Patent Publication Number: US-2015068521-A1

Title: Container and pharmaceutical product

Description:
BACKGROUND 
     This patent is directed to an anesthetic container and a pharmaceutical product, and, in particular, to an anesthetic container and a pharmaceutical product to be used with a halogenated anesthetic. 
     Liquid anesthetic is conventionally shipped from the manufacturer to the user (medical professional, hospital, etc.) in a container. While the design of the container may vary, it is often the case that the container will include an adapter with a valve assembly disposed in the neck of the container. The valve assembly controls the flow of liquid anesthetic from the container into a vaporizer, where the liquid anesthetic vaporizes typically in the presence of a carrier gas. The valve assembly may also control the return flow of vapor from the vaporizer into the container as the liquid is displaced from the container. 
     U.S. Patent Application No. 20060048842 illustrates one example of such a valve assembly (or valve, for short). A valve member and an associated cylindrical partition move within a conduit to control the exchange of liquid anesthetic and anesthetic vapor with a vaporizer. The illustrated valve or valve assembly is held in place through the cooperation of a rim of a cage, a rim disposed about the container neck, and a crimped ferrule. To seal the connection between the rim of the cage and the rim of the neck, a deformable gasket is disposed between the opposing rims. While not illustrated, a deformable gasket typically is disposed on the valve member, to seal the valve member to the conduit when the valve member is in the closed position. In addition, an o-ring is disposed about the valve assembly to seal the exterior interface between the valve assembly and the vaporizer port. 
     While different configurations of valve assembly have been tried over the years, it has remained conventional practice to place a gasket between the valve assembly and the container, and between the valve member and the conduit. Loss of seal between the valve assembly and the neck of the container, or between the valve member and the conduit, could have a multiple negative consequences. For example, leakage of anesthetic from the container into the environment is generally undesirable. Additionally, leakage of anesthetic represents a loss of value to the customer and to the supplier, from whom the customer is likely to seek compensation for the lost product. 
     However, the presence of the sealing gaskets in the assembly is not without its own set of consequences. The additional part count represented by the inclusion of these gaskets may add to the manufacturing costs and complexity. Further, each part within the assembly must be verified for safety, relative to its use in a medical device or system. Additionally, each part within the assembly must be verified for quality, relative to its intended use. 
     Moreover, the o-ring used to form the seal between the valve and vaporizer port must also be verified for safety and quality. The o-ring is subject to significant forces to deform the o-ring, and thereby provide a secure, fluid-tight seal. These forces are also applied to the o-ring when the valve is advanced into and withdrawn from the vaporizer port, which wears the o-ring and reduces the life of the o-ring. 
     As set forth in more detail below, the present disclosure sets forth a container with an improved valve assembly embodying advantageous alternatives to the valve assemblies of prior art devices. 
     SUMMARY 
     In one aspect, an anesthetic container includes a receptacle for holding an anesthetic and having a wall defining an interior space and a passage in fluid communication with the interior space, and a valve assembly that is attachable to the receptacle to control flow of anesthetic through the passage to a vaporizer. The valve assembly includes a valve seat with a first sloped surface and a valve member with a second sloped surface, the first sloped surface and the second sloped surface having different slopes. The first and second sloped surfaces abut each other to form a gasketless, fluid-tight seal therebetween with the valve assembly in a closed configuration to limit the flow of the anesthetic from the receptacle. The valve member is spaced from the valve seat with the valve assembly in an open configuration to permit the flow of the anesthetic from the receptacle. 
