Cap design for a medicament container closure system

Abstract

A cap for sealing a glass container and maintaining the integrity of the sealed object at -80°C or lower is disclosed. The cap (108) includes a cap skirt (160) having an annular body (162) and a crimping region (164). The crimping region is a crimpable metal. The annular body of the cap skirt has a coefficient of thermal expansion (CTE) greater than that of a metal made of aluminum, and a stiffness greater than or equal to twice the stiffness of the crimping region, or both. The greater CTE and stiffness (or both) of the cap skirt increase the sealing pressure and contact area between the stopper and the glass container when cooled to -80°C or lower. The cap enables the sealing assembly to maintain a seal of less than or equal to 1.4 x 10⁻⁶ at -80°C or lower. ‑6 cm 3 The rate of helium leakage in a sealed glass container is 1 / s.

Description

[0001] This application claims priority to U.S. Provisional Application No. 63 / 281,826, filed November 22, 2021, pursuant to 35 U.S. SC §119, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] This specification generally relates to container-sealed object systems, such as glass or plastic containers used for storing pharmaceutical products or biological materials. Background Technology

[0003] Drug containers (e.g., bottles and syringes) are typically sealed with stoppers or other closures to maintain the integrity of the contained material. Closures (e.g., stoppers) are usually made of synthetic rubber and other elastomers. Stoppers are typically held in place by a cap that is pressed against the drug container. Some biological materials (e.g., blood, serum, proteins, stem cells, and other perishable biological fluids) require storage at low temperatures, such as below -45°C, below -80°C, or even below -180°C. For example, some 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 closure components (e.g., glass or plastic containers, stoppers, aluminum caps), leading to issues with seal integrity and potential contamination of the stored material. Summary of the Invention

[0004] A first aspect of this disclosure includes a cap for sealing a pharmaceutical glass container. The cap includes a cap skirt comprising an annular body and a crimping region at a first end of the annular body. The cap also includes a top cover connected to a second end of the cap skirt, the top cover comprising a solid disc or an annular disc. The crimping region may comprise a crimpable metal. The annular body of the cap skirt comprises a coefficient of thermal expansion (CTE) greater than that of a metal made of aluminum, and a stiffness greater than or equal to twice the stiffness of the crimping region, or both. CTE refers to CTE at 20°C, and stiffness is defined as Young's modulus multiplied by the cross-sectional area divided by the axial length.

[0005] The second aspect of this disclosure may include the first aspect, wherein the CTE of the annular body of the cap skirt may be greater than the CTE of the metal made of aluminum, with a difference of at least 100 x 10. -7 K -1 .

[0006] The third aspect of this disclosure may include either the first or the second aspect, wherein the CTE of the annular body of the cap skirt may be greater than or equal to 260x10. -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥350x10 -7 K -1 400x10 -7 K -1 500x10 -7 K -1 or even greater than or equal to 100x10 -7 K -1 .

[0007] The fourth aspect of this disclosure may include any one of aspects 1 to 3, wherein the CTE of the annular body of the cap skirt can be greater than or equal to 260 x 10 at a temperature less than or equal to the glass transition temperature of the stopper (e.g., less than or equal to -45°C). -7 K -1 .

[0008] The fifth aspect of this disclosure may include any one of the first to fourth aspects, wherein the stiffness of the annular body of the cap skirt may be greater than or equal to twice the stiffness of an equivalent cap skirt annular body made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length.

[0009] The sixth aspect of this disclosure may include any one of aspects 1 to 5, and also includes a stopper, wherein, at a temperature less than or equal to the glass transition temperature Tg of the stopper, the stiffness of the annular body of the cap skirt may differ from the stiffness of the stopper in a compressed state by within 30%.

[0010] The seventh aspect of this disclosure may include any one of the first to sixth aspects, wherein the annular body of the cap skirt may have a Young's modulus greater than or equal to 140 GPa, a radial thickness greater than or equal to 0.24 mm, or both.

[0011] The eighth aspect of this disclosure may include any one of aspects 1 through 7, wherein the CTE of the annular body of the cap skirt may be greater than 260x10. -7 K -1The stiffness of the annular body is more than twice that of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length.

[0012] The ninth aspect of this disclosure may include any one of aspects 1 to 8, wherein the pressable metal of the press-fit region may include aluminum or an aluminum alloy.

[0013] The tenth aspect of this disclosure may include any one of aspects 1 through 9, wherein the annular body of the cap skirt may include a metal or metal alloy having a CTE greater than that of a metal made of aluminum.

[0014] The 11th aspect of this disclosure may include the 10th aspect, wherein the cap skirt comprises one or more of the following metals or metal alloys: zinc, aluminum, magnesium, copper, lithium, or combinations thereof.

[0015] The 12th aspect of this disclosure may include any one of aspects 1 through 11, wherein the cap skirt may include a polymer-metal composite structure.

[0016] The 13th aspect of this disclosure may include the 12th aspect, wherein the annular body of the cap skirt may include a polymer material, and the crimping region may include a crimpable metal connected to the polymer material of the annular body.

[0017] The 14th aspect of this disclosure may include the 13th aspect, wherein the polymer material of the ring-shaped body may have a size of 260x10. -7 K -1 Up to 3000x10 -7 K -1 CTE, for example, 280x10 -7 K -1 Up to 3000x10 -7 K -1 Or even 300x10 -7 K -1 Up to 3000x10 -7 K -1 .

[0018] The 15th aspect of this disclosure may include any one of the 13th or 14th aspects, wherein the stiffness of the annular body of the cap skirt may be greater than or equal to 80% of the stiffness of an equivalent cap skirt annular body made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length.

[0019] The 16th aspect of this disclosure may include any one of aspects 13 to 15, wherein the plastic material may include: high-density polyethylene, acrylonitrile butadiene styrene copolymer, polypropylene, ultra-high molecular weight polyethylene, or combinations thereof.

[0020] The 17th aspect of this disclosure may include any one of aspects 1 to 16, wherein the cap skirt may include an attachment flange disposed at a second end of the annular body, and a top cover that may be attached to the attachment flange of the cap skirt.

[0021] The 18th aspect of this disclosure may include the 17th aspect, wherein the top cover may be removable from the cap skirt.

[0022] The 19th aspect of this disclosure may include any one of aspects 1 through 18, wherein the top cover may be integrally formed with the annular body of the cap skirt to form a one-piece cap.

[0023] The 20th aspect of this disclosure may include any one of aspects 1 to 19, wherein the top cover may include an annular disc having an axial opening in the center of the top cover.

[0024] The 21st aspect of this disclosure may include any one of aspects 1 through 20 and may relate to a sealed drug container. The sealed drug container 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 defining an outer diameter of the flange, and a sealing surface extending between the outer surface and an inner surface defining an opening in the sealed drug container. The sealed drug container also includes a sealing assembly comprising a stopper extending above the sealing surface of the flange of the glass container and covering the opening, and a cap of any one of aspects 1 through 20. The cap secures the stopper to the flange in place. When the sealed drug container is cooled to a temperature less than or equal to -45°C, the sealing assembly maintains a value less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

[0025] The 22nd aspect of this disclosure may include the 21st aspect, wherein the stopper may have a glass transition temperature (Tg) greater than or equal to -70°C and less than or equal to -45°C.

[0026] The 23rd aspect of this disclosure may include the 21st aspect, wherein the glass transition temperature (Tg) of the stopper may be less than or equal to -75°C.

[0027] The 24th aspect of this disclosure may include any one of aspects 21 to 23, wherein when the sealed drug container is cooled to a temperature less than or equal to -80°C, less than or equal to -100°C, less than or equal to -120°C, or even less than or equal to -180°C, the sealing assembly can maintain a temperature less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

[0028] The 25th aspect of this disclosure may include any one of aspects 21 to 24, wherein the glass container may be made of material with a coefficient of thermal expansion greater than or equal to 0 and less than or equal to 70 x 10⁻⁶. -7 K -1 The glass composition was constructed.

[0029] The 26th aspect of this disclosure may include any one of aspects 21 to 25, wherein the absolute value of the difference between the CTE of the cap skirt and the CTE of the plug may be less than or equal to 50 x 10. -7 K -1 .

[0030] The 27th aspect of this disclosure may include any one of aspects 21 to 26, wherein the CTE of the annular body of the cap skirt may be greater than the CTE of the plug.

[0031] The 28th aspect of this disclosure may include any one of aspects 21 to 29, wherein, at a temperature less than or equal to the glass transition temperature Tg of the stopper, the stiffness of the annular body of the cap skirt may differ from the stiffness of the compressed rubber stopper by within 30%.

[0032] The 29th aspect of this disclosure may include any one of aspects 21 to 28, wherein when cooled to said temperature at a rate of less than or equal to 5°C per minute, the sealed drug container can maintain a temperature of less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate is 1 / s.

[0033] The 30th aspect of this disclosure may include the 29th aspect, wherein when the sealed drug container is cooled, the cap can maintain the continuous compression of the stopper against the flange of the glass container.

[0034] The 31st aspect of this disclosure may include any one of aspects 21 to 30, wherein the glass container may include: ion-exchangeable aluminosilicate glass, type 1B borosilicate glass, or ion-exchangeable borosilicate glass.

[0035] The 32nd aspect of this disclosure may include any one of aspects 1 to 31 and relates to a sealing method for sealing a drug container. The method includes providing a drug container comprising: a shoulder, a neck extending from the shoulder, and a flange extending from the neck. The flange may include: a lower surface extending from the neck, an outer surface extending from the lower surface and defining an outer diameter of the flange, and an upper sealing surface extending between an outer surface and an inner surface of the sealed drug container, wherein the inner surface defines an opening. The method may further include providing a sealing assembly comprising a stopper and a cap of any one of aspects 1 to 20. The method may further include: inserting a drug composition into the drug container, inserting the stopper into the opening such that the stopper extends above the upper sealing surface of the flange and covers the opening, and pressing the cap over the stopper and against the flange to compress the stopper against the upper sealing surface. The method may further include cooling the sealed drug container to a temperature less than or equal to -45°C, wherein, after cooling, compression on the sealing surface is maintained, such that the helium leakage rate of the sealed drug container at that temperature is less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s.

[0036] Other features and advantages of the apparatus and methods 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.

