Bags with ports and bags with caps

Abstract

To provide a bag that can be sealed without using a complicated sealing device or method even in a sterile environment, and can more easily realize a sterile state. [Solution] This ported bag (1) has a bag body (3) formed into a bag shape from a sheet, and a cylindrical port member (2) attached to the bag body (3), and an inner plug (50) and a cap (4) can be attached to the port member (2). The port member (2) has an attachment portion (25) that is covered by the cap (4) when the cap (4) is attached, and an annular lip (26) that protrudes outward from the port member (2). The lip (26) has an annular engagement surface (26A) facing the bag body (3), and the engagement surface (26A) forms an angle of 90° to 135° with the outer peripheral surface of the attachment portion (25) in a cross section taken along the axial direction of the attachment portion (25), and the port member is made of a material with a flexural modulus of elasticity of 140 MPa or more.

Description

Technical Field

[0001] The present invention relates to a bag with a port provided with a port which is an inlet / outlet for contents in a bag body, and further to a bag with a cap provided with a stopper for preventing the opening of the port and a cap for engaging with the port to hold down the stopper, and is particularly suitable for use in aseptically filling biopharmaceuticals and the like.

Background Art

[0002] As a container for accommodating a liquid medicine such as an injection, an infusion bag made of synthetic resin is widely used. The infusion bag has a bag body (pouch part) for accommodating a liquid such as a liquid medicine and a port for filling / discharging the liquid into / from the bag body, and the port is formed by joining a cylindrical synthetic resin port member in a state of penetrating a part of the bag body.

[0003] When filling a bag with a port with a liquid, a nozzle of a liquid supply source is inserted into the port, and a liquid medicine is injected into the bag body through the nozzle by a machine or an operator. After the filling is completed, the opening of the port is closed with a rubber stopper, and then a cap for covering this stopper is attached to the port, and it is common to further melt-seal the boundary between the port and the cap.

[0004] When melt-sealing the cap, conventionally, there are methods of heating the open end of the port and the top plate part of the cap by radiant heat from an electric heater and then crimping and cooling both, or after covering the port with the cap, pressing a horn against the top plate part of the cap to oscillate ultrasonic waves to melt the "rib" formed on the cap and integrate it with the port. Such melt-sealing is essential for preventing the cap from coming off during heat sterilization, transportation, and storage of the infusion bag, ensuring the sealing performance of the bag, and preventing contamination of the medicine and invasion of bacteria.

[0005] After sealing the cap, the infusion bag is sterilized by heating it with pressurized steam or hot water to sterilize the drug solution it contains. This is a standard procedure defined as the manufacturing of sterile pharmaceuticals by the final sterilization method.

[0006] Incidentally, in recent years, "biopharmaceuticals" have been gaining popularity as a new type of medicine. Many biopharmaceuticals are derived from substances produced by living organisms, such as proteins, mammalian cells, viruses, and bacteria. Unlike conventional "small molecule drugs" manufactured through chemical synthesis, these types of biopharmaceuticals have complex molecular structures, and their structure can change due to various influences such as heating during the manufacturing process, leading to a decrease in safety and efficacy.

[0007] For this reason, in many cases, final sterilization by heating cannot be used to sterilize biopharmaceuticals. In such cases, an "aseptic manufacturing method" is used, in which a series of processes from the manufacture of the active pharmaceutical ingredient to formulation, filling, and sealing are completed in a sterile environment. Typical pharmaceuticals manufactured using the aseptic manufacturing method include, for example, component preparations produced by centrifuging blood and used for transfusions, and plasma-derived products in which therapeutically useful proteins are purified from plasma components.

[0008] The filling of pharmaceutical containers using aseptic techniques must be performed in an aseptic area isolated from workers, such as a clean booth, a Restricted Access Barrier System (RABS), or an isolator. In recent years, filling operations in isolators, which allow for complete physical isolation from the environment and direct intervention by staff, have become the mainstream method.

[0009] When using an isolator, it is necessary to decontaminate the inside of the isolator and then supply air filtered through a HEPA or ULPA filter to prevent contamination from the external environment. This decontamination is carried out by spraying disinfectants and cleaning agents consisting of high concentrations of hydrogen peroxide, peracetic acid, formaldehyde, etc., into the isolator. Because these chemicals have strong oxidizing properties and are corrosive and irritating to the skin, care must be taken to prevent corrosion of equipment installed inside the isolator and to avoid residues after the decontamination work.

[0010] The aforementioned operations are crucial steps in ensuring the quality of pharmaceuticals manufactured using aseptic techniques, and their implementation procedures and management are defined by guidelines such as Non-Patent Document 1 and Non-Patent Document 2.

[0011] Incidentally, sealing ported bags as described above is difficult within sterile areas. This is because the structure and materials of the equipment used for sealing hinder decontamination operations. Furthermore, there is a risk that disinfectants and cleaning agents used in decontamination may remain on the equipment used for sealing. Therefore, an alternative sealing method to sealing is needed.

[0012] On the other hand, vials are widely used as pharmaceutical containers that can be handled using aseptic techniques and do not require smelting. Two types of vials are used: glass vials and synthetic resin vials. Glass vials have significantly higher gas barrier properties than synthetic resin vials and are used as pharmaceutical containers where high gas barrier properties are required.

