SK12702003A3 - Albumin in a flexible polymeric container - Google Patents

Abstract

A flexible polymeric container for holding albumin. The container (12) is made of a sheet of flexible polymeric film (34) formed into a bag having a cavity enclosed by a first wall, an opposing second wall, and seals about a periphery of the first and second walls. The seals join an interior portion of the opposing first and second walls and create a fluid-tight chamber within the cavity of the container for storing a concentration of the albumin. A method of packaging the albumin protein into a flexible polymeric container is also provided. Therein a flexible polymeric material is converted into bags, the bags are filled with a quantity of albumin by a filler (44), and a seal area of the bags is sealed to enclose the albumin within the bag.

Description

Albumin in flexible polymeric packaging

Technical field

The present invention relates generally to the coating of proteins into a flexible polymeric coating and more particularly to the coating of albumin with a material forming a flexible polymeric coating, wherein the coating is carried out in an aseptic environment of a molding machine forming a closed package.

BACKGROUND OF THE INVENTION

Many peptides and proteins are known for pharmaceutical or other uses, including glycoproteins, lipoproteins, immunoglobulin, monoclonal antibodies, enzymes, blood proteins, receptor proteins, and hormones.

One type of such mixture is albumin. Albumin is a water-soluble sulfur-containing protein that solidifies on heating and occurs in egg white, milk, blood, and other animal and plant tissues and secretions. Albumin is often used as a blood-enhancing agent, thereby contributing to maintaining a patient's blood pressure, or sometimes contributing to an increase in the patient's blood pressure during bleeding.

Proteins, such as albumin, are adsorbed by most of the artificial materials including liquid shells made of different polymers. Adsorption of proteins to an artificial polymer surface causes the protein content of such a solution to be reduced. Some protein solutions may be adversely affected by protein adsorption on artificial surfaces through a process called denaturation. Denaturation is a process in which the protein is not permanently adsorbed onto the polymeric shell, but the protein molecules are adsorbed into the shell and then released. Adsorption and release can alter the shape of the molecule (i.e., deprive it of its original properties). Often, when protein molecules in protein drug solutions are subjected to denaturation, they may lose their efficacy and utility. Therefore, to date, proteins such as albumin have been stored for individual use in glass ampoules to eliminate the risk of denaturation. Because of the cost of manufacturing, packaging, crate, transport and storage of glass ampoules, as well as the cost of glass ampoules and the weight of the glass ampoule and the high risk of glass ampoule breakage, it is desirable to overcome these disadvantages and use more efficient, inexpensive and user friendly means for packaging proteins such as albumin.

One type of packaging used for coating non-protein drugs is a polymer bag formed on a packaging machine for forming, filling and sealing the packaging. Packaging machines for forming, filling and sealing packaging are devices for packaging certain medicaments and many other products in a cheap and efficient way.

In accordance with the requirements of the FDA, certain drugs, packaged in a packaging machine for forming, filling and sealing packages, are typically autoclaved after packaging. This step of packaging the drug comprises placing the sealed package containing the drug in an autoclave and sterilizing it by steam or heating the package and its contents to a desired temperature, often about 250 ° F, at a predetermined time interval. This stabilization step causes the destruction of bacteria and other contaminants inside the package, whether on the inner layer of the coating or in the drug itself.

However, certain types of packaged drugs, including proteins such as albumin, cannot generally be sterilized in this way. This is because the heat needed to kill the bacteria used in the autoclave destroys or destroys certain drugs. In addition, in the case of albumin protein, heat can cause protein coagulation.

A package in which the package is formed, filled, and sealed may also present other problems in addition to the aforesaid sterilization in coating certain proteins, such as e.g. albumin.

In particular, a conventional packaging device for forming, filling and sealing the packages brings heat to certain regions of the polymeric material of the package to form a tight seal there. If heat comes into contact with the protein, during this sealing step the protein may coagulate or otherwise lose its properties during high temperature sterilization. Moreover, since certain proteins, such as albumin, act as insulators, all surfaces to be sealed must be protein-free in order for the polymeric materials to be sealed together by heat. If any protein, e.g. albumin, present on the sealing surface prior to sealing, the integrity of the tight joint may be compromised.

Therefore, there is a need to provide suitable, economically advantageous means for coating certain proteins, including proteins such as albumin.

SUMMARY OF THE INVENTION

The present invention provides a flexible polymeric coating for storing concentrated peptides and / or proteins. Such peptides and proteins include: glycoproteins, lipoproteins, immunoglobulin, monoclonal antibodies, enzymes, blood proteins, receptor proteins, and hormones. Further, the present invention provides a method of packaging such a composition in a flexible polymeric package. Generally, the flexible polymeric wrapper comprises a flexible film sheet formed into a bag. The bag has a cavity bounded by a first wall and an opposite second wall. The bag further has a seal around the periphery of the first and second walls, which connects the inner portion of the opposing first and second walls, thereby forming a waterproof chamber within the cavity of the package. Inside the waterproof chamber, a compound of unchanged concentration is stored. In one embodiment, the compound is albumin.

According to one aspect of the present invention, the flexible polymeric coating for maintaining the concentration of water-soluble albumin comprises a layer of flexible polymeric material which is first formed into a tube shape by means of a forming apparatus and subsequently transformed into a row of adjacent bags. The bags have a first side member and a second side member closely coupled to the first side member and a cavity between the interior of the first and second side members. A dose of concentrated water-soluble albumin is stored inside the bag cavity. The bag openings are then sealed to form a waterproof chamber.

