U.S. patent number 3,756,390 [Application Number 05/232,440] was granted by the patent office on 1973-09-04 for two-compartment aspirating disposable hypodermic syringe package.
Invention is credited to Anthony Abbey, Robert Clayton Squire.
United States Patent |
3,756,390 |
Abbey , et al. |
September 4, 1973 |
TWO-COMPARTMENT ASPIRATING DISPOSABLE HYPODERMIC SYRINGE
PACKAGE
Abstract
A two compartment aspirating disposable hypodermic syringe
package consists of a rupturable partically pre-slit diaphragm
having a fluorohalocarbon polymer film as a primary moisture-proof
barrier across and dividing the syringe barrel into a compartment
containing a dry component and a compartment containing a liquid
component which components are to be mixed at time of use. A
slidable piston in the barrel, on application of pressure, ruptures
the diaphragm, permits mixing of the two components, clearing of
air, aspiration and injection of the contents as the piston passes
over the ruptured remains of the diaphragm.
Inventors: |
Abbey; Anthony (Milltown,
NJ), Squire; Robert Clayton (Dover, NJ) |
Family
ID: |
22873119 |
Appl.
No.: |
05/232,440 |
Filed: |
March 7, 1972 |
Current U.S.
Class: |
206/219; 206/365;
604/87; 604/416; 222/80 |
Current CPC
Class: |
A61M
5/284 (20130101); B65D 81/3255 (20130101); A61M
5/286 (20130101); A61M 2005/3104 (20130101) |
Current International
Class: |
A61M
5/28 (20060101); B65D 81/32 (20060101); A61M
5/31 (20060101); B65d 025/08 (); B65d 081/32 () |
Field of
Search: |
;206/47A,63.2R,43
;220/20.5 ;128/218M,272 ;222/80 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Dixson, Jr.; William T.
Claims
We claim:
1. A combination aspirating hypodermic syringe and two compartment
package adapted for storage of separate liquid and solid components
of medicaments with internal mixing of the two components to form a
single injectable liquid at the time of use, with effective
protection of the solid component from the effects of moisture or
other components in the liquid compartment during storage, and
which maintains sterility during mixing comprising:
a generally cylindrical barrel having a holding flange and at the
front end a transverse wall means and
transversely of the barrel and in liquid tight relationship
therewith, a pressure rupturable plastic dividing diaphragm
consisting of at least one film of a material having a high
resistance to the permeation of moisture with weakening slits cut
into the diaphragm to form cut zones of weakness, which are readily
ruptured by liquid operating pressure at the time of use, and which
are geometrically small so that the moisture permeation through the
slits is over a small area and the predominant area of the
diaphragm is much thicker with a correspondingly high moisture
impermeability, whereby during storage the thicker film retards the
diffusion of moisture over the major area of the diaphragm, and the
thin slits form a readily rupturable zone of weakness,
a flexible piston in the barrel, in a part of the barrel on the
opposite side of the diaphragm from the transverse wall means, and
in cooperation therewith forming a liquid compartment, flexible
sealing rings on the piston to contact the walls of the barrel,
which rings are sufficiently flexible to slide readily over and
past the diaphragm after rupture, while maintaining a liquid tight
seal with the walls of said barrel,
a filter adjacent said transverse wall to filter out and prevent
the injection of fine solid particles,
a solid medicament in soluble form in the front compartment for
solids formed by the barrel between the diaphragm and the
transverse wall means and,
a liquid component in the liquid compartment formed by the barrel
between the diaphragm and the flexible piston,
whereby at time of use pressure on the piston transmitted to the
liquid behind the diaphragm ruptures the diaphragm and displaces
liquid from the rear of the diaphgram into the solid containing
chamber in front of the diaphragm whereby the liquid and the solid
can be mixed, the solid dissolved in the liquid by shaking, air
expelled by pointing the needle end upwards and expressing any air
and foam until a clear liquid is ob-tained, and which assembly
permits aspiration on insertion into the subject.
2. The package of claim 1 in which the barrel comprises two
telescoping pieces, and the diaphragm is sealed across one end of
one of the pieces, to provide a liquid tight seal of the diaphragm
to the one such piece, and in telescoping, mechanical stress on the
barrel is transferred without stress or strain on the
diaphragm.
3. The package of claim 2 in which the front compartment barrel has
a shoulder and enlarged rear portion to concentrically receive and
retain the liquid compartment in hermetically sealed
relationship.
