Glass containers and sealing assemblies for maintaining seal integrity at low storage temperatures

Abstract

The sealed glass container includes a glass container and a sealing assembly. The glass container includes a flange having a lower side surface, an outer surface extending from the lower side surface, and a sealing surface (140) extending between the outer surface and an inner surface of the sealed glass container defining an opening. The sealing assembly includes a stopper (106) extending above the sealing surface of the flange and covering the opening; and a metal-containing cap (108) pressed against the flange. The metal-containing cap causes the stopper to compress. Compression on the sealing surface is maintained when the sealed glass container is cooled to a temperature less than or equal to -80°C. In an embodiment, the sealing surface includes an inclined sealing surface extending at an angle (150) greater than 5 degrees relative to a plane extending perpendicular to the inner surface.

Description

[0001] Cross-reference of related applications

[0002] This application claims priority to U.S. Provisional Application No. 3 / 111,718, filed November 10, 2020, pursuant to 35 U.S. SC §119, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This specification generally relates to glass containers, such as glass containers for storing pharmaceutical compositions. Background Technology

[0004] Drug containers (e.g., bottles and syringes) are typically sealed with stoppers or other closures to maintain the integrity of the contained material. Closures are usually made of synthetic rubber and other elastomers. These materials advantageously possess high impermeability and elasticity, facilitating insertion into the container to seal its interior. However, the elasticity of commonly used closure materials can decrease at low temperatures. For example, synthetic rubber currently used as closure material may have a transition temperature greater than or equal to -70°C and less than or equal to -45°C. Below the transition temperature, closures constructed from such synthetic rubber may exhibit solid behavior and may not be able to compensate for the large difference in coefficients of thermal expansion between the glass and the compression cap used to secure the closure to the container through elastic expansion. Consequently, existing sealing assemblies for drug containers may fail at temperatures below or equal to -45°C.

[0005] Some biological materials (e.g., blood, serum, proteins, stem cells, and other perishable biological fluids) need to be stored at temperatures below the glass transition temperature at which conventional elastomers remain usable. For example, certain RNA-based vaccines may require storage at dry ice temperatures (e.g., approximately -80°C) or liquid nitrogen temperatures (e.g., approximately -180°C) to maintain their activity. Such low temperatures can cause dimensional changes in enclosed components (e.g., glass or plastic containers, stoppers, aluminum caps), leading to issues with seal integrity and potential contamination of the materials stored within. Summary of the Invention

[0006] A first aspect of this disclosure includes a glass container comprising: a shoulder; a neck extending from the shoulder; and a flange extending from the neck. The flange includes: a lower surface extending from the neck; an outer surface extending from the lower surface, the outer surface defining an outer diameter of the flange; and an inclined sealing surface extending between the outer surface and an inner surface defining an opening in the glass container. The inclined sealing surface extends at an angle relative to a plane extending through the end of the opening, such that the distance between the inclined sealing surface and the plane increases as the radial distance relative to the outer surface decreases. This angle is greater than 5 degrees.

[0007] The second aspect of this disclosure includes a glass container according to the first aspect, wherein the angle is less than or equal to 45 degrees.

[0008] The third aspect of this disclosure includes a glass container according to any one of the first to second aspects, wherein the surface roughness of the inclined sealing surface is greater than or equal to 3 μm.

[0009] The fourth aspect of this disclosure includes a glass container according to any one of the first to third aspects, wherein the surface roughness of the inclined sealing surface is predetermined based at least in part on the shrinkage assessment of the sealing assembly associated with the glass container when the sealing assembly is cooled to a temperature less than or equal to -80°C.

[0010] The fifth aspect of this disclosure includes a glass container according to any one of the first to fourth aspects, wherein the inclined sealing surface has a surface roughness of less than or equal to 0.1 μm.

[0011] The sixth aspect of this disclosure includes a glass container according to any one of aspects 1 to 5, wherein the flatness of the inclined sealing surface is less than or equal to 5 μm.

[0012] The seventh aspect of this disclosure includes a glass container according to any one of the first to sixth aspects, wherein the inclined sealing surface includes a first edge disposed near the inner surface and a second edge disposed near the outer surface.

[0013] The eighth aspect of this disclosure includes a glass container according to any one of the first to seventh aspects, wherein a second edge is arranged radially inward of an outer surface, and the glass container further includes a chamfer extending between an inclined sealing surface and an outer surface.

[0014] The ninth aspect of this disclosure includes a glass container according to any one of aspects 1 to 8, wherein the glass container is made of materials with a coefficient of thermal expansion greater than or equal to 0 x 10⁻⁶. -7 / K and less than or equal to 70x10 -7 / K glass composition structure.

[0015] A tenth aspect of this disclosure includes a glass container comprising: a shoulder; a neck extending from the shoulder; a flange extending from the neck; and an inner surface defining an opening extending through the neck and the flange, wherein the flange includes an upper sealing surface extending from the inner surface. In an embodiment, the upper sealing surface includes an inclined sealing surface extending at an angle greater than 5 degrees relative to a plane perpendicular to the inner surface. In an embodiment, a portion of the upper sealing surface includes a length of at least 4 mm and a surface flatness of less than or equal to 5 μm.

[0016] The 11th aspect of this disclosure includes a glass container according to the 10th aspect, wherein the upper sealing surface includes an inclined sealing surface, wherein the angle is less than or equal to 45 degrees.

[0017] The 12th aspect of this disclosure includes a glass container according to any one of aspects 10 to 11, wherein the angle is greater than or equal to 7 degrees.

[0018] The 13th aspect of this disclosure includes a glass container according to any one of aspects 10 to 12, wherein the surface roughness of the inclined sealing surface is greater than or equal to 3 μm.

[0019] The 14th aspect of this disclosure includes a glass container according to any one of aspects 10 to 13, wherein: the upper sealing surface includes a portion having a length of at least 4 mm and a surface flatness of less than or equal to 5 μm, and the portion extends relative to the inner surface at an angle greater than or equal to 89.5 degrees and less than or equal to 90.5 degrees.

[0020] The 15th aspect of this disclosure includes a glass container according to any one of aspects 10 to 14, wherein the upper sealing surface includes a chamfered edge extending from the outer surface of the flange.

[0021] The 16th aspect of this disclosure includes a glass container according to any one of aspects 10 to 15, wherein the glass container is made of materials with a coefficient of thermal expansion greater than or equal to 0 x 10⁻⁶. -7 / ℃ and less than or equal to 70x10 -7 The glass composition structure is at / ℃.

[0022] The 17th aspect of this disclosure includes a sealed glass container comprising a glass container and a sealing assembly. The glass container includes: a shoulder; a neck extending from the shoulder; and a flange extending from the neck. The flange includes: a lower surface extending from the neck; an outer surface extending from the lower surface defining an outer diameter of the flange; and a sealing surface extending between the outer surface of the sealed glass container and an inner surface defining an opening. The sealing assembly includes: a plug extending above the sealing surface of the flange and covering the opening; and a metal-containing cap pressed against the flange. The metal-containing cap causes the plug to compress. As the sealed glass container cools to a temperature below or equal to 80°C, compression is maintained on the sealing surface, such that the helium leakage rate of the sealed glass container at said temperature is less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s.

[0023] The 18th aspect of this disclosure includes a sealed glass container according to the 17th aspect, wherein the difference between the coefficient of thermal expansion (“CTE”) of the metal cap and the CTE of the stopper is less than or equal to 50 x 10⁻⁶. -7 / K.

[0024] The 19th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 18, wherein the CTE of the container with a metal lid is greater than or equal to 250 x 10 mm. -7 / K.

[0025] The 20th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 19, wherein the metal lid contains at least one of Zn and Mg.

[0026] The 21st aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 20, wherein the metal-containing lid is constructed of an aluminum-containing polymer composite material.

[0027] The 22nd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 21, wherein the metal lid is constructed of a metal alloy comprising at least one of Zn, Al, Mg, and Cu.

[0028] The 23rd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 22, wherein the metal lid is constructed of a Pb-Sn alloy.

[0029] The 24th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 22, wherein the CTE of the stopper is less than or equal to 290 x 10⁻⁶. -7 / K.

[0030] The 25th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 24, wherein the stopper is constructed of a polymer composite comprising greater than or equal to 0% by weight and less than or equal to 30% by weight of a silicon-based filler material.

[0031] The 26th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 25, wherein the silicon-based filler material comprises SiO2 glass particles.

[0032] The 27th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 26, wherein the silicon-based filler material comprises silicate / ester.

[0033] The 28th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 27, wherein the glass transition temperature of the stopper is less than or equal to -75°C.

[0034] The 29th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 28, wherein: the sealing surface includes an inclined sealing surface extending between an outer surface and an inner surface, the inclined sealing surface extending at an angle relative to a plane extending through an end of an opening, such that the distance between the inclined sealing surface and the plane increases as the radial distance relative to the outer surface decreases, and the angle is greater than or equal to 6 degrees.