According to another aspect of the present invention, the wrapper has a plurality of peripheral skirts. The three peripheral flanges are sealed by heating and one of the peripheral flanges comprises a fold that separates the first wall or the first side member from the opposite second wall or the second side member.

According to another aspect of the present invention, a folding device is attached to the package. This device extends from the outer portion of the package upon folding and is provided with a channel connected to the liquid-tight chamber of the package. The sealed channel opens into the container cavity to allow the passage of albumin from the fluid tight chamber. On opposite sides of the device and along the fold, a cuff seal may be provided at some distance to assist the outflow of albumin from the container.

According to another aspect of the present invention, the circumferential rim of the wrapper opposite to the fold comprises a first seal and a second seal. The first and second seals connect the opposite first and second walls. Between the first and second seals there is an opening that extends between the first and second and opposite walls.

According to yet another aspect of the present invention, the flexible flat polymeric material comprises a laminated film having an outer layer of linear low density polyethylene, a gas tight layer, a central layer of polyamide, and an inner layer of linear low density polyethylene. These layers are glued together using a polyurethane adhesive.

According to a further aspect of the present invention, the 20% and 25% albumin is packaged in a flexible polymeric container. The flexible polymer packages may have a volume of 50 ml or 100 ml.

Another further aspect of the present invention is a method of packaging albumin proteins comprising forming a flexible polymeric shell having an opening opening into the polymeric cavity, preparing a dose of sterile concentrated albumin solution, injecting albumin using pressure into the polymeric cavity through the aperture, and sealing the aperture to the albumin was sealed tightly in the liquid-tight chamber of the container cavity.

Another further aspect of the present invention is a filling device used to incorporate albumin into a flexible container. The filling device is provided with a distal tip with adjacent first and second inner channels. The first inner channel has a cross-sectional area larger than the second inner channel. The second inner channel adjoins the first inner channel and passes to the tip surface, wherein the albumin is dispersed from the feed device through the second inner channel.

According to another aspect of the present invention, the transition between the first inner channel and the second inner channel is the interior of the outer tip portion and the second inner channel enters the outer tip portion. The albumin is maintained at the transition between the first and second inner channels during the interruption of the bag filling.

Another aspect of the present invention is to position the cover on the outside of a portion of the filling device adjacent to the tip. The cover prevents contact between the polymeric shell and the filling device.

It is also an aspect of the present invention that the cover is positioned concentrically with the filling device. An air duct extends between the inside of the housing and the outside of the filling device. Sterilized air passes through the air duct and is deflated at the tip of the charging device and before the albumin outlet.

According to a further aspect of the present invention, the albumin is packaged in a series of flexible polymeric packages in a packaging machine for forming, filling and sealing the packages. A certain amount of filtered albumin and a resilient polymeric material is used, wherein the packaging machine for forming, filling and sealing the packages converts the resilient, polymeric material into a variety of bags. The bags are filled with doses of albumin in the packaging machine, wherein the sealing surface of the bags is sealed by the packaging machine, thereby closing the dose of albumin in the bag.

According to another aspect of the present invention, the adjacent bags are initially joined, then sequentially filled with doses of albumin and separated after filling.

According to a further aspect of the present invention, the packaging machine for forming, filling and sealing the packages is provided with an aseptic zone. The sterilized, resilient polymeric material is located in the aseptic zone and is also formed into sachets in the aseptic zone. In addition, filtered albumin is introduced into sachets in this aseptic zone, and the sachets are sealed in this aseptic zone to form a liquid-tight coating.

According to a further aspect of the present invention, the albumin is packaged in a series of polymeric containers in a packaging machine for forming, filling and sealing the containers by the following process: the resilient polymeric material is transformed into a tube shape in the packaging machine of the packaging machine; the tube is transformed into a series of bags in a packaging machine, which are gradually filled with doses of albumin in the packaging machine to form, fill and seal the packages, then sealing the sealing area in the packaging machine and thereby sealing the albumin doses inside the bag. The bags may be filled with a filling device that feeds the albumin into the bag without coming into contact with the seal area of the bag opening.

According to yet another aspect of the present invention, the albumin is packaged in a flexible polymeric package by the following process: preparing concentrated albumin; utilizing a packaging machine having a forming portion, a filling portion, and a sealing portion each located within the aseptic environment of the packaging machine to provide a flexible polymeric film; forming a flexible polymeric film into an elongate tube in the forming portion; sealing a portion of the elongated polymeric film tube in the sealing portion of the apparatus, forming a sealed polymeric film into a bag having a sealing region around its periphery, a cavity situated within the bag between the sealed regions and an opening connecting the cavity to the outer bag; filling the sachet with albumin under pressure in the filling section. The filling section is provided with a filling tube passing through an opening in the bag into the bag cavity and a cover that is concentric to the outer surface of the filling tube. The feed tube directs albumin to the interior of the bag, without touching the perimeter of the bag opening, with the cover preventing contact between the feed tube and the bag. The bag opening is then sealed to seal the albumin inside the bag cavity.