[0037] It should be understood that the foregoing general description and the following detailed description describe various embodiments and are intended to provide an overall assessment 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

[0038] 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:

[0039] Figure 1 A schematic cross-sectional view of a sealed drug container according to one or more embodiments described herein;

[0040] Figure 2 Schematic illustration of one or more embodiments described herein Figure 1A cross-sectional view of the upper part of a glass container used for sealing medicines;

[0041] Figure 3 The schematic diagram shows a cross-sectional view of the upper portion of another glass container according to one or more embodiments described herein;

[0042] Figure 4 The diagram schematically shows a cross-sectional view of the upper portion of another glass container according to one or more embodiments described herein;

[0043] Figure 5 Schematic illustration of one or more embodiments described herein Figure 1 A cross-sectional view of the sealing assembly of a sealed drug container;

[0044] Figure 6A This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of 25°C, according to one or more embodiments described herein, wherein the cap has a diameter of 256 x 10 mm. -7 CTE at / ℃;

[0045] Figure 6B This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of 25°C, according to one or more embodiments described herein, wherein the cap has a diameter of 352 x 10 mm. -7 CTE at / ℃;

[0046] Figure 6C This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of 25°C, according to one or more embodiments described herein, wherein the cap has a size of 698 x 10 mm. -7 CTE at / ℃;

[0047] Figure 7A This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -80°C, according to one or more embodiments described herein, wherein the cap has a diameter of 256 x 10 mm. -7 CTE at / ℃;

[0048] Figure 7B This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -80°C, according to one or more embodiments described herein, wherein the cap has a diameter of 352 x 10 mm. -7 CTE at / ℃;

[0049] Figure 7C This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -80°C, according to one or more embodiments described herein, wherein the cap has a size of 698 x 10 mm. -7CTE at / ℃;

[0050] Figure 8A The illustration shows one or more embodiments according to the present document. Figure 7A The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading pattern is used to indicate the difference in sealing pressure;

[0051] Figure 8B The illustration shows one or more embodiments according to the present document. Figure 7B The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading patterns is used to indicate the difference in sealing pressure;

[0052] Figure 8C The illustration shows one or more embodiments according to the present document. Figure 7C The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading pattern is used to indicate the difference in sealing pressure;

[0053] Figure 9A This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -180°C, according to one or more embodiments described herein, wherein the cap has a diameter of 256 x 10 mm. -7 CTE at / ℃;

[0054] Figure 9B This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -180°C, according to one or more embodiments described herein, wherein the cap has a diameter of 352 x 10 mm. -7 CTE at / ℃;

[0055] Figure 9C This illustrates simulated compression of a stopper with a cap abutting against the flange of a glass container at a storage temperature of -180°C, according to one or more embodiments described herein, wherein the cap has a size of 698 x 10 mm. -7 CTE at / ℃;

[0056] Figure 10A The illustration shows one or more embodiments according to the present document. Figure 9A The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading pattern is used to indicate the difference in sealing pressure;

[0057] Figure 10B The illustration shows one or more embodiments according to the present document. Figure 9B The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading patterns is used to indicate the difference in sealing pressure;

[0058] Figure 10C The illustration shows one or more embodiments according to the present document. Figure 9C The interface between the stopper and the flange of the glass container in the simulation, where the difference in shading patterns is used to indicate the difference in sealing pressure;

[0059] Figure 11 The illustration shows a function of the contact area (y-axis) between the flange and the stopper versus the temperature (x-axis) for a plurality of sealed glass containers cooled at a constant cooling rate, according to one or more embodiments described herein, wherein the sealing assembly of the glass containers has caps with different CTEs when cooled at a first cooling rate;

[0060] Figure 12 The illustration shows the function relationship between the contact area (y-axis) between the flange and the stopper and the temperature (x-axis) for a plurality of sealed glass containers cooled at a constant cooling rate, according to one or more embodiments described herein, wherein the sealing assembly of the sealed glass containers has caps with different stiffnesses.

[0061] Figure 13 The illustration shows the function relationship between the contact area (y-axis) between the flange and the stopper and the temperature (x-axis) for multiple sealed glass containers cooled at a constant cooling rate, according to one or more embodiments described herein, wherein the sealing assembly of the sealed glass containers has caps with different CTEs and stiffnesses.

[0062] Figure 14 The illustration shows a cross-sectional view of another embodiment of the cap of a sealing assembly for sealing a glass container according to one or more embodiments described herein;

[0063] Figure 15 The illustration shows a cross-sectional view of yet another embodiment of a cap for sealing a glass container according to one or more embodiments described herein;

[0064] Figure 16 The illustration shows a cross-sectional view of another embodiment of a cap for sealing a glass container according to one or more embodiments described herein;

[0065] Figure 17A The display shows that, according to one or more embodiments described herein, at a storage temperature of 25°C... Figure 16 The cap abuts against the flange of the glass container to simulate compression of the stopper, wherein the cap's skirt has a size of 1264x10. -7 K -1 High CTE and increased stiffness;

[0066] Figure 17B The display shows the effect of storage at -80°C according to one or more embodiments described herein. Figure 16 The cap abuts against the flange of the glass container to simulate compression of the stopper, wherein the cap's skirt has a size of 1264x10. -7 K -1 High CTE and increased stiffness;

[0067] Figure 17C The display shows the effect of storage at -180°C according to one or more embodiments described herein. Figure 16 The cap abuts against the flange of the glass container to simulate compression of the stopper, wherein the cap's skirt has a size of 1264x10. -7 K -1 High CTE and increased stiffness;

[0068] Figure 18 The illustration shows one or more embodiments described herein, including Figure 16 It has 1264x10 -7 K -1 A graph showing the relationship between the contact area (y-axis) between the flange and the stopper and the temperature (x-axis) when a sealed glass container with a CTE and a cap with a thickness of 2.14 mm is cooled at a constant cooling rate, compared to a conventional cap made of aluminum with a thickness of 0.2 mm, when cooled at a constant cooling rate. Detailed Implementation

[0069] Specific embodiments of a sealed glass container will now be referenced, the sealed glass container comprising a sealing assembly that maintains the integrity of the sealed contents at low 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, less than or equal to -180°C). See now. Figure 1 and 5This illustration schematically shows an embodiment of a sealed glass container 100. The sealed glass container 100 includes a glass container 102 and a sealing assembly 104 comprising a stopper 106 and a cap 108. This application relates to the design of the cap 108 of the sealing assembly 104, which increases the contraction of the cap 108 relative to the stopper 106 and the flange 126 of the glass container 102, increasing the stiffness of the cap 108 (or both), thereby maintaining container closure integrity (CCI) at low-temperature storage temperatures (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, or even less than or equal to -180°C). In an embodiment, the cap 108 includes a cap skirt 106 having: a coefficient of thermal expansion (CTE) greater than that of a metal made of aluminum; and a stiffness greater than or equal to twice that of a comparable cap skirt annular body made of aluminum with a radial thickness of 0.19 mm and a uniform axial length, or both. An increase in the CTE and stiffness (or both) of the cap skirt 160 of the cap 108 can increase the contact area and sealing pressure (or both) between the stopper 106 and the upper sealing surface 110 of the glass container 102 at temperatures 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, and less than or equal to -180°C.

[0070] 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:

[0071]

[0072] 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.

[0073] 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 process described in (2016) is maintained at less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s maintains the integrity of the enclosed object in the container.

[0074] As used herein, the term "cryogenic storage temperature" refers to a temperature at which biological material (e.g., plant or animal cells) can be stored indefinitely for cells while minimizing the level of freezing damage. As used herein, the term "cryogenic storage temperature" refers to a temperature greater than or equal to -80°C.

[0075] 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.

[0076] When used to describe the concentration and / or absence of a specific 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 in an indeterminate amount, less than 0.05 mol%.

[0077] Unless otherwise stated, as used herein, the term “CTE” refers to the coefficient of linear thermal expansion of a material at a temperature of 25°C.

[0078] 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.

[0079] 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.

[0080] 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.

[0081] See now Figure 1 A schematic cross-sectional view of one embodiment of a sealed glass container 100 for storing pharmaceutical preparations is shown. The sealed glass container 100 includes a glass container 102 and a sealing assembly 104 connected to the glass container 102 via an opening 105. The sealing assembly 104 includes a stopper 106 and a cap 108. The stopper 106 may include an insertion portion 117 and a sealing portion 119. The insertion portion 117 can be 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 a crimp with the cap 108 against the glass container 102, thereby forming a seal at the upper sealing surface 110. Various aspects of the glass container 102 and the sealing assembly 104 are designed to ensure the container closure integrity of the glass container 102 is maintained at low storage temperatures, as described herein.

[0082] 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 and includes a central axis C. The body 112 surrounds the internal volume 118 of the glass container 102. In such a way... Figure 1In the embodiment of the glass container 102 shown, the body 112 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 this 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 C, and each of the barrel 115, the neck 128, and the flange 126 is substantially cylindrical.

[0083] The main body 112 has a wall thickness T W It is defined as the distance between the inner surface 114 and the outer surface 116, such as Figure 1 As shown. The wall thickness T of the glass container 102. W This can vary depending on the practice. In one implementation, the wall thickness T of the glass container 102 is... W It 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 the embodiment, 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.

[0084] 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 following are type 1B borosilicate glass compositions. In embodiments, the glass container 102 can be formed from ion-exchangeable borosilicate glass compositions, such as those described in co-pending U.S. Patent Application No. 16 / 533,954, filed August 7, 2019, entitled “Ion Exchangeable Borosilicate Glass Compositions and Glass Articles Formed from the Same,” which is incorporated herein by reference in its entirety. Alternatively, the glass container 102 can be formed from alkaline aluminosilicate glass compositions, such as those described in U.S. Patent No. 8,551,898 (which is incorporated herein by reference in its entirety) or from alkaline earth aluminosilicate glasses, such as those described in U.S. Patent No. 9,145,329 (which is incorporated herein by reference in its entirety). In embodiments, the glass container 102 can be constructed from a soda-lime silicate glass composition. In embodiments, the glass container 102 has a coefficient of thermal expansion greater than or equal to 0 K. -1 And less than or equal to 100x10 -7 K -1 (For example, greater than or equal to 30 x 10) -7 K -1 And less than or equal to 70x10 -7 K -1 The glass container 102 is constructed of a glass composition. In an embodiment, the glass container 102 may include a coefficient of thermal expansion greater than or equal to 0 K. -1 And less than or equal to 70x10 -7 K -1 Glass composition.

[0085] although Figure 1 The glass container 102 shown has a specific shape (i.e., a vial), but it should be understood that the glass container 102 can have other shapes, including but not limited to, Cartridges, syringes, ampoules, bottles, flasks, medicine bottles, tubes, or beakers, etc. Furthermore, it should be understood that the glass container 102 described herein can be used for a variety of applications, including but not limited to, pharmaceutical packaging or beverage containers.

[0086] See you again Figure 1The flange 126 of the glass container 102 may include an upper sealing surface 110, a lower surface 132, and an outer surface 134. The outer surface 134 may define the outer diameter of the flange 126. The upper sealing surface 110 is the surface where the flange 126 contacts the stopper 106, thereby forming a fluid-tight seal between the stopper 106 and the flange 126. See also Figure 2-4 The upper sealing surface 110 of the flange 126 of the glass container 102 can have different constructions. See also Figure 2 In one embodiment, the upper sealing surface 110 may include an inclined sealing surface 140. The inclined sealing surface 140 may extend at least partially or all the way between the outer surface 134 of the flange 126 and the inner surface 114 of the glass container 102. The inclined sealing surface 140 may extend 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 one embodiment, the plane 152 may connect to a reference point about the upper sealing surface 110 relative to the glass container 102 (e.g., the bottom portion 122, see below). Figure 1 The point extending furthest. Plane 152 may extend through the top of glass container 102, in a direction perpendicular to the central axis C of glass container 102 (e.g., Figure 2 (The XY plane of the coordinate axes in the diagram). In an embodiment, plane 152 perpendicular to inner surface 114 defines a portion of the extension of opening 105. As described herein, angle 150 may be referred to as the "flange angle". In an embodiment, angle 150 is greater than 5 degrees and less than or equal to 45 degrees.

[0087] See now Figure 3 In one embodiment, the glass container 102 may include an upper sealing surface 110 extending in a plane 152 extending through an end 154 of the opening 105 in the glass container 102. In another embodiment, the upper sealing surface 110 may extend substantially perpendicular to the central axis C of the glass container 102 (e.g., at an angle greater than or equal to 89.5 degrees and less than or equal to 90.5 degrees). In yet another embodiment, the upper sealing surface 110 may extend substantially perpendicular to an inner surface 114 of the glass container 102 that defines the opening 105. Such an upper sealing surface 110 may be used to add a stopper 106 (see [link to documentation]). Figure 1 The contact area between the seal and the upper sealing surface 110 increases the probability of maintaining seal integrity.