     In another aspect, an anesthetic container includes a receptacle for holding an anesthetic and having a wall defining an interior space and a passage in fluid communication with the interior space, the anesthetic selected from the group of halogenated anesthetics consisting of sevoflurane, desflurane, isoflurane, enflurane, methoxyflurane and halothane. The anesthetic container also includes a valve assembly that is attachable to the receptacle to control flow of anesthetic through the passage to a vaporizer. The valve assembly includes a conduit having a wall defining a conduit passage with a first end and a second end, a valve seat defined at the second end of the conduit passage and a valve member, the valve member and the valve seat abutting each other in a closed configuration to limit the flow of the anesthetic from the receptacle, and spaced from each other with the valve assembly in an open configuration to permit the flow of the anesthetic from the receptacle. The wall of the conduit has an external surface with a groove formed therein at the first end, and further comprising a toroidal sealing member disposed in the groove, the toroidal sealing member having an X-shaped cross-section. 
     Additional aspects of the disclosure are defined by the claims of this patent. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       It is believed that the disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may have been simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omissions of elements in some figures are not necessarily indicative of the presence or absence of particular elements in any of the exemplary embodiments, except as may be explicitly delineated in the corresponding written description. None of the drawings is necessarily to scale. 
         FIG. 1  is a fragmentary, cross-sectional view of a container according to the present disclosure, with a valve assembly in a closed configuration; 
         FIG. 2  is an enlarged, partial cross-sectional view of a container according to the present disclosure, highlighting the interface between the valve member and the valve seat; 
         FIG. 3  is a partial cross-sectional view of the valve assembly of  FIG. 1 , with the receptacle and the ferrule removed and the valve assembly in an open configuration; 
         FIG. 4  is a perspective view of the conduit of  FIG. 1 ; and 
         FIG. 5  is a partial cross-sectional view of the toroidal sealing member used with the conduit of  FIG. 1 . 
     
    
    
     DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS 
       FIG. 1  illustrates an embodiment of an anesthetic container  100 . The container  100  may be used with halogenated inhalation anesthetics such as sevoflurane (fluoromethyl 2,2,2-trifluoro-1-[trifluoromethyl]ethyl ether), desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether), isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), enflurane (2-chloro-1,1,2-trifluoroethyl-difluoromethyl ether), methoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) and halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), for example, which may be disposed in the container to define a pharmaceutical product. According to certain embodiments, the anesthetic may be selected from a group consisting of sevoflurane, desflurane, isoflurane, enflurane, methoxyflurane and halothane. All of these halogenated anesthetics may be liquids under ambient conditions. The container  100  may be used to store these anesthetics for prolonged periods of time (e.g., weeks, months, or years), and thus may be referred to as a storage container. 
     The container  100  includes a receptacle  102  for holding the anesthetic, a valve assembly  104 , and a ferrule (or cover)  106 . The container  100  may also include a cap  107  that is fitted over the end of the valve assembly  104 , as illustrated. The cap  107  may provide a barrier to anesthetic loss as well as limiting access to and contamination of the valve assembly  104 . A sealing gasket (which may be made of low density polyethylene (LDPE)) may be disposed between the valve assembly  104  and the cap  107 . 
     The receptacle  102  (which may in the form of a bottle as illustrated) has a wall  108  that defines an interior space  110  and a neck  112  with a passage  114  in fluid communication with the interior space  110 . The anesthetic may be disposed in the interior space  110 , so as to be contained within the receptacle  102 . As illustrated in  FIG. 1 , the embodiment of the receptacle  102  has a neck  112  with a smaller cross-section than the widest part of the receptacle  102 ; this need not be the case according to all embodiments of the present disclosure. In addition, the receptacle  102  has a flange  116 , preferably positioned at the neck  112  of the receptacle  102 . As illustrated in  FIG. 1 , the flange  116  may depend from an exterior surface  118  of the wall  108  to define a rim  120  about an opening  122  in communication with the passage  114  through the neck  112 . 
     According to an embodiment of the present disclosure, the receptacle  102  is made of glass. According to other embodiments, the receptacle  102  may be made of metal, for example, steel, aluminum or an aluminum alloy; according to still other embodiments, the receptacle  102  may be made of a polymer, such as polyethylene terephthalate (PET). Furthermore, according certain embodiments, a polymer or other material may be applied as a thin layer to define the exterior surface  118  of the wall  108 . Additionally, according to further embodiments, a polymer or other material may be applied as a thin layer to define an interior surface  124  of the wall  108 . 