The flexible polymeric albumin storage container formed in accordance with the present invention provides an inexpensive, easy-to-manufacture, and efficient container, and the invention also provides a manufacturing process. The effective coating and process of the invention overcome the disadvantages associated with the previously known packaging and albumin packaging processes.

in

Other features and advantages of the invention will be apparent from the following description taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a side elevational view of a packaging machine for forming, filling, and sealing containers in cross-section to produce polymeric containers holding a concentrated albumin of the invention;

Fig. 2 is a schematic view of a process for manufacturing a flexible polymeric wrapper of the present invention capable of storing concentrated albumin;

Fig. 3 shows a side view of the flexible polymeric envelope of the present invention for storing concentrated albumin;

Fig. 4 is a partial side view of the flexible polymeric envelope of Fig. 3 according to the present invention capable of storing concentrated albumin;

Figure 5 is a side view of a portion of the filling device of the present invention;

Fig. 6 shows an enlarged side view of part of the filling device of Fig. 5;

Fig. 7 is a side cross-sectional view of a housing for a filling device according to the present invention;

Figure 8 is a view of the ends of the housing of Figure 7;

Fig. 9 shows schematically a cross-section of one embodiment of a laminated film structure according to the present invention; and Fig. 10 is a cross-sectional view of an end of a feed tube and a cover according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

While the present invention may be practiced in many different embodiments, it is shown in the drawings and described in detail in the preferred embodiments of the invention, and it is understood that the present description is intended to be exemplary of the principles of the invention and is not intended to limit the scope of aspects of the invention to shown embodiments.

As mentioned above, the scope of the present disclosure includes forming a shell for any type of certain pharmaceutical compound, such as peptides and proteins for pharmaceutical or other uses. Such compounds are known and include: glycoproteins, lipoproteins, immunoglobulins, monoclonal antibodies, enzymes, blood proteins, receptor proteins, and hormones. For purposes of example, however, there is a detailed description of the present invention directed to packaging albumin in a flexible polymeric package.

Referring now to Figure 3, the flexible polymeric package 12 of the present invention storing concentrated albumin is shown in detail.

The flexible polymeric wrapper 12 is preferably manufactured on an aseptic packaging machine 10 for forming, filling and sealing the wrappers as shown in Figure 1, using the process schematically shown in Figure 2.

The aseptic packaging machine 10 for forming, filling and sealing packages generally includes a unwinding section 14, a sterilizing section 16 for sterilizing the film, a drying section 18 for drying the film, a carrier roller, a section 20 of tensioning rolls / tensioning rollers, section (not shown) assembled from animal drive rollers, forming section assembly 22, seam sealing section assembly 24, attachment section assembly assembly 26, filling section assembly 30, end sealing / cutting section assembly 32, and a transport section (not shown). Each of these assemblies located downstream of the unwinding section 14 is located in the internal aseptic environment of the packaging machine 10 for forming, filling and sealing the packages.

One function of one possible assembly of the packaging machine 10 for forming, filling and sealing the packages is as follows: the unwinding section 14 comprises a roll of wound, flexible polymeric film 34, which is finally formed into the package. A peroxide bath is used to sterilize the flexible polymeric film 34, which is in the sterilization section 16. The drying section 18 for drying the flexible polymeric film 34 is provided with means for drying and removing the peroxide from the film 34. The forming section 22 is provided with a film forming rod 36 into the shape of a tube 38 which eventually turns into a flexible container or bag 12.

Its sealing section 24 forms a longitudinal seal 40 on the tube 38, which eventually becomes a longitudinal seal 40 on the flexible package 12. The attachment section 26 attaches the device 42 to the pipe 38. The feed section 30 comprises filling devices 44 that fill the flexible containers 12 with a substance that is a concentrated water-soluble albumin in this preferred embodiment of the present invention. The end sealing / shearing section 32 comprises shearing and sealing jaws 46 that form end seals 76, 78 of the resilient polymeric sleeve 12 so as to seal the albumin within the resilient polymeric sleeve 12.

In a preferred embodiment, either 20% human albumin or 25% human albumin is used as the albumin to be packaged. To achieve the desired degree of concentration, albumin is usually mixed with sterilized water and stabilizers. Prior to packaging, albumin at a given concentration is pasteurized and stored in large stainless steel storage tanks (not shown) having a capacity of 500 to 600 liters, maintaining the temperature at 2 ° C to 8 ° C. Just before packing, albumin containers are removed from refrigerators and allowed to equilibrate with the packaging room temperature (approximately 68 ° F). It is important that the albumin is processed at a temperature that does not lead to protein denaturation at about 60 ° C. However, a temperature between 0 ° C and 60 ° C is acceptable, but more preferably between 20 ° C and 45 ° C. In one embodiment of the invention, the process temperature is 68 ° F to 77 ° F. The albumin is filtered through a 0.2 µm filter when it enters the packaging machine 10.

The resilient polymeric film 34 used in the preferred embodiment of the present invention is a linear low density polyethylene laminate. It has been found that such a film 34 having gas-tight properties is particularly suitable for encapsulating oxidation-prone solutions such as e.g. said proteins, including albumin. In particular, it has been found that this film 34 reduces or eliminates the denaturation process previously associated with the placement of proteins such as albumin in a plastic container. As shown in FIG. 9 of the preferred embodiment, the laminated film 34 has an outer layer of linear low density polyethylene (LLDPE) 52, a gas tight layer 54, a core layer of polyamide 56, and an inner layer of linear low density polyethylene 58, the layers being bonded together with polyurethane adhesive 60. the material of the laminated structure is most preferred when the structure has the following characteristics:

Linear Low Density Polyethylene (LLDPE) layer 52 (about 61 µm ± 10 µm) 2; a polyurethane adhesive layer 60, a polyvinylidene chloride (PVDC) layer 54 (about 19pm ± 5pm); a polyurethane adhesive layer 60; a nylon layer 56 (about 15 µm ± 5 µm), a polyurethane adhesive layer 60, and a linear low density polyethylene LLDPE layer 52 (about 61 µm ± 10 µm). The total thickness of the film 34 is approximately 160 µm ± 25 µm.