[0088] exist Figure 3In the glass container 102 shown, the upper sealing surface 110 extends from the outer surface 134 to the inner surface 114. It should be understood that the upper sealing surface 110 may include various different features consistent with this disclosure. See now. Figure 4 In an embodiment, the upper sealing surface 110 of the glass container 102 may include a flat portion 136, a chamfered portion 137, a rounded corner 138, or a combination thereof. When present, the chamfered portion 137 may extend between the flat portion 136 of the flange 126 and the outer surface 134. When present, the rounded corner 138 may extend between the flat portion 136 and the inner surface 114. In an embodiment, the flat portion 136 may extend in a plane 152, as per [the relevant context]. Figure 3 As described in the upper sealing surface 110. In other embodiments, the flat portion 136 may be at an angle relative to the plane 152, as per [the description of the other embodiment]. Figure 2 As described for the upper sealing surface 110. In an embodiment, the beveled portion 137 may extend at a 45-degree angle relative to the flat portion 136. In an embodiment, the beveled portion 137 may increase the integrity of the seal produced by the plug 106 by allowing the plug 106 to enclose the upper sealing surface 110 in multiple directions. In an embodiment, as an alternative to the rounded corner 138, the upper sealing surface 110 may include an inner beveled portion, which similarly extends between the flat portion 136 and the inner surface 114, having similar features to those described for the beveled portion 137. It should be understood that this text is relative to... Figure 4 Any of the features described herein (e.g., bevel 137, fillet 138, or other sealing features) may also be incorporated into this document relative to... Figure 2 The inclined sealing surface 140 (for example, the upper sealing surface 110 forming an angle 150 with respect to the plane 152 may include: a chamfer extending between the inclined sealing surface 140 and the outer surface 134, a fillet 138 extending between the inclined sealing surface 140 and the inner surface 114, or having both a chamfer 137 and a fillet 138).

[0089] See now Figure 5The sealed glass container 100 includes a sealing assembly 104 that is at least partially attachable to the glass container 102 by engagement with an opening 105 of the glass container 102. The sealing assembly 104 includes a stopper 106 and a cap 108. The stopper 106 may include an insertion portion 117 and a sealing portion 119. The insertion portion 117 may be 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 stopper 106 may be made of an elastic material capable of compression through the cap 108 during the sealing process. In embodiments, the stopper 106 may be constructed of synthetic rubber or other elastomers. Such materials advantageously possess high impermeability and elasticity, thereby facilitating the insertion of the stopper 106 into the glass container 102 to seal the interior of the glass container 102. Synthetic rubber may include, but is not limited to, butyl rubber or other synthetic rubbers.

[0090] Cap 108 may contain a metal cap. See again. Figure 5 The cap 108 may include a cap skirt 160 and a cap cover 170 connected to the cap skirt 160. The cap skirt 160 may include at least an annular body 162 and a crimping region 164 disposed at one axial end of the annular body 162. The cap skirt 160 may also include an attachment flange 166 connected to the other axial end of the annular body 162. The annular body 162 of the cap skirt 160 may have an inner surface 168 and an outer surface 169. The inner surface 168 may face radially inward toward the flange 126 of the glass container 102 and may contact a portion of the outer surface 134 of the flange 126, a portion of the plug 106 (or both) when the sealing assembly 104 is mounted onto the glass container 102. The outer surface 169 of the annular body 162 may face radially outward toward the flange 126 away from the glass container 102. The thickness t of the annular body 162 of the cap skirt 160 is... CS It is the distance between two relative points on the inner surface 168 and the outer surface 169 of the annular body 162.

[0091] See you again Figure 5 The attachment flange 166 can be configured to engage with the cap cover 170 to connect the cap cover 170 to the cap skirt 160. In one embodiment, the attachment flange 166 can be an annular flange extending radially inward from the annular body 162 toward axis A of the glass container 102. The attachment flange 166 can be located at the end of the annular body 162 opposite to the end containing the crimping region 164.

[0092] The crimping area 164 can be arranged at the bottom end of the annular body 162 of the cap skirt 160. The bottom end of the annular body 162 refers to the point where the annular body 162 is oriented as... Figure 5The -Z end of the coordinate axis. The crimping area 164 can be constructed of a crimpable metal, such as aluminum or an aluminum alloy. Any other crimpable metal can be used to construct the crimping area 164 of the cap skirt 160.

[0093] A cap 108 may be positioned above a stopper 106 and around a flange 126 of a glass container 102. The cap 108 may be pressed against the flange 126. Pressing the cap 108 against the flange 126 involves deforming the pressing area 164 of the cap skirt 160 around a lower surface 132 of the flange 126, thereby compressing the stopper 106. This compresses the sealing portion 119 of the stopper 106 against the upper sealing surface 110 of the flange 126, thus forming a seal between the upper sealing surface 110 of the flange 126 and the sealing portion 119 of the stopper 106. In an embodiment, the cap 108 of the sealing assembly 104 is pressed around the flange 126 of the glass container 102 by any suitable pressing method (e.g., a pneumatic pressing device). During the sealing process, the stopper 106 is inserted into the opening 105 of the glass container 102, and a compressive force is applied to the cap 108 during the crimping process. For example, as Figure 5 As shown, the cap 108 includes a crimping region 164 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 generates a residual sealing force within the flange 126, which maintains the compression of the stopper 106 after the cap 108 is crimped into place. In an embodiment, the length 111 of the crimping region 164, which directly contacts the lower surface 132 of the flange 126, is greater than or equal to 1 mm, thereby helping to maintain the residual sealing force within the stopper 106 at storage temperatures less than or equal to -80°C.

[0094] Cooling existing sealed containers to cryogenic storage temperatures, such as -80°C or lower, may result in a loss of seal integrity between the stopper and the glass container. Without being limited to any particular theory, it is believed that the loss of seal integrity at temperatures below -80°C may be due to factors such as differences in thermal shrinkage between the various components, loss of elasticity of the stopper at temperatures greater than or equal to the glass transition temperature of the material used to manufacture the stopper, or a combination of these.

[0095] 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 -100°C, less than or equal to -125°C, less than or equal to -150°C, less than or equal to -175°C, or even less than or equal to -180°C), each component of the sealed glass container 100 may undergo volume shrinkage depending on the thermal properties of that component. Figure 5As shown, the volume of material disposed between the crimping area 164 of the cap skirt 160 and the attachment flange 166 or top cover 170 of the cap 108 includes the sealing portion 119 of the stopper 106 and the flange 126 of the glass container 102. If the amount of shrinkage of the combination of the stopper 106 and the flange 126 is greater than the amount of shrinkage of the cap 108, the compression provided by the cap 108 on the stopper 106 may be reduced, which increases the possibility of seal failure at the upper sealing surface 110.

[0096] See you again Figure 5 The total height 154 of the flange 126 (flange height 156) and the compressed stopper 106 (stopper height 158 ​​when the stopper 106 is compressed via the cap 108) (e.g., in Figure 5 The length of the annular body 162 (e.g., the distance between the pressing area 164 of the cap skirt 160 of the cap 108 and the attached flange 166) is approximately equal to the axial length of the annular body 162 (in the + / -Z direction of the coordinate axis). When pressed, the cap 108 can press the plug 106 against the upper sealing surface 110 to form a seal. However, if the total height 154 shrinks more than the annular body 162 of the cap skirt 160, the compression of the plug 106 may be reduced, which reduces the residual sealing force. In order to maintain the compression of the plug 106, the shrinkage ΔL of the annular body 162 of the cap 108, the sealing portion 119 of the plug 106, and the flange 126 of the glass container 102 can satisfy the following relationship in equation (1):

[0097] ΔL cap ≥ ΔL flange + ΔL plug (1)

[0098] In Equation 1, the contraction ΔL of each component can be approximated by the relation in Equation (2).

[0099] ΔL=Lx(efα(T)-1)(2)

[0100] In equation (2), L i α is the initial size of the component, and α(T) is the temperature-dependent CTE of the material of each of the components, namely the cap 108, the stopper 106, and the glass container 102.

[0101] A further complication of the problem is that the stopper 106 may lose elasticity at temperatures less than or equal to -80°C. The stopper 106 can be constructed from polymer-based materials (e.g., butyl or other synthetic rubbers). Each of these materials has a glass transition temperature (Tg). Below Tg, the material of the stopper 106 may exhibit solid behavior (e.g., loss of elasticity), resulting in a reduced sealing force at the upper sealing surface 110 of the flange 126. For example, if the stopper 106 cools to a temperature less than or equal to its Tg, the stopper 106 may not completely fill the gap between the upper sealing surface 110 and the attached flange 166 or top cover 170 of the cap 108, thereby increasing the likelihood of seal failure. That is, when cooled below its glass transition temperature, the stopper 106 effectively exhibits two different material behaviors: above the transition temperature, an elastic material; and below the transition temperature, a solid glass. Using equation (2) above, when cooled from an initial temperature T greater than Tg... i Cool to a final temperature T less than Tg F At that time, the contraction of the plug 106 arranged between the flange 126 and the attached flange 166 or the top cover 170 of the cap 108 can be approximated by Equation 3.

[0102]

[0103] In equation 3, α 玻璃 This refers to the CTE of the rubber of stopper 106 when it transforms into a glassy material below its glass transition temperature Tg.

[0104] In an embodiment, to maintain a seal, the cap 108 and the stopper 106 can be configured such that the shrinkage of the cap 108 is greater than or equal to the total shrinkage of the stopper 106 and the stopper 106 of the glass container 102. A typical commercially available sealing assembly for a glass container includes a metal crimp cap made entirely of aluminum. The aluminum crimp cap encloses the rubber stopper and the flange of the glass container. A typical aluminum crimp cap made entirely of aluminum does not have a sufficiently large coefficient of thermal expansion (CTE) to maintain the sealing force of the stopper against the upper sealing surface of the flange of the glass container when cooled to temperatures less than or equal to -80°C (e.g., 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, or even less than or equal to -180°C). A typical crimp cap made entirely of aluminum may have a coefficient of thermal expansion of approximately 255 x 10⁻⁶ at 20°C. -7 K -1 The CTE. Typical rubbers used to construct stopper 106 (e.g., butyl 325, butyl 035, etc.) can have a thickness greater than or equal to 300 x 10. -7 K -1The CTE (Coefficient of Tightness) of aluminum press-fit caps is relatively low. In other words, based solely on CTE differences, press-fit caps made entirely of aluminum tend to shrink less than stoppers, resulting in reduced sealing force at lower storage temperatures below or equal to -80°C. Furthermore, the Young's modulus (resistance to deformation) of existing aluminum press-fit caps is not high enough to maintain the sealing force of the stopper against the upper sealing surface of the glass container's flange.

[0105] This application relates to the design of a cap 108 for a sealing assembly 104 that increases the contraction of the cap 108 relative to the stopper 106 and the flange 126 of the glass container 102, thereby increasing the stiffness of the cap 108 (or both) to maintain container closure integrity (CCI) at temperatures 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, or even less than or equal to -180°C. In embodiments, the relationship between the CTE and stiffness of the cap 108 can be defined to ensure container closure integrity (CCI) at temperatures from -80°C to -180°C and even less than or equal to -180°C. To help satisfy this relationship, the contraction of the cap 108 can be increased, the stiffness of the cap 108 can be increased, or both can be achieved simultaneously. In an embodiment, the CTE of the cap 108 (particularly the cap skirt 160 of the cap 108) can be approximately 255 x 10⁻⁶ compared to the CTE at 20°C. -7 K -1 The CTE of existing caps or cap skirts made of aluminum is at least 100x10 -7 K -1 In an embodiment, at a temperature less than or equal to the glass transition temperature Tg of the stopper 106 (e.g., less than or equal to -45°C), the CTE of the cap 108 (particularly the cap skirt 160 of the cap 108) can be at least 100 x 10⁻⁶ greater than that of existing caps or cap skirts made of aluminum. -7 K -1 In embodiments, the stiffness of the cap 108 or the cap skirt 160 of the present disclosure can be at least twice the stiffness of a conventional aluminum press-fit cap made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length, for example, a stiffness greater than or equal to 140 GPa. In embodiments, the CTE of the cap 108 or the cap skirt 160 of the cap 108 can be greater than the CTE of a metal made of aluminum, and its stiffness is greater than that of a conventional aluminum press-fit cap made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length.