[0035] The 30th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 29, wherein the surface roughness of the sealing surface is greater than or equal to 3 μm.

[0036] The 31st aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 30, further comprising a sealing material disposed between a stopper and a metal-containing cap, the CTE of the sealing material being less than that of the stopper and the metal-containing cap.

[0037] The 32nd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 31, wherein the sealing material includes at least one of Ir, W, Ti and Si.

[0038] The 33rd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 32, wherein the sealing material comprises a polymer-based composite.

[0039] The 34th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 33, wherein the sealing material includes at least one of SiO2, Ti-doped SiO2, ZrW2O8 and AM2O8 ceramics.

[0040] The 35th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 34, wherein the composition of the metal lid along the central axis of the sealed glass container is non-uniform.

[0041] The 36th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 35, wherein the metal-containing lid comprises an aluminum layer and at least one multilayer structure in contact with the aluminum layer.

[0042] The 37th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 36, wherein the multilayer structure comprises an elastomer layer and a glassy polymer layer having a glass transition temperature greater than 25°C.

[0043] The 38th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 37, wherein the metal lid comprises a multilayered structure with a thickness greater than or equal to 200 μm and less than or equal to 300 μm.

[0044] The 39th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 38, wherein the stopper comprises a radially heterogeneous composition.

[0045] The 40th aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 39, wherein the stopper includes a low-T component in contact with a sealing surface. g Section.

[0046] The 41st aspect of this disclosure includes a sealed glass container according to any one of aspects 17 through 40, wherein low T g The section includes low T g Elastomers comprising one or more of the following: polybutadiene, silicone, fluorosilicone, nitrite / ester, and EPDM elastomers.

[0047] The 42nd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 41, wherein low T g The section contains 0% or more and 30% or less of filler material by weight.

[0048] The 43rd aspect of this disclosure includes a sealed glass container according to any one of aspects 17 to 42, wherein the filler material comprises silicon-based particles.

[0049] Other features and advantages of the processes and systems described herein are set forth in the following detailed description, some of which will be readily apparent to those skilled in the art from the description, or will be recognized by practicing the embodiments described herein, including the following detailed description, the claims, and the accompanying drawings.

[0050] It should be understood that the foregoing general description and the following detailed description both depict various embodiments and are intended to provide an overall overview or framework for understanding the nature and characteristics of the claimed subject matter. The included drawings provide a further understanding of the various embodiments and are incorporated in and form a part of this specification. The drawings illustrate the various embodiments described herein and, together with the description, serve to explain the principles and operation of the claimed subject matter. Attached Figure Description

[0051] The embodiments illustrated in the accompanying drawings are illustrative and exemplary in nature and are not intended to limit the subject matter defined by the claims. A detailed description of the illustrative embodiments can be understood by reading the following drawings, in conjunction with which the same structures are indicated by the same reference numerals, wherein:

[0052] Figure 1A A schematic cross-sectional view of a sealed glass container according to one or more embodiments described herein is shown.

[0053] Figure 1B A schematic cross-sectional view of a glass container according to one or more embodiments described herein is shown.

[0054] Figure 1C The schematic diagram shows a cross-sectional view of the upper portion of a metal-containing lid according to one or more embodiments described herein;

[0055] Figure 1D A schematic cross-sectional view of a plug according to one or more embodiments described herein;

[0056] Figure 2A A schematic cross-sectional view of a glass container according to one or more embodiments described herein is shown.

[0057] Figure 2B A schematic cross-sectional view of a glass container according to one or more embodiments described herein is shown.

[0058] Figure 3 A schematic cross-sectional view of a sealed glass container according to one or more embodiments described herein is shown.

[0059] Figure 4AThe illustration schematically shows a compression simulation of a stopper abutting against the flange of a glass container at various storage temperatures according to one or more embodiments described herein, wherein the flange includes a first flange angle;

[0060] Figure 4B The illustration schematically shows a compression simulation of a stopper abutting against the flange of a glass container at various storage temperatures according to one or more embodiments described herein, wherein the flange includes a second flange angle;

[0061] Figure 4C The illustration schematically shows a compression simulation of a stopper abutting against the flange of a glass container at various storage temperatures according to one or more embodiments described herein, wherein the flange includes a third flange angle;

[0062] Figure 4D The illustration schematically shows a compression simulation of a stopper abutting against the flange of a glass container at various storage temperatures according to one or more embodiments described herein, wherein the flange includes a fourth flange angle;

[0063] Figure 4E This illustrates how, according to one or more embodiments described herein, when cooled at a first cooling rate... Figures 4A-4D The graph showing the functional relationship between the contact area between the flange and the plug and temperature; and

[0064] Figure 4F This illustrates how, according to one or more embodiments described herein, when cooled at a second cooling rate... Figures 4A-4D The graph shows the relationship between the contact area between the flange and the plug and the temperature. Detailed Implementation

[0065] Specific reference will now be made to embodiments of sealed glass containers comprising a sealing assembly that maintains the integrity of the sealed contents at lower storage temperatures (e.g., less than or equal to -40°C, less than or equal to -50°C, less than or equal to -60°C, less than or equal to -70°C, less than or equal to -80°C, less than or equal to -100°C, less than or equal to -125°C, less than or equal to -150°C, less than or equal to -175°C, -180°C). In embodiments, the structure of the glass container described herein may be modified in one or more aspects relative to existing pharmaceutical containers to help maintain a seal at the interface between the glass container and the sealing assembly inserted therein. For example, embodiments of the glass container described herein may be vials (but other container shapes also fall within the scope of this disclosure) comprising: a shoulder, a neck, a flange including a sealing surface, and a stopper of the sealing assembly pressed against the sealing surface by a metal cap. Various characteristics of the sealing surface may be modified to help maintain a seal when the sealed glass container is cooled to such low storage temperatures. For example, in one embodiment, the sealing surface may include a sloped sealing surface that slopes downwards with increasing radial distance from the central axis of the glass container. The sloped sealing surface may slope downwards at an angle greater than 5 degrees (e.g., greater than 5 degrees and less than or equal to 45 degrees) relative to a plane extending above the end of the glass container, thereby increasing the initial force against the stopper during the crimping process and increasing tolerance to stopper shrinkage when cooled to lower temperatures. In another embodiment, the sealing surface extends perpendicular to the central axis of the glass container (e.g., at an angle greater than or equal to 90 degrees and less than or equal to 89.5 degrees), thereby maximizing the contact area between the sealing surface and the stopper. In yet another embodiment, various other characteristics of the sealing surface (e.g., surface roughness and flatness, etc.) may be adjusted to increase seal integrity.

[0066] In embodiments, the sealing assemblies connected to glass containers described herein can be formed from a variety of material combinations to help maintain a seal at low storage temperatures. The sealing assemblies of this specification may comprise a stopper and a metal-containing cap, formed from a composition adjusted to prevent excessive deformation of the stopper relative to the cap at low storage temperatures, thereby maintaining sufficient sealing force applied to the stopper via the metal-containing cap. For example, in embodiments, the metal-containing cap may be constructed from a material that increases its CTE compared to existing aluminum press-fit caps. In embodiments, the metal-containing cap may be constructed from at least one of Zn or Mg instead of Al to provide a higher CTE. In embodiments, the metal-containing cap is constructed from an aluminum-containing polymer composite material. In embodiments, the metal-containing cap is constructed from a metal alloy containing at least one of Zn, Al, Mg, and Cu. In embodiments, the stopper is constructed from a material with a lower CTE than existing pure rubber stoppers. For example, in embodiments, the stopper may be constructed from a polymer composite containing greater than 0% by weight and less than or equal to 30% by weight of a silicon-based filler material. Silicon-based filler materials may include SiO2 glass particles or various silicates / esters (e.g., cordierite, β-nepheline, β-spodumene) or combinations thereof. The CTE of the stopper may be less than or equal to 290 x 10⁻⁶. -7 / K thereby reducing its shrinkage at low storage temperatures. Various implementations may include additional sealing material disposed between the metal cap and the stopper. The sealing material may include a low CTE (e.g., less than or equal to 50 x 10). -7 / K) to allow the metal cap to shrink at lower storage temperatures at a rate greater than that of the sealing material, thereby enabling the metal cap to exert a sealing force on the stopper and the sealing material. In embodiments, the sealing material may comprise at least one of the following: Ir, W, Ti, and Si. In embodiments, the sealing material comprises a polymer-based composite.