In addition, polyvinylidene chloride (PVDC) layer 54 is most preferably manufactured by Dow Chemical and sold under the trademark SARAN. This film is described in U.S. Pat. 4,629,361. US Patent No. 4,629,361 is the owner of the present invention. This document is incorporated into and constitutes a part of this invention. This flexible polymeric film 34 is manufactured by Fujimori under the trade name FTR-13F.

The inner aseptic zone of the packaging machine 10 must be sterilized daily before use. This sterilization is carried out with hydrogen peroxide vapors passing through the aseptic zone of the packaging machine.

As shown in FIG. 1, a roll of film 34 is placed in the unwinding section 14 of the packaging machine 10. While the packaging machine is running, the film 34 is conveyed through a hydrogen peroxide bath 16 to be sterilized before entering the aseptic zone of the packaging machine 10. In the sterilization step, the film 34 is cleaned so that it can be used to form a sterile product. Sterilization and cleaning of the film is critical in health care when the film 34 is packaged with parenteral or enteral products. In particular, this sterilization step is critical when the final product is not sterilized at the end of production, i. i. when a packaging machine 10 equipped with an aseptic zone is used. After the film 34 has been washed, cleaned or sterilized, liquid or other residues typically remain on the film 34, for example, a sterilizing chemical or wetting agent such as hydrogen peroxide. It is therefore necessary to remove this liquid and / or residues from the film 34. To remove liquid and other residues from the film 34, an air curtain is used (an air stream driven through the surface of the film 34 to blow away the liquid remaining there) located in the drying section 18 to remove liquid and other residues from the film 34 before it enters the aseptic zone of the packaging machine 10.

In the aseptic zone of the packaging machine 10, the film 34 passes before it enters the forming section assembly 22 through the tension roller section 20 and through the drive roller section. Before it enters the forming section assembly 22, the film web 34 is substantially planar and has a first surface 62 and a second surface 64. The first surface 62 faces downwardly as the film 34 enters the forming section assembly 22, eventually becoming the interior of the package 12, while the second surface 64 of the film 34 faces up as the film 64 enters the forming section assembly 22 and finally becomes the outside of the package 12.

As shown in FIG. 3 and 4, the film 34 has a theoretical bending line positioned approximately at the location of the longitudinal centerline of the web of film 34. The theoretical bending line becomes a bending region 67 that separates the first side member 66, respectively. a first wall from the second side member 68, respectively; the second wall of the package 12.

The shaping rod 36 is disposed in the shaping section 22. The shaping rod 36 causes the original, substantially planar web of polymeric material 34 to be converted into an elongated and substantially cylindrical member 38. Of course, the elongated tubular member 38 or tube is not generally in the form of 4, but has a slightly flattened shape as shown in FIG. In connection with the marking of the webs of the film web 34, as described above, after the film 34 has passed through the forming section assembly 22, the first surface 62 of the first side member 66 faces the first surface 62 of the second side member 68.

After the cylindrical member 38 has been formed, this tubular member is provided with a longitudinal seal 40 in the seam seal assembly 24, wherein the device 42 connects to the tube 38 in the equipment of the attachment section 26. Specifically, the device is connected to the outer portion of the package 12 in the bend area 67. a container 12 around which it is guided using a heated device to seal the contact between the device 42 and the bending area 67. Typically, the sealing device operates at a temperature of from about 415 ° F to about 450 ° F, at a pressure of from about 55 psig to about 70 psig, although any range at the indicated intervals is useful. As shown in Fig. 4, the device 42 is provided with a sealed channel that cooperates with the interior of the tube 38. Specifically, the channel opens into the cavity 82 of the container 12 and allows the albumin to be released from the liquid tight chamber. It should be understood that in some embodiments, albumin may be injected into the cavity 82 of the container 12 by the device 42.

The seam sealing section 24 supplies heat and exerts pressure on the film 34 to form a longitudinal seal 40 at the peripheral edge of the tube 38, which lies opposite the bending area 67. Typically, the seam sealing section 24 operates at a temperature of about 350 ° F to about 380 ° F and at a pressure of about 40 psig to about 80 psig, but any range within these ranges is possible. In a preferred embodiment of the package 12 shown in Fig. 3, the longitudinal seal 40, the first longitudinal seal 70 and the second longitudinal seal 72. The first longitudinal seal 70 and the second longitudinal seal 72 connect the first surface 62 of the first side wall 66 to the opposite first surface. 62 of the second side wall 68 ..

The aperture 74 typically used to suspend the shaped container 12 is formed between the first longitudinal seal 70 and the second longitudinal seal.

