US 2647513 A
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All@ 4 1953 A. D. HOLMES 2,647,513
LYOPHILIZATION CONTAINER Filed March 28, 1951 ALAN D. HOLMES INVENTOR ATTOR NEY Patented ug. 4, 1953 LYOPHILIZATION CONTAINER Alan D. Holmes, Oak Park, Ill., assignor to Armour and Company, Chicago, Ill., a corporation of Illinois Application March 28, 1951, Serial No. 217,949
4 Claims. (Cl. 12S-272) My invention relates to containers, and particularly to specially adapted closures and receptacles for drying,l lyophilizing, and storing materials aseptically. My invention relates especially to containers for material which is unstable to heat in the presence of water, and which may be administered with a hypodermic syringe or the like.
My containers may be used in the conventional drying processes employing heat or a vacuum or both. As well as this, my containers are peculiarly suited for use in lyophilizing heat-labile materials such as animal tissue. Lyophilization consists in withdrawing moisture from waterbearing materials under the effect `of a high vacuum and a certain amount of heat. This moisture may be loosely associated in these materials, and it may also occur in more tightly bound forms, such as water of hydration. In a typical lyophilization process, a fresh sample o-f a given heat-labile material is frozen and is then subjected to an extremely high vacuum until the moisture is withdrawn. It is then possible to preserve this material in a dry atmosphere for a long period of time without appreciably impairing its desired activity. This lyophilic material may be utilized as needed either in dry form or in solution.
` An important object of my invention is the provisio-n of an improved container, susceptible of l economic manufacture, in which material may be either dried or lyophilized under reduced pressure and if desired, in an aseptic area. Another object of my invention is the provision of a container of this type having a single opening which may be partly covered by a closure so as to prevent the entrance o-f foreign contaminants and yet to permit the exit of gases and vapors during evacuation of the container atmosphere. Still another object of my invention is the provision of a container of the kind referred to, having a dispensing zone into which a hypodermic needle or the like may be unerringly inserted and from which liquid contents may be completely withdrawn without waste.
A specific embodiment of my invention is illustrated in the accompanying drawing wherein:
Fig. 1 is a side view of a receptacle and a cover having spacing means and aligning projections, showing the cover supported on the receptacle in a position suitable for evacuation;
Fig. 2 is a side view of the cover, and a vertical section of the receptacle and a collar-and-cap assembly showing the container in a position suitable for storage; and
Fig. 3 is a side view of the cover and a` hypodermic-type needle, and a vertical section of the receptacle and an inner collar showing the container in a position suitable for Withdrawal of the contents.
Referring now to the drawing, numeral I0 designates a receptacle provided with a neck-portion I I having a cylindrical wall. The top of the neck-portion II has an opening I2 bounded by a flange I3 which is disposed in a plane at right angles to the vertical axis of the receptacle II). The receptacle It may take any convenient shape or form, while the neck-portion II of the receptacle I0 is desirably cylindrical in shape. A material such as glass or clear plastic is suitable for the construction of receptacle Ill.
The numeral I4 refers to a closure structure which includes a flexible disc-like cover I5, a number of spacing knobs I6, aligning projections I'I, an inner collar I8, a cap 2|, and an outer collar 22.
The cover I5 is desir-ably flexible and resilient and yet is sufficiently firm so as to maintain a disc-like shape when placed upon the receptacle I0. When placed loosely on the receptacle ID, the cover I5 serves as a shield or dust-cap for the opening I2, and when pressed toward the receptacle II), the cover I5 engages the flange I3 and closes the opening I2.
The knobs I6 are disposed in a suitable position between the cover I5 and the flange I3 so as to space the cover from the flange. Preferably, these knobs I 6 are made of a collapsible material such as live rubber or material having like characteristics and are sufiiciently bulky and firm so as to support the weight of the cover I5 and its aligning projections I'l, yet are thinly constructed so that they may be collapsed to a substantially iiat position by a downward force greater than the weight of I5 and I'I. When the cover I5 is placed in a position over the opening I2, the knobsv I6 engage the flange I3, support the weight of the cover I5 and its projections I'I, and prevent I5 from seating iiatly onto I3. In this position air space is provided between the bottom surface of I5 and the top surface of I3, so that the interior of the receptacle I0 is in open communication with the atmosphere surrounding the container. When the cover I5 is urged toward the receptacle I0 by a suiciently strong exterior force, the knobs IG collapse, the cover I5 moves toward the receptacle I0, conforms itself over the collapsed knobs I6 onto the ange I3, and closes the opening I2 in the receptacle I. An equivalent result is obtained if the knobs IB aremade rigid and incompressible and if the cover I5 is made sufficiently pliant and flexible so that it may yield to a downward force and conform itself about the knobs I6 and onto the flange I3.