[0013] When a drug is filled into a vial, the opening of the vial is sealed with a rubber stopper or the like. Similar to bags with ports, simply fitting a rubber stopper onto the vial opening is insufficient as a sealing method. Therefore, it is common practice to attach an aluminum cap over the rubber stopper, and then crimp the lower end of this cap with a crimping machine and fit it onto the lip of the port (Patent Document 1).

[0014] Aluminum caps are easy to deform and offer excellent protection against detachment. However, aluminum caps have drawbacks: during manufacturing and use, they are prone to generating and scattering fine aluminum particles due to collisions between caps and the operation of crimping machines; and separate disposal of caps after vial use is difficult. For these reasons, the use of aluminum caps has been increasingly discouraged in medical settings in recent years.

[0015] In particular, in a work environment using aseptic techniques, care must be taken to note that the cleanliness of the controlled area will decrease because work must be performed in an isolated space to prevent contamination from the outside. Non-patent document 1 also stipulates that "since aluminum cap crimping machines are equipment that generates a large amount of dust, they must be installed in a separate location equipped with an appropriate exhaust system," which presents problems such as increased equipment complexity and reduced work efficiency.

[0016] Furthermore, while glass vials are easy to handle during storage and preparation because they stand upright, they lack flexibility. Therefore, if used directly for intravenous infusion, the pressure inside the vial decreases as the infusion progresses and the amount of fluid in the vial decreases, slowing down the infusion rate. This decrease in infusion rate as the infusion progresses prolongs the time required for the infusion. In addition, it becomes difficult to predict when the infusion will end, so if multiple infusions are administered, it becomes necessary to check the infusion status at any time, making intravenous treatment more complicated.

[0017] Therefore, when administering directly from a vial container, a venting needle is inserted into the container to introduce air from the outside in order to maintain a constant infusion rate. However, even with a venting needle, it is difficult to maintain a constant infusion rate, and the use of a venting needle may contaminate the IV fluid.

[0018] Instead of glass vial containers, the use of infusion bags made of flexible film has also been considered, for example, in Patent Document 2. This type of infusion bag has excellent flexibility, and as the infusion decreases, the bag deflates, so the infusion rate does not decrease easily even without using a venting needle, and it has the advantage of eliminating the need for an infusion pump to maintain a constant administration rate.

[0019] Patent Document 3 discloses a method for filling an infusion bag with an albumin preparation. In this method, the unwound roll film is sterilized by passing through a sterilization section, a drying section, an assembly section for seal and port components, a filling section, and further through an end seal and cutting section to complete the infusion bag. However, this method requires sterilizing most of the complex FFS (Form-Fill-Seal) device, making it difficult to completely remove the aforementioned disinfectants and cleaning agents, which presents undesirable management issues. [Prior art documents] [Patent Documents]

[0020] [Patent Document 1] Japanese Patent Publication No. 2007-282891 [Patent Document 2] Japanese Patent Publication No. 2010-279624 [Patent Document 3] Japanese Patent Publication No. 2008-273631 [Non-patent literature]

[0021] [Non-Patent Document 1] The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (GMP Annex 1) [Non-Patent Document 2] April 20, 2011 Ministry of Health, Labour and Welfare, Pharmaceutical and Food Safety Bureau, Monitoring and Guidance Division, Narcotics Control Section Administrative Notice [Overview of the Initiative]

Problems to be Solved by the Invention

[0022] As described above, the conventional infusion bag is a promising container for drugs that cannot be sterilized by heating. However, there are many manufacturing restrictions, and the spread of bag preparations manufactured by aseptic operation methods has been limited. The present invention has been made in view of the above circumstances, and for example, even in a sterile environment, it is an object to provide a bag with a port and a bag with a cap that can be sealed without using a complicated sealing device or method and can more easily achieve a sterile state.

Means for Solving the Problems

[0023] The Bag with cap of the present invention includes a bag body formed in a bag shape by a sheet and having a storage portion inside, and a cylindrical port member attached to the bag body with one end communicating with the storage portion and the other end opening exposed outside the bag. and, The port member Block the upper end a stopper and , The aforementioned holding the stopper The port member is attachable to the port member. a cap A bag with a cap that has wherein the port member has an adhered portion covered by the cap when the cap is attached to the port member, and an annular lip formed at the periphery of the opening and protruding outward from the port member. The lip has an annular engaging surface facing the side of the bag body, and the upper surface of the lip is a surface that abuts against the lower surface of the outer peripheral portion of the stopper to support the stopper. The engaging surface forms an angle of 90° to 135° with respect to the outer peripheral surface of the adhered portion in a cross-section along the axial direction of the adhered portion. The port member is made of a material having a flexural modulus of elasticity of 140 MPa or more. The protruding height of the lip from the outer peripheral surface of the adhered portion is 0.5 mm to 5 mm. The tip width of the lip in the longitudinal direction of the port member is 1 to 10 mm. The length of the port member is 30 to 50 mm. The inner diameter of the port member including the lip is constant in its longitudinal direction. Furthermore, a protrusion is formed in the center of the lower surface of the inner stopper, which is inserted into the opening of the port member, and the cap has a top plate portion, a cylindrical skirt portion that can stand up from around the top plate portion and cover the attached portion, and a plurality of engaging pieces provided at the lower end of the inner surface of the skirt portion, the engaging pieces having a tip portion that protrudes toward the top plate portion and can elastically approach the inner circumferential surface of the skirt portion, and when the cap is attached to the port member, the tip portion of the engaging piece is made to abut against the engaging surface of the lip and be able to engage, the upper surface of the lip abuts against the lower surface of the outer circumferential portion of the inner stopper, and the protrusion in the center of the lower surface of the inner stopper is inserted into the opening of the port member.The inclination angle is more preferably 90° to 120°, and even more preferably 90° to 105°.