72. The aperture 74 extends through the first side wall 66 and the opposite second side wall

68th

The sealed tubular member 38 advances from the seam sealing section 24 to the filling section 30 and to the end sealing section 32. In the end sealing section 32, the packaging machine 10 for forming, filling and sealing the packages utilizes heat and pressure to convert the sealed tube 38 into a row. bags 12 also referred to as containers 12. Typically, the end sealing section 32 operates at a temperature of from about 375 ° F to about 405 ° F and a pressure of about 500 psig to about 850 psig, although any range within these intervals may be utilized. The sealed tube 38 is initially provided with a lower sealing joint 76 to form a bag 12 having a cavity 82 disposed between the first side wall 66 and the second side wall 68 of the container 12 and the lower seal 76 of the container 12 and the opening 80 connecting the container cavity 82 It is understood that during the manufacturing process, when the container 12 is formed, filled and sealed, the opening 80 from the cavity 82 of the container 12 extends to the center of the tube 38. After the bottom seal 76 has been formed, the bag 12 is filled through the opening 80 albumin, and thereafter an upper seal 78 is formed, thereby sealing and sealing, respectively. the opening 80 closes and a fluid-tight chamber 82 is formed in which the albumin is placed. After the bottom seal 76 has been formed, the dimension of the open bag 12 having the sealing regions around its periphery (the longitudinal seal 34 opposite the bending region 67 and the bottom seal 76 connecting the bending region 67 and the longitudinal seal 40) can be determined for the polymer film 34. a cavity 82 disposed within the bag 12 and between the sealing regions 40, 76 and the bending region 67. By forming, filling and sealing the package 12, the final package 12 has sealed areas on three sides of the bag 12: an upper seal 78, a lower seal 76, and a longitudinal seal 40. The longitudinal seal 40 connects the upper seal 78 and the lower seal 76. In a preferred embodiment of the process, the upper seal 78 of the first bag 12 is formed at the same time as the lower seal 76 of the adjacent subsequent bag 12, in the end sealing section 32. The adjacent bags 12 lying in the row of bags 12 are initially joined by being part of the tubular member 38 of which the bags 12 are formed as well as having end seals which are formed in the same end sealing section 32.

In a preferred embodiment of the method for forming and filling the containers 12 of the present invention with albumin, the containers 12, as shown in FIG. 1 and 2, filled with albumin by a feed section 30 that extends down the tube 38. This feed section 30 fills the cavity 82 of the bag 12 through the opening 80 after forming an open bag 12 equipped with three sides.

The filling section 30 according to a preferred embodiment is shown in FIG. 5 to 8 and 10. The filling section 30 includes a pressure filling device 44 formed from a filling tube 84, and a cover 86 disposed concentrically around the periphery of the filling tube 84. The pressure filling device 44 typically operates under pressure in a solution line that moves from about 4 psig to about 20 psig, but any ranges that are within the indicated range are possible. In a preferred embodiment, the pressure feeder 44 operates with a solution line pressure ranging from about 10 psig to about 16 psig, with the most preferred mode where the solution line pressure is from about 12 psig to about 16 psig. Said ranges are used to reduce turbulence and spattering of albumin and other proteins when filling the container 12. As mentioned above, after forming the bottom seal 76 of the next bag 12, an upper seal 78 is formed. tubes 38 and so on. Adjacent bags 12 in the row of bags 12 are initially joined and separated after successive filling and sealing of each respective bag 12.

As shown in FIG. 5, in a preferred embodiment, the feed device 44 of the feed section 30 is arranged as a pipe 86 disposed over the pipe 84. The cover pipe 86 is arranged concentrically around the feed pipe 84 with the air channel 88 extending in the space between the inner diameter of the cover pipe 86 and the outside diameter of the feed tube 84. Sterilized air passes through the air passage 88 and is blown out at the end of the feed tube 84 prior to exit 92 from the feed tube 84.

In a preferred embodiment of the feed tube 84 shown in FIG. 5, the feed tube 84 is provided with a diffuser 85 in which the feed tube 84 conically extends from its first diameter to a second, larger diameter. 6, the tip 90 of the feed tube 84 has a first inner channel 94 concentric and adjacent to the second inner channel 96. In a preferred embodiment of the present invention, the first inner channel 94 typically has a circular, cross-section with a first inner diameter and a second the inner channel 96 typically has a circular cross-section having a second inner diameter.

The inner diameter of the first inner duct 94 is dimensionally larger than the inner diameter of the second inner duct 96, and thus the cross-sectional area of the first inner duct 94 is larger than the cross-sectional area of the second inner duct 96. The passage 98 between the first inner duct 94 and the second inner duct 96 an inner channel 94 and a second inner channel 96 at a location that is within the outer outlet 92 of the tip 90 of the feed tube 84 of the filling device 44.

In a preferred embodiment, the passage comprises a tapered step 98 between the first inner channel 94 and the second inner channel 96 so as to sharply reduce the diameter of the first inner channel 94 to the diameter of the second inner channel 96. The passage 98 between the first inner channel 94 and the second inner channel 96 fills an important function during operation of the filling device.

Since the albumin is dispensed from the outlet of the second inner channel 96 of the filling device 44, the capillary forces in the feed tube act such that the albumin present at the transition 98 between the first inner channel 94 and the second inner channel 96 creates meniscus here during the dose interruption. Thus, even when albumin is scattered from the filling device 44 through the second inner channel 96, during each interruption of filling between the successive filling of the bags 12, the albumin is kept within the filling device 44 at a certain distance from the outlet of the feeder 44 at the transition 98 between the first inner channel 94 and the second inner channel 96. Such an arrangement greatly contributes to preventing the migration of albumin from the outlet of the feeder 44. Any migration of albumin may cause transfer of albumin to the outside of the feeder. 44 and contacting the film 34. As explained above, albumin acts as an insulator. If the albumin were transferred to the foil 34, this would probably compromise the integrity of the top seal region. Thus, the arrangement of the solution of the present invention provides a means to overcome this problem. In the tightness tests of the container 12 of the present invention, 99.90% of the formed containers 12 had a minimum breaking strength of 20 psi.