It is important to provide spacing means such as the knobs IG. The spacing means may be of either solid or hollow construction and may have a variety oi shapes. For example, vit 'may take the form of a hollow hemisphere or a thin strip but is not limited to these specific shapes.
Aligning projections Il, equally spaced fat points equidistant from the center of the bottom surface of the cover I5, are attached to, and extend down lengthwise fro-in, the bottom :of
from each other so that when inserted within the opening I2 of the receptacle IE5 they Isl-id'ably engage the cylindrical wall of the neck-portion II and prevent lateral movement of the cover I5. In this position a channel I2a, defined by the Ywalls of the projections Il and fthe wall of the neck-portion il, is provided within the ropening It. it will be seen 4that :an equivalent `embodiment of these projections iis a single cylindrical plug adapted to ll the zone within Vthe -neok-portion II except Ifor a vertical channel bounded on one side by the wall of .the neck-:portion IzI. This channel I2@ serves Aa's an yout-let passage during vevacuation and also provides a sone into which the contents may now during the dispensing stage.
The in-'ner fcolflar I3 engages the cover VI5 and the ila-nge i3 'and holds ythe 'cover I5 ilat upon the -lange I3 with suc'e'nt force to lseal the opening TIE in the receptacle ill'. The inner 'collar Iil desirably is provided with an aperture I9 adjacent the center of the top surface of thecover I5. The visible portion of the cover I5 seen through the aperture .t9 may be :punctured with 'hypodermic needle 2D which may be thrust into an open zone within the container between or a'inong the projections kI The larca of the cover I5 outlined by the aperture i9 i's purposely arranged opposite an open zone with-ih the container so that 'when the 'cover I5 is punctured vertically at a point lwithin this area, it is virtually impossible to Acontact `the .projections H, the lange I3, vor the neck-portion II. 1n the case 4of a cover l5 having a single projection of the plug type referred to above, the needle 1may be inserted into the vertical channel.
vIn vthe embodiment 'of the invention shown in the drawing I provide the cap 2i and the outer collar 22 for lmy container. The cap 2I Icovers the aperture t9 and slidably engages the sides oi the inner collar iii. This cap 24 serves to protect the lcove-r 'I5 from 'accidental rupture. The outer collar 22 engages the cap 2i 'and the inner collar I8 and 4prevents the 'cap 2I from sliding -o the inner collar I8. The outer collar 22 also serves to strengthen the .seal and protect the inner seal members. The outer "collar 22 maybe provided with a 'tear strip which may be easily detached so as to permit the ready removal of the :collar 22 from .the container.
While I prefer to 2fabricate the cover I5, kh'obs I6 fand aligning projections Il from a single piece of live rubber stock, any suitable material may vserve for the construction of "I5 and II. The inner collar I8, cap EI and 'outer collar 22 may be made of a pliable metal or a plastic material.
In operation, I place the `cover I5 over the -fopening I2 in receptacle `Ill containing a subystance which is to vbe dried or lyophilized. This :is accomplished by inserting the yaligning projec- 4 tions I1 downward within the opening I2 until the knobs I6 engage the ange I3. The aligning projections I1 loosely contact the wall of the neck-portion II and serve to center the cover I5 over the opening I2. In this position the weight of the cover I5 is supported by the knobs I5 which bear upon the flange I3 and provide an .air ULSoe between -I5 and l3. Although the cover I5 spaced from the flange I3 sufficiently far to permit the passage of eiTluent vapors, yet it is disposed suiiiciently close to the ilange I3 so as toeiectively imp-ede dust, airborne bacteria, and Jthe like rom entering the receptacle I0 by "way of :the opening 12.
The assembly .shown in Fig. 3 is then placed in a suitable eva-cating chamber and subjected to A.a sustained .high vacuum. As a result, the water associated with the substance within the receptacle I0 vaporizes or sublimes and passes between the projections Il through the opening I2 in the receptacle I-G and out of the container by way o-f the passage between the cover yI and the flange I-3` Thisevacuation step is continued `until .the desireddegree of desiccation is attained, at point the vac-sum is broken by introducing ,-aifr within the chamber. Ifatmospherie pressure is krestored withinth'e Chamber rapidly, the sudden surge of incoming air forces the :cover 'I5 down onto the ange I3 thereby collapsing .the Ispacing knobsA .-l'i and sealing the opening I2 .in the receptacle I0. At this point, the pressure within .the container is subatmos- Vpheric, with the result that the cover I5 is constantly beingpressedl down and held firmly by .the pressurediiierential. The cover I5 remains in t'is positionr-aslong as thepressure differential is maintained. If atmospheric pressure is restoredwithin .the chamber'slOWIy, air enters the receptaclel I0 `by vway of the space afforded by the lknobs IS and the aligning projections I 'l until the` pressure 'is uniform uthroi'lghout the chamber .and the receptacle I 5.