[0024] The port member is made of a material with a flexural modulus of 140 MPa or higher. The bag with the port may be sterilized.

[0025] The bag body may be rectangular in shape, with a length of 80 to 400 mm in the major axis direction, a width of 60 to 350 mm in the minor axis direction, and a filling capacity of 20 to 1000 mL. The inner surface of the sheet may be provided with hydrophilic or lipophilic groups to protect the active pharmaceutical ingredient. The tensile modulus of the sheet may be 1500 MPa or less, or it may be 50 to 550 MPa.

[0026] The thickness of the sheet may be 100 to 400 μm, 150 to 300 μm, or 180 to 270 μm. The product (M × T) of the tensile modulus M (MPa) of the sheet and the thickness T (μm) of the sheet may be 20,000 or more and 300,000 or less, 30,000 or more and 250,000 or less, or 35,000 or more and 200,000. The tensile modulus M can be measured by the measurement method specified in ISO 527-1.

[0027] The aforementioned ported bag is sterilized by high-temperature sterilization, ultraviolet sterilization, or radiation sterilization such as gamma ray sterilization, to achieve a sterility assurance level (SAL) of 10. -6 The following is also acceptable: The dimensions of the port member may be such that the outer diameter excluding the protrusion is 10 to 20 mm, the wall thickness is 0.5 to 5 mm, and the length is 30 to 50 mm. The height of the flange portion from the surface of the port member may be set to approximately 30-150% of the height of the outer surface of the cap when the cap is attached.

[0028] The protrusion height of the lip from the attached portion may be 0.5 to 5 mm, or 1 to 3 mm. The tip width of the lip may be 1 to 10 mm, or 3 to 6 mm. The port member may have a pressure of 200 MPa or more, or 400 to 2000 MPa. The port member may be made of polyethylene, polypropylene, or cyclic polyolefin. The maximum downward force applied to the cap when it is placed over the port member and pressed down until the engaging piece elastically deforms and overcomes the lip may be 10 to 200 N. The distance from the tip of the engagement piece in its free state to the central axis of the cap may be 95 to 105% of the distance from the outer circumferential surface of the attached portion to the central axis of the port member.

[0029] The cap-equipped bag of the present invention comprises a port-equipped bag, an inner plug that can be attached to the port member, and a cap that holds the inner plug in place. The cap has a top plate portion, a cylindrical skirt portion that rises from around the top plate portion and can cover the attachment portion, and a plurality of engaging pieces provided at the lower inner end of the skirt portion. The engaging pieces have a tip portion that protrudes toward the top plate portion and can elastically approach the inner circumferential surface of the skirt portion. When the cap is attached to the port member, the tip portions of the engaging pieces can contact and engage with the engaging surface of the lip. The upper surface of the lip abuts against the lower surface of the outer circumference of the inner stopper. It is.

[0030] The top plate portion of the cap may have an opening, and a seal that closes the opening may be detachably fixed to the top plate portion, so that the opening can be exposed by removing the seal.

[0031] In another embodiment of the present invention, the capped bag is aseptically filled in the storage portion of the bag body with contents comprising at least one selected from a plasma-derived preparation such as an albumin preparation or a globulin preparation, an enzyme, a blood coagulation fibrinolytic factor, a hormone, a vaccine, interferons, erythropoietins, cytokines, antibodies, and a fusion protein, and the cap is attached to the port member to seal the contents. [Effects of the Invention]

[0032] According to the ported bag and capped bag of the present invention, by placing the inner stopper and the cap that holds the inner stopper over the opening of the port and pressing them, a plurality of engaging pieces provided on the lower end of the inner surface of the skirt portion elastically deform to overcome the lip, and the tips of the engaging pieces abut and engage with the engaging surface of the lip. Therefore, no special device is required to attach the cap, and the cap can be attached easily, so it can be used, for example, without hindering sterilization work in a sterile working area. Furthermore, after attachment, the cap is securely fixed to the lip by the elasticity of the engaging pieces, so it is highly reliable in terms of maintaining a sterile state. In addition, it has the effect of keeping the discharge rate of the contents constant without using a venting needle during use. [Brief explanation of the drawing]