As explained above, the cover 86 rests concentrically around the periphery of the fill tube 84, with an air channel 88 being guided in the space between the inner diameter of the cover tube 86 and the outer diameter of the fill tube 84.

In a preferred embodiment, a distal end portion 100 is mounted to the housing 86 as an adapter, which end portion 100 may be formed as part of the housing 86 without interfering with the intended function of the housing 86. As shown in Figs. the housing portion 100 is provided with a tapered end 104. A plurality of vent holes 102 are provided near the end of the end portion 100 of the housing 86. These vent holes 102 disperse sterilized air from the air passage 88. Since the vent holes 102 are located at the bevelled edge 104 of the cover 86 of the sterilized air flow profile corresponds from outside the circumference of the albumin flow profile that is supplied from the feed tip, so that there is no mixing of the albumin flow with the sterilized air flow. This reduces the possibility of swirling in the introduced albumin. In addition, since the airflow profile is situated from the outside and outside the liquid albumin flow profile, there is minimized the possibility of foaming that could arise when the air contacts the albumin. As well as the advantages associated with the dual inner diameters of the feed tube 84, the advantages associated with the use of sterilized air flow are particularly useful. Such an arrangement greatly contributes to preventing splash and foaming of the albumin as it exits the filling device 44 thereby avoiding contact of the albumin with a portion of the film 34 which is then converted to the top seal region, thereby also helping to smoothly form a firmer top seal.

The first inner diameter 106 of the end portion 100 of the housing 86 is sized to engage the housing 86 and is secured thereto by an adjusting screw 110. The second inner diameter 108 of the end portion 100 of the housing 86 is sized to allow air channel 88 to form. 7, a chamfer 112 is provided at the end of the end portion 100 with the second inner diameter 108 to further reduce the internal diameter of the housing 86. An inverted chamfer 114 is formed on the outer portion of the end of the housing 86.

The cover 86 and the feed tube 84 are shown in the assembly of FIG. 10. As shown in FIG. 10, the outer diameter of the tube is sized to be equal to or slightly less than the reduced inner diameter of the cover 86 at chamfer 112. In a preferred embodiment, the second inner diameter of the cover 86 is about 0.584 inches and is reduced at chamfer 112 to about 0.500 inches. . The outer diameter of the feed tube 84 in a preferred embodiment of the present invention is about 0.500 inch. In this arrangement, the transition between the bevel 112 and the feed tube 86 acts to close the air passage 88, expelling sterilized air out of the air vents 102 located upstream of the exit 92 of the second internal passage of the feed tube 84 for albumin.

As shown in FIG. 10, the outer diameter of the cover 86 is larger than the diameter of the feed tube 84 extending beyond the cover 86. During the filling of the film tube 38, the tube 38 often comes into contact with the feed section 30. with said arrangement of the filling tube 84 and the cover 86, the filling tube 84 of the filling section 30 passes through the opening 80 of the bag 12 into the cavity 82 of the bag 12, the cover 86 is outside of the portion of the filling tube 84 and hence only the cover 86 can touch the tube 38 thereby it prevents contact between the polymeric casing and the filler tube 84. The outlet 92 of the filler tube 84 is located at a distance from the inner wall of the flexible polymeric casing 12. The position and size of the cover 86 in conjunction with the inner surface 98 of the first and second inner ducts and the inverted bevel 114 prevents albumin from coming into the outside of the feed section 30 and coming into contact with the sealing surface which eventually becomes the top seal 78 of the finished package. Since albumin acts as an insulator, it is necessary to keep all sealing surfaces clean, in the absence of proteins, so that the polymeric materials can be tightly joined together with heating.

If any amount of albumin was present on the sealing surface prior to sealing, this could compromise integrity and thus seal the joint. In said embodiment, the albumin is supplied from the feed tube 84 to the bottom of the bag 12 without contacting the region for sealing the opening of the bag 12, which eventually becomes the top seal 78.

Typical embodiments of the invention have been illustrated and described above. It will be understood, however, that a number of modifications can be made without departing from the spirit of the invention. The scope of protection is limited only by the scope of the appended claims.

Claims (48)