4. The package of claim 3 in which the diaphragm is sealed
liquid-tight to both the front and rear compartments.
Description
BACKGROUND OF THE INVENTION
In the treatment of humans and animals there are many medicaments
to be injected hypodermically which are not storage stable in the
form in which they are to be injected. In many cases, the
medication to be injected can be prepared at the time of use by
mixing a storage stable dry component and a storage stable liquid
component. Sometimes the liquid component contains only water,
other times it is water with therapeutic components, synergistic
components, solubilizing components, pH control components, or
other elements. For the storage of such medication it is desirable
that the shelf life be at least 1 and preferably 5 years at ambient
room conditions of temperature and humidity. Shorter storage-life
packages are only acceptable where the longer storage time cannot
be economically attained.
As the package is a single use device, making but one trip from the
manufacturer to the point of use, after which the container is
discarded, it is desirable that the package have a maximum of
product security, a maximum of convenience in use, and a minimum of
cost.
These requirements are in part inconsistent and as a result there
are many patents and commercial products representing compromises
between the various requirements. One such U.S. Pat., of common
assignment, is No. 3,161,195, Taylor and Sandhage, TWO-COMPARTMENT
ASPIRATING HYPODERMIC SYRINGE, Dec. 15, 1964. This patent describes
some of the prior art, some of the problems and some of the
expedients which are used. Reference thereto and incorporating by
reference is hereby made. U.S. Pat. No. 3,161,195 shows various
methods of attaching a needle to the front of the package and
various methods of packaging the needle assembly in the operating
plunger. Such expedience may be used with the present package and
such combinations are within the concepts of the present
invention.
Other conventional needle attaching and puncturing mechanisms may
be used, as may various carrier assemblies for temporarily or
permanently storing the hypodermic needles with the package.
It has now been found that two compartments may be formed by
dividing a hypodermic syringe barrel by a diaphragm of a pressure
rupturable plastic having at least one layer of a film of a
fluorohalocarbon plastic which has an extremely high resistance to
water and water vapor and which diaphragm is effectively sealed in
moisture proof configuration with the walls of the barrel.
Conveniently the barrel is formed in two parts which are in
telescoping relationship with the diaphragm being sealed across the
end of one of the telescoping sections.
The barrels may be formed of glass or plastic but most conveniently
and economically are formed from a translucent or transparent
plastic such as linear polyethylene or isotactic polypropylene
which is strong, inert to nearly all types of medication, liquid or
solid, and is economically worked and formed. Polystyrene,
polymethylstyrene, polycarbonates or different plastics or plastic
and glass may be used for the different elements. But from the
standpoint of cost of raw materials and the cost of manufacture,
the polyethylenes and polypropylenes are presently particularly
economically advantageous.
In forming, the front part of the barrel is conveniently formed
with a transverse wall means closing the front end of the barrel
with either an integral needle or needle attaching means, and very
slightly tapered walls, for a solid compartment; and an offset and
larger coaxial section for the fitting of the inner telescoping
portion of the barrel containing the liquid. A puncturable member
may be incorporated at the needle attaching end in order to seal
the front end of the front compartment during storage. Conveniently
a needle attaching hub is used with a cap over th needle attaching
hub giving a moisture proof seal. A filter is conveniently
installed in the front of the barrel adjacent to the liquid
discharge tip bore to filter out any solid particles or portions of
the diaphragm which may be broken loose.
Telescoping part way or all the way into the enlarged rear portion
of the front chamber is the compartment adapted to contain the
liquid. The diaphragm is conveniently sealed across the front end
of the rear compartment and with the telescoping relationship,
essentially no stress or strain is placed on the diaphragm to
barrel wall assembly and hence compromise during shipment and
storage is minimized. A conventional flexible piston having sealing
rings is incorporated in the end of the barrel adjacent the liquid
and conveniently seals the liquid compartment without air space.
The plunger assembly to drive the piston may be of any convenient
cross section but conveniently is either a X cross-section for
mechanical strength or hollow and adapted to contain the hypodermic
needle. The hypodermic needle may be in a sterile package so that
it may be removed and attached to the front end of the package
without compromising sterility. This method of attachment and the
techniques involved are conventional.
Conveniently, but not essentially, the entire barrel assembly has a
slight taper and is larger at the rear than at the front. A taper
of a few thousands of an inch on the diameter permits a draft in
the molding operation so that the molded assemblies may be more
easily removed from the mandrel. A taper of about 0.005 inch per
inch and, molding manufacturing tolerances are with in the sealing
characteristics of the flexible sealing rings on the piston and
permit economical manufacture.