[0033] [Figure 1] This is a front view of a capped bag according to the first embodiment of the present invention. [Figure 2] This is a front view of the ported bag according to the first embodiment. [Figure 3] This is a front view of the port member used in the first embodiment. [Figure 4] This is an enlarged cross-sectional view of the lip of the port member. [Figure 5] This is a front view of the cap according to the first embodiment. [Figure 6] This is a bottom view of the cap of the first embodiment. [Figure 7] This is a partially broken front view showing the port member of the first embodiment with a cap attached. [Figure 8] This is an enlarged cross-sectional view showing the state in which the engaging piece is engaged with the lip of the first embodiment. [Figure 9] This is an enlarged cross-sectional view showing the state in which the engaging piece is engaged with the lip of another embodiment of the present invention. [Modes for carrying out the invention]

[0034] Embodiments of the present invention will now be described in detail with reference to the drawings. Figure 1 is a plan view showing a capped bag according to one embodiment of the present invention, which has a ported bag 1, an inner stopper 50 (see Figure 7), and a cap 4. Figure 2 is a plan view showing only the ported bag 1 with the cap 4 and inner stopper 50 removed. In the following description, the explanation will be given with the port facing upwards for clarity, but the ported bag and capped bag of the present invention are not fixed in this orientation and may be used in any position.

[0035] The bag with a port 1 has a rectangular bag body 3 having a storage section 12 that can hold contents inside, and a cylindrical port member 2 that is inserted through and fixed to an opening 14 formed in the center of one end of the bag body 3. The bag body 3 is made by bonding or heat-sealing the outer edges of two rectangular resin sheets to join them together, forming a seal section 10 around the entire periphery except for the opening 14, and forming the storage section 12 inside the seal section. A circular hole 16 is formed in the seal section 10 at the end of the bag body 3 opposite the opening 14. Non-sealed sections 18 are formed on both sides of the hole 16, and non-sealed sections 20 are also formed on both sides of the opening 14, and the non-sealed sections 18 and 20 make the seal width of each section approximately constant.

[0036] The bag body 3 is not limited to the illustrated shape; it can be any shape as long as it is bag-like. For example, a single sheet may be folded in half, with the central fold line forming the bottom of the bag body 3 and the other parts joined together, or the sheet may be rolled into a tube and the ends and bonding surfaces joined together. It may also be formed into a three-dimensional box shape from the sheet. Even if formed into a box or tube shape, the bag body 3 can maintain its flexibility.

[0037] The dimensions of the bag body 3 are not limited in this invention, but a length in the major axis direction of 80 to 400 mm, a width in the minor axis direction of 60 to 350 mm, and a filling capacity of 20 to 1000 mL are suitable for use as an infusion bag for pharmaceuticals and the like.

[0038] The material of the sheet is not limited in this invention, but a laminate film can be used in which a sealant is provided on at least one side, for example, a polyolefin resin layer such as polyethylene (PE), polypropylene (PP), ethylene-vinyl acetate copolymer (EVA), or cyclic polyolefin is used as the innermost layer with the sealant facing inward, and a stretched film such as a biaxially oriented nylon film, biaxially oriented polyethylene terephthalate film, or biaxially oriented polypropylene film is used as the base material, and an intermediate layer such as an ethylene-vinyl alcohol copolymer, a vapor-deposited layer of metal or inorganic compound, or a metal foil such as aluminum foil is provided between the two as needed. Each sheet may be the same or different in material and thickness, as long as they can be joined to each other by welding or adhesive. Films with high barrier properties against water vapor and oxygen gas, which are commonly used, can also be used as the sheet. Furthermore, the sheet may have a deterioration prevention ability that prevents deterioration of the contents due to the permeation or adsorption of the active ingredients of the internal solution or the elution of low molecular weight components contained in the resin that constitutes it. For example, it is possible to provide the inner surface of the sheet bag with hydrophilic or lipophilic groups that can protect the active ingredient of the formulation to be contained, depending on the active ingredient of the formulation to be contained.

[0039] The bag body 3 is preferably highly flexible, to the extent that it does not cause manufacturing or usage problems, from the viewpoint of maintaining a constant supply rate during infusion by appropriately deflating the bag body 3 as the contents decrease. For this reason, the tensile modulus M (MPa) of the sheet constituting the bag body 3 is not limited, but is preferably 1500 MPa or less, more preferably 50 to 550 MPa. The sheet thickness T (μm) is not limited, but is preferably 100 to 400 μm, more preferably 150 to 300 μm, and even more preferably 180 to 270 μm. If the tensile modulus M is too small, or the sheet thickness T is too small, the sheet will stretch easily during manufacturing, making manufacturing difficult. If the tensile modulus M is too large, or the sheet thickness T is too large, the bag body 3 will not be flexible, making it difficult to maintain a constant infusion rate. The product of the tensile modulus M (MPa) and the sheet thickness T (μm) (M × T) is preferably 20,000 or more and 300,000 or less, more preferably 30,000 or more and 250,000 or less, and even more preferably 35,000 or more and 200,000. The tensile modulus M of the sheet can be measured by the measurement method specified in ISO 527-1.