[0067] As used herein, the term "surface roughness" refers to the Ra value or Sa value. The Ra value is a measurement of the arithmetic mean of the filtered roughness distribution, determined by the deviation relative to the centerline of the filtered roughness. For example, the Ra value can be determined based on the following relationship:

[0068]

[0069] In the formula, H i It is the measurement of the surface height, and H CLThe surface height is measured corresponding to the centerline of the data points in the filtered distribution (e.g., the center between the maximum and minimum surface height values). The Sa value can be determined by area extrapolation using Equation 1 of this document. The filter value (e.g., the cutoff wavelength) used to determine the Ra or Sa value described herein can be found in ISO 25718 (2012). Surface height can be measured using various tools (e.g., optical interferometers, stylus-based profilometers, or laser confocal microscopes). To assess the roughness of the surface described herein (e.g., a sealed surface or a portion thereof), the largest possible measurement area in practice should be used to assess the variability that may exist on a large spatial scale.

[0070] As used herein, the term "container closure integrity" refers to maintaining a seal at the interface between the glass container and the sealing assembly (e.g., between the sealing surface of the glass container and the stopper), based on the material stored in the glass container, that the seal does not contain gaps larger than a threshold size for maintaining the likelihood of contaminant intrusion or reduces the likelihood of gas permeability falling below a predetermined threshold. For example, in an embodiment, if in USP <1207> The helium leakage rate during the helium leakage test described in (2016) is less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s maintains the integrity of the enclosed object in the container.

[0071] In the embodiments of the glass containers described herein, unless otherwise stated, the concentrations of the constituent components (e.g., SiO2, Al2O3, and B2O3, etc.) of the glass composition forming the glass container are specified as mole percentages (mol%) based on oxides.

[0072] When used to describe the concentration and / or absence of a particular component in a glass composition, the term "substantially absent" means that the component has not been intentionally added to the glass composition. However, the glass composition may contain trace amounts of the component as a contaminant or contain an indeterminate amount less than 0.05 mol%.

[0073] Unless otherwise stated, as used herein, the term “CTE” refers to the coefficient of thermal conductivity over a temperature range of about -200°C to about 300°C.

[0074] As used herein, the term "about" indicates that a quantity, size, formulation, parameter, and other variable and characteristic is not, and does not need to be, exact, but may be approximate and / or larger or smaller as required, reflecting tolerances, conversion factors, rounding and measurement errors, and other factors known to those skilled in the art. When the term "about" is used to describe a value or endpoint of a range, the specific value or endpoint referenced is included. Whether or not the numerical values ​​or endpoints of a range in the specification are described with "about," there are two implementations: one modified with "about" and one not modified with "about." It will also be understood that each endpoint of a range is important both in relation to and independently of another endpoint.

[0075] The directional terms used in this article, such as up, down, right, left, front, back, top, and bottom, are only for reference to the accompanying drawings and are not intended to imply absolute orientation.

[0076] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein include plural references. Thus, for example, a reference to a “one” component includes aspects having two or more such components, unless otherwise explicitly stated in the text.

[0077] See now Figure 1A Figure 1 schematically illustrates one embodiment of a sealed glass container 100 for storing pharmaceutical preparations in cross-section. The sealed glass container 100 includes a glass container 102 and a sealing assembly connected to the glass container 102 via an opening 105. The sealing assembly includes a stopper 106 and a metal cap 108. In the embodiment shown in Figure 1, the stopper 106 includes an insertion portion 117 and a sealing portion 119. The insertion portion 117 is inserted into the opening 105 of the glass container 102 until the sealing portion 119 contacts the upper sealing surface 110 of the glass container 102. The sealing portion 119 then presses against the upper sealing surface 110 via the metal cap 108, thereby forming a seal at the upper sealing surface 110. Various aspects of the glass container 102 and the sealing assembly are designed to ensure the container closure integrity of the glass container 102 is maintained at low storage temperatures, as described herein.

[0078] The glass container 102 typically includes a body 112. The body 112 extends between an inner surface 114 and an outer surface 116 of the glass container 102, includes a central axis A, and substantially encloses an internal volume 118. Figure 1AIn the illustrated embodiment of the glass container 102, the body 112 generally includes a wall portion 120 and a base portion 122. The wall portion 120 transitions to the base portion 122 via a heel portion 124. In the illustrated embodiment, the glass container 102 includes: a flange 126, a neck 128 extending from the flange 126, a barrel 115, and a shoulder 130 extending between the neck 128 and the barrel 115. The base portion 122 is connected to the barrel 115 via the heel portion 124. In this embodiment, the glass container 102 is symmetrical about a central axis A, and each of the barrel 115, the neck 128, and the flange 126 is substantially cylindrical. The body 112 has a wall thickness T. w It extends between the inner surface 114 and the outer surface 116, such as Figure 1A As shown.

[0079] In this embodiment, the glass container 102 can be made of materials such as USP <660> The defined Type I, Type II, or Type III glass formations include borosilicate glass compositions, such as USP <660> The glass container 102 may be formed from a type 1B borosilicate glass composition. Alternatively, the glass container 102 may be formed from an alkaline aluminosilicate glass composition, such as those described in U.S. Patent No. 8,551,898 (the entire contents of which are incorporated herein by reference) or from an alkaline earth aluminosilicate glass, such as those described in U.S. Patent No. 9,145,329 (the entire contents of which are incorporated herein by reference). In an embodiment, the glass container 102 may be constructed from a soda-lime silicate glass composition. In an embodiment, the glass container 102 has a coefficient of thermal expansion greater than or equal to 0 x 10⁻⁶. -7 / K and less than or equal to 100x10 -7 / K (e.g., greater than or equal to 30x10) -7 / K and less than or equal to 70x10 -7 The glass composition is constructed of / K).

[0080] Although Figure 1A The glass container 102 shown has a specific shape element (i.e., vial), but it should be understood that the glass container 102 may have other shape elements, including but not limited to, Cartridges, syringes, ampoules, bottles, flasks, medicine bottles, tubes, or beakers, etc. Furthermore, it should be understood that the glass containers described herein can be used for a variety of applications, including but not limited to, pharmaceutical packaging or beverage containers.

[0081] The wall thickness T of glass container 102 W This can vary depending on the practice. In one implementation, the wall thickness T of the glass container 102 is... WIt can be less than or equal to 6 millimeters (mm), for example: less than or equal to 4 mm, less than or equal to 2 mm, less than or equal to 1.5 mm, or less than or equal to 1 mm. In some embodiments, the wall thickness T W It can be: greater than or equal to 0.1 mm and less than or equal to 6 mm, greater than or equal to 0.3 mm and less than or equal to 4 mm, greater than or equal to 0.5 mm and less than or equal to 4 mm, greater than or equal to 0.5 mm and less than or equal to 2 mm, or greater than or equal to 0.5 mm and less than or equal to 1.5 mm. In the embodiment, the wall thickness T W The wall thickness T can be greater than or equal to 0.9 mm and less than or equal to 1.8 mm. W It can vary depending on the axial position within the glass container 102.

[0082] like Figure 1A As shown, flange 126 includes a lower surface 132, an outer surface 136, and an upper sealing surface 110. The outer surface 136 may define the outer diameter of flange 126. In an embodiment, the metal-containing cap 108 of the sealing assembly is crimped around flange 126 by any suitable crimping method (e.g., pneumatic crimping equipment, etc.). During the sealing process, plug 106 is inserted into opening 105, and a compressive force is applied to metal-containing cap 108 during crimping. For example, as... Figure 1A As shown, the metal cap 108 includes a lower portion 109 that contacts the lower surface 132 of the flange 126, thereby forcing the stopper 106 to remain compressed and forming a seal after the crimping process. The compression of the stopper 106 creates a residual sealing force within the flange 126, which maintains the compression of the stopper 106 after the metal cap 108 is crimped into place. In this embodiment, the length of the lower portion 109 of the metal cap 108 that directly contacts the lower surface 132 of the flange 126 has a length (e.g., Figure 1A The value in the X direction shown is greater than or equal to 1 mm, which helps to maintain the residual sealing force within the stopper 106 at storage temperatures less than or equal to -80°C.

[0083] When the sealed glass container 100 is cooled to a lower storage temperature of less than or equal to -80°C (e.g., less than or equal to -80°C, less than or equal to -100°C, less than or equal to -125°C, less than or equal to -150°C, less than or equal to -175°C, -180°C), each component of the sealed glass container 100 may undergo volumetric shrinkage depending on the thermal properties of that component. Figure 1AAs shown, the volume of material disposed between the lower portion 109 and the upper portion 113 of the metal cap 108 includes the sealing portion 119 of the stopper 106 and the flange 126 of the glass container 102. If the amount of contraction of the combination of the stopper 106 and the flange 126 is greater than the amount of contraction of the metal cap 108, the compression provided by the metal cap 108 on the stopper 106 may be reduced, increasing the possibility of seal failure at the upper sealing surface 110.

