined within the range is in the range of 0.3 mm to 4.5 mm; iv. The volume of the interior (121) is in the range of 0.1 ml to 150 ml; s. in p B and p + The average thickness of the layer (106) determined between p A and p - The average thickness of the layer is at least 1.5 times that determined between the two.

2. The container (100) according to claim 1, wherein, In p A and p - The average thickness of the layer (106) determined between the two is at most 300 nm.

3. The container (100) according to claim 1 or 2, wherein, In p A and p - The maximum thickness of the layer (106) determined between p is at a distance of p. - Comparison P A At a closer axial position.

4. The container (100) according to claim 1 or 2, wherein, The booster (203) includes halogen.

5. The container (100) according to claim 1 or 2, wherein, The maximum force required to remove the pressurizing element (203) from the container (100) through the first hole (102) is no greater than 10N.

6. The container (100) according to claim 1 or 2, wherein, The maximum force required to remove the pressurizing element (203) from the container (100) through the first hole (102) occurs when the front of the pressurizing element (203) is at a distance p. A Comparison distance p B More recently.

7. The container (100) according to claim 1 or 2, wherein, The lubricant includes one or more silicone oils.

8. The container (100) according to claim 1 or 2, comprising contents present in p + and p B The liquid drug composition in the internal portion between.

9. The container (100) according to claim 1 or 2, wherein, The container relates to a method for preparing a disposal product, comprising the following steps: a. Provide the container (100); b. Convert the container (100) into a disposal product.

10. The container (100) according to claim 9, comprising the following steps: - The pressurizing element (203) is removed from the container (100) through the first hole (102).

11. The container (100) according to claim 9, including a heating step.

12. The container (100) according to claim 9, wherein, The treatment products include less than 50 ppm of halogen by mass.

Images