[0040] When using the ported bag 1 as an infusion bag for pharmaceuticals, it is preferable that the inner surface of the ported bag 1, i.e., at least the inner surfaces of the bag body 3 and the port member 2, be sterilized. As a sterilization treatment, methods such as high-temperature sterilization, ultraviolet sterilization, and radiation sterilization such as gamma ray sterilization are used to achieve a sterility assurance level (SAL) of 10. -6 The following is preferable. Similarly, the cap 4 and inner stopper 50 are also sterilized. The sterilization treatment should be performed at least on the inner surface of the bag, but in practice, the entire bag, including the cap 4 and inner stopper 50, is sterilized by the above means while sealed in the outer bag. When in use, for example, the outer bag is opened in a sterile chamber, the contents are injected into the ported bag 1, and the inner stopper 50 and cap 4 are attached before use.

[0041] As shown in Figure 3, the port member 2 is cylindrical in shape, and its base end is inserted through the opening 14 of the bag body 3, and is joined to the sheets on both sides without any gaps by adhesive or heat sealing. The dimensions of the port member 2 are not limited in this invention, but as an example, an outer diameter excluding the protrusions of 10 to 20 mm, a wall thickness of 0.5 to 5 mm, and a length of 30 to 50 mm would be suitable for use as an infusion bag for pharmaceuticals.

[0042] An annular lip 26 is formed coaxially with the port member 2, projecting outward from the port member 2, around the periphery of the tip opening of the port member 2. An annular flange portion 24 is formed on the outer circumferential surface of the port member 2 at a certain distance from the lip 26 and with a certain width. When the cap 4 is attached to the port member 2, the opening end of the cap 4 and the flange portion 24 face each other with a small gap between them. The height of the flange portion 24 from the surface of the port member 2 is set to approximately 30-150% of the height of the outer circumferential surface of the cap 4 when the cap 4 is attached. The flange portion 24 prevents the lower end of the cap 4 from being pushed up and causing the cap 4 to come off unintentionally. However, it is also possible to omit the formation of the flange portion 24 on the port member 2.

[0043] The space between the lip 26 and the flange portion 24 is a fixed-width attachment portion 25 that will be covered by the cap 4 when the cap 4 is attached to the port member 2. In this embodiment, the port member 2 is straight, but if necessary, the attachment portion 25 can be bent relative to the main body of the port member 2.

[0044] The lip 26 has an annular engaging surface 26A facing the side of the bag body 3. The engaging surface 26A has a constant width around its entire circumference, and in a cross-section along the axial direction of the attached portion 25, the inclination angle θ with respect to the outer circumferential surface of the attached portion 25 is 90° to 135°, as shown in Figure 4. The inclination angle θ is more preferably 90° to 120°, and even more preferably 90° to 105°. If it is 90° or less, the engaging surface 26A will be in an overhanging state. Even with an overhanging shape, it is possible to manufacture by devising the mold structure. If the inclination angle θ is large, the cap 4 is more likely to come off the port member 2 when removing the seal 30 (see Figures 1, 5, and 6) provided on the upper surface of the cap 4. If the inclination angle θ is too small, although the locking performance of the cap 4 is high, it imposes limitations on the mold structure for injection molding the port member 2, reducing productivity. In order to achieve both the prevention of the cap 4 coming off and the productivity of the port member 2, the inclination angle θ is preferably within the above range. The engaging surface 26A may be rounded in cross-section, or its inclination angle may vary in part, but it is desirable that the inclination angle of the region in contact with the engaging piece 32 meets the aforementioned range.

[0045] As shown in Figure 9, a groove 52 of a constant depth extending around the entire circumference of the engaging surface 26A may be formed in the region of the engaging surface 26A that contacts the engaging piece 32, so that the tip 32A of the engaging piece 32 fits into this groove 52. In this case, the force that locks the engaging piece 32 is increased compared to when the engaging surface 26A is simply a flat surface. The inclination angle θ of the engaging surface 26A is defined as the inclination angle at the point where the tip 32A contacts, and if there are contact points, it is defined as the average value of those points. In the example shown in Figure 9, a shallow groove 52 with a circular arc cross-section is formed in the part of the engaging surface 26A close to the attached portion 25, but the location and shape are not limited to this, and a groove 52 with a rectangular cross-section or the like may be formed in the center of the engaging surface 26A.

[0046] The protrusion height H of the lip 26 from the attached portion 25, as shown in Figure 3, is not limited in this invention, but is preferably 0.5 to 5 mm, and more preferably 1 to 3 mm. The tip width W of the lip 26 is also not limited in this invention, but is preferably 1 to 10 mm, and more preferably 3 to 6 mm. A groove may be formed on the outer circumferential surface of the lip 26 along its entire length. In this case, the groove has the advantage of suppressing a decrease in shape accuracy due to sink marks during molding, but the strength of the lip 26 will be reduced due to the formation of the groove. The lip 26 may have one or more notches (not shown) spaced apart in the circumferential direction, and even in this case, the "annular" condition is satisfied. The width of the notches in the lip in the circumferential direction must be smaller than the width of the tip portion 32A of the engaging piece 32 in the circumferential direction. The lip 26 does not have to be a perfect annulus; as long as the necessary width can be secured for the engaging surface 26A, it may be a polygonal shape, for example, with an outer surface formed of many planes, and even in such a case, the "annular" condition is satisfied. In other words, "annular" is not limited to an annular shape, and slight changes in shape are permitted as long as it can perform the same sealing function as in the annular case.