A method of packaging an albumin protein comprising the steps of: providing a flexible polymeric shell having an opening extending from the cavity of the polymeric shell; providing a dose of concentrated albumin in a sterile solution; introducing albumin into the cavity of the polymeric shell, through the opening formed therein, under pressure in the solution line from about 4 psig to about 20 psig; sealing the opening for enclosing the liquid albumin in the liquid-tight chamber of the cavity of the polymeric shell. The method of claim 1, wherein the albumin is maintained at a temperature of about 68 ° F before being introduced into the container cavity. The method of claim 1, wherein the albumin is introduced into the cavity of the flexible polymeric shell under pressure in a solution line from about 12 psig to about 16 psig. The method of claim 1, wherein the flexible polymeric wrapper is formed in an aseptic environment of the packaging machine for forming, filling and sealing the packages, wherein in the aseptic environment of the packaging machine for forming, filling and sealing the packages, albumin is introduced into the cavity of the polymeric package. and the opening of the polymer package is also sealed in the aseptic environment of the packaging machine for forming, filling and sealing the packages. The method of claim 1, further comprising the step of providing a feeder device having a distal tip with a first inner channel and a second adjacent inner channel, the first inner channel having a greater cross-sectional area than the second inner channel, the second inner channel adjacent to the first inner channel is discharged to the outside of the tip and the albumin is supplied from the filling device through the second inner channel. The method of claim 1, further comprising the step of providing a feeder equipped with a spike with concentric first inner channel and second inner channel, the first inner channel having an inner diameter greater than the inner diameter of the second inner channel, the transition between the first inner channel the channel and the second inner channel are inside the outside of the tip and the second inner channel is led to the outside of the tip and the albumin exits from the feed device through the second inner channel. The method of claim 1, further comprising the step of providing an outer cover of the portion adjacent the tip of the filling device, wherein the cover prevents the polymeric wrapper from contacting the filling device. The method of claim 1, wherein the albumin is supplied at a 20% concentration. The method of claim 1, wherein the albumin is supplied at a 25% concentration. The method of claim 1, wherein the resilient plastic container has a volume of 50ml. The method of claim 1, wherein the flexible plastic wrapper has a volume of 100 µm. The method of claim 1, further comprising the step of providing a flexible polymeric wrapper comprising a laminated film having an outer layer of linear low density polyethylene, a gas-tight layer, a central layer of polyamide, and an inner layer of linear low density polyethylene. bonded together with polyurethane adhesive. 13. A method of packaging an albumin protein into flexible polymeric envelopes arranged in a row, comprising the steps of: providing a dose of filtered albumin; providing a flexible polymeric material; providing a packaging machine for forming, filling and sealing the packages and converting the resilient polymeric material into a series of bags in a packaging machine for forming, filling and sealing the packages; filling the bags with doses of albumin in a packaging machine for forming, filling and sealing the packages; and sealing the sealing area of the bags with a packaging machine to seal the albumin doses inside the bags. well Z-Z Method according to claim 13, characterized in that adjacent bags in the row of bags are initially joined together and separated after each bag has been filled. 15. The method of claim 14, further comprising the step of providing a packaging machine for molding, filling, and sealing with the forming bar. 16. The method of claim 15, further comprising the step of converting the flexible polymeric material into a tube shape by means of a forming rod and further forming the tube into a row of adjacent bags. The method of claim 13, wherein the bags are sequentially filled with doses of albumin. The method of claim 13, further comprising sealing the periphery of the sachets with heat to seal the albumin doses within the sachets. 19. The method of claim 13, further comprising providing a flexible polymeric wrapper comprising a laminated film having an outer layer of linear low density polyethylene, a gas tight layer, a central layer of polyamide, and an inner layer of linear low density polyethylene, bonded with polyurethane glue. The method of claim 13, wherein the packaging machine for forming, filling and sealing the packages is provided with an aseptic zone in which a sterilized resilient polymeric material is obtained, wherein the sterilized resilient polymeric material is formed into a row of adjacent bags within the aseptic zone. the albumin is gradually filled into sachets in an aseptic zone, wherein the sachets are successively sealed in that aseptic zone to form a liquid-tight container. The method of claim 13, further comprising the step of providing a reusable filling device having a spike with concentric first inner channel and second inner channel, the first inner channel having a cross-sectional area greater than the cross-sectional area of the second inner the passage between the first and second inner channels being within the outer portion of the spike, wherein the second inner channel opens to the outer spike and the albumin exits the filling device through the second inner channel, while the albumin is maintained at the passage between the first inner channel and the second internal channel. The method of claim 21, further comprising the step of providing an outer cover of the portion adjacent the tip of the filling device, the cover limiting contact between the polymeric wrapper and the filling device. 23. The method of claim 21, further comprising the step of providing an outer cover concentric to the filling device and an air passage extending between the interior of the cover and the outside of the filling device, the cover restricting contact between the polymeric casing and the filling device, through the air channel. it passes sterilized air and is blown out at a point adjacent to the tip of the feeder prior to the albumin exit. The method of claim 13, further comprising the step of filtering the albumin through a 0.2 µm filter. 25. A method for packaging an albumin protein in a series of flexible polymeric coatings comprising the steps of: providing a dose of filtered albumin; providing a flexible polymeric material; providing a packaging machine for forming, filling and sealing the packages and converting the flexible polymeric material into a tube in the packaging machine for forming, filling and sealing the packages by means of a forming apparatus; converting the tube into a row of bags in a packaging machine for forming, filling and sealing the packages; filling the bags through the holes in the bags with doses of albumin in a packaging machine for forming, filling and sealing the packages; and sealing the seal area of the bag opening with a packaging machine to seal the albumin dose within the bags. The method of claim 25, wherein the bags are filled sequentially with a dose of albumin. The method of claim 25, further comprising dispensing the albumin into the bags from the filling device, wherein the filling device does not come into contact with the sealing region of the bag opening. 