[0084] For example, such as Figure 1A As shown, the total height 138 of the flange 126 and the plug 106 (e.g., Figure 1A The distance in the Z direction shown is approximately equal to the distance between the upper portion 113 and the lower portion 109 of the metal cap 108. In this state, the metal cap 108 can press the stopper 106 against the upper sealing surface 110 to form a seal. However, if the total height 138 shrinks more than the metal cap 108, the compression of the stopper 106 may decrease, which reduces the residual sealing force. To maintain the compression of the stopper 106, the shrinkage ΔL of the metal cap 108, the stopper 106, and the glass container 102 can satisfy the following relationship:

[0085] ΔL 盖子 =ΔL 小瓶 +ΔL 塞子 (1)

[0086] In the formula, the contraction ΔL of each component can be approximated as:

[0087] ΔL=L i x(e ∫α(T) -1), (2)

[0088] In the formula, L i α is the initial size of the component, and α(T) is the temperature-dependent CTE of the material used to construct each of the metal cap 108, stopper 106, and glass container 102.

[0089] In this embodiment, the stopper 106 is constructed from a polymer-based material (e.g., butyl or gas-synthetic rubber). Such materials may include a glass transition temperature (Tg) greater than or equal to -70°C and less than or equal to -45°C. g ). Below T g At this time, the stopper 106 may exhibit solid behavior (e.g., lose its elasticity), resulting in a reduction in the sealing force at the upper sealing surface 110. For example, if the stopper 106 is cooled below its T... gIf this happens, the stopper 106 may not completely fill the gap between the sealing surface 110 and the upper portion 113 of the metal cap 108, increasing the likelihood of seal failure. In other words, when cooled below its glass transition temperature, the stopper 106 effectively exhibits two distinct material behaviors: above the transition temperature, it is an elastic material; and below the transition temperature, it is solid glass. According to Equation 2 of this paper, when cooled from the initial temperature T... i Cooled to final temperature T F At that time, the contraction of the plug 106, which is located between the flange 126 and the upper portion 113 containing the metal cap 108, can be approximated as follows:

[0090]

[0091] In the formula, α 玻璃 This refers to the CTE (Crystal Transition Temperature) of the rubber of the stopper 106 when it transforms into a glassy material below its glass transition temperature Tg. In embodiments, to maintain a seal, the metal cap 108 and the stopper 106 can be configured such that the shrinkage of the metal cap 108 is greater than or equal to the total shrinkage of the glass container 102 and the stopper 106. To facilitate compliance with this relationship, the shrinkage of the metal cap 108 can be increased, the shrinkage of the stopper 106 and the flange 126 can be decreased, or any combination thereof. Alternatively or supplementarily, the structure of the glass container 102 can be designed to increase the initial cap compression imparted to the stopper 106, thereby providing greater tolerance to the shrinkage of the stopper 106.

[0092] In an embodiment, the metal cap 108, as defined by CTE, can be approximately 240x10. -7 / K aluminum construction. Typical rubber used to construct stopper 106 (e.g., butyl 325, butyl 035, etc.) may have a density greater than or equal to 300 x 10⁻⁶. -7 / K's CTE. In other words, solely based on CTE differences, the metal cap 108 tends to shrink less than the stopper 106, resulting in reduced sealing force at lower storage temperatures. Besides the CTE mismatch mentioned above, such as... Figure 1A As shown, the volume percentage of the sealing assembly occupied by the plug 106 may be greater than that of the metal cap 108, further exacerbating the tendency of the compounding plug 106 to undergo greater thermal shrinkage.

[0093] exist Figure 1A In the embodiment shown, in order to counteract the tendency of the stopper to shrink and overwhelm the shrinkage of the metal cap 108 at low storage temperatures, the structure of the glass container 102 is modified to deviate from that of existing glass containers to provide greater compression of the stopper 106 during the crimping process of the metal cap 108. Figure 1B A schematic view of the glass container 102 from the shoulder 130 upwards. (See diagram.) Figure 1B As shown, the upper sealing surface 110 includes an inclined sealing surface 140. The inclined sealing surface 140 extends between the outer surface 136 of the flange 126 and the inner surface 114 of the glass container 102. The inclined sealing surface 140 extends at an angle 150 relative to a plane 152 extending through the end 154 of the opening 105. The plane 152 may be a flat surface located at the opening 105 on the top of the glass container 102 (e.g., at the peak of the inclined sealing surface 140). In an embodiment, the plane 152 connects a reference point about the upper sealing surface 110 relative to the glass container 102 (e.g., the bottom plate portion 122, see below). Figure 1A The point extending furthest. Plane 152 may extend through the top of glass container 102, in a direction perpendicular to the central axis A of glass container 102 (e.g., Figure 1B (shown in the X direction). In this embodiment, plane 152 perpendicular to inner surface 114 defines a portion of the extension of opening 105.

[0094] As described herein, angle 150 may be referred to as the “flange angle.” The flange angle relative to plane 152 can be measured in various ways. For example, in one embodiment, to determine the extension direction of the inclined sealing surface 140, an image of the glass container 102 can be captured, and image processing techniques can be used to determine the angle 150 of the inclined sealing surface 140 relative to plane 152. In another embodiment, the extension direction of the inclined sealing surface 140 is measured by finding a plane extending between the peak of the inclined sealing surface 140 (e.g., having the maximum distance in the Z direction relative to the lower surface 132) and a second highest point on the inclined sealing surface 140 (e.g., measuring the extension direction of the inclined sealing surface 140 via a plane located on the peak of the inclined sealing surface and another point of the inclined sealing surface 140 relative to the peak of plane 152). In one embodiment, the extension direction of the inclined sealing surface 140 is measured via points on the inclined sealing surface 140 that connect the inner surface 114 and the outer surface 136 at predetermined inward distances (e.g., 0.1 mm, 0.2 mm, 0.5 mm, 1.0 mm, etc.). In another embodiment, the extension direction of the inclined sealing surface 140 is measured by curve fitting a linear plane relative to multiple different points distributed throughout the inclined sealing surface 140.

[0095] In this embodiment, angle 150 is greater than or equal to 5 degrees and less than or equal to 45 degrees (e.g., greater than or equal to 5 degrees and less than or equal to 40 degrees, greater than 5 degrees and less than or equal to 40 degrees, greater than 5 degrees and less than or equal to 30 degrees, greater than 5 degrees and less than or equal to 20 degrees, greater than 5 degrees and less than or equal to 10 degrees). In this embodiment, angle 150 is substantially uniform around the circumference of glass container 102 (e.g., when measured in multiple azimuth directions, each measurement differs from the others by less than 0.5 degrees). In conventional glass containers, a typical angle 150 is approximately 3 degrees. Thus, in glass container 102, the inclination of the upper sealing surface 110 relative to plane 152 is increased by at least 50% compared to conventional glass containers. The greater inclination of the upper sealing surface 110 tends to increase stopper compression at low storage temperatures. As a result of the compression of the metal cap 108, angle 150 can create a compression gradient within the stopper 106. For example, in one embodiment, the compression of the plug 106 can increase with increasing radial distance relative to the outer surface 136, resulting in greater plug compression closer to the inner surface 114. This greater compression closer to the inner surface 114 can prevent gaps from forming in the seal as the plug 106 shrinks due to cooling.

[0096] See Figure 1A As a result of the angle 150, the distance 156 between the upper portion 113 of the metal cap 108 and the upper sealing surface 110 can vary as a function of radial distance relative to the central axis A, to a greater extent than in conventional glass containers. Consequently, the stopper 106 experiences greater compression near the opening 105 than the peripheral region of the stopper 106 located near the outer surface 136 of the flange 126. This greater compression results in greater compression of the stopper 106 under the same crimping process, providing greater tolerance for shrinkage of the stopper 106. Furthermore, the inclined sealing surface 140 reduces the term L near the opening 105 in Equation 3 above. i,塞子 This reduces the amount of shrinkage of the metal cap 108 required to maintain the relationship in Equation 1 of this paper.

[0097] See Figure 1BThe inclined sealing surface 140 includes a first edge 142 disposed near the inner surface 114 and a second edge 144 disposed near the outer surface 136 of the flange 126. In the illustrated embodiment, the inclined sealing surface 140 extends the entire distance between the outer surface 136 and the inner surface 114 such that the inclined sealing surface 140 corresponds to the upper sealing surface 110 (e.g., the upper sealing surface 110 corresponds to the inclined sealing surface 140). In another embodiment, the inclined sealing surface 140 extends only a portion of the distance between the outer surface 136 and the inner surface 114 such that the inclined sealing surface 140 is only a part of the upper sealing surface 110. In yet another embodiment, the length of the inclined sealing surface 140 (e.g., in a direction extending at an angle 150 relative to the plane 152) is greater than or equal to 3 mm, thereby contributing to a sufficient contact area with the stopper 106 (see [link to relevant documentation]). Figure 1A ).