[0047] The port member 2 is preferably made of a material with a flexural modulus of 140 MPa or higher. Examples of materials that satisfy this condition include synthetic resins such as polyethylene, polypropylene, and cyclic polyolefins, which can be appropriately selected according to the material of the bag body 3. If a material that is highly flexible and easily deformed when force is applied is used, even if the inclination angle θ of the engagement surface 26A is appropriate, the cap 4 may come off when removing the seal 30 of the cap 4. Therefore, it is preferable that the flexural modulus is 140 MPa or higher. More preferably it is 200 MPa or higher, and even more preferably 400 to 2000 MPa. The flexural modulus can be measured by the measurement method specified in ISO 178. Figure 7 shows the state in which the seal 30 has been removed from the cap 4.

[0048] As shown in Figures 5 and 6 (bottom view), the cap 4 has a cap body 28 and a seal 30 fixed on the cap body 28, and the seal 30 can be removed from the cap body 28 by lifting the periphery of the seal 30 with a finger.

[0049] The cap body 28 has a disc-shaped top plate portion 34, a cylindrical skirt portion 33 extending vertically from the periphery of the top plate portion 34, and a plurality (four in this embodiment) of engaging pieces 32 provided on the lower inner surface end of the skirt portion 33. Recesses 46 are formed on the outer circumferential surface of the skirt portion 33 at positions corresponding to the spaces between the engaging pieces 32 to prevent the hand from slipping. The engaging pieces 32 are rectangular plate-shaped and have a base portion 32B formed integrally with the inner circumferential surface of the lower end of the skirt portion 33, and a tip portion 32A that protrudes upward toward the inside of the cap toward the top plate portion 34 from the base portion 32B, and the tip portion 32A is elastically able to approach the inner circumferential surface of the skirt portion 33.

[0050] The distance from the tip of the tip portion 32A of the engaging piece 32 in its free state to the central axis of the cap 4 is smaller than the distance from the outer circumferential surface of the lip 26 to the central axis of the port member 2. At the same time, the distance from the tip of the tip portion 32A to the central axis of the cap 4 when the engaging piece 32 is elastically deformed and closest to the inner circumferential surface of the skirt portion 33 is greater than or equal to the distance from the outer circumferential surface of the lip 26 to the central axis of the port member 2. As a result, when the cap 4 is placed over the port member 2 and pressed down, the tip portion 32A of the engaging piece 32 elastically deforms to overcome the lip 26, then opens again to contact and engage with the engaging surface 26A of the lip 26. The maximum downward force required to press down on the cap 4 until the engaging piece 32 elastically deforms to overcome the lip 26 is approximately 10 to 200 N, which is ideal for ease of use. More preferably, it is 20 to 100 N. However, when the cap 4 is attached mechanically, the maximum downward force applied to the cap 4 is usable as long as it does not cause plastic deformation to the port member 2 and the cap 4.

[0051] The distance from the tip of the tip portion 32A of the engaging piece 32 in its free state to the central axis of the cap 4 is slightly greater than, approximately equal to, or slightly less than the distance from the outer circumferential surface of the attached portion 25 to the central axis of the port member 2. Within this range, it is preferable that the distance from the tip of the tip portion 32A of the engaging piece 32 in its free state to the central axis of the cap 4 is approximately 95-105% of the distance from the outer circumferential surface of the attached portion 25 to the central axis of the port member 2.

[0052] The number of engaging pieces 32 is not limited, but from the viewpoint of stability in fixing the cap, 3 to 6 are preferred, and 4 are most preferred. It is desirable that the tip portion 32A of the engaging piece 32 is curved to match the curved shape of the lip 26 so as to contact the engaging surface 26A along its entire horizontal length. Rectangular openings 44 are formed in the top plate portion 34 at positions corresponding to each engaging piece 32, serving as escape routes for the core when injecting the overhanging engaging pieces 32.

[0053] The inner plug 50, which seals the opening of the port, is made of a highly elastic rubber or elastomer and has a disc-shaped portion 50A having an outer diameter approximately the same as the upper end of the port member 2, and a protrusion 50B that protrudes from the center of the lower surface of the disc-shaped portion 50A. The outer diameter at the base of the protrusion 50B is slightly larger than the opening diameter of the port member 2, so when the inner plug 50 is fitted into the port member 2, the protrusion 50B enters the inside of the port member 2 and the disc-shaped portion 50A contacts the upper surface of the lip 26 of the port member 2. When the cap 4 is attached over the inner plug 50, the inner plug 50 is compressed by the cap 4, the disc-shaped portion 50A is pressed against the end face of the port member 2, and the protrusion 50B expands and is pressed against the inner circumferential surface of the port member 2. As a result, the port member 2 is airtightly sealed and maintains a sterile state.

[0054] The inner stopper 50 may be mechanically bonded, glued, welded, or integrally molded with the cap 4 in advance. The inner stopper 50 may have a body made of rubber or elastomer and a coating layer made by coating at least the surface of the body that comes into contact with the contents with fluororesin. The method of forming the coating layer is not limited and may be laminated or formed by a spray method.