The characteristics of the diaphragm are such as to insure the
permeation of a minimum of water. Many plastics pass water or water
vapor when in thin sheets. Plastics of th fluorohalocarbon series
such as ACLAR, sold by Allied Chemical Company, have a
comparatively slow water vapor transmission rate. The water
transmission rate is commercially specified as 0.025 grams per mil
per 100 square inch per 24 hours. A Mylar polyester film has a
water transmission rate of from 200 to 400 times as great. Low
density poly-ethylene has a water transmission rate approximately
30 times as great as the fluorohalocarbon film. The polyvinyls,
polystyrenes and cellulosic films are also comparatively high in
their water vapor transmission. Additionally the fluorohalocarbon
film has a tensile strength of one-third to one-half of that of
Mylar a Mullen Burst strength of around one-third of that of Mylar
and a much lower impact strength. These characteristics permit
forming a highly water resistant but readily mechanically
repturable seal.
Sealing of the diaphragm to the front of the rear portion of the
barrel is accomplished in conventional ways. Among the more rapid
and convenient methods is the use of an ultrasonic seal in which
either an annular mandrel is used, or a point energy source, which
is rotated with respect to the seal, so that ultrasonic energy is
concentrated along the area of contact between the diaphragm and
the end of the barrel. The diaphragms are cut to size, placed in
contact with the rear barrel portion, and as ultrasonic energy is
concentrated on the seal area, the discontinuity of an unsealed
portion causes the reflection and refraction of energy resulting in
intense local heating which fuses the two portions together. Once
fused the energy can pass through and heating is reduced. This
inherently gives a particularly effective type of seal. Ordinary
heat sealing systems may be used with the heating elements shaped
to fit the seal area. The diaphragm may be adhesively united to the
barrel.
Because of the nature of the usage it is essential that highly
reliable seals be formed.
An alternative configuration is to form a cap of the laminate film
so that the side walls of the cap slide over the end of the barrel
which gives a larger area for sealing of the laminate to the
barrel.
In use, as the barrel portions telescope with respect to each
other, any stresses and strains are transferred from barrel portion
to barrel portion and do not pass through the diaphragm itself. The
telescope portions can be held to each other with a clip or clamp
or may be adhesively united or heat or ultrasonically sealed to
each other. Alternatively, after assembly, by using heat or
ultrasonic techniques, the barrel portions can be sealed to each
other and also the diaphragm, to give a unitary seal so that in
effect the two barrel portions and the diaphragm are a single
monolithic piece.
The choice of methods of assembly and techniques to be practiced
vary in part with the size of the run, the equipment that is
available, and the characteristics of the two components.
Sterility against contaminants is mandatory in hypodermically
injected medications.
If the solid component can stand the cycle, the solid component may
be filled into its compartment under non-sterile conditions and
sterilized by the use of heat, radiation or a sterilizing gas such
as ethylene oxide, sufficiently diluted with carbon dioxide or
other inert gas as to avoid an explosion hazard. The two portions
of the barrel can then be assembled to each other under sterile
conditions and the liquid compartment filled and the piston
implaced using sterile techniques and sterile components.
Alternatively at times, the assembly may be made under non-sterile
conditions and sterility achieved by the use of radiation as for
example by cobalt 60 beta rays. The effect of radiation, such as
the beta rays or X-rays, on the packaging materials must be
considered. With some materials even intense radiation during the
sterilizing cycle can be used to aid in sealing components together
as for example, sealing the diaphragm in to the barrels. With
particularly rugged materials, heat sterilization is acceptable.
Often with medications which require separate solid and liquid
components, the medication may be adversely affected by a heat
sterilizing cycle.
Another method of assembly is to assemble the diaphragm into the
barrels and the barrels to each other and sterilize the assembly
with the solid component being fed as a powder subsequently through
the hole in the needle hub after which the hole is capped, with
sterility being attained by ethylene oxide, or other procedures,
and the complete assembly being inverted and the liquid compartment
sterilely filled with liquid and the piston emplaced. Such methods
of assembly are within the contemplation of utilization of the
present invention. The filling and sterilizing cycles must be
chosen with due respect to the characteristics of the medication
and the materials of construction of the container.
Without being restricted thereto the present invention is
exemplified and shown in the following examples and the
accompanying drawings in which:
FIG. 1 is a cross section of a flat diaphragm with a fully
telescoped liquid compartment.