[0098] In the implementation method, it is possible to... Figure 1A and 1B Various other characteristics of the upper sealing surface 110 and / or the inclined sealing surface 140 shown are adjusted to maintain a seal at storage temperatures less than or equal to -80°C. For example, in one embodiment, the upper sealing surface 110 has a surface roughness (e.g., Ra value) less than or equal to a threshold (e.g., 0.1 μm, 50 nm, etc.). Such low surface roughness advantageously prevents the stopper 106 from being pulled away from the upper sealing surface 110 after cooling. In another embodiment, the upper sealing surface is substantially free of defects (e.g., wrinkles, bumps, bulges, etc.). Such defects can cause gaps to form at the interface between the upper sealing surface 110 and the stopper 106, thereby reducing the seal quality. The flatness of the inclined sealing surface 140 can be maintained within a threshold to facilitate adhesion between the stopper 106 and the upper sealing surface 110.

[0099] In one embodiment, the upper sealing surface 110 includes a surface roughness (e.g., Sa value) greater than or equal to a threshold (e.g., 3 μm, 5 μm, 10 μm), thereby increasing friction at the upper sealing surface 110 between the glass container 102 and the stopper 106. In such embodiments, the surface roughness of the upper sealing surface 110 can be relatively uniform throughout. For example, the variation of the Sa value of the upper sealing surface 110 over a plurality of different measurement windows (e.g., 100 μm by 100 μm) can be less than or equal to 0.1 μm. In one embodiment, the roughness of the upper sealing surface 110 can be determined at least in part based on the properties of the stopper 106 (e.g., surface roughness). In one embodiment, the roughness of the upper sealing surface 110 can be approximately equal to the shrinkage difference between the combination of the metal cap 108 and the flange 126 and the stopper 106. For example, in one embodiment, the surface roughness of the upper sealing surface 110 can be within a threshold for evaluating the shrinkage difference between the combination of the metal cap 108 and the flange 126 and the stopper 106. Providing this type of surface roughness ensures at least some contact between the upper sealing surface 110 and the plug 106 after cooling.

[0100] See Figure 1A In addition to the inclined sealing surface 140 and the composition of the sealing assembly (e.g., including the metal cap 108 and the stopper 106), additional structural modifications can be made to the sealed glass container 100 to ensure the integrity of the sealed object at cold storage temperatures. For example, in one embodiment, the flange thickness 158 (the distance between the upper sealing surface 110 and the lower side surface 132) can be increased compared to existing glass containers. In such embodiments, if the pressing process of the stopper 106 and the metal cap 108 is not modified, the total height 138 of the material containing the higher CTE stopper 106 sealed by the metal cap 108 is reduced, thereby reducing the shrinkage of the metal cap 108 required to satisfy Equation 1 described herein. As a supplement or alternative, the dimensions of the stopper 106 can be reduced (e.g., in terms of the thickness of the sealing portion 119). In one embodiment, the flange height 158 ​​is greater than or equal to 4.0 mm and constitutes at least 61% of the total height 138.

[0101] Besides being able to compare this article with Figure 1A and 1BIn addition to designing the structure of the glass container 102 to maintain a seal at low storage temperatures, the composition of the sealing assembly can be adjusted to help satisfy Equation 1 at cold storage temperatures. For example, in one embodiment, the metal-containing cap 108 is constructed of a material with a CTE higher than that of aluminum, which helps it shrink more after cooling and thus helps compress a larger stopper 106. In another embodiment, the metal-containing cap 108 is configured such that the difference between the CTE of the metal-containing cap and the CTE of the glass container 102 is greater than or equal to 180 x 10⁻⁶. -7 / K. In this embodiment, the CTE containing the metal cap 108 is greater than or equal to 250 x 10. -7 / K (greater than or equal to 260x10) -7 / K, greater than or equal to 270x10 -7 / K, greater than or equal to 280x10 -7 / K, greater than or equal to 290x10 -7 / K). In an embodiment, the CTE of the metal cap 108 is greater than or equal to that of aluminum (at a desired storage temperature of less than or equal to -70°C), but less than or equal to the CTE of the material that forms the stopper 106.

[0102] In one embodiment, the metal cap 108 contains Zn or Mg to increase the cap's CTE relative to aluminum. In another embodiment, the metal cap 108 is constructed of a metal alloy containing at least one of Zn, Mg, Al, and Cu (e.g., a ZAMAK alloy). In yet another embodiment, the metal alloy contains less than 5% by weight of Al. In yet another embodiment, the metal cap 108 includes other alloys, such as suitable Pb-Sn alloys. In yet another embodiment, any suitable metal alloy can be used. The metal alloy can be advantageously used in existing crimping processes. Thus, no significant modifications to current bottle-making processes are required to achieve the sealing improvements described herein.

[0103] In one embodiment, the metal-containing cap 108 is constructed of a polymer-metal composite material. For example, in one embodiment, the metal-containing cap 108 is constructed of an aluminum-polymer composite, comprising a polymer matrix coated with an aluminum-containing coating. In another embodiment, the metal-containing cap 108 is constructed of an aluminum-polymer composite, comprising an aluminum matrix having polymer-based reinforcements disposed therein.

[0104] In one embodiment, the metal-containing lid 108 includes a heterogeneous structure along the central axis A of the sealed glass container 100. In another embodiment, the metal-containing lid 108 includes a multilayer laminated structure. The multilayer laminated structure may comprise a metal layer and at least one polymer layer. For example, Figure 1CThe diagram schematically shows a cross-sectional view of the upper portion 113 of an embodiment containing a metal cap 108. The metal cap 108 comprises: an aluminum layer 160, a first multilayer structure 162, and a second multilayer structure 168. In one embodiment, the aluminum content of the metal cap 108 is greater than or equal to 40% by volume and less than or equal to 90% by volume. In another embodiment, all the aluminum content of the metal cap 108 is contained in the aluminum layer 160, and the first and second multilayer structures 162 and 164 are substantially aluminum-free. In another embodiment, the aluminum layer 160 has a thickness less than or equal to that of caps currently used for sealing glass containers. In another embodiment, the thickness of the aluminum layer is greater than or equal to 1 μm and less than or equal to 100 μm. In another embodiment, the aluminum layer 160 is a solid aluminum layer. In yet another embodiment, the aluminum layer is a perforated aluminum layer comprising a plurality of perforations extending between the first and second multilayer structures 162 and 168. Perforation advantageously reduces the overall volume percentage of aluminum in the metal-containing cap 108, thereby increasing the proportion of the metal-containing cap 108 occupied by the first and second multilayer structures 162 and 168. This larger proportion of polymer material increases the overall CTE of the metal-containing cap 108, thus contributing to greater shrinkage and maintaining a seal after cooling.

[0105] In one embodiment, the first and second multilayer structures 162 and 168 respectively include elastomeric layers 164 and 170 and glassy polymer layers 166 and 172. In another embodiment, the glassy polymer layers 166 and 172 are constructed of a polymer material with a glass transition temperature greater than or equal to 25°C. The glassy polymer layers 166 and 172 can help the metal cap 108 maintain a sufficiently high degree of rigidity for use in existing crimping processes, while reducing the amount of material reaching the elastomeric layers 164 and 170 after cooling to low storage temperatures. g The impact.

[0106] In one embodiment, elastomer layers 164 and 170 are constructed of butyl rubber. In another embodiment, elastomer layers 164 and 170 are constructed of one or more low-T... gThe elastomeric material is constructed, for example, polybutadiene, silicone, fluorosilicone, nitrite / ester, and EPDM elastomers (e.g., PDMS), or any combination thereof. In an embodiment, elastomeric layers 164 and 170 have a glass transition temperature less than or equal to -100°C. In an embodiment, elastomeric layers 164 and 170 contain additives, such as silica nanoparticles (e.g., comprising a particle size greater than or equal to 10 nm and less than or equal to 100 nm). In an embodiment, the additives comprise less than or equal to 30% by weight of elastomeric layers 164 and 170. Glassy polymer layers 166 and 172 may also contain such additives. The additives can modulate the mechanical properties of the first and second multilayer structures 162 and 168 to provide a CTE mismatch between the metal cap 108 and the stopper 106 that maximizes compression of the stopper 106 after cooling to a lower storage temperature.

[0107] See still Figure 1C In one embodiment, the metal cap 108 comprises a plurality of multilayer structures (e.g., including an aluminum layer 160 and first and second multilayer structures 162 and 178) stacked on top of each other. In another embodiment, the overall thickness of the metal cap 108 (e.g., the total thickness of the stacked multilayer structures) is greater than or equal to 200 μm and less than or equal to 300 μm. In yet another embodiment, the thickness of the metal cap 108 is increased beyond that of metal caps currently used for sealing drug containers, thereby increasing its tendency to shrink after cooling to temperatures less than or equal to -70°C.