[0055] A circular opening 48 is formed in the center of the top plate portion 34 of the cap 4, and a seal 30 that closes the opening 48 is joined to the top plate portion 34 via a connecting portion 42. The outer diameter of the seal 30 is slightly larger than the outer diameter of the cap 4, and if the periphery of the seal 30 is pulled up strongly, the connecting portion 42 breaks and the seal 30 detaches from the cap body 28. As a result the opening 48 is opened, and the contents of the bag body 3 can be discharged by inserting a syringe needle or the like into the inner stopper 50.

[0056] The storage section 12 of the bag body 3 can contain any substance that can pass through the port member 2, such as liquids, powders, gases, or mixtures thereof. However, this embodiment is particularly suitable for biopharmaceuticals that cannot be heat-sterilized. Examples of such pharmaceuticals include at least one selected from plasma-derived preparations such as albumin or globulin preparations, enzymes, blood coagulation and fibrinolytic factors, hormones, vaccines, interferons, erythropoietins, cytokines, antibodies, and fusion proteins. The contents containing the biopharmaceutical are aseptically filled into the storage section 12 in a sterile environment, the stopper 50 is fitted into the opening of the port member 2, the cap 4 is attached to the port member 2 and pressed down, and the engaging piece 32 is engaged with the lip 26, thereby sealing and preserving the contents in a sterile state. Therefore, unlike conventional bags with ports that require melting or vial containers that require the tightening of aluminum caps, this method can be used simply without requiring special equipment for sealing, which would hinder the sterilization process or generate dust that reduces cleanliness.

[0057] To remove the medicine from the capped bag containing the medicine, instead of removing the cap 4, the seal 30 is pulled up to cut the connection 42 and the seal 30 is removed from the cap body 28. By inserting an injection needle or the like through the opening 48 into the inner stopper 50 and passing the hole 16 in the bag body 3 through a hook to suspend the capped bag, the medicine can be dispensed through the injection needle and tube using gravity, and the bag body 3 will shrink as the contents decrease. Therefore, there is no need to use a venting needle like with vial containers, and there is no risk of outside air entering through the venting needle and contaminating the contents.

[0058] As described above, unlike conventional ported bags that require sealing equipment and vial containers that require aluminum cap crimping equipment, the ported bags and capped bags of this embodiment do not require special equipment for sealing, thus avoiding the need to hinder sterilization work or generate dust that could impair sterility. This makes the sealing process easier and reduces costs. Furthermore, because they are flexible and deflate as the contents are discharged, there is no need to use a venting needle like with vial containers, eliminating the risk of contaminating the contents through the venting needle. Therefore, they offer the advantages of lowering pharmaceutical manufacturing costs and being easy to use in medical settings. [Examples]

[0059] The following describes some examples of the effects of the present invention, but the present invention is not limited to these examples.

[0060] The ported bags of Examples 1-4 and Comparative Example 1 of the present invention were prepared by the following method. As a sheet material, a film of LLDPE (linear low-density polyethylene) polymerized with a metallocene catalyst was prepared to a thickness of 250 μm, and two of these sheets were joined together by heat sealing to create the bag body. The tensile modulus of the sheet material was measured by the method of ISO 527-1 and was found to be 360 ​​MPa. The density of the sheet material was measured by the method described in ISO 1872-1 and was found to be 924 kg / m³. 2 That was the case.

[0061] The port material has a flexural modulus of 1140 MPa and a density of 964 kg / m³. 2 The components were manufactured using HDPE (high-density polyethylene) by injection molding. The total height of the port component is 38.3 mm, the outer diameter of the lip is φ19.7 mm, the inner diameter of the port component is φ12.7 mm, the radial thickness of the lip portion from the inner circumferential surface of the port is 3.8 mm, the outer diameter of the attachment portion is 16.6 mm, and the inclination angle θ of the engagement surface between the attachment portion and the lip is set to 90°, 105°, 120°, 135°, and 150° in 15° increments.

[0062] The bag body and the port component were heat-sealed together to create a bag with a port, the inner dimensions of the storage compartment of the bag body being 140mm x 105mm, the total length of the bag body and port component combined being 196mm, and the total width of the bag body being 116mm.

[0063] For the inner stopper, we used a butyl rubber stopper "product number: S10-F451" manufactured by Daikyo Seikou Co., Ltd. For the cap, we used "Plascap" (trademark), product number "20GD-2," made of polypropylene, also manufactured by Daikyo Seikou Co., Ltd.

[0064] On the other hand, Comparative Examples 2-6 had a flexural modulus of 130 MPa and a density of 915 kg / m³. 2 Port components molded from LLDPE were used, and ported bags were prepared under the same conditions as in Examples 1-4 and Comparative Example 1. Table 1 shows a list of materials and port shapes for Examples 1-4 and Comparative Examples 1-6.

[0065] Evaluation tests were conducted on Examples 1-4 and Comparative Examples 1-6 using the following methods. (1) Cap fixation test Each ported bag was filled with 100 mL of water colored with food coloring and sealed with the rubber stopper and cap. 100 bags of samples were prepared for each example and comparative example. When the seals on the top of the caps of these samples were manually separated, the number of samples was counted by visually observing which cap engagement pieces detached from the lip.