FIG. 2 is a cross section of a cap diaphragm with a short
telescope.
FIG. 3 is a diagrammatically exploded view showing the various
components in section for assembly into the package of FIG. 2.
FIG. 4 is an embodiment in which the diaphragm cap fits in the
valve walls with a protective sleeve over the joint between the
barrel sections.
FIG. 5 is a view showing the partially slit cap diaphragm.
FIG. 6 is a partially broken away view showing a flat
diaphragm.
FIG. 7 is a cross section of a diaphragm showing the partial
scoring of a three layer laminated diaphragm.
In the embodiment shown in FIG. 1, a cylindrical barrel 11 of
polyethylene has a transverse end wall 12 which wall has a needle
tip formed integrally therewith and adapted to fit a standard
hypodermic needle hub. Over the needle tip 13 is fitted a
protective tip shield 14 having a bore pin 15 which fits into the
tip bore 16. A filter 17 which may be woven or felted or paper
stock with a thin reinforcing rim is placed against the transverse
wall to filter out and prevent the injection of any fine solid
particles which may find there way into the assembly.
The rear of the cylindrical barrel is enlarged to form a concentric
coaxial external telescoping barrel 18. A finger flange 19 is
formed integrally with the rear of the external telescoping barrel.
Inside of and cooperating with the external telescopic barrel 18 is
the internal telescoping barrel 20 which fits snuggly into and is
held by the external telescoping barrel 18. A retaining flange 21
on the rear of the internal telescopic barrel fits adjacent to the
finger flange 19 and is held thereto by an annular clip 22.
Across the front of the internal telescopic barrel 20 is a
diaphragm 23.
An enlarged view of the diaphragm 23 is shown in FIGS. 6 and 7. One
configuration as shown in FIGS. 6 and 7 consists of a
poly(chlorotrifluoroethylene) film 24 laminated on each side to
polyethylene layers 25. The polyethylene layers have score marks 26
over the major portion of their surface. The diaphragm is such size
as to fit against and close to the end of the internal telescoping
barrel. It is sealed thereto using an ultrasonic generator and a
mandrel which is of such size and shape as to give annular seal
around the entire external periphery of the diaphragm as it
contacts the end of the internal telescoping barrel 20. Preferably
the score marks do not extend to the sealed portion or if they do
extend to the seal areas, are obliterated during the sealing
operation thereby giving a reliably liquid tight seal.
The thickness of the diaphragm is such that it may be readily
ruptured by liquid pressure during mixing prior to use. One
convenient size is to have an internal diameter of about one-half
inch with the poly(chlorotrifluoro-ethylene) layer about 0.001 inch
thick, and each of the polyethylene layers about 0.003 inch
thick.
Th poly(chlorotrifluoroethylene) may range in thickness from about
1/2 thousandth inch to about 11/2 thousandths inch in thickness.
For larger syringes a thicker layer and for smaller syringes a
thinner layer is convenient. As the polyethylene layers are scored
their thickness does not markedly affect the pressure required to
rupture.
The complete diaphragm though needs to be thin enough so that when
ruptured it will lie against the walls of the barrel without
interfering with free passage of the piston 27.
In the barrel is a piston 27 having sealing rings 28 thereon,
attached to a stem 29. The piston and stem are conventional in the
hypodermic package art. The piston is conveniently formed with a
recess into which the end of the operating stem is inserted
although detachable screw connections or integral connections may
be used. The piston is conveniently of rubber either natural or
synthetic and the sealing rings give a higher bearing pressure over
a small area for low friction seal to the barrel walls.
Conveniently but not necessarily the entire barrel assembly tapers
slightly so that the front of the barrel is a few thousandths of an
inch smaller in diameter than the rear of the barrel which permits
a draft in the mandrel on which the plastic barrel parts are
molded. The flexibility of the sealing rings compensates for any
minor irregularities from either designed or accidental size
variations in the barrels and also permits the piston sealing rings
to pass over the residues of the ruptured diaphragm in the
barrel.
While not part of the container assembly, as a package, the
container has therein a solid medicament 30 in the compartment
formed by the transverse wall, the cylinder barrel 11 and the
diaphragm 23 and has a liquid component 31 in the compartment
formed by the diaphragm, the internal telescoping barrel, and the
piston. It is not necessary that either compartment be full.