[0106] When the sealed drug container 100 cools, the cap 108 structure disclosed herein can maintain continuous compression of the stopper 106 against the upper sealing surface 110 of the flange 126 of the glass container 102. Maintaining continuous compression of the stopper 106 against the flange 126 during cooling can maintain container closure integrity (CCI) during cooling to temperatures 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, or even less than or equal to -180°C. As discussed above, this can be achieved by performing procedures such as USP <1207> The helium leak test described in (2016) is used to evaluate CCI. The sealed glass container 100 disclosed herein, including the cap 108, can maintain a pressure of less than or equal to 1.4 x 10⁻⁶ when cooled to that temperature at a rate of less than or equal to 5 °C per minute. -6 cm 3 The helium leakage rate is 1 / s.

[0107] When the sealed drug container is cooled to a temperature less than or equal to -45°C, the sealing assembly 104 including the cap 108 disclosed herein can maintain the sealed glass container 100 at a temperature less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate is [value missing] / s. When the sealed drug container is cooled to a temperature less than or equal to -80°C, the sealing assembly 104 including the cap 108 disclosed herein can maintain a sealed glass container 100 with a helium leakage rate less than or equal to 1.4 x 10⁻⁶ m / s. -6 cm 3 The helium leakage rate is [value missing]. When the sealed drug container is cooled to a temperature less than or equal to -100°C, less than or equal to -120°C, less than or equal to -150°C, or even less than or equal to -180°C, the sealing assembly 104 including the cap 108 disclosed herein can maintain a sealed glass container 100 at a temperature less than or equal to 1.4 x 10⁻⁶ m³ / s. -6 cm 3 The helium leakage rate is 1 / s.

[0108] See you again Figure 5 As described above, the cap 108 includes a cap skirt 160 and a top cover 170. The cap skirt 160 includes: an annular body 162, and a crimping area 164 at the bottom end of the annular body 162 (e.g., the annular body 162 is located at...). Figure 5The top cover 170 is located at the end of the -Z direction of the coordinate axis in the figure, and at the top end of the annular body 162 opposite to the crimping area 164, with an attachment flange 166. The top cover 170 can be shaped like a solid disc or an annular disc and can be constructed of a polymer material. In an embodiment, the top cover 170 can be an annular disc having an axial opening (not shown) extending axially (e.g., in the + / -Z direction in the figures) through the top cover 170. The axial opening provides access to the stopper 106 through the cap 108, allowing the contents of the sealed glass container 100 to be removed without removing the cap 108 and the stopper 106 from the glass container 102 using a syringe to penetrate through the stopper 106. The top cover 170 can be attached to the attachment flange 166 of the cap skirt 160.

[0109] The crimping region 164 may include a crimpable metal. The crimpable metal is a metal that can be crimped using commercially available crimping equipment. In this embodiment, the crimpable metal of the crimping region 164 may include aluminum or an aluminum alloy.

[0110] In one embodiment, the CTE of the cap skirt 160 can be greater than that of a metal made of aluminum. In another embodiment, the CTE of the annular body 162 of the cap skirt 160 can be greater than that of a metal made of aluminum. The greater CTE of the annular body 162 of the cap skirt 160 can increase the contraction of the cap skirt 160 when the sealed glass container 100 cools, which allows the cap 108 to transfer a greater sealing force to the stopper 106 when the sealed glass container 100 is cooled to temperatures 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, or even less than or equal to -180°C.

[0111] See now Figure 6A , 6B Simulations were performed on the sealing pressure between the stopper 106 and the upper sealing surface 110 of the flange 126 of the glass container 102 at different CTE values ​​and temperatures, using a cap skirt 160. A CTE of 256 x 10⁻⁶ was simulated. -7 K -1 ( Figure 6A CTE is 352x10 -7 K -1 ( Figure 6B ) and CTE is 698x10 -7 K -1 The sealing pressure of the cap ring skirt 162 at 25°C. For example... Figures 6A-6CAs shown, each simulation displays the basic sealing pressure along the entire interface between the plug 106 and the upper sealing surface 110 at 25°C. At 25°C, the sealing pressure as a function of the CTE of the cap skirt 162 exhibits very small differences.

[0112] See now Figure 7A , 7B And 7C, for each cap ring skirt 162, the simulation was repeated at a temperature of -80°C. See Figure 8A , 8B Figure 8C illustrates a magnified view of the interface between the stopper 106 and the flange 126 of the glass container 102, with different shading patterns indicating different sealing pressure areas to better show the differences in sealing pressure and contact area. (See Figure 8C for details.) Figure 8A As shown, for a CTE of 256x10 -7 K -1 The cap skirt 162 shows a significant reduction in sealing pressure and an increase in the area with no sealing pressure (e.g., less than 0.0001), which is compared to Figure 6A This is based on the simulation at 25℃. Figure 8A The interface between the plug 106 and the upper sealing surface 110 shows a large portion with zero sealing pressure. See also Figure 8B When the CTE of the 162-inch cap ring skirt is increased to 352x10 -7 K -1 At -80°C, a larger portion of the interface between the plug 106 and the upper sealing surface 110 has a positive sealing pressure, and the sealing pressure in these areas is greater than that at [other temperatures]. Figure 8A The CTE is 256x10 -7 K -1 Regarding the sealing pressure curve achieved by the cap and skirt 162, see now. Figure 8C When the CTE of the 162-inch cap ring skirt is increased to 698x10 -7 K -1 At -80°C, the sealing pressure extends a much larger percentage across the width of the upper sealing surface 110, which is compared to... Figure 8A and 8B This applies to lower CTE simulations. Furthermore, for 698x10... -7 K -1 The CTE, at a temperature of -80°C, has a contact pressure magnitude compared to Figure 8A and 8B The lower CTE simulation is larger.

[0113] See now Figure 9A , 9B And 9C, for each cap ring skirt 162, the simulation was repeated at a temperature of -180°C. See Figure 10A , 10B Figure 10C illustrates a magnified view of the interface between the stopper 106 and the flange 126 of the glass container 102, with different shading patterns indicating different sealing pressure areas to better show the differences in sealing pressure and contact area. (See Figure 10C for more details.) Figure 10A As shown, for a CTE of 256x10 -7 K -1 The cap skirt 162 has an area without sealing pressure (e.g., less than 0.0001) compared to Figure 8A The simulation at -80℃ is increased. Figure 10A This indicates the sealing pressure only at the outer edge of the upper sealing surface 110, which significantly increases the probability of loss of container closure integrity during cooling. See also Figure 10B When the CTE of the 162-inch cap ring skirt is increased to 352x10 -7 K -1 At -180°C, a larger portion of the interface between the plug 106 and the upper sealing surface 110 has a positive sealing pressure, and the sealing pressure in these areas is greater than that at [other temperatures]. Figure 10A The CTE is 256x10 -7 K -1 The sealing pressure curve achieved by the cap and skirt 162 is comparable to... Figure 10A The single-point sealing pressure shown is Figure 10B The two regions of sealing pressure shown will greatly reduce the likelihood of CCI failure at -180°C. See now. Figure 10C When the CTE of the 162-inch cap ring skirt is increased to 698x10 -7 K -1 At a temperature of -180°C, the percentage of sealing pressure extending across the width of the upper sealing surface 110 is much greater, compared to... Figure 10A and 10B This applies to lower CTE simulations. Furthermore, for 698x10... -7 K -1 The CTE, at a temperature of -180°C, has a sealing pressure compared to Figure 10A and 10B The lower CTE simulation is larger.

[0114] See now Figure 11 The graphic display has a range of 236x10. -7 K -1 Up to 1160x10 -7 K -1 The graph shows the relationship between the contact area (y-axis) and temperature (x-axis) between the plug 106 and the upper sealing surface 110 of the cap skirt 162 of different CTEs. Figure 11 As shown, for 236x10 -7 K -1 For the CTE, at temperatures below -90°C, the contact area between the plug 106 and the upper sealing surface 100 is less than 25 mm². 2 As the CTE of the cap skirt 162 increases, the contact area between the plug 106 and the upper sealing surface 100 increases. The CTE of the cap skirt 162 is increased to exactly 352x10. -7 K -1 Compared to CTE, which is 236x10 -7 K -1 The contact area between the plug 106 and the upper sealing surface 100 more than doubles. As the CTE of the cap skirt 162 increases, the contact area continues to increase. These simulations confirm that increasing the CTE of the cap skirt 162 leads to an increase in sealing pressure and contact area between the plug 106 and the upper sealing surface 110 of the flange 126 at temperatures as low as -180°C. This increase in sealing pressure and contact area leading to an increase in the CTE of the cap skirt 162 can reduce the probability of CCI failure at temperatures below -80°C.

[0115] See you again Figure 5 In embodiments, the CTE of the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be greater than that of conventional metal crimp caps. The CTE of the material comprising the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be greater than that of a typical crimp cap made of aluminum. In embodiments, the CTE of the material comprising the cap skirt 160 (particularly the annular body 162) can be greater than that of a metal made of aluminum (e.g., at least 99% aluminum), by at least 100 x 10⁻⁶. -7 K -1 In an embodiment, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) may contain a material with a CTE greater than that of the stopper 106. In an embodiment, the CTE of the material contained in the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) is such that the absolute value of the difference between the CTE of the cap skirt 160 or the annular body 162 and the CTE of the stopper is less than or equal to 50 x 10⁻⁶. -7 K -1 A typical 106 stopper will have a diameter of 1311x10 at 20°C. -7 K -1 Up to 3134x10 -7 K -1The CTE of the material contained in the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) satisfies the following equation 4, where α 环裙 The CTE of the cap skirt 160 at the glass transition temperature of the stopper 106 is α. 塞子 It is the CTE, α of stopper 106 at the glass transition temperature of stopper 106. 凸缘 The CTE, h of the flange 126 of the glass container 102 at the glass transition temperature of the stopper 106. 塞子 It is the height of the plug 106 surrounded by the 160mm hood and skirt, and h 凸缘 It is the height of flange 126.

[0116]

[0117] In an embodiment, the annular body 162 of the cap skirt 162 or cap skirt 160 may include a material having a CTE greater than 255x10 -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 or even greater than or equal to 500x10 -7 K -1 In an embodiment, at a temperature less than or equal to the glass transition temperature of the stopper 106 (e.g., less than or equal to -45°C), the annular body 162 of the cap skirt 162 or cap skirt 160 may comprise a material having a CTE greater than 255 x 10 -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 or even greater than or equal to 500x10 -7 K -1 .

[0118] In the implementation, this can be achieved by using a CTE greater than that of aluminum metal (e.g., greater than 255 x 10 at 20°C). -7 K-1 The cap skirt 160 or a portion thereof is constructed from materials to achieve a larger CTE of the annular body 162 of the cap skirt 160. The material of the cap skirt 160 (particularly the annular body 162) may include materials selected from metals, metal alloys, or polymer-metal composites, wherein the material has a CTE greater than 255 x 10⁻⁶. -7 K -1 ≥280x10 -7 K -1 300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 High CTE.