     The valve assembly  104  is attachable or is attached to the receptacle  102  to control flow of fluids (e.g., anesthetic) through the passage  114  out of (and in to) the receptacle  102  to (and from) a vaporizer. The valve assembly  104 , as illustrated, includes a conduit  130 , a valve seat  132 , a cage (or basket)  134 , a valve member (or core)  136 , and a resilient or biasing member  138 . Other elements may be included as well, but as explained in greater detail below, the valve assembly  104  is designed to be gasketless in regard to the interface between the valve member  136  and the conduit  130 , or more particularly between the valve member  136  and the valve seat  132 . 
     Beginning then with the conduit  130 , the conduit  130  has a cylindrical wall  140  that defines a passage  142  with a first end  144  and a second end  146 . The cylindrical wall  140  may have a frusto-conical surface  148  (see  FIG. 2 ) disposed about the second end  146  of the passage  142 . The surface  148  may define the valve seat  132 , the further details of which will be described in greater detail below; the valve seat  132  may thus be described as defined at the second end  146  of the conduit passage  142  according to the illustrated embodiment. The conduit  130  also includes a conduit flange  150  (see  FIG. 1 ) that depends outwardly from the wall  140 . The conduit flange  150  is disposed proximate to the second end  146  of the passage  142 , as illustrated. The conduit flange  150  has opposing first and second surfaces  152 ,  154 . 
     The cage  134  (which may be made of nylon (e.g., nylon  66 )) has a cage flange  160  that is disposed between the conduit flange  150  and the neck  112  of the receptacle  102 . In particular, the cage flange  160  has opposing first and second surfaces  162 ,  164 , and the first surface  162  of the cage flange  160  abuts the second surface  154  of the conduit flange  150 , while the second surface  164  of cage flange  160  abuts a gasket  166  (which may be made of low density polyethylene (LDPE)) disposed on the rim  120  of the receptacle  102  (i.e., between the conduit flange  150  and/or cage flange  160  and the neck  112  of the receptacle  102 , or more particularly, the rim  120  of the receptacle  102 ). A fluid-tight seal may be formed as a consequence. 
     Even though a fluid-tight seal may be formed, a layer of resilient polymer may define the exterior surface  118  of the receptacle  102 , at least in the region of the neck  112  of the receptacle  102 . For example, a layer of low-density polyethylene may be disposed on a layer of aluminum or aluminum alloy in the region of the neck  112  of the receptacle  102 . According to certain embodiments, the low-density polyethylene may be applied using powder coating techniques, in particular where the wall  108  of the receptacle  102  is includes a layer of aluminum or an aluminum alloy. Other methods of including or applying the low-density polyethylene may also be used. 
     It should be noted that the entirety of the wall  108  of the receptacle  102  need not include the layer of low-density polyethylene. For example, it may be that other regions of the wall  108  of the receptacle  102  include other polymers, as discussed above. According to an exemplary embodiment, the receptacle  102  may include a wall  108  with a layer of a lacquer or an enamel disposed on a layer of aluminum or aluminum alloy, the layer of lacquer or enamel defining, at least in part, the interior surface  124  of the wall  108  of the receptacle  102 . According to certain embodiments, the lacquer or enamel may include an epoxyphenolic resin. 
     As illustrated, the ferrule  106  is disposed over at least a portion of the conduit flange  150  and the cage flange  160  and about at least a portion of the neck  112  to attach the valve assembly  104  to the receptacle  102 . The ferrule  106  has a cylindrical shape, with a first end  170  having an opening  172  with a rim  174  disposed about the opening  172  and defining the opening  172 . The conduit  130  depends through the opening  172  in the first end  170  of the ferrule  106 . The second end  176  of the ferrule  106  may be crimped about the flange  116  of the receptacle  102  to attach the valve assembly  104  to the receptacle  102 . The ferrule  106  may be made of aluminum. 