l Material which is to v'be lyoph'ilized, rather than merely dried, is first frozen in order to preserve its ractivity andstrii'cture and, inadvertently, of the material is sometimes -frozen Vonto the .ang'e I3 :or the adjacent 'parts of 'the cover I5. When this occurs with a container which is ynot provided with spacing knobs I6, the cover g5 occasionally is .frozen 'Shut upon the opening a consequence, such a container cannot be smoothly evacuated, ii at Aall, until the cover I5 'thaws fout 'so that air within the 'container can move out 'into the vacu'urn Zone. ln these cases ywhen the cover 'I5 'does thaw, the air is sometimes released with almost explosive violence, and material within 'the receptacle IG is often carried out 'by 'the air and lost. I The purpose of the knobs 'I5 is t'o avoid these ill e'iiects by spacing the cover I5 from the flange I3 so that this undesirable pressure differential is not established. v
After air has been introduced intothe receptacle 'I0 containing the dried material, the inner collar It is t't'ed over the cover 'i5 and flange I3. rThis collar I8 is pressed downward 'upon the cover I5 'so as 'to sealthe opening "I2, and is held this position by lcriiiflping the lower portion of the .collar .i8 Under tlie ange I3. Here, the cover rfili nia'y .advantageously serve as a gasket. Of course, a tight seal may be undesirable for 'certain purposes, and in these cases it would be yadvisable to .fasten the inner collar l1 loosely as lwitha.-loose, partial crimp or without the gasket effect. The cap 2i is placed upon the inner collar I8, and in turn the outer collar 22 is placed upon the cap 2i so as to envelop the exposed surfaces of the cap 2I and the collar I8. The outer collar 22 is held in position by crimping its lower portion under the flange I3. The container may now be held in storage.
The contents of my container are removed through the cover I5 with a hypodermic needle 20 and syringe. In order to expose the cover` I5 for injection, the outer collar 22 and cap 2| are removed. After the collar 22 has been removed, the cap 2l readily slides off of the inner collar I8 and exposes the top surface of the cover I5 through the aperture I9 in the collar I3.
The hypodermic needle 2Q is inserted through the cover I5 and a suitable solvent is injected within the receptacle I9 so as to dissolve the contents. When the material has dissolved, the container is inverted and the liquid is withdrawn through the needle 29. In draining to the tip of the needle 29 the liquid is free to move between the aligning projections I'I to the surface of the disc-like cover I5. When the bottom surface of the cover I5 is held in a horizontal position, substantially all of the liquid may be withdrawn conveniently and without delay.
Other modications of my container as herein described, all within the spirit of my invention, will readily occur to those skilled in the art.
1. A container comprising a receptacle having a neck-portion provided with an opening bounded by a flange, a cover for said opening, spacing means disposed between said cover and flange to provide an air passage therebetween, said spacing means being collapsible to permit closing of said opening when said cover is pressed toward said ilange, and means projecting from said cover to align said cover over said opening, said aligning means extending at right angles from said cover into said opening and neck-portion, said aligning means providing a channel within said neckportion for the free passage of material into and from said receptacle, said channel communicating with at least part of said opening whereby said channel is in open communication with said air passage when said cover is spaced with respect to said flange.
2. A container comprising a receptacle having a neck-portion provided with an opening bounded by a flange, a cover for said opening, spacing means disposed between said cover and ange to provide an air passage therebetween, said spacing means being collapsible to permit closing of said opening when said cover is pressed toward said flange, and a plurality of projections extending at right angles from said cover into said opening and neck-portion, said projections providing a channel within said neck-portion for the free passage of material into and from said receptacle, said channel communicating with said opening whereby said channel is in open communication with said air passage when said cover is spaced with respect to said flange.
3. A container comprising a receptacle having a neck-portion provided with an opening bounded by a flange, a cover for said opening, spacing means disposed between said cover and flange to provide an air passage therebetween, said spacing means being collapsible to permit closing of said opening when said cover is pressed toward said flange, means projecting from said cover to align said cover over said opening, said aligning means extending at right angles from said cover into said opening and neck-portion, said aligning means providing a channel within said neck-portion for the free passage of material into and from said receptacle, said channel communicating with at least part of said opening whereby said channel is in open communication with said air passage when said cover is spaced with respect to said flange, and a collar to engage said cover and flange and adapted to press and to hold said cover upon said flange.
4. The container as in claim 3 wherein said collar has an aperture adjacent the top surface of said cover to permit the insertion of a hollow needle through said cover.
ALAN D. HOLMES.
References Cited in the le of this patent UNITED STATES PATENTS Number Name Date '718,659 Ruin Jan. 20, 1903 1,587,167 Marsden June 1, 1926 1,770,057 Anderson July 8, 1930 2,222,371 Nesset Nov. 19, 1940