[0119] In an embodiment, the cap skirt 160 or the annular body 162 of the cap skirt 160 may include a metal or metal alloy with a CTE greater than that of aluminum (i.e., a metal made of aluminum), for example, a CTE greater than 255 x 10. -7 K -1 ≥280x10 -7 K -1 300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 In an embodiment, at a temperature less than or equal to the glass transition temperature Tg of the stopper 106 (e.g., less than or equal to about -45°C), the metal or metal alloy may have a CTE greater than 255 x 10⁻⁶. -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 or even greater than or equal to 500x10 -7 K -1In this embodiment, the cap skirt 160 can be manufactured from a high CTE metal capable of being crimped. Examples of high CTE metals capable of being crimped include, but are not limited to, Li, Li-containing alloys, Pb, Sb-Pb alloys, Zn, Zn-containing alloys, Zn-Pb-Cd alloys, Cd, or combinations thereof. However, some of these high CTE metals may be unstable in the atmosphere or may pose unacceptable health and safety risks.

[0120] Therefore, in embodiments, the cap skirt 160 may be constructed from a composite material comprising aluminum or a high CTE metal alloy (or combination thereof) comprising one or more of zinc (Zn), aluminum (Al), magnesium (Mg), and copper (Cu). In embodiments, the cap skirt 160 (or the annular body 162 of the cap skirt 160) may comprise Zn or Mg to increase the cap's CTE relative to aluminum. In embodiments, the cap skirt 160 or the annular body 162 of the cap skirt 160 may comprise a metal alloy comprising one or more of zinc, aluminum, magnesium, and copper (or combination thereof). In embodiments, the cap skirt 160 (or the annular body 162 of the cap skirt 160) may comprise an alloy of Zn, such as a Zn alloy comprising one or more metals selected from Al, Mg, Cu (and combinations thereof). The Zn alloy may have a CTE that is up to 15% greater than that of a metal composed of aluminum. In one embodiment, the metal alloy of the cap skirt 160 (or the annular body 162 of the cap skirt 160) may contain less than or equal to 5% by weight Al. In another embodiment, the metal cap 108 may include other metal alloys, such as suitable Pb-Sn alloys. In yet another embodiment, the high CTE metal or metal alloy of the cap skirt 160 may be a press-fit metal or metal alloy. The metals and metal alloys can be advantageously used in existing press-fit processes. Thus, no significant modifications to current bottle-making processes are required to achieve the sealing improvements described herein.

[0121] In one embodiment, the entire cap skirt 160 (including the annular body 162, the crimping region 164, and the attachment flange 166) can be constructed from a high CTE metal alloy, such as any high CTE metal alloy described above. In another embodiment, the annular body 162 of the cap skirt 160 may include a high CTE metal alloy, and the crimping region 164, the attachment flange 166 (or both) may include a metal or metal alloy different from the high CTE metal alloy of the annular body 162.

[0122] In some embodiments, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be constructed from a polymer-metal composite material. In some embodiments, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be constructed from a metal-polymer composite comprising a polymer matrix coated with a metal-containing coating. In some embodiments, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be constructed from a metal-polymer composite comprising a metal matrix having polymer-based reinforcements disposed therein. The polymer-based reinforcements can be disposed throughout the aluminum matrix. In these embodiments, the polymer can have a high CTE, for example (at a temperature of 20°C and / or less than or equal to the glass transition temperature of the stopper 106), greater than or equal to 280 x 10⁻⁶. -7 K -1 300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 500x10 -7 K -1 Or even greater than or equal to 1000x10 -7 K -1 The CTE of the polymer-metal composite material is greater than that of aluminum (i.e., a metal composed of aluminum). The metal in the polymer-metal composite material can be any metal or metal alloy discussed above. In embodiments, the metal in the polymer-metal composite material can be aluminum or an aluminum-containing alloy.

[0123] See you again Figure 5 In one embodiment, the cap 108 may be a polymer-metal composite structure having a polymer with high CTE and a pressable metal for the press-fit region 164 of the cap skirt 160. Specifically, the cap 108 may include a cap skirt 160, which may be a polymer-metal composite structure. In one embodiment, the annular body 162 of the cap skirt 160 may include a polymer with high CTE, and the press-fit region 164 of the cap skirt 160 may include a pressable metal (e.g., an aluminum-containing metal) connected to the polymer of the annular body 162. The aluminum-containing metal may comprise aluminum or an aluminum-containing alloy. The pressable metal of the press-fit region 164 may be located at the bottom end of the annular body 162 (e.g., the annular body 162 is oriented as...). Figure 5The end of the coordinate axis in the -Z direction is directly connected to the polymer material of the annular body 162. In an embodiment, the crimping region 164 includes a crimpable metal that can be molded into the polymer material of the annular body 162.

[0124] The annular body 162 may include a polymer with a high CTE, greater than that of a metal made of aluminum. In an embodiment, the attachment flange 166 may also include a polymer material with a high CTE. The polymer material of the annular body 162 may have a CTE greater than 255 x 10⁻⁶. -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 500x10 -7 K -1 or even greater than or equal to 1000x10 -7 K -1 In an embodiment, at a temperature less than or equal to the glass transition temperature Tg of the stopper 106 (e.g., ≤-45°C), the polymer material of the annular body 162 may have a CTE greater than 255 x 10⁻⁶. -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 400x10 -7 K -1 500x10 -7 K -1 or even greater than or equal to 1000x10 -7 K -1 The polymer can have a size less than or equal to 3000 x 10⁻⁶. -7 K -1 CTE, for example, less than or equal to 2500x10 -7 K -1 Or less than or equal to 2000x10 -7 K -1 In an embodiment, the polymer of the annular body 162 may have a CTE greater than 255 x 10⁻⁶.-7 K -1 Up to 3000x10 -7 K -1 260x10⁻⁷ K -1 Up to 3000x10 -7 K -1 260x10 -7 K -1 Up to 2500x10 -7 K -1 260x10 -7 K -1 Up to 2000x10 -7 K -1 300x10⁻⁷ K -1 Up to 3000x10 -7 K -1 300x10 -7 K -1 Up to 2500x10 -7 K -1 300x10 -7 K -1 Up to 2000x10 -7 K -1 350x10-7 K -1 Up to 3000x10 -7 K -1 350x10 -7 K -1 Up to 2500x10 -7 / K, 350x10 -7 K -1 Up to 2000x10 -7 K -1 400x10-7 K -1 Up to 3000x10 -7 K -1 400x10 -7 K -1 Up to 2500x10 -7 K -1 400x10 -7 K -1 Up to 2000x10 -7 K -1 500x10⁻⁷ K -1 Up to 3000x10 -7 K -1 500x10 -7 K -1 Up to 2500x10 -7 K -1 Or 500x10-7 K -1 Up to 2000x10 -7 K -1 .

[0125] The polymer used for the annular body 162 of the cap skirt 160 can be any polymer with a higher CTE than those described above, such as, but not limited to, high-density polyethylene (HDPE), acrylonitrile butadiene styrene polymer (ABS), polypropylene (PP), ultra-high molecular weight polyethylene (UHMWPE), or other high-CTE polymers. In embodiments, the polymer material can be a high-CTE plastic. In embodiments, the annular body 162 of the cap skirt 160 can include polymers selected from the group consisting of HDPE, ABS, PP, UHMWPE, and combinations thereof.

[0126] For the most common polymer materials, although polymers have a much larger CTE than metals, their Young's modulus is very low compared to metals used in existing metal crimp caps. This reduction in the Young's modulus of the polymer material can lead to a decrease in the stiffness of the cap skirt 160, which may cause the cap skirt 160 to flex during cooling. Flexing of the cap skirt during cooling may reduce the amount of force transmitted through the cap 108 to the stopper 106, thereby increasing the probability of CCI loss when the sealed glass container 100 cools to temperatures below -80°C. Therefore, the reduced stiffness of the polymer material may diminish any benefit to the sealing force provided by the increased CTE of the polymer material.

[0127] See now Figure 14 To ensure that the polymer portion of the cap skirt 160 is sufficiently robust to allow the cap 108 to hold the plug 108 tightly against the upper sealing surface 110 with sufficient sealing force, the rigidity of the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be increased. This can be achieved by increasing the radial thickness t of the annular body 162 of the cap skirt 160. CS To increase the rigidity of the annular body 162 of the cap skirt 160. The radial thickness t of the annular body 162. CS It can be the distance along a radial line between the inner surface of the annular body 162 and the outer surface 169 of the annular body, the radial line being perpendicular to the central axis C of the sealed glass container 100 and extending radially outward from the central axis C. The stiffness of the annular body 162 is defined by the following Equation 5.

[0128]

[0129] In Equation 5, k is the stiffness, E is the Young's modulus, A is the cross-sectional area of ​​the annular body 162 of the cap skirt 160, and L is the axial length of the annular body 162 of the cap skirt 160. The cross-sectional area A is the cross-section cut by a plane perpendicular to the central axis C of the sealed glass container 102. The length L of the annular body 162 is the length of the annular body 162 in the direction parallel to the central axis C of the sealed glass container 100 (i.e., Figure 14 The length of the coordinate axes in the + / -Z direction.

[0130] The stiffness of the annular body 162 of the cap skirt 160 can differ from the stiffness of a comparable cap skirt annular body by within 20%, said comparable cap skirt annular body being made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length L. In other words, the absolute difference between the stiffness of the polymer annular body 162 of the cap skirt 160 and the stiffness of a comparable cap skirt annular body made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length L is less than or equal to 20% of the stiffness of the comparable cap skirt annular body made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length L. The ratio of the stiffness of the annular body 162 of the cap skirt 160 to the stiffness of a comparable cap skirt annular body made of aluminum metal and having a radial thickness of 0.19 mm and a uniform axial length L can be greater than 0.8, for example, from 0.8 to 1.2.

[0131] In an embodiment, at a temperature less than or equal to the glass transition temperature Tg of the stopper 106 (e.g., ≤-45°C), the annular body 162 of the cap skirt 160 can have a stiffness that differs from the stiffness of the compressed rubber stopper 106 by within 30%. Considering the need to maintain 20% of the sealing surface of the rubber stopper 106 on the upper sealing surface 110 of the flange 126, the stiffness of the annular body 162 of the cap skirt 160 can be estimated from the following Equation 6.

[0132]

[0133] In equation 6, E 聚合物 and A 聚合物 These are the Young's modulus and area of ​​the ring-shaped body 162 constructed from polymer material, E. 塞子 It is the Young's modulus of the stopper 106, A 凸缘顶表面 It is the sealing surface area of ​​the upper sealing surface 110 of the flange 126 of the glass container 102, L 塞子 It is the axial length of plug 106, and L 聚合物This is the axial length of the cap skirt. In most cases, the inner radius of the annular body 162 containing polymer material is approximately equal to the inner radius of the corresponding cap skirt annular body made of aluminum. Therefore, one way to change the stiffness is to change the thickness δt of the annular body 162 containing polymer material. Equation 6 can be approximated by the following Equation 7.

[0134]

[0135] In an embodiment, the annular body 162 of the cap skirt 160 may comprise a polymer material having a CTE greater than 255x10 -7 K -1 ≥280x10 -7 K -1 ≥300x10 -7 K -1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 500x10 -7 K -1 or even greater than or equal to 1000x10 -7 K -1 Furthermore, the thickness of the annular body 162 of the cap skirt 160 is sufficient to ensure that the ratio of the stiffness of the annular body 162 of the cap skirt 160 to the stiffness of the compressed stopper 106 at the glass transition temperature Tg of the stopper 106 is greater than or equal to 0.7. In an embodiment, the annular body 162 may have a radial thickness t greater than 0.19 mm. CS For example: greater than or equal to 0.20mm, greater than or equal to 0.21mm, greater than or equal to 0.25mm, greater than or equal to 0.50mm, or even greater than or equal to 1mm.