[0108] In addition to the compositional modifications of the metal cap 108 described herein, the composition of the stopper 106 can be selected to lower its CTE or glass transition temperature. Selecting such a composition for the stopper 106 can reduce its shrinkage and thus help maintain the compressibility of the stopper 106 via the metal cap 108. For example, in an embodiment, the polymer formulation of the stopper 106 can be selected (or additives can be added to the stopper 106) such that the glass transition temperature of the stopper 106 is less than or equal to -75°C (e.g., less than or equal to -80°C, less than or equal to -85°C). In an embodiment, the glass transition temperature of the stopper 106 can be lowered below the desired storage temperature of the sealed glass container 100 (e.g., to a dry ice storage temperature less than or equal to approximately -80°C), thereby keeping the stopper 106 elastic and creating a seal at the upper sealing surface 110. In an embodiment, the stopper 106 is made of one or more low-T g The elastomer material is constructed from, for example, polybutadiene, silicone, fluorosilicone, nitrite / ester, and EPDM elastomers (e.g., PDMS), or any combination thereof. In an embodiment, the elastomer layer has a glass transition temperature of less than or equal to -100°C.

[0109] In one embodiment, the stopper 106 comprises a polymer-based composite material with a CTE lower than that typically used in rubber. In another embodiment, the stopper 106 is constructed from a rubber-filler mixture. For example, in one embodiment, the stopper 106 contains up to 15% by volume of filler material. In another embodiment, the stopper 106 contains less than or equal to 40% by weight of filler material (e.g., less than or equal to 30% by weight of filler material). More than 40% by weight of filler material may reduce the sealing quality due to decreased elasticity of the stopper 106. The CTE of the filler material can be lower than that of rubber typically used to construct stoppers (e.g., less than or equal to 50 x 10⁻⁶). -7 / K, less than or equal to 20x10 -7 / K, less than or equal to 10x10 -7 / K, less than or equal to 5x10 -7 / K). In embodiments, the filler comprises silicon. For example, in embodiments, the filler material comprises SiO2 glass particles. In embodiments, the SiO2 glass particles may have a particle size greater than or equal to 10 nm and less than or equal to 100 nm. In embodiments, the SiO2 glass particles may be functionalized with organosilanes to adjust the particle distribution in the elastomeric material of the stopper 106. In embodiments, the filler material comprises silicates / esters (e.g., cordierite, β-nepheline, β-spodumene). In embodiments, the filler material is a high-melting-point metal (e.g., Ir, W, Ti, Si). In embodiments, the filler material comprises Mg2PO4. In embodiments, the filler material comprises oxides, such as SiO2, Ti-doped SiO2, ZrW2O8, or other ceramics in the AM2O8 family. In embodiments, the filler material comprises any other suitable material having a low or negative CTE. In embodiments, the CTE of the stopper 106 containing the filler material is less than or equal to 300 x 10⁻⁶. -7 / K (for example, less than or equal to 290x10) -7 / K, less than or equal to 280x10 -7 / K, less than or equal to 270x10 -7 / K). By adding the filler material described herein to the stopper 106, the CTE difference between the metal cap 108 and the stopper 106 is reduced, thereby reducing the likelihood of the stopper 106 decompressing when the sealed glass container 100 is cooled to a storage temperature of less than or equal to -80°C.

[0110] In one embodiment, the plug 106 includes a radially heterogeneous structure with varying composition. For example, Figure 1DAn exemplary embodiment of the stopper 106 is shown schematically in cross-section. As shown, the stopper 106 includes a body 166 defining an insertion portion 117 and a sealing portion 119. In an embodiment, the body 166 is constructed of an elastomeric material that has high elasticity at room temperature, such as butyl rubber or any other suitable stopper material. The dimensions and dimensions of the body 166 may be similar to those of stoppers currently used for sealing pharmaceutical glass containers. For example, in the illustrated embodiment, the sealing portion 119 includes a thickness 168 and a width 170. In an embodiment, the width 170 is greater than or equal to the radial distance between the inner surface 114 and the outer surface 136 of the glass container 102 (see [link to documentation]). Figure 1B This maximizes the contact area between the sealing portion 119 and the upper sealing surface 110 of the glass container 102.

[0111] exist Figure 1D In the embodiment shown, the plug 106 further includes a low-T content in the sealing portion 119. g Section 172. Low T g Section 172 can be arranged in the sealing portion 119 to achieve low T g Section 172 contacts the upper sealing surface 110 of the glass container 102 (after the stopper 106 is inserted therein). In an embodiment, the stopper 106 can be constructed by compression molding or injection molding. In an embodiment, the body 166 and the low T g Section 172 can be formed separately and then bonded together. For example, as... Figure 1D As shown, low T g Section 172 protrudes slightly from the sealing portion 119. This protrusion indicates a low T g Segment 172 is constructed separately from the body 166 (e.g., via injection molding or compression molding) and then bonded later. In this embodiment, once the stopper 106 is constructed and inserted into the glass container 102, the low T... g Section 172 is pressed into the body 166 (e.g., via a metal cap 108) so that the body 166 and the low T g Section 172 presses against the upper sealing surface 110.

[0112] In the implementation, low T g Section 172 includes a radial width 174 that is greater than or equal to 10% and less than or equal to 50% of the width 170 of the sealing portion 119 of the body 166. Low T g Section 172 also includes a sealing portion 119 with a thickness 176 greater than or equal to 10% and less than or equal to 90% of the body 166. Depending on the storage application, low T g Section 172 may contain greater than or equal to 1% and less than or equal to 45% of the volume of the sealed portion 119. In an embodiment, low T gThe volume ratio of segment 172 to body 166 may depend on the dimensions of glass container 102 (e.g., flange thickness 152) and the composition of stopper 106 and metal cap 108.

[0113] In the implementation, low T g Section 172 is from low T g Elastomer material construction. In the embodiment, low T g The glass transition temperature of the elastomer material is less than or equal to -75°C (e.g., less than or equal to -80°C, less than or equal to -90°C, less than or equal to -100°C, less than or equal to -110°C, less than or equal to -120°C). In embodiments, low T... g Section 172 contains one or more low T g Elastomer materials, such as polybutadiene, silicone, fluorosilicone, nitrite / ester and EPDM elastomers (e.g., PDMS), or any combination thereof. The lower glass transition temperature of the low Tg segment 172 compared to the body 166 advantageously maintains the elasticity of the stopper 106 at the contact point between the sealing portion 119 and the upper sealing surface 110 of the glass container 102 when cooled to a lower temperature less than or equal to -70°C.

[0114] Low T g Low T in section 172 g The elastomer material can have higher gas permeability than the material of the bulk 166. In the embodiment, in order to improve low T g Gas permeability of section 172, low T g The segment contains up to 30% by weight of filler material. In one embodiment, the filler material comprises silicon. For example, in one embodiment, the filler material comprises SiO2 glass particles. In one embodiment, the SiO2 glass particles may have a particle size greater than or equal to 10 nm and less than or equal to 100 nm. In one embodiment, the SiO2 glass particles may be functionalized with organosilanes to modulate the particle distribution in the elastomeric material of the stopper 106. In one embodiment, the filler material comprises silicates / esters (e.g., cordierite, β-nepheline, β-spodumene). The filler material in the low Tg segment 172 reduces its CTE relative to the body 166, thereby helping to maintain contact and compression at the upper sealing surface 110 of the glass container 102.

[0115] It should be understood that any combination of the above-described schemes (e.g., reducing the CTE and / or T of plug 106) gIncreasing the CTE of the metal cap 108 (or modifying the structure of the glass container 102 in any manner described herein) can be used to seal the glass container 100. For example, in one embodiment, a sloped sealing surface 140 can significantly increase the compressibility of the stopper 106, allowing conventional materials to be used for the stopper 106 (e.g., butyl rubber) and the metal cap 108 (e.g., aluminum) while still maintaining a seal at temperatures less than or equal to -80°C. Similar results can be achieved if the upper sealing surface 110 meets certain requirements (e.g., flatness, surface roughness uniformity, etc.). In one embodiment, the sloped sealing surface 140 can be combined with one or more material modifications to the sealing assembly (e.g., a stopper 106 with reduced CTE, a metal cap 108 with increased CTE) to provide an even more robust seal for storage temperatures less than or equal to -100°C (e.g., less than or equal to -125°C, less than or equal to -150°C, less than or equal to -170°C). The specific combination of structural or compositional modifications used can depend on the storage application.