Conveniently the solid medicament is a finely powdered material
such as powdered chlortetracycline or a powdered vitamin mixture
and the diluent is either water or a saline solution of a liquid
mixture of vitamins. Preferably the medicament is in such finely
divided form that if moisture leaks in through either the tip
shield or past the diaphragm or around and between the internal and
external telescoping barrels, the medica-ment is discolored, and
gives warning to the user. If care is used in assembly, such
leakers should be few or non-existant.
Alternatively, the internal and external barrel assemblies in the
telescoping section may be adhesively united to each other by
placing a liquid adhesive composition between them at the time of
assembly. Alternatively, the diaphragm and the two barrel sections
can be sealed together by a suitably shaped mandrel in contact with
an ultrasonic generator and against which the assembly is placed.
As the ultrasonic energy is primarily released at points of
discontinuity, up until a seal is accomplished between the
elements, energy is absorbed and heat generated. Once the plastic
unites and becomes essentially homogeneous, energy is passed
through and hence the joint is not over heated even if the more
ultrasonic energy than is required is fed into the system.
One suitable diaphragm is commercially available from Allied
Chemical Co. under the trademark ACLAR, either 22A for an amorphous
film, or better 33C for a crystalline film. These are apparently
either a chlorotrifluoroethylene polymer with a small percentage of
vinylidene fluoride, or a small percentage of tetrafluoroethylene.
Other related types of very moisture resistant films may be used.
Laminates with polyethylene are readily handled and fabricated. The
moisture resistance is preferably better than about 0.025 grams of
water per mil thickness per 100 square inches per day at room
temperature. Alternatively, a laminate consisting of aluminum foil
sandwiched between two layers of polyethylene film can be utilized
as the diaphragm.
In the embodiment shown in FIG. 2, the cylinder barrel 32 is formed
with a shorter external telescoping section 33 and a separate
assembly rim 34 is formed on both the internal and the external
telescopic section forward of the finger flange 35. In this
modification, there is sufficient clearance between the internal
and external barrel for a diaphragm cap 36. The diaphragm is formed
as a cap which can be conveniently molded from sheet stock by a
deep drawing operation or by casting, and such cap has the
advantage of being integral with the diaphragm portion which
stretches across the barrel and has a larger area for adhesive or
heat or ultrasonic sealing with the barrel.
By having a cap with a discrete axial length, seal may be forme
using an internal mandrel inside of the barrel and an external
concentric anvil with pressure being used to transmit heat or
ultrasonic energy and press softened materials into sealing
relationship with each other. Such construction requires somewhat
more specialized equipment and is hence advantageous on the larger
production runs.
The parts before assembly are shown in FIG. 3. Other parts are the
same as in FIG. 1, and have the same numbers.
The cap type diaphragm as shown in FIG. 5 has walls extended back
parallel to the axis to give the additional sealing area with the
internal and external barrel portions.
In FIG. 4 is shown a configuration in which the internal and
external telescopic sections of the barrels are essentially
concentric and coaxial with uniform external walls and without
flanges. In this configuration an ultrasonic seal can be used to
seal the cap against and between the internal and the external
telescopic portions and a sealing band 37 is used to cover and
reinforce the joint between the two sections.
The needle hub may be shaped as a mastitis point, or other
configuration for appropriate uses.
As the materials of construction vary, the temperature or amount of
ultrasonic energy or the type of adhesive composition for sealing
can vary widely within the skill in the art. An adhesive which is
adapted to unite the materials to be joined or an amount of heat or
ultrasonic energy which is adapted in accordance with conventional
procedures to secure a substantially perfect union and not over
energize and unduly soften the joint is preferred.
As above mentioned in assembly, the assembly techniques can be
varied depending upon the characteristics of the medicaments in the
two compartments. If the solid and liquid components are both
labile and unable to stand sterilizing temperatures, the portions
of the barrel are assembled under conventional clean but not
sterile conditions and then these portions are sterilized by heat
or sterilizing gas such as ethylene oxide with the portions being
filled and assembled using sterile techniques for the filling and
assembly operations. Such filling and assembly operations are
conventional in the industry and are herewith incorporated by
reference rather than by further extending the specification.
The stem and the needle hub are illustrated as one conventional
configuration. It is to be understood that the needle may be
attached in any of the many variations of needles and needle hubs
assembly methods which are known to those skilled in the art. The
needle tip or for the construction of the stem, which may be
hollowed to contain a hypodermic needle in sterile condition
preparatory to assembly for use, are also conventional.
Such variations are within the scope of the present invention which
is defined by the following claims.
* * * * *