[0066] (2) Sealing performance evaluation test by pressure resistance test For ported bags in which the cap did not come off in the above test (1), the bag body was placed on a horizontal surface, and a horizontal press was applied to the inflated storage area, applying a load of 90 kgf continuously for 5 minutes. After that, the contents, colored water, were visually inspected to see if any had leaked out of the bag around the rubber stopper, and the number of bags in which leakage was observed was counted.

[0067] The results of the above tests (1) and (2) are shown in Table 1. In the case of the highly rigid HDPE port, it was found that the engaging piece was more likely to detach from the lip when the inclination angle was greater than 135°, as in Comparative Example 1. Pressure resistance tests were performed on the ported bags in which the engaging piece did not detach, and no leakage was observed in any of the samples.

[0068] [Table 1]

[0069] On the other hand, in Comparative Examples 2-6, bags with ports molded from low-rigidity LLDPE and welded to them, the caps detached even at small inclination angles. This was because the port molding material was flexible, causing the force applied during the lid removal operation to deform the lip, resulting in insufficient locking. Furthermore, pressure tests revealed some liquid leakage. Although the caps did not detach, it was presumed that the deformation of the lip resulted in insufficient compression of the rubber stopper, leading to inadequate liquid sealing performance due to the pressurization inside the pouch. However, it is possible that the issue of insufficient rigidity could be resolved by changing the dimensions of the lip. [Industrial applicability]

[0070] The ported bag and capped bag according to the present invention do not require special equipment for cap attachment and the cap can be easily attached. Therefore, they can be used, for example, in a sterile environment without hindering the sterilization process. Furthermore, after attachment, the cap is securely fixed to the lip by the elasticity of the engaging piece, making them highly reliable in terms of maintaining a sterile state. Therefore, they have industrial applicability. [Explanation of Symbols]

[0071] 1...Bag with port, 2...Port component, 3...Bag body, 4...Cap, 10...Sealed part, 12...Storage part, 14...Opening, 16...Hole, 18...Non-sealed part, 20...Non-sealed part, 22...Grip part, 24...Flange, 25...Attached part, 26...Lip, 26A...Engaging surface, 26B...Tip surface, 28...Cap body, 30...Seal, 32...Engaging piece, 32A...Tip part, 32B...Base part, 33...Skirt part, 34...Top plate part, 36...Peripheral wall part, 38...Skirt part, 40...Top plate part, 42...Connecting part, 44...Opening, 46...Recess, 48...Opening, 50...Inner plug, 50A...Disc-shaped part, 50B...Convex part, 52...Concave part.

Claims

1. A bag with a cap comprising: a bag body formed in the shape of a sheet and having a storage compartment inside; a cylindrical port member attached to the bag body, one end of which communicates with the storage compartment and the other end of which has an opening exposed to the outside of the bag; an inner stopper that closes the upper end of the port member; and a cap that can be attached to the port member by holding down the inner stopper, The port member has a portion to be covered by the cap when the cap is attached to the port member, and an annular lip formed on the periphery of the opening and protruding outward from the port member. The lip has an annular engaging surface facing the side of the bag body, The upper surface of the lip is a surface that abuts against the lower surface of the outer circumference of the inner stopper and supports the inner stopper. The engaging surface, in a cross-section along the axial direction of the attached portion, is at an angle of 90° to 135° with respect to the outer circumferential surface of the attached portion. The port member is made of a material with a bending modulus of 140 MPa or higher. The protrusion height of the lip from the outer circumferential surface of the attached portion is 0.5 mm to 5 mm. The tip width of the lip in the longitudinal direction of the port member is 1 to 10 mm. The length of the port member is 30 mm or more. The inner diameter of the port member is constant in its longitudinal direction, including the opening. A protrusion is formed in the center of the lower surface of the aforementioned stopper, which is inserted into the opening of the port member. The cap comprises a top plate portion, a cylindrical skirt portion that rises from around the top plate portion and covers the portion to be attached, and a plurality of engaging pieces provided on the lower inner surface end of the skirt portion. The engaging piece has a tip that protrudes toward the top plate portion and is elastically able to approach the inner circumferential surface of the skirt portion. A bag with a cap, characterized in that when the cap is attached to the port member, the tip of the engaging piece abuts against the engaging surface of the lip and can be engaged, the upper surface of the lip abuts against the lower surface of the outer circumference of the inner stopper, and the protrusion in the center of the lower surface of the inner stopper is inserted into the opening of the port member.

2. A cap bag according to claim 1, wherein an opening is formed in the top plate portion of the cap, and a seal that closes the opening is detachably fixed to the top plate portion, and the opening can be exposed by removing the seal.

3. A capped bag according to claim 1 or 2, wherein the storage portion of the bag body is aseptically filled with contents comprising at least one selected from plasma-derived products, enzymes, blood coagulation and fibrinolytic factors, hormones, vaccines, interferons, erythropoietins, cytokines, antibodies, and fusion proteins, and the cap is attached to the port member to seal the contents.

4. A capped bag according to claim 1 or 2, characterized in that the contents of the storage portion of the bag body are sterile-filled with contents comprising at least one of an albumin preparation and a globulin preparation, and the cap is attached to the port member to seal the contents.

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