[0116] In this embodiment, both a high-CTE metal cap 108 (e.g., constructed from a polymer-aluminum composite) and a low-CTE stopper 106 (e.g., constructed from a rubber-SiO2 composite) can be used simultaneously. In this type of embodiment, structural modifications to the glass container 102 can be avoided because the shrinkage difference between the metal cap 108 and the stopper 106 is reduced through formulation. This approach may be advantageous for use with existing glass containers (where the angle 150 of the inclined sealing surface 140 can be approximately 3 degrees). The final structure of the glass container 102 and the sealing assembly can vary depending on the practical application.

[0117] It should be understood that this can be used as a reference to the text. Figure 1A and 1B The glass container 102 is an alternative to the conventional method, while still maintaining the integrity of the sealed contents when stored at a temperature less than or equal to -80°C. For example, Figure 2A A schematic cross-sectional view of another glass container 200 is shown. The glass container 200 may include similar components as described herein. Figure 1A and 1B The components of the glass container 102. Therefore... Figure 2A Similar reference numerals have been integrated to indicate the integration of such components.

[0118] Glass container 200 and relative to Figure 1A and 1B The difference between the glass container 102 and the glass container 200 is that the glass container 200 includes a flange 202, which includes a lower surface 204, an outer surface 206, and an upper sealing surface 208. For example... Figure 2AAs shown, the upper sealing surface 208 extends in a plane 152 extending through the end 154 of the opening 105 in the glass container 200. In one embodiment, the upper sealing surface 208 extends substantially perpendicular to the central axis A of the glass container 200 (e.g., an angle greater than or equal to 89.5 degrees and less than or equal to 90.5 degrees). In another embodiment, the upper sealing surface 208 extends substantially perpendicular to the inner surface 114 of the glass container 200 that defines the opening 105. This type of upper sealing surface 208 advantageously enhances the stopper 106 (see...). Figure 1A The contact area between the seal and the upper sealing surface 208 can increase the probability of maintaining seal integrity.

[0119] In an embodiment, the upper sealing surface 208 may be configured to have, as described herein, relative to, Figure 1A and 1B The surface characteristics described by the inclined sealing surface increase the contact quality with the stopper 106. For example, in one embodiment, the upper sealing surface 208 includes a surface roughness less than or equal to a threshold (e.g., 0.1 μm) to reduce the likelihood of a gap forming at the interface between the upper sealing surface 208 and the stopper 106. In one embodiment, the upper sealing surface 208 includes a uniform surface roughness (e.g., greater than or equal to 3 μm, greater than or equal to 5 μm) based on the estimated shrinkage of the flange 202 and the stopper 106 when cooled to any cold storage temperature described herein. In another embodiment, the upper sealing surface includes a surface flatness less than or equal to a threshold.

[0120] exist Figure 2A In the example shown, the upper sealing surface 208 extends from the outer surface 206 to the inner surface 114. It should be understood that the upper sealing surface 208 may include various different features consistent with this disclosure. For example, Figure 2B The diagram schematically shows a cross-sectional view of a glass container 210 including an upper sealing surface 212, which includes: a flat portion 214, a chamfer 216 extending between the flat portion and the outer surface 206 of the flange 202, and a fillet 218 extending between the flat portion 214 and the inner surface 114. The flat portion 214 may extend in a plane 152, similar to... Figure 2A The entire upper sealing surface 208 is shown. In one embodiment, the bevel 216 extends at an angle of 45 degrees relative to the flat portion 214. In one embodiment, the bevel 216 increases the integrity of the seal produced by the plug 106 by allowing the plug to enclose the upper sealing surface 212 in multiple directions. In one embodiment, as an alternative to the fillet 218, the bevel included in the upper sealing surface 212 is structurally similar to the bevel 216 extending between the flat portion 214 and the inner surface 114. It should be understood that this text is relative to... Figure 2BAny of the aforementioned features (e.g., bevel 216, fillet 218, at least one sealing feature 220) can also be incorporated into this document relative to Figure 1B The inclined sealing surface 140 (for example, the upper sealing surface 110 may include a bevel extending between the inclined sealing surface 140 and the outer surface 136).

[0121] See now Figure 3 The image shows a cross-sectional view of a sealed glass container 300. The sealed glass container 300 comprises components similar to those described herein with respect to... Figure 1A and 1B The glass container 102 is described. Therefore, in Figure 3 Similar reference numerals are used to indicate the incorporation of such similar components. The sealed glass container 300 includes a sealing assembly 302 that is inserted into the glass container 102 to seal an opening 105 therein. The sealing assembly 302 includes a plug 304 that is inserted into the opening 105 and presses against an upper sealing surface 110 via a press-fitted metal-containing cap 308. In embodiments, the plug 304 and the metal-containing cap 308 are structurally and functionally similar to those described herein with respect to... Figure 1A and 1B The stopper 106 and the metal cap 108 are described herein and can be constructed from any of the materials described herein to increase the seal integrity at low sealing temperatures.

[0122] Figure 3 The sealing assembly 302 shown is relative to this document. Figure 1A and 1B The difference in the sealing assembly is that sealing assembly 302 includes sealing material 306 disposed between the metal cap 308 and the stopper 304. Depending on the implementation, sealing material 306 may be secured to the metal cap 308 and / or the stopper 304. In embodiments, the CTE of the material constituting sealing material 306 is less than that of both the metal cap 308 and the stopper 304. Compared to embodiments without sealing material 306, incorporating sealing material 306 can reduce the overall CTE (e.g., average CTE) of the material stack disposed in the metal cap 308 (e.g., flange 126, stopper 304, and sealing material 306). This reduction in overall CTE reduces the overall shrinkage of the material disposed in the metal cap 308, thereby helping to maintain the compressibility of the stopper 304.

[0123] In this embodiment, the sealing material 306 comprises less than or equal to 50x10 -7 / K CTE (e.g., less than or equal to 25x10) -7 / K, less than or equal to 10x10 -7 / K, less than or equal to 5x10 -7 / K). In one embodiment, the sealing material is constructed of a high-melting-point metal (e.g., Ir, W, Ti, Si). In another embodiment, the sealing material 306 is constructed of a polymer or a rubber-based composite (e.g., those described herein with respect to stopper 106). In another embodiment, the sealing material 306 comprises oxides, such as SiO2, Ti-doped SiO2, ZrW2O8, or other ceramics in the AM2O8 family. Depending on the practice, the sealing material 306 may have any suitable size or shape. In another embodiment, the sealing material 306 is symmetrical with respect to the central axis A of the glass container 102, thereby helping to maintain uniform compression of the stopper 304.

[0124] Figures 4A-4D The simulation of plug compression as a function of the flange angle is shown. Figure 4A The simulation results for the flange 400 are shown, including an inclined sealing surface 402 extending at an angle of -3 degrees relative to a plane 404 located on the top of the flange 400 (see [link]). Figure 4A (The top part). Figure 4B The simulation results for flange 412 are shown, including a sealing surface 414 extending at an angle of 0 degrees relative to a plane 416 located on the top of flange 412 (see [link]). Figure 4B (The top part). Figure 4C The simulation results for flange 424 are shown, including an inclined sealing surface 426 extending at an angle of 2.4 degrees relative to a plane 428 located on the top of flange 424 (see [link]). Figure 4C (The top part). Figure 4D The simulation results for flange 434 are shown, including an inclined sealing surface 436 extending at an angle of 7 degrees relative to a plane 438 located on top of flange 434 (see [link]). Figure 4A (The top part).

[0125] The simulation results predicted the insertion into Figure 4A , 4B The compression of plugs 406, 418, 428, and 440, which are flanges 400, 412, 424, and 434 as shown in 4C and 4D and are crimped via an aluminum cap (not shown) to provide a residual sealing force of approximately 25 lbf (e.g., greater than or equal to 24.8 lbf and less than or equal to 25.6 lbf), was then performed using finite element analysis to simulate the compression of plugs 406, 418, 428, and 440 at various temperatures. Figure 4A , 4B The middle section of 4C and 4D shows the simulation results at room temperature (e.g., 25°C). Figure 4A The compression of the plug 406 against the flange 400 results in a compression distribution 408 at 25°C. Figure 4BThe crimped stopper 418 against the flange 412 causes a compression distribution 420 at 25°C. Figure 4C The crimped contact of the plug 428 against the flange 424 results in a compression distribution 430 at 25°C. Figure 4D The press-fit of the plug 440 against the flange 434 results in a compression distribution 442 at 25°C. As shown in each of the compression distributions 408, 420, 430, and 442, each of the plugs 406, 418, 428, and 440 presses continuously along a section of each of the sealing surfaces 402, 414, 426, and 436 (e.g., sections of compression distributions 408, 420, 430, and 442 contain no gaps with zero compression), indicating a large contact area and the presence of a seal at 25°C.