     While the illustrated embodiment of the present disclosure has been illustrated with the valve assembly  104  attached to the receptacle  102  with a ferrule  106 , it will be recognized that the container  100  need not be only defined as such. For example, the valve assembly  104  may be in the form of an adapter that is mated with the receptacle  102  only just prior to use, the passage  114  being closed instead through the use of a cap that may be threaded on to the receptacle  102  or held in place by a “snap-off” fit. According to such an embodiment, the cap is removed from the receptacle  102  prior to use, and the valve assembly  104  inserted into the passage  114  to attach the valve assembly  104  to the container. As such, the embodiment of the container  100  thus defined does not require the ferrule  106  illustrated in  FIG. 1 . 
     With reference to  FIGS. 1 and 3 , it will be recognized that the valve member  136  is disposed between the conduit  130  and the cage  134 , or more particularly between the valve seat  132  and the cage  134 . The valve member  136  has a first end  180  that abuts the valve seat  132  when the valve member  136  is in the closed position (as seen in  FIG. 1 ). This may coincide with a closed configuration of the valve assembly  104 . The valve member  136  is spaced from the second end  146  of the passage  142  and the valve seat  132  with the valve member  136  in the open position ( FIG. 3 ). This may coincide with an open configuration of the valve assembly  104  that permits the flow of the anesthetic from the receptacle  102 . 
     As illustrated in  FIG. 2 , the valve member  136  may have a head  182  formed at the first end  180 . The head  182  may include at least one sloped surface  184 , as illustrated. The sloped surface  184  faces the sloped surface  148  that defines the valve seat  132 , and abuts the surface  148  to form a gasketless, fluid-tight seal therebetween with the valve assembly  104  in the closed configuration so as to limit the flow of the anesthetic from the receptacle  102 . As illustrated, neither surface  148 ,  184  exhibits any curvature, such that the cross-section of the surfaces  148 ,  184  appears linear instead of exhibiting any arcuate section. 
     Elimination of a gasket between the surfaces  148 ,  184  is advantageous in that it eliminates the gasket material that comes into contact with the fluid, thereby eliminating a potential source of extractables or leachables that may impact the shelf life or other characteristic of the fluid. As observed by Schulte and Ellis, in Anesthesia and Analgesia, vol. 2, no. 2, pp. 644-645 (February 2010), a yellow discoloration may result from use of conventional anesthetic containers, which containers include the use of gaskets between valve members and valve seats. While they report that no patient harm is likely to result, the limitation or elimination of the compounds reported by Schulte and Ellis is believed to be possible through the elimination of gaskets in the anesthetic container. 
     As illustrated, the first sloped surface  148  of the valve seat  136  has a slope that is different than a slope of the second sloped surface  184  of the valve member  136 . With reference to  FIG. 2 , a first line S 1  has been extended from the sloped surface  148  and a second line S 2  has been extended from the sloped surface  184  for ease of visualization. The first line S 1  represents the slope of the surface  148 , and the second line S 2  represents the slope of the surface  184 . With the valve seat  132  and valve member  136  oriented as illustrated in  FIGS. 1-3 , it will be recognized that the slope of line S 2  is steeper than the slope of line S 1 ; that is, the rise of the line S 2  in the vertical direction is larger than the rise of the line S 1  for a comparable run in the horizontal direction. 
     In addition, it will be recognized that the slopes of the first and second surfaces  148 ,  150  are not horizontal, nor are they vertical. Instead, the slopes are such that the angle formed between the surface and the horizontal is between 0° and 90°. For example, the slope of the surface  148  may be described as 45°, while the slope of the surface  184  may be described as 60°, with reference to  FIG. 2 . 