[0136] It was also found that the increased stiffness of the cap 108 itself can increase the sealing pressure and reduce the probability of CCI failure, independent of the increase in the CTE of the material containing the cap 108. See now. Figure 12 The graphic shows that the CTE at 20°C is 25x10. -7 K -1 Furthermore, a graph showing the functional relationship between the contact area (y-axis) between the plug 106 of the stiffened cap skirt 160 and the upper sealing surface 110 and temperature (x-axis). Figure 12In the figure, the line indicated by reference numeral 1202 provides data for a typical cap skirt made of aluminum with a thickness of 0.19 mm. For reference numeral 1204, the stiffness of the cap skirt 160 is increased to 1.5 times the stiffness of the typical cap skirt in reference numeral 1202, while keeping the CTE constant. For reference numeral 1206, the stiffness is increased to twice the stiffness of the typical cap skirt (reference numeral 1202); and for reference numeral 1208, the stiffness is increased to four times the stiffness of the typical cap skirt (reference numeral 1202). The CTE remains constant. Figure 12 As shown, with the increase in stiffness of the cap skirt 160, the contact area between the plug 106 and the upper sealing surface 110 increases at temperatures below approximately -100°C. At a temperature of -180°C, the stiffness increases by a factor of 2, nearly doubling the contact area between the plug 106 and the upper sealing surface 110. Therefore, by increasing the stiffness of the cap skirt 160, the contact area between the plug 106 and the upper sealing surface 110 can be increased at temperatures below -100°C, -110°C, -120°C, -150°C, or even -180°C, thereby reducing the likelihood of CCI failure at these reduced storage temperatures.

[0137] See you again Figure 5 In one embodiment, the stiffness of at least a portion or all of the cap skirt 160 can be greater than or equal to twice the stiffness of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length. In another embodiment, the stiffness of at least a portion or all of the annular body 162 of the cap skirt 160 can be greater than or equal to twice the stiffness of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length. The stiffness of the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) can be increased by increasing the Young's modulus of the material comprising the cap skirt 160, or by changing the geometry of the cap skirt 160 (e.g., increasing the thickness t of the annular body 162). CS ), or both of these situations at the same time.

[0138] The Young's modulus of the cap skirt 160 can be increased by constructing at least part or all of the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) from a metal or metal alloy having a Young's modulus greater than that of aluminum or aluminum alloys. In embodiments, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) may comprise a metal or metal alloy having a Young's modulus greater than or equal to twice that of a metal composed of aluminum or an aluminum-based alloy, wherein an aluminum-based alloy refers to a metal alloy containing at least 50% by weight of aluminum. Aluminum and aluminum-based alloys have a Young's modulus range of 67 GPa to 73 GPa. In one embodiment, the cap skirt 160 (particularly the annular body 162 of the cap skirt 160) may comprise a metal or metal alloy having a Young's modulus greater than or equal to 134 GPa, greater than or equal to 140 GPa, greater than or equal to 145 GPa, greater than or equal to 150 GPa, or even greater than or equal to 160 GPa. Examples of suitable metals may include, but are not limited to, iron, nickel, steel, and alloys of iron, nickel, or steel. In another embodiment, the cap skirt 162 and the press-fit region 164 may be constructed from the same metal or metal alloy having a Young's modulus greater than or equal to 134 GPa. In other embodiments, the cap skirt 162 may be a metal or metal alloy having a Young's modulus greater than or equal to 134 GPa, and the press-fit region 164 may comprise aluminum or an aluminum-based alloy having a smaller Young's modulus.

[0139] See you again Figure 14 The stiffness of the cap skirt 160 (or the annular body 162 of the cap skirt 160) can also be increased by modifying the geometry of the annular body 162. For a constant axial length L of the annular body 162, the radial thickness t of at least part or all of the annular body 162 of the cap skirt 160 can be increased. CS To increase the rigidity of the annular body 162 of the cap skirt 160. In an embodiment, at least part or all of the annular body 162 of the cap skirt 160 may have the following radial thickness t. CS The radial thickness t is greater than that of a typical commercially available aluminum-containing cap skirt, thus the stiffness of the annular body 162 of the cap skirt 160 is greater than or equal to twice the stiffness of such a typical commercially available aluminum-containing cap skirt. In an embodiment, at least a portion or all of the annular body 162 of the cap skirt 160 may have a radial thickness t. CS It is greater than or equal to 2 times the radial thickness of a typical commercially available aluminum cap skirt. 1 / 3 In an embodiment, at least a portion or all of the annular body 162 of the cap skirt 160 may have a radial thickness t. CS: greater than or equal to 0.22mm, greater than or equal to 0.23mm, greater than or equal to 0.24mm, greater than or equal to 0.25mm, or even greater than or equal to 0.30mm.

[0140] In one embodiment, this can be achieved by simultaneously increasing the Young's modulus of the material of the annular body 162 including the cap skirt 160 and increasing the radial thickness t of at least a portion of the annular body 162 of the cap skirt 160. CS These two factors increase the stiffness of the cap skirt 160. Therefore, the increase in the Young's modulus of the annular body 162 of the cap skirt 160 is related to the radial thickness t. CS The added combination can increase the stiffness of the cap skirt 160 to more than twice the stiffness of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length. In an embodiment, the annular body 162 of the cap skirt 160 may include a material having a Young's modulus greater than 73 GPa (e.g., greater than 73 GPa to 140 GPa or even greater than 140 GPa), and at least a portion of the annular body 162 of the cap skirt 160 may have a radial thickness t greater than 0.19 mm, greater than or equal to 20 mm, greater than or equal to 21 mm, or even greater than or equal to 22 mm. CS Thus, the Young's modulus and radial thickness t of the annular body 162 are... CS The combination results in the cap skirt 160 having a stiffness greater than or equal to twice the stiffness of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a consistent axial length.

[0141] Furthermore, the inventors of this disclosure have discovered that the increase in CTE of the cap skirt 160, combined with the increase in stiffness of the cap skirt 160, produces a synergistic effect, which further improves the contact area and sealing pressure between the plug 106 and the upper sealing surface 110 of the flange 126 beyond what could be achieved by simply increasing either CTE or stiffness. See now. Figure 13 The diagram illustrates the relationship between the contact area (y-axis) between the plug 106 and the upper sealing surface 110 and temperature (x-axis) for a sealed glass container 100 with a cap skirt 160 having various CTEs and stiffnesses. Figure 13 In the figure, the line indicated by reference numeral 1302 shows that the cap skirt 160 has a size of 236x10. -7 K -1 The CTE and the contact area of ​​the sealed glass container 102 with first stiffness are shown as a function of temperature. The first stiffness corresponds to the stiffness of the cap ring skirt, which is made of aluminum and has a radial thickness of 0.19 mm. The cap ring skirt of reference numeral 1302 has a thickness of less than 10 mm when the temperature is less than -120°C. 2The contact area. For reference numeral 1304, the stiffness of the cap skirt 160 is increased to 1.5 times the stiffness of the first stiffness. For example... Figure 13 As shown, increasing the stiffness to 1.5 times the initial stiffness (see figure 1304) results in an increase in the contact area, but the contact area remains approximately 12 mm². 2 For reference numeral 1306, the stiffness of the cap skirt 160 is equal to the first stiffness (the same as reference numeral 1302), but the CTE of the cap skirt 160 is increased to 352x10. -7 K -1 .like Figure 13 As shown, by maintaining the same stiffness but increasing the CTE of the cap skirt by 160, the contact area at temperatures ranging from -120°C to -180°C increases to 25 mm. 2 Up to 30mm 2 The range.

[0142] For reference numeral 1308, the CTE of the cap skirt 160 is increased to 352x10. -7 K -1 Furthermore, the stiffness of the cap skirt 160 is increased to 1.5 times the first stiffness. For example... Figure 13 As shown, simultaneously increasing both CTE and stiffness (see figure 1308) results in an increase in contact area to 50 mm² at temperatures ranging from -120°C to -180°C. 2 Up to 62mm 2 This exceeds what alone would increase CTE to 352x10. -7 K -1 The contact area increased by a factor of two without changing the stiffness. The result was unexpected, as the observed increase in contact area derived from both the increase in CTE and the increase in stiffness was significantly greater than the simple sum of the individual effects of increasing CTE (reference numeral 1304) and increasing stiffness (reference numeral 1306). The simple sum of the effects shown in reference numerals 1304 and 1306 would have resulted in a contact area of ​​35 mm² at temperatures ranging from -120°C to -180°C. 2 Up to 38mm 2 The range. However, simultaneously increasing the CTE and stiffness (reference numeral 1308) of the cap skirt 160 results in a 55mm increase in temperature over a range of -120°C to -180°C. 2 Up to 62mm 2 The contact area is almost twice the contact area expected by simply adding the individual effects together (i.e., adding the difference between 1304 and 1302 to the difference between 1306 and 1302).

[0143] In an implementation, the cap skirt 160 may have the following CTE: greater than 255x10 -7 K-1 ≥280x10 -7 K -1 300x10 -7 K -1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 The stiffness of the cap skirt 160 can be greater than that of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length. The stiffness of the cap skirt 160 can be greater than or equal to 1.2 times, 1.3 times, 1.4 times, 1.5 times, or 2.0 times that of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length.

[0144] As described above, the stiffness of the cap skirt 160 can be increased by increasing the Young's modulus of the annular body 162 of the cap skirt 160, increasing the thickness of at least a portion of the annular body 162 of the cap skirt 160 (or both). The annular body 162 of the cap skirt 160 can have any of the features, materials, or properties described above that result in both an increase in the CTE and stiffness of the cap skirt 160 (compared to a typical commercially available cap skirt made of aluminum with a thickness of 0.19 mm and a uniform axial length). In an embodiment, the cap skirt 160 may include an annular body 162 comprising a material having a thickness greater than or equal to 260 x 10 mm. -7 K -1 300x10 -7 K -1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 The CTE, and Young's modulus greater than 73 GPa, greater than or equal to 80 GPa, greater than or equal to 90 GPa, greater than or equal to 100 GPa, greater than or equal to 120 GPa, or even greater than or equal to 140 GPa. In an embodiment, the cap skirt 160 may include an annular body 162 comprising a material having a size greater than or equal to 260 x 10⁻⁶ cm². -7 K -1300x10 -7 K -1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 The CTE, and at least a portion of the annular body 162, may have the following radial thickness t. CS : greater than or equal to 0.20 mm, greater than or equal to 0.21 mm, greater than or equal to 0.22 mm, greater than or equal to 0.23 mm, greater than or equal to 0.24 mm, greater than or equal to 0.25 mm, greater than or equal to 0.50 mm, or even greater than or equal to 1.0 mm. In an embodiment, the cap skirt 160 may include an annular body 162, which includes: (1) a material having the following CTE: greater than or equal to 260 x 10 mm. -7 K -1 300x10 -7 K -1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 and Young's modulus: greater than 73 GPa, greater than or equal to 80 GPa, greater than or equal to 90 GPa, greater than or equal to 100 GPa, greater than or equal to 120 GPa or even greater than or equal to 140 GPa; and (2) at least a portion of the annular body 162 may have the following radial thickness t CS : greater than or equal to 0.20mm, greater than or equal to 0.21mm, greater than or equal to 0.22mm, greater than or equal to 0.23mm, greater than or equal to 0.24mm, greater than or equal to 0.25mm, greater than or equal to 0.5mm, or even greater than or equal to 1.0mm.

