Note: Descriptions are shown in the official language in which they were submitted.
CA 02404360 2002-08-30
1
Boehringer Ingelheim International GmbH
Needle-less injector of miniature type
The invention concerns a needle-less injector in the form of a hand-held unit,
preferably of miniature type, with which a liquid is intracutaneously injected
for
example into human or animal tissue. The invention aims to expand the area of
use of
an injector of that kind.
Liquids in the sense of the present invention are preferably solutions,
suspensions or dispersions which contain an active substance. Active
substances can be
pharmacologically active substances for treatment of the human or animal body
or they
may be substances for diagnostic or cosmetic uses.
Active substances for non-pharmaceutical uses can be for example in the area
of
plant protection insecticides, fungicides, growth-promoting or growth-
inhibiting agents
or fertilisers. The needle-less injector according to the invention permits
the
environmentally friendly application of agents with a systemic action, as the
active
substance is applied directly to the plant.
EP 0 063 341 and EP 0 063 342 disclose a needle-less injector which includes a
piston pump for expelling the liquid to be injected, which is driven by a
motor by
means of a pressure agent. The liquid container is mