US3337041A

US3337041A - Layered lyophilized product in a disposable syringe

Info

Publication number: US3337041A
Authority: US
Inventors: Charles W Damaskus
Original assignee: Individual
Current assignee: Individual
Priority date: 1965-10-23
Filing date: 1965-10-23
Publication date: 1967-08-22
Anticipated expiration: 1984-08-22

Description

22, 1967 c. w. DAMASKUS 3,337,041

BLE SYRINGE LAYERED LYOFHILIZED PRODUCT IN A UISPOSA I 2 Sheets-$heet Filed Oct. 23, 1965 1967 c. w. DAMASKUS 3,337,041

LAYERED LYOPHILIZE'D PRODUCT IN A Filed Oct. 23, 1965 DISPOSABLE SYRINGE 2 Sheets-Sheet United States Patent Office 3,337, 64. 1 Patented Aug. 22, 1967 3,337,041 LAYERED LYUPHILIZED PRGDUCT IN A IDKSPUSABLE SYRHNGE Charles W. Damaskus, 703 Madison, La Grange, ill. 60525 Filed Oct. 23, 1965, Ser. No. 5i 3,224 9 iClaims. (Cl. 20663.2)

This invention relates to pharmaceuticals, and to methods and apparatus for dispensing pharmaceuticals, and concerns particularly a novel pharmaceutical package particuarly adapted to facilitate the making of a pharmaceutical solution, and the administering thereof to a patient.

In the administering of pharmaceutical solutions, as for example intravenous post-operative injections, two methods are now commonly employed. In accordance with one commonly used method, a special container is used, containing in dry form the pharmaceutical or the medicine to be administered. Such special container is provided with a special penetrating point adapted for cooperation with a special stopper of a second container filled with a liquid solvent or the like, so that by an exchange of the liquid between the containers the dry pharmaceutical may be reconstituted and subsequently administered, as for example by use of a standard syringe. The disadvantage of the foregoing is that special apparatus, and special techniques and procedures are required, frequently requiring special instruction of operating personnel.

A second method now employed involves the use of andard containers and a standard syringe throughout, which, while employing standard apparatus and techniques, is generally cumbersome and slow in operation.

In accordance with the present invention, maceutic-al package is prepared, erally standard syringe, within which is pharmaceutical, preferably in layered lyophilized form. The unit is so arranged that the pharmaceutical may be readily reconstituted within the syringe, by manipulation of the syringe in accordance with standard techniques, and the reconstituted pharmaceutical thereafter administered to a patient, again by manipulation of the syringe in accordance with standard techniques, tire operation may be carried out by personnel using standard techniques with which they are familiar, but also in a rapid and facile manner. Preferably the package is so constructed that its sterility is preserved and insured, and the reconstitution of the pharmaceutical is facilitated 'so that in most instances it may be substantially instantaneous.

Preferably, but not necessarily, the dry pharmaceutical within the syringe, and comprising the novel package of the present invention, may be in layered lyophilized form, and prepared in accordance with the general method set forth in the application to Charles W. Damaskus and James E. Alder, Ser. No. 487,109, filed Sept. 14, 1965, and now issued as Patent No. 3,269,905, dated Aug. 30, 1966.

An object of the present invention is to provide a novel pharmaceutical package, comprising in part, a syringe of generally standard structure, and a pharmaceutical contained therein, in dried readily reconstitutable form.

A further object of the invention is to provide a novel pharmaceutical package of the type defined, wherein the contained pharmaceutical is in layered lyophilized form.

A still further object of the invention is to provide in a pharmaceutical package of the type defined, improved means forinsuring and maintaining the sterility of the package, and means for facilitating the reconstitution of the pharmaceutical material.

Another object of the present invention is to provide a whereby the ena contained dry pharmaceutical, and administer the reintravenously to a patient.

Various other objects, advantages and features of the invention will be apparent from the following specification when taken in connection with the accompanying drawings, wherein a preferred embodiment of the invention is set forth for purposes of illustration.

In the drawings, wherein like reference numerals refer to like parts throughout:

FIG. 1 is an exploded view of a syringe structure forming a part of the novel pharmaceutical package hereof;

FIG. 2 is a longitudinal sectional view of the syringe structure of FIG. 1, on an enlarged scale, showing the pharmaceutical package in completed form, prior to use;

FIG. 3 is a longitudinal sectional View, similar to FIG. 2, but showing the syringe structure as used during the reconstitution of the dried pharmaceutical, and in association with a diluent vial;

FIG. 4 is a partial detail view of the outlet end of the syringe, in association with an injection needle, as used in the administering of the pharmaceutical or medi cine to a patient; and

FIGS. 5 and 6 show alternate methods of reconstitution.

Referring more particularly to the drawings, and first to the exploded view, FIG. 1, there is illustrated an essentially standard syringe structure comprised of a cylinder 10 and a piston 12. The cylinder has an enlargement or flange 14 at its upper end, the lower end of the cylinder being tapered to provide cylindrical portions 16 and 18 of successively smaller size. The cylinder member 10 may also be provided, along its length, with an intermediate flange or stop portion 20, the purpose of which will later be more particularly described.

Referring further to FIG. 1, it will be seen that the piston member 12 preferably has a flange portion 22 at its upper end, the piston proper of the piston member being formed at the lower end thereof, as indicated at 24. The piston body may preferably be formed as a plurality of radially extending wings 26, as is conventional, there being four such wings illustrated in the present embodiment. As will be understood, the piston 24-, and wings 26, are adapted to have sliding fit within the cylinder member 10, in the use of the structure.

Preferably the syringe structure, comprising the body member 10 and piston member 12, may be formed of glass or low cost plastic, providing a single use disposable structure. As will be understood, however, the piston member or portion 24 is preferably formed of rubber, so that it will have a proper compressible slidable fit within the cylinder lit), in the use of the structure.

The syringe structure further preferably comprises a cap member 26 and a pin member 28 of any suitable material, also shown in FIG. 1, and the purpose of which will be presently described.

Referring to FIG. 2, it will be seen that the pharmaceutical package of the present invention, comprises not syringe structure, but also pharmaceutical material contained therein, such pharmaceutical preferably being in dry lyophilized form, and preferably, in the case of multiple component pharmaceuticals, in layered lyophilized form, produced by layered freeze-drying techniques, as more particularly set forth in said Damaskus and Alder patent application to which reference has hereinbefore been made.

By way of example, the pharmaceutical package, in the particular illustrative embodiment herein set forth,

iay comprise a multiple vitamin composed of a loweriost layer 30 of B complex, an intermediate layer 32 of itamin C or ascorbic acid, and a superposed or upperiost layer 34 of vitamin B In forming the pharmaceutical package, in accordnce with the present invention, and in accordance with 1e techniques as set forth in said Damaskus and Alder atent application, the pin 28 is first fitted into the lower- ."iOSt cylindrical end 18 of the syringe body into the |osition as shown in FIG. 2, with the knob or handle lOItlOIl 36 of the pin in engagement with the lowermost .nd of the portion 18. The pin 28 which may be metal )r plastic is adapted to have relatively tight sliding fit vithin the outlet portion 18 of the syringe body member, as to provide a seal therewith, when the pin is in as- ;embled position as shown in FIG. 2. Preferably the lower and of the syringe outlet 18 is sterilized, and the pin nandle portion 36 may be immersed within a sealing soluzion, such for example as wax, whereby to provide a fluid-tight and hermetic sterile seal.

With the pin 28 in assembled position, as shown in FIG. 2, and with the syringe body member upright, and the piston member 12 removed, a body of sterile water may first be poured into the syringe as indicated at 38 in FIG. 2. This water is then frozen to form an ice pellet. Thereafter a liquid solution of B complex is poured into the syringe body, and frozen, to form the layer 30 of the complex. Thereafter a solution of ascorbic acid is poured onto the frozen layer 30, and itself in turn frozen to form the frozen layer 32 of vitamin C. Thereafter a solution of vitamin B is poured onto the frozen pellet or layer 32 of vitamin C to form the layer 34, which layer is then also frozen to form an ice pellet or superposed layer of vitamin material. The entire syringe body is then subjected to lyophilization, or freeze-drying techniques, as set forth in said Damaskus and Alder patent application, whereby to provide the vitamin material in freeze-dried form, and specifically in layered lyophilized form whereby to provide a product having a long shelf life with maintained stability and potency, and minimum deterioration and interaction between the component parts of the product. During the freeze-drying operation the ice pellet 38 evaporates leaving a space below the lowermost vitamin layer 30, and between such layer and the outlet end 13 of the syringe body.

After completion of the foregoing, may be applied to the lower end of shown in FIG. 2, for further protection, and the piston member 12 inserted into the syringe body, partially along its length, into the position shown in FIG. 2. In such position, it will be seen that the piston member 24 is brought into abutting relationship with the uppermost end of the pin 28, and the piston cannot be further projected without disrupting the position of the pin. Thus when the doctor or nurse receives the package, in the form shown in FIG. 2, if the pin 28 has not been disturbed, it is insured that the piston 24 has not been projected beyond the position shown in FIG. 2, whereby the sterility of the inner wall of the syringe body, below the piston, is insured. The parts above the piston 24, in the subsequent use of the apparatus presently to be described, normally do not come into contact with the pharmaceutical product to be administered. Thus pin 28 provides an indicator for the maintained sterility of the product.

Referring to FIG. 3, the parts are shown in the position occupied during thereconstitution of the pharmaceutical product. More particularly, the cap member 26 and the pin 28 have been removed, and the lower end of the syringe body has been projected into a container 38, preferably containing a quantity of saline solution, or other solution or liquid for reconstituting the dried pharmaceutical product within the syringe body.

As shown in FIG. 3, as the piston plunger 24 is projected downwardly, and then withdrawn, the reconstitution liquid is drawn from the container 38 into the body the cap member 26 the syringe body, as

10 of the syringe. Abutments or stops 39, formed internally of the cylinder 10, provide an upward stop for the piston, and a stop member 20 formed externally of the cylinder optionally may be provided to limit the penetration of the syringe body into the solution or liquidcontaining vial 38'.

It will further be seen by reference to FIG. 3, that the removal of the pin 23 from the structure leaves a passageway 40 extending longitudinally of the syringe through the vitamin layers 30, 32 and 34, whereby to facilitate penetration of the reconstituting liquid into and through the layers of the vitamin product, to facilitate the reconstituting of the product, and effect the reconstitution with a minimum of time.

After the reconstituting liquid has been drawn from vial 38' int-o the body of the syringe, as shown in FIG. 3, the syringe may be shaken or the like to further facilitate the reconstitution of the pharmaceutical product, as 'will be understood, whereupon a standard injection needle, as indicated at 42 in FIG. 4, may be applied to the lowermost outlet end of the syringe body, for injection of the reconstituted pharmaceutical product into the patient, in accordance with standard administering techinques.

Alternate methods of reconstitution are shown in FIGS. 5 and 6. In FIG. 5 the vial 38a is provided with a stopper 44 having an opening 46 for receiving the end 18 of the syringe, said opening being normally closed by a puncturable plastic sheet 48. Upon insertion of the syringe end into the opening 46 and upon inversion of the vial, the syringe piston may be manipulated for reconstitution as before.

In FIG. 6 the needle 42 is applied to the vial prior to reconstitution, and used to puncture the stopper 50 of vial 38b, and withdraws the reconstituted liquid from the vial.

It will thus be seen that in accordance with the present invention a pharmaceutical package has been provided, which is composed essentially of a standard or conventional syringe, and a contained pharmaceutical, so constructed that by the operation of standard syringe techniques a dried pharmaceutical product may be reconstituted, and then administered to a patient in a rapid and facile manner, and by use of techniques well known to operation personnel, without special instruction.

When in layered lyophilized form, the dried pharmaceutical has maximum stability and shelf life, and minimum interaction between the component parts. The pin 28 not only provides an indicator for the maintained sterility of the package, until use, but upon removal also provides a passageway through the dried pharmaceutical product, facilitating the reconstitution operation.

In accordance with the present invention, the pharmaceutical product is packaged directly within an essentially standard syringe, for manipulation of the syringe in accordance with standard techniques, and for low cost disposability after single use.

It is obvious that various specific embodiment set forth and hereinabove referred to, without departing from the spirit of the invention. The invention is accordingly not to be limited to the specific embodiment shown and described, but only as indicated in the following claims.

The invention is hereby claimed as follows:

1. A pharmaceutical package comprising a syringe, said syringe comprising a cylinder having an outlet and a movable piston within the cylinder, a pharmaceutical comprising a body of material in dry form within the cylinder, and a removable pin member within said outlet and projecting through the pharmaceutical body to provide a perforation therethrough whereby upon removal of said pin member and upon manipulation of the piston within the cylinder reconstitution liquid may be drawn through said outlet and through the perforation in said body to facilitate the reconstitution thereof.

2. A pharmaceutical package as in claim 1, wherein changes may be made in the means is provided for hermetically sealing the pin member within the outlet.

3. A pharmaceutical package as in claim 1, wherein the pin member is provided with a handle, and wherein a cap member is provided encompassing the handle and mounted upon the outlet end of the syringe.

4. A pharmaceutical package as in claim 1, wherein the pin member extends longitudinally of the cylindrical syringe body into engagement with the piston When the piston is in withdrawn position, whereby the piston cannot be projected within the cylindrical syringe body toward the outlet end thereof without displacing the pin member.

5. A pharmaceutical package comprising a syringe, said syringe comprising a container and a piston reciprocable therein, said container having a discharge opening, and a pharmaceutical body in dry form disposed within the container, said body being perforated therethrough whereby upon the introduction of liquid into the container through said discharge opening by manipulation of the piston the liquid will be brought into contact with the body and through said perforation to bring the body and liquid into intimate contact for reconstitution.

6. A pharmaceutical package as set forth in claim 5, wherein said pharmaceutical comprises a lyophilized body having an area substantially commensurate with the area of the container chamber and a thickness substantially less than the length of the container chamber to facilitate the reconstitution of said body Within the container.

7. A pharmaceutical package as set forth in claim 5, wherein said pharmaceutical body is in the form of a perforated stratum within the syringe.

8. A pharmaceutical package as set forth in claim 5, wherein the pharmaceutical body is in the form of superposed strata of lyophilized material within the syringe.

9. A pharmaceutical package as set forth in claim 5, wherein stop means is provided on the container for limiting the movement of the piston within the container in a direction away from said discharge opening.

References Cited UNITED STATES PATENTS 1,247,678 11/1917 Hentschel. 1,466,132 8/ 1923 Lippert. 2,195,429 4/ 1940 Shaler. 2,862,616 12/1958 Capozzi et al. 2,982,396 5/1961 Shihadeh. 3,107,785 10/1963 Roche 20643 X THERON E. CONDON, Primary Examiner. I. M. CASKIE, Assistant Examiner.

Claims

1. A PHARMACEUTICAL PACKAGE COMPRISING A SYRINGE, SAID SYRINGE COMPRISING A CYLINDER HAVING AN OUTLET AND A MOVABLE PISTON WITHIN THE CYLINDER, A PHARMACEUTICAL COMPRISING A BODY OF MATERIAL IN DRY FORM WITHIN THE CYLINDER, AND A REMOVABLE PIN MEMBER WITHIN SAID OUTER AND PROJECTNG THROUGH THE PHARMACEUTICAL BODY TO PROVIDE A PERFORATION THERETHROUGH WHEREBY UPON REMOVAL OF SAID PIN MEMBER AND UPON MANIPULATION OF THE PISTON WITHIN THE CYLINDER RECONSTITUTION LIQUID MAY BE DRAWN THROUGH