28. A process for wrapping albumin in a flexible polymeric package comprising the steps of: procuring albumin concentrate; providing a packaging machine having a filling section and a sealing section, wherein the filling and sealing sections are located in the internal aseptic environment of the packaging machine; providing a sterile flexible polymeric shell having an opening opening into the cavity; filling the container with albumin under pressure by means of a filling section within the aseptic zone of the packaging machine, wherein the filling section is provided with a discharge tube outlet at a certain distance from the wall of the flexible polymeric container, the discharge tube outlet directs albumin into the cavity at a distance from the periphery of the container opening; keeps the albumin within a certain distance from its output during the interruption of filling; and sealing the opening of the container within the aseptic zone of the packaging machine to enclose the albumin in the container cavity. The method of claim 28, further comprising the step of providing an outer cover of a portion of the feed section, wherein the cover limits contact between the polymeric shell and the feed section. 30. A process for wrapping albumin in a flexible polymeric package comprising the steps of: procuring albumin concentrate; providing a packaging machine having a forming section, a filling section and a sealing section, each section being positioned within the aseptic environment of the packaging machine; providing a flexible polymeric film; forming a flexible polymeric film into an elongate tube in the shaping section; sealing a portion of the elongate polymeric film tube in the sealing section, wherein the sealed polymeric film is sized to form a bag having a sealing area around its periphery, a cavity within the bag between the sealing regions and an opening extending from the cavity to the outer bag; filling the bag with albumin under pressure in the solution line in the filling section, which is equipped with a filling tube passing through the opening of the bag into the bag cavity, with a cover concentric to the outside of the filling tube; limits the contact between the filling tube and the bag; and sealing the opening of the bag to seal the albumin in the cavity of the bag. Method according to claim 30, characterized in that the sealing regions are formed around the entire circumference of the bag except the opening. 32. The method of claim 30, further comprising converting the tube into a plurality of adjacent bags. 33. The method of claim 32, further comprising sealing at least three sides of the bags. 34. The method of claim 32, further comprising sequentially filling the sachets with a dose of albumin. 35. The method of claim 34, further comprising sequential sealing of the bag opening. The method of claim 30, wherein the filling step comprises providing a filling device having a tip concentric to the first inner channel and the second inner channel, wherein the first inner channel has a cross-sectional area greater than the cross-sectional area of the second inner channel and the transition between the first inner channel and the second inner channel is from within the outer tip portion and the second inner channel extends into the outer portion of the tip, wherein the albumin exits the filling device through the second inner channel and during interruption of filling. 37. A flexible polymeric container for storing a water-dilutable albumin concentrate comprising: a bag formed of a flat flexible polymeric material first converted into a tube by means of a shaping device, then the tube in the aseptic zone of the packaging machine for forming, filling and sealing the packages gradually transforms into a row of adjacent bags, the bags having a first side member, second side member which is circumferentially connected to the first side member and further has a cavity between the interior of the first side member and the second side member, wherein a dose of water soluble albumin concentrate is placed in the bag cavity in successive filling of the cavities of adjacent bags with albumin through the bag openings the filling device in the aseptic zone of the packaging machine for forming, filling and sealing the packages, then the bag openings in the aseptic zone of the packaging machine for forming, filling and sealing the packages are sealed one by one to form a liquid-tight chamber. 38. The flexible polymeric package of claim 37, wherein the flexible polymeric flat material comprises a laminated film having an outer layer of linear low density polyethylene, a gas tight layer, a central layer of polyamide, and an inner layer of linear low density polyethylene, wherein the layers are bonded. together with polyurethane glue. 39. The flexible polymeric coating of claim 38, wherein the gas-tight layer is polyvinylidene chloride. 40. The elastic polymeric shell of claim 37, wherein the polyamide core layer is nylon. 41. The flexible polymeric package of claim 38, wherein the gas-tight layer is formed from SARAN. 42. An albumin-filled, flexible, polymeric coating comprising: an outer wrapper formed of a resilient polymeric sheet material comprising a laminate film having an outer layer of linear low density polyethylene adhesively bonded together by a polyurethane adhesive 29 to the first side of the polyvinylidene chloride layer, the second side of the polyvinylidene chloride layer and the second SAR side layers of SARAN adhesively bonded together with a polyurethane adhesive to the inner layer of linear low density polyethylene, the outer shell having a first side and an opposed second side which are heat sealed together on the periphery of the outer shell and a cavity between the first side and the second side forming a liquid-tight chamber with the stored albumin concentrate, the device extending from the outer shell having a sealed channel opening into the cavity of the shell to release albumin from the liquid tight chamber. 43. Albumin storage container, comprising: a flat flexible polymeric film formed into a bag having a cavity enclosed by a first wall and an opposed second wall and sealed around the periphery of the first and second walls, sealing the inner portion of the opposing first and second walls to form a liquid tight chamber within the cavity of the package; inside the liquid-tight chamber is stored albumin concentrate mixed with a solution of sterilized water and stabilizers. 44. The container of claim 43 having a plurality of peripheral edges, wherein the three peripheral edges are sealed by heat and one of the peripheral edges comprises a fold that separates the first wall from the opposite second wall. Packaging according to claim 44, characterized in that the packaging is connected to a folding device having a channel which cooperates with a liquid-tight chamber of the packaging. The package of claim 44, wherein the peripheral edge opposite to the fold comprises a first longitudinal seal and a second longitudinal seal, wherein the first longitudinal seal and the second longitudinal seal connect the first wall and the opposite second wall, and wherein between the first longitudinal seal and a second longitudinal seal is provided with an aperture extending through the first and opposite second walls. 47. The container of claim 45, further comprising at least one collar seal in the fold. 48. The container of claim 45, further comprising a cuff seal in the fold on opposite sides of the device.