[0145] See you again Figure 14 The cap 108 may have a cap skirt 160 comprising a polymer-metal composite structure and a top cover 170. At least a portion of the annular body 162 of the cap skirt 160 may comprise a polymer material having a CTE greater than 255 x 10⁻⁶. -7 K -1 ≥260x10 -7 K -1 300x10 -7 K-1 ≥350x10 -7 K -1 or even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 The crimping region 162 may contain a crimpable metal (e.g., aluminum or an aluminum alloy). The annular body 162 of the cap skirt 160 may have a reinforcing region 180, wherein the radial thickness t CS The values ​​are: greater than or equal to 0.20 mm, greater than or equal to 0.21 mm, greater than or equal to 0.22 mm, greater than or equal to 0.23 mm, greater than or equal to 0.24 mm, greater than or equal to 0.25 mm, or even greater than or equal to 0.30 mm. The reinforced region 180 may include part or all of the annular body 162. In an embodiment, the reinforced region 180 may include at least 30%, at least 40%, at least 50%, at least 60%, or even at least 70% of the axial length L of the annular body 162 of the cap skirt 160. The radial thickness t of the annular body 162... CS The stiffness of the cap skirt 160 can be increased to 1.2 times, 1.3 times, 1.4 times, 1.5 times, or 2.0 times that of a comparable cap skirt annular body made of aluminum metal with a radial thickness of 0.19 mm and a uniform axial length. The cap skirt 160 can simultaneously have increased CTE and increased stiffness, which allows the cap skirt 160 to maintain the contact area and sealing pressure between the stopper 106 and the upper sealing surface 110 of the glass container 102 when the sealed glass container 100 is cooled to a temperature below -80°C.

[0146] like Figure 14 As shown, the cap 108 may have a top cover 170 that is separate from and removably attachable to the cap skirt 160. In such embodiments, the top cover 170 can be removed from the cap skirt 160 prior to use of the sealed glass container 100, for example, to provide access to the stopper 106, or to recover the contents of the sealed glass container 100 using a syringe or other means. The top cover 170 may be engageable with an attachment flange 166 of the cap skirt 160. In one embodiment, the top cover 170 may include a groove 172 shaped to receive the attachment flange 166, wherein engagement of the attachment flange 166 with the groove 172 connects the top cover 170 to the cap skirt 160. In another embodiment, the annular body 162 of the cap skirt 160 may have a notch 182 positioned to receive an end 174 of the top cover 170.

[0147] The top cover 170 may include a polymer material, such as a polymer having a CTE greater than 255x10. -7 K -1 ≥260x10 -7 K -1 ≥300x10 -7 K -1 ≥350x10 -7 K -1 Even greater than or equal to 400x10 -7 K -1 Or even greater than or equal to 500x10 -7 K -1 In one embodiment, the top cover 170 may be constructed of the same polymer material as the annular body 162 of the cap skirt 160. In another embodiment, the top cover 170 may be made of a different material than the annular body 162 of the cap skirt 160.

[0148] See now Figure 15 In one embodiment, the cap 108 may include a one-piece structure, wherein the cap skirt 160 and the top cover 170 are integrally molded together to create a single one-piece structure. In one embodiment, the reinforcing region 180 of the annular body 162 can extend from the crimping region 164 all the way to the top 171 of the top cover 170 portion of the cap 108. The cap 108, which includes the cap skirt 160 and the top cover 170 integrally molded as a one-piece structure, may also include a portion extending downward from the cap skirt 160 of the cap 108 (e.g., approximately...). Figure 15 The crimping area 164 extends in the -Z direction of the coordinate axis. The annular body 162 of the cap skirt 160 and the top cover 170 portion of the cap 108 may include a material having a CTE greater than 255x10 -7 K -1 ≥260x10 -7 K -1 ≥300x10 -7 K -1 ≥355x10 -7 K -1 Even greater than or equal to 400x10 -7 K -1 or even greater than or equal to 500x10 -7 K -1 .

[0149] The annular body 162 of the cap 108 may have any of the features, materials, or dimensions described above for the annular body 162. In embodiments, according to any of the embodiments described above, the annular body 162 of the cap 108 may have increased CTE, increased stiffness, or both. Increased CTE, increased stiffness (or both) of the annular body 162 of the cap 108 can increase the sealing pressure and contact area between the stopper 106 and the upper sealing surface 110 of the flange 126 of the glass container 102. The increased sealing pressure and contact area provided by the cap 108 disclosed herein can reduce the probability of CCI failure.

[0150] When integrally molded as a single structure, the top cover 170 may not be removable from the cap skirt 160 of the cap 108. In an embodiment, the top cover 170 portion of the cap 108 may include an opening 176 extending axially through the top cover 170 portion. The opening 176 provides accessibility to the stopper 106 surrounding the cap 108. The accessibility to the stopper 106 provided by the opening 176 in the top cover 170 portion allows for the removal of the contents of the sealed glass container 100 by piercing the stopper 106 and extracting the contents of the sealed glass container 100 without removing the cap 108 and the stopper 106. The needle or other penetrating device may pass through the opening 176 in the top cover 170 portion of the cap 108, then through the stopper 106, and into the sealed glass container 100. The opening 176 in the top cover 170 portion of the cap 108 may be coaxial with the central axis C of the sealed glass container 100.

[0151] See now Figure 16 The illustration schematically shows an embodiment of a cap 180 with a cap skirt 160, the cap skirt 160 comprising an annular body 162 having high CTE and high rigidity. The radial thickness t of the annular body 162 of the cap skirt 160 is shown. CS to increase to provide Figure 16 The stiffness of the cap 108 is increased. See now. Figure 17A , 17B And 17C, at different temperatures, for Figure 16 The sealing pressure between the stopper 106 and the upper sealing surface 110 of the flange 126 of the glass container 102 (cap 108) was simulated. This was achieved using a 1264x10... -7 K -1 The annular body of the cap skirt is constructed from CTE and high-density polyethylene (HDPE) with a Young's modulus of only 1 GPa. Stiffness is increased by increasing the thickness of the annular body 162 of the cap skirt 160 from 0.2 mm to 2.14 mm. At 25°C ( Figure 17A -80℃ Figure 17B ) and -180℃ Figure 17C Simulates the sealing pressure between the plug 106 and the upper sealing surface 110 of the flange 126. For example... Figure 17A , 17B As shown in 17C, the increased CTE and stiffness of the cap skirt 162 can maintain sufficient sealing contact area and pressure between the plug 106 and the upper sealing surface 110, even at temperatures as low as -180°C.

[0152] See now Figure 18 , showing for those containing Figure 16 The CTE at 20°C is 1264 x 10. -7 K -1 Furthermore, when a sealed glass container with a cap 108 of 2.14 mm thickness is cooled at a constant cooling rate, a graph showing the relationship between the contact area (y-axis) between the upper sealing surface 110 of the flange 126 and the plug 106 and the temperature (x-axis) is plotted, and compared with the contact area of ​​a sealed glass container containing a conventional cap made of aluminum and 0.2 mm thick. Figure 18 In the figure, reference numeral 1802 relates to a sealed container comprising a conventional cap made of aluminum metal and having an annular body thickness of 0.2 mm. Reference numeral 1804 relates to a sealed container comprising a cap with an HDPE cap skirt. Figure 16 A sealed glass container with a cap, the HDPE cap skirt having a size of 1264x10 at 20°C. -7 K -1 The CTE, Young's modulus of 1 GPa, and thickness of 2.14 mm. For example... Figure 18 As shown, at temperatures below -80°C, compared to sealed glass containers with conventional caps constructed of aluminum, [the following parameters are considered:] ... Figure 16 The sealing glass container with a cap having a larger CTE and stiffness provides a significantly larger contact area. Specifically, at temperatures below -80°C, compared to a conventional aluminum cap (1802), Figure 16 The cap (1804) provides nearly 10 times the contact area.

[0153] The increased CTE and stiffness (or both) of the cap 108 disclosed herein can increase the sealing pressure and contact area between the stopper 106 and the upper sealing surface 110 of the flange 126 of the glass container 102. The increased sealing pressure and contact area provided by the cap 108 disclosed herein can reduce the probability of CCI failure. Specifically, the cap 108 disclosed herein can ensure that when the sealed drug container is cooled to a temperature less than or equal to -45°C, less than or equal to -80°C, less than or equal to -100°C, less than or equal to -120°C, or even less than or equal to -180°C, the sealed glass container 100 maintains a temperature less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed glass container is 100 per second.

[0154] The cap 108 disclosed herein can be used in conjunction with other features of the glass container 102, the stopper 106 (or both) to further reduce the probability of CCI failure at low storage temperatures below -80°C. See again Figure 1-4 The structure of the glass container 102 can be modified to deviate from the existing glass container to provide greater compression of the stopper 106 during the crimping process of the cap 108. See again Figure 2 The upper sealing surface 110 may include an inclined sealing surface 140. The inclined sealing surface 140 extends between the outer surface 134 of the flange 126 and the inner surface 114 of the glass container 102. The inclined sealing surface 140 may extend 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 102 located on the top of the glass container 102 at the opening 105 (e.g., located on the peak of the inclined sealing surface 140) and parallel to the central axis C of the glass container 102 (e.g., ...). Figure 1 (The X direction is shown).

[0155] 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 one 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 relative to the lower surface 132 in the + / -Z direction) and a second highest point on the inclined sealing surface 140 (e.g., via a plane located on the peak of the inclined sealing surface and below another point of the inclined sealing surface 140 relative to 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 extend outward from the inner surface 114 and inward from the outer surface 134 at predetermined distances (e.g., 0.1 mm, 0.2 mm, 0.5 mm, 1.0 mm, etc.). (For example, the selected points may be a uniform distribution of spatial points extending between the inner surface 114 and the outer surface 134.) 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.

[0156] In this embodiment, angle 150 can be greater than 5 degrees and less than or equal to 45 degrees (e.g., greater than 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.

[0157] A greater inclination of the upper sealing surface 110 can increase stopper compression at low storage temperatures, thereby increasing the sealing pressure between the stopper 106 and the upper sealing surface 110 of the flange 126. As a result of the crimping of the cap 108, angle 150 can create a compression gradient within the stopper 106. For example, in an embodiment, the compression of the stopper 106 can increase with increasing radial distance relative to the outer surface 134, resulting in greater compression closer to the inner surface 114. This greater compression near the inner surface 114 can prevent gaps from forming in the seal as the stopper 106 shrinks due to cooling. The degree of compression of the stopper 106 near the opening 105 is greater than that in the peripheral region of the stopper 106 located near the outer surface 134 of the flange 126. This greater compression results in greater compression of the stopper 106 under the same crimping process, providing greater tolerance to shrinkage of the stopper 106. In addition, the inclination of the sealing surface 140 reduces the term L near the opening 105 in Equation 3 above. i,塞子 This reduces the amount of shrinkage required by the cap 108 to maintain the relationship in Equation 1 of this paper.

[0158] See you again Figure 3 In one embodiment, the upper sealing surface 110 may extend in a plane 152 extending through the end 154 of the opening 105 in the glass container 102. In another embodiment, the upper sealing surface 110 may extend substantially perpendicular to the central axis C of the glass container 102 (e.g., at an angle greater than or equal to 89.5 degrees and less than or equal to 90.5 degrees). Such an upper sealing surface 110 may be used to add a stopper 106 (see...). Figure 1 A) The contact area between the upper sealing surface 110 and the sealing surface 110, and can increase the probability of maintaining the integrity of the seal.