     It is believed that the valve seat  132  and the valve member  136 , or more particularly the surfaces  148 ,  184 , abut along a line of contact that runs about the circumference of the surface  184 . It is also believed that the difference in the slopes of the surfaces  148 ,  184  permits a gap to be defined between sections of the facing surfaces  148 ,  184  disposed radially outward (relative to a longitudinal axis of the valve assembly  104 ) of the line of contact between the surfaces  148 ,  184 . The gap between the sections of the facing surfaces  148 ,  184  may accommodate manufacturing tolerances in the surfaces  148 ,  184 . 
     As also best illustrated in  FIG. 2 , the valve member  136  may have a third sloped surface  186 . The third sloped surface may be disposed radially inward (again relative to the longitudinal axis of the valve assembly  104 ) of the second sloped surface  184 , and the second and third sloped surfaces  184 ,  186  may meet at an interface  188  along adjoining edges. The interface  188  may be disposed radially inward (relative to the afore-mentioned longitudinal axis) of the line of contact between the first and second sloped surfaces  148 ,  184 . The third sloped surface  186  may have a slope (represented by the line S 3 ) that is not as steep as the slope of the second sloped surface  184 . 
     With reference to  FIGS. 1 and 3 , it will be recognized that the valve member  136  includes a plate (or core seat)  190  and a tube (or core extension)  192 , as illustrated. It will be recognized that other valve members may be designed wherein the plate  190  and tube  192  are formed as a single unit (i.e., integrally with each other). Thus, the illustrated embodiment is not intended to be limiting in this regard. The plate  190  may be made of low density polyethylene (LDPE), for example, while the tube  192  may be made of nylon (e.g., nylon  66 ). 
     The plate  190  defines the first end  180  of the valve member  136  with the surface  184 , and occludes the second end  146  of the passage  142  through the conduit  130  with the valve member  136  in the closed position. The plate  190  may be referred to as a poppet valve. The valve member  136  is biased towards a closed position, illustrated in  FIGS. 1 and 3 , through the action of the resilient member  138 , which may be a spring, as illustrated. The spring  138  may be made of stainless steel. The resilient member  138  is disposed between the valve member  136  and the cage  134 , and specifically the plate  190  of the valve member  136  and a surface  194  of the cage  134 . 
     The tube  192  is an exemplary structure or partition that may be included in the valve member  136  to guide the flow of more than one fluid at a time. In particular, the tube  192  has an opening  196  at a first end  198  (see  FIG. 1 ) and at least one opening  200  at a second end  202  (see  FIG. 3 ); as illustrated, a plurality of openings  200  are provided in the second end  202 . While the tube  192  is illustrated as coaxial with the conduit  130 , this need not be the case according to all embodiments of the present disclosure. 
     The tube  192  depends from the plate  190 . The tube  192  is configured with an interior surface which is preferably generally cylindrical to define a passage  210  through the tube (see  FIG. 1 ). A series of ribs may extend along a portion of the length and outwardly from an outer surface  212  of the tube  192  to close proximity to the cylindrical wall  140  to define annular gaps or passageways between the tube  192  and the conduit  130 . In an embodiment, there may be four ribs spaced equally around the outer circumference of the tube  192  that define four annular passageways. 
     In operation, when the valve member  136  is biased away from the closed position (through interaction between the tube  192  and a structure of the vaporizer, for example), liquid anesthetic is permitted to flow through openings  220  in the cage  134 , the second end  146  of the conduit  130 , and the passageways defined between the tube  192  and the conduit  130  into an associated vaporizer. At the same time, the first end  198  of the tube  192  is in fluid communication with a portion of the vaporizer through which vapor and possibly some fluid returns to the receptacle  102 . This vapor and possible fluid passes through the opening  196  in the first end  198  of the tube  192 , through the passage  210  defined through the tube  192 , out of the at least one of the openings  200  in the second end  202  of the tube  192 , and into the receptacle  102 . 