[0126] Figure 4A , 4B The bottom sections of 4C and 4D show simulation results at a lower temperature of -80°C. Figure 4A The compression of the plug 406 against the flange 400 results in a compression distribution 410 at -80°C. Figure 4B The press-fit of the plug 418 against the flange 412 results in a compression distribution 422 at -80°C. Figure 4C The crimped contact of the plug 428 against the flange 424 results in a compression distribution 432 at -80°C. Figure 4D The press-fit of the plug 440 against the flange 434 results in a compression distribution 444 at -80°C. Each of the compression distributions 410, 422, and 432 contains at least one gap (where the plug compression is zero), indicating a reduced contact area and a higher likelihood of seal breakage. In other words, according to simulation results, a flange angle of less than 5 degrees leads to a reduced contact area at lower storage temperatures. Conversely, Figure 4D The compression distribution 444 of the flange 434 shown results in continuous compression of the plug 440 at -80°C. That is, the compression distribution 444 includes sections at the inclined sealing surface 436 that do not contain zero compression gaps, indicating that a seal is maintained at such temperatures.

[0127] Figure 4E Figure 446 shows the functional relationship between the contact area of ​​the plugs and flanges 400, 412, 424, and 434 and the temperature when cooled at a rate of 1°C / min. Figure 4F Graph 448 shows the relationship between the contact area of ​​the plugs and flanges 400, 412, 424, and 434 and the temperature when cooled at a rate of 5°C / min. (See graph 448 for details.) Figure 4E As shown, when cooling is performed at a rate of 1°C / minute, Figure 4DThe flange 434 shown (with a flange angle of 7 degrees) maintains a contact area at temperatures less than or equal to -70°C that is at least 55% of the contact area at room temperature. Flange 434 also maintains this contact area at temperatures less than or equal to -100°C (e.g., less than or equal to 110°C, less than or equal to 120°C, less than or equal to 130°C, less than or equal to 140°C, less than or equal to 170°C). This result differs from that of flanges 400, 412, and 424 (with flange angles less than or equal to 5°C) (where the contact area at -70°C is less than 40% compared to 25°C, and further decreases to less than 10% at temperatures less than -90°C). That is, flange angles with values ​​greater than 5 degrees (e.g., compared to...) are also present. Figure 1A and 1B The angle 150° helps maintain the contact area of ​​the stopper at low storage temperatures, indicating that the seal is maintained. Figure 4F Figure 448 shows similar results, except that the stopper contact area appears to decrease at a greater rate than in Figure 446 as the glass cools (particularly for flanges 400, 412, and 424). Thus, cooling the glass container described herein at a rate of less than 5°C / min can also promote the maintenance of a seal.

[0128] Based on the foregoing, it should be understood that a sealed glass container capable of maintaining the integrity of the sealed object at storage temperatures less than or equal to -70°C has been disclosed. Depending on the practice and storage application, the structure of the glass container can be specifically designed to account for the shrinkage of the sealing assembly during storage cooling. For example, the glass container may include an inclined sealing surface extending at an angle greater than 5 degrees relative to a plane located on the top of the glass container, thereby increasing the compression of the stopper during the crimping process and thus increasing tolerance to stopper shrinkage. Aspects of the sealing surface (e.g., surface roughness, flatness, other features such as cutting or sealing features) can also be adjusted to prevent the stopper from peeling off from the sealing surface during shrinkage. Furthermore, the dimensions of the glass container (e.g., flange thickness) can be increased to provide a greater probability of maintaining seal integrity. In addition to structural modifications to the glass container, the composition of the components of the sealing assembly (e.g., cap, stopper, any additional sealing material) can be selected to ensure sufficient compression of the stopper to maintain its position during its thermal shrinkage events.

[0129] Unless otherwise expressly stated, no method described herein should be construed as requiring its steps to be performed in a specific order or requiring any device to have a particular orientation. Therefore, if a method claim does not actually describe the order in which its steps are to be followed, or any device claim does not actually describe the order or orientation of the components, or the claims or description do not otherwise specifically state that the steps are limited to a specific order, or do not describe a specific order or orientation of the device components, then in no way should the order or orientation be inferred. This also applies to any possible unexpressed basis for interpretation, including: the logic regarding setup steps, operational flow, component order, or component orientation; the general meaning obtained from grammatical structures or punctuation; and the number or type of embodiments described in the specification.

[0130] It will be apparent to those skilled in the art that various modifications and variations can be made to the embodiments described herein without departing from the spirit and scope of the claimed subject matter. Therefore, this specification is intended to cover modifications and variations of the various embodiments described herein, provided that such modifications and variations fall within the scope of the appended claims and their equivalents.

Claims

1. A sealed glass container comprising: A glass container comprising: Shoulders; The neck extending from the shoulders; A flange extending from the neck, the flange comprising: The lower surface extending from the neck; An outer surface extending from the lower surface defines the outer diameter of the flange; as well as An inclined sealing surface extends between the outer surface and the inner surface of the sealed glass container that defines the opening, wherein, The inclined sealing surface extends at an angle relative to the plane extending through the end of the opening, such that the distance between the inclined sealing surface and the plane increases as the radial distance relative to the outer surface decreases; A sealing assembly comprising: a plug extending above a sealing surface of a flange and covering an opening, and a cap securing the plug to the flange, wherein: The stopper has a diameter of less than or equal to 290 x 10 mm. -7 The coefficient of thermal expansion (CTE) at / K and the glass transition temperature (T) greater than or equal to -70°C and less than or equal to -45°C. g ); The cap is press-fitted to the flange with a CTE greater than or equal to 260 x 10 mm. -7 / K contains a metal cap that causes the stopper to compress, wherein the metal cap comprises solid metal, metal alloy or polymer metal composite material; as well as As the sealed glass container cools to temperatures below or equal to -80°C, the sealing assembly maintains a helium leakage rate of less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s.

2. The sealed glass container as described in claim 1, wherein, The difference between the coefficient of thermal expansion (CTE) of the metal cap and the CTE of the stopper is less than or equal to 50 x 10⁻⁶. -7 / K.

3. The sealed glass container as described in claim 1, wherein, The metal cap contains at least one of Zn and Mg.

4. The sealed glass container as claimed in claim 1, wherein, The metal-containing cap has the following construction: Aluminum-containing polymer composites; A metallic alloy containing at least one of Zn, Al, Mg, and Cu; or Pb-Sn alloy.

5. The sealed glass container as claimed in claim 1, wherein, The stopper is constructed from a polymer composite containing more than 0% (by weight) and less than or equal to 30% (by weight) of silicon-based filler material.

6. The sealed glass container as described in claim 5, wherein, Silicon-based filler materials include SiO2 glass particles or silicates / esters.

7. The sealed glass container as claimed in claim 1, wherein, The glass transition temperature of the stopper is less than or equal to -75°C.

8. The sealed glass container as claimed in claim 1, wherein: The sealing surface includes an inclined sealing surface extending between an outer surface and an inner surface, the inclined sealing surface extending at an angle relative to a plane extending through the end of the opening, such that as the radial distance relative to the outer surface decreases, the distance between the inclined sealing surface and the plane increases, and The angle is greater than or equal to 6 degrees.

9. The sealed glass container as claimed in claim 1, wherein, The surface roughness of the sealing surface is greater than or equal to 3 µm.

10. The sealed glass container of claim 1, further comprising a sealing material disposed between the stopper and the metal-containing cap, the sealing material having a CTE less than that of the stopper and the metal-containing cap.

11. The sealed glass container as claimed in claim 10, wherein, Sealing materials include: At least one of Ir, W, Ti and Si; Polymer-based composites; or At least one of the following: SiO2, Ti-doped SiO2, ZrW2O8 and AM2O8 ceramics.

12. The sealed glass container as claimed in claim 1, wherein, The composition of the metal-containing lid along the central axis of the sealed glass container is non-uniform.

13. The sealed glass container as claimed in claim 12, wherein, The metal-containing cover includes an aluminum layer and at least one multi-layer structure in contact with the aluminum layer.

14. The sealed glass container as claimed in claim 13, wherein, The multilayer structure comprises an elastomer layer and a glassy polymer layer, the glassy polymer layer having a glass transition temperature greater than 25°C.

15. The sealed glass container as claimed in claim 12, wherein, The metal cap comprises a multi-layered structure with a thickness greater than or equal to 200 µm and less than or equal to 300 µm.

16. The sealed glass container as claimed in claim 1, wherein, The plug comprises radially heterogeneous components.

17. The sealed glass container as claimed in claim 16, wherein, The plug includes a low T that contacts the sealing surface. g Section.

18. The sealed glass container as claimed in claim 17, wherein, Low T g Section includes low T g Elastomers, including one or more of the following: polybutadiene, silicone, nitrite / ester and EPDM elastomers.

19. The sealed glass container as claimed in claim 18, wherein, Silicones include fluorosilicones.

20. The sealed glass container of claim 18, wherein, Low T g The section contains 0% or more (by weight) and less than or equal to 30% (by weight) of filler material.

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