[0159] In the implementation method, it is possible to... Figure 2 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 an embodiment, the upper sealing surface 110 may include 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 can advantageously prevent the stopper 106 from being pulled away from the upper sealing surface 110 after cooling. In an embodiment, the upper sealing surface 110 may be substantially free of defects (e.g., wrinkles, bulges, protrusions, 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.

[0160] 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 cap 108 and the combination of the flange 106 and the stopper 126. Providing this surface roughness ensures at least some contact between the upper sealing surface 110 and the plug 106 after cooling.

[0161] 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 cap 108 is not modified, the proportion of the total height 138 of the material enclosed by the stopper 106 containing the cap 108 is reduced, thereby reducing the shrinkage of the 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.

[0162] The features of the cap 108 disclosed herein can also be used in conjunction with changes to the composition of the stopper 106 to further increase sealing pressure and contact area, and reduce the likelihood of CCI failure. In embodiments, 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 compression of the stopper 106 via the cap 108. In embodiments, 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 -45°C, less than or equal to -70°C, less than or equal to -75°C, less than or equal to -80°C, or even less than or equal to -85°C. In embodiments, the stopper 106 may comprise a polymer composition with a glass transition temperature greater than or equal to -70°C and less than or equal to -45°C. In one embodiment, the glass transition temperature of the stopper 106 can be lowered below the storage temperature of the desired sealed glass container 100 (e.g., to a dry ice storage temperature less than or equal to approximately -80°C), thereby maintaining the elasticity of the stopper 106 and creating a seal at the upper sealing surface 110. In another embodiment, the stopper 106 may comprise one or more low-Tg elastomer materials, such as polybutadiene, silicone, fluorosilicone, nitrite / ester, and EPDM elastomers (e.g., PDMS), or any combination thereof. In yet another embodiment, the elastomer material may comprise a material with a glass transition temperature less than or equal to -100°C.

[0163] In one embodiment, the stopper 106 may include a polymer-based composite material with a CTE lower than that typically used in rubber materials. In another embodiment, the stopper 106 may include a rubber-filler mixture. For example, in one embodiment, the stopper 106 may contain a polymer or rubber material and up to 15% by volume of filler material. In another embodiment, the stopper 106 may contain 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 may be lower than that of rubber typically used to construct the stopper (e.g., less than or equal to 50 x 10). -7 K -1 Less than or equal to 20x10 -7 K -1 Less than or equal to 10x10 -7 K -1 Less than or equal to 5x10 -7 K -1In embodiments, the filler may comprise silicon. For example, in embodiments, the filler material may comprise SiO2 glass particles having 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 may comprise silicates / esters (e.g., cordierite, β-nepheline, β-spodumene). In embodiments, the filler material may be a high-melting-point metal (e.g., Ir, W, Ti, Si). In embodiments, the filler material may comprise Mg2PO4. In embodiments, the filler material may comprise oxides, such as SiO2, Ti-doped SiO2, ZrW2O8, or other ceramics in the AM2O8 family. In embodiments, the filler material may comprise any other suitable material having a low or negative CTE. In embodiments, the CTE of the stopper 106 containing the filler material may be less than or equal to 300 x 10⁻⁶. -7 K -1 (For example, less than or equal to 290x10) -7 K -1 Less than or equal to 280x10 -7 K -1 Less than or equal to 270x10 -7 K -1 By adding the filler material described herein to the stopper 106, the CTE of the stopper 106 (relative to the CTE of the metal cap 108) can be 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.

[0164] It should be understood that any combination of the above-described solutions (e.g., increasing the CTE and / or stiffness of the cap 108, decreasing the CTE and / or Tg of the stopper 106, or structurally modifying the glass container 102 in any manner described herein) can be used to seal the glass container 100. In embodiments, a structure containing 260x10 is included. -7 K -1 Both a high CTE and / or high stiffness 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. In such embodiments, 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 by the formulation.

[0165] The cap 108 disclosed herein can be incorporated into sealing methods for glass containers, such as sealing methods for pharmaceutical containers. See again Figure 5In one embodiment, the sealing method for sealing a drug container may include providing a glass container 102 comprising a shoulder 130, a neck 128 extending from the shoulder 130, and a flange 126 extending from the neck 128. The glass container 102 may be a drug container and may include any of the features, compositions, or properties described above for the glass container 102. The flange 126 may include: a lower surface 132 extending from the neck 128, an outer surface 134 extending from the lower surface 132 and defining an outer diameter of the flange 126, and an upper sealing surface 110 extending between the outer surface 132 and an inner surface 114 of the sealed glass container 100. The inner surface 114 defines an opening 105 in the glass container 102. The method may also include inserting a drug composition into the glass container 102 and providing a sealing assembly 104 comprising a stopper 106 and a cap 108. The stopper 106 and the cap 108 may each have any of the features, materials or properties described above for the stopper 106 and the cap 108.

[0166] The method may further include inserting a stopper 106 into an opening 105 in the glass container 102 such that the stopper 106 extends over and covers the opening 105 above the upper sealing surface 110 of the flange 126. The method may further include pressing a cap 108 against the flange 126 above and against the stopper 106, thereby compressing the stopper 106 against the upper sealing surface 110. The method may further include cooling the sealed glass container 100 to a temperature less than or equal to -45°C, for example: less than or equal to -80°C, less than or equal to -100°C, less than or equal to -120°C, or even less than or equal to -180°C. After cooling, the compression on the upper sealing surface 110 is maintained, such that at this temperature, the helium leakage rate of the sealed glass container 100 is less than or equal to 1.4 x 10⁻⁶. -6 cm 3 / s.

[0167] 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.

[0168] 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 cap for sealing a pharmaceutical glass container, the cap comprising: plug; A cap-shaped skirt, comprising a ring-shaped body and a crimping area at the first end of the ring-shaped body; as well as A top cover connected to the second end of the cap skirt, the top cover comprising a solid disc or annular disc; in: The crimping area includes the crimpable metal; The coefficient of thermal expansion (CTE) of the annular body of the cap skirt is greater than that of the metal made of aluminum, and the stiffness of the included part is greater than or equal to twice the stiffness of the crimping area, or both of these conditions are met simultaneously. CTE refers to the CTE within the temperature range of -200°C to 30°C; and Stiffness is defined as Young's modulus multiplied by the cross-sectional area divided by the axial length. At temperatures less than or equal to the glass transition temperature Tg of the stopper, the stiffness of the annular body of the cap skirt differs from the stiffness of the stopper under compression by less than 30%.

2. The cap as claimed in claim 1, wherein, The CTE of the ring body of the cap skirt is greater than that of the metal made of aluminum, with a difference of at least 100 x 10. -7 K -1 .

3. The cap as described in claim 1, wherein, The CTE of the ring body of the cap skirt is greater than or equal to 260x10. -7 K -1 .

4. The cap as claimed in claim 1, wherein, At temperatures less than or equal to -45 °C, the CTE of the annular body of the cap skirt is greater than or equal to 260 x 10. -7 K -1 .

5. The cap as claimed in claim 1, wherein, The stiffness of the annular body of the cap skirt is greater than or equal to twice the stiffness of the equivalent cap skirt annular body, which is made of aluminum and has a radial thickness of 0.19 mm and a consistent axial length.

6. The cap as claimed in claim 1, wherein, The annular body of the cap skirt has a Young's modulus greater than or equal to 140 GPa and a radial thickness greater than or equal to 0.24 mm, or both.

7. The cap as claimed in claim 1, wherein, The CTE of the ring body of the cap skirt is greater than 260x10. -7 K -1 The stiffness of the annular body is greater than twice that of the equivalent cap skirt annular body, which is made of aluminum and has a radial thickness of 0.19 mm and a uniform axial length.

8. The cap as claimed in claim 1, wherein, The pressable metal in the press area includes aluminum or aluminum alloy.

9. The cap as claimed in claim 1, wherein, The CTE of the annular body of the cap skirt is greater than that of a metal made of aluminum.

10. The cap as claimed in claim 1, wherein, The cap skirt comprises a polymer-metal composite structure.

11. The cap as claimed in claim 10, wherein, The annular body of the cap skirt comprises a polymer material, and the crimping area comprises a crimpable metal of polymer material connected to the annular body.

12. The cap as claimed in claim 11, wherein, The polymer material of the ring-shaped body has a size of 260x10. -7 K -1 Up to 3000x10 -7 K -1 CTE.

13. The cap as claimed in claim 11, wherein, The stiffness of the annular body of the cap skirt is greater than or equal to 80% of the stiffness of the equivalent cap skirt annular body, which is made of aluminum and has a radial thickness of 0.19 mm and a consistent axial length.

14. The cap as claimed in claim 1, wherein, The cap skirt includes an attachment flange disposed at the second end of the ring body, and a top cover attached to the attachment flange.

15. The cap as claimed in claim 14, wherein, The top cover is removable from the hooded skirt.

16. The cap as claimed in claim 1, wherein, The top cover and the ring body of the cap skirt are formed as one piece to create a single cap.

17. The cap as claimed in claim 1, wherein, The top cover includes an annular disc with an axial opening in the center of the top cover.

18. A sealed drug container, comprising: A glass container comprising a shoulder, a neck extending from the shoulder, and 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 A sealing surface extending between an outer surface and an inner surface that defines an opening in a sealed drug container; A sealing assembly comprising: a plug extending above a sealing surface of a flange of a glass container and covering an opening; and a cap comprising a cap skirt having an annular body and a crimping region at a first end of the annular body, and a top cover connected to a second end of the cap skirt, the top cover comprising a solid disc or an annular disc, wherein: The cap secures the plug to the flange in place; At temperatures less than or equal to the glass transition temperature Tg of the stopper, the stiffness of the annular body of the cap skirt differs from that of a compressed rubber stopper by within 30%; and When the sealed drug container is cooled to a temperature less than or equal to -45°C, the sealing assembly maintains a value less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

19. The sealed drug container as claimed in claim 18, wherein, The stopper has a glass transition temperature Tg greater than or equal to -75°C and less than or equal to -45°C.

20. The sealed drug container as claimed in claim 18, wherein, The glass transition temperature of the stopper is less than or equal to -75°C.

21. The sealed drug container as claimed in claim 18, wherein, When the sealed drug container is cooled to a temperature less than or equal to -80°C, the sealing assembly maintains a value less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

22. The sealed drug container as claimed in claim 18, wherein, When the sealed drug container is cooled to a temperature less than or equal to -100°C, the sealing assembly maintains a value of less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

23. The sealed drug container as claimed in claim 18, wherein, When the sealed drug container is cooled to a temperature less than or equal to -120°C, the sealing assembly maintains a value less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate of a sealed drug container is 1 / s.

24. The sealed drug container as claimed in claim 18, wherein, Glass containers are made of materials with a coefficient of thermal expansion greater than or equal to 0 and less than or equal to 70 x 10⁻⁶. -7 K -1 The glass composition structure.

25. The sealed drug container as claimed in claim 18, wherein, The absolute value of the difference between the CTE of the cap ring and the CTE of the plug is less than or equal to 50 x 10. -7 K -1 .

26. The sealed drug container as claimed in claim 18, wherein, The CTE of the ring body of the cap skirt is greater than the CTE of the plug.

27. The sealed drug container as claimed in claim 18, wherein, When cooled to that temperature at a rate of less than or equal to 5°C per minute, the sealed drug container maintained a temperature of less than or equal to 1.4 x 10⁻⁶. -6 cm 3 The helium leakage rate is 1 / s.

28. The sealed drug container as claimed in claim 27, wherein, As the sealed medicine container cools, the cap maintains the continuous compression of the stopper against the flange of the glass container.

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