     To limit leakage between the valve assembly  104  (and particularly, the conduit  130 ) and a vaporizer port, a sealing member  230  is disposed about a first end  232  of the conduit  130 . In particular with reference to  FIGS. 1 and 4 , the wall  140  of the conduit  130  has an exterior surface  234  with at least one groove  236  formed therein at the first end  232 . The exterior surface  234  may also include other features, such as ribs to improve the rigidity of the conduit  130 , for example. As seen in  FIG. 1 , a toroidal sealing member  230  is disposed in the at least one groove  236 , and depends radially outward (relative to the longitudinal axis of the valve assembly  104 ) from the exterior surface  234  of the conduit  130 . In use, the sealing member  230  abuts an inner surface of a passage of a vaporizer port with the conduit  130  disposed through the passage to limit the passage of fluids between the conduit  130  and the vaporizer port. 
     As best seen in  FIGS. 1 and 5 , the toroidal sealing member  230  has an X-shaped cross-section, and may be referred to as a quad-ring. The X-shaped cross-section may have four equal lobes  240 , with each of the lobes  240  having a first end  242  joined to the first ends  242  of the other lobes  240  and a second, rounded end  244 . The sealing member  230  may be made of rubber, and in particular ethylene propylene diene monomer (EPDM) rubber. 
     The sealing member  230  provides twice the sealing surface in comparison with a conventional o-ring. Further, less force is required to maintain an effective seal with the sealing member  230  relative to the conventional o-ring. The reduction in force required to maintain a fluid-tight seal relative to conventional technology leads to a consequential reduction in friction forces generated when the valve assembly  104  is introduced into and withdrawn from a vaporizer port. The reduction in friction forces leads to a increase in the effective life of the sealing member  230 . 
     It will be appreciated that the advantageous structures of the valve assembly and the toroidal sealing member disclosed above need not both be present in every container according to the present disclosure. That is, the illustrated container includes a valve assembly with a gasketless interface between the valve member and the valve seat, the valve member and the valve seat having sloped surfaces with different slopes. In addition, the conduit of the valve assembly has an exterior sealing member that is in the form of a toroidal sealing member having an X-shaped cross-section. However, in a particular embodiment according to the present disclosure, the gasketless interface between the valve member and the valve seat may be used with a conventional exterior sealing member (e.g., an O-shaped cross-section o-ring). Similarly, the exterior sealing member with an X-shaped cross-section may be used without the gasketless interface defined by the sloped valve member and valve seat having different slopes; other gasketless interfaces may be used, or a gasket may be introduced between the valve member and valve seat, for example. The illustrated embodiment is not intended to limit the claims, but to illustrate the manifold advantages of a container including both gasketless interfaces and the particular sealing member selections according to the present disclosure. 
     Although the preceding text sets forth a detailed description of different embodiments of the invention, it should be understood that the legal scope of the invention is defined by the words of the claims set forth at the end of this patent. The detailed description is to be construed as exemplary only and does not describe every possible embodiment of the invention since describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments could be implemented, using either current technology or technology developed after the filing date of this patent, which would still fall within the scope of the claims defining the invention. 
     It should also be understood that, unless a term is expressly defined in this patent using the sentence “As used herein, the term ‘______’ is hereby defined to mean . . . ” or a similar sentence, there is no intent to limit the meaning of that term, either expressly or by implication, beyond its plain or ordinary meaning, and such term should not be interpreted to be limited in scope based on any statement made in any section of this patent (other than the language of the claims). To the extent that any term recited in the claims at the end of this patent is referred to in this patent in a manner consistent with a single meaning, that is done for sake of clarity only so as to not confuse the reader, and it is not intended that such claim term be limited, by implication or otherwise, to that single meaning. Finally, unless a claim element is defined by reciting the word “means” and a function without the recital of any structure, it is not intended that the scope of any claim element be interpreted based on the application of 35 U.S.C. §112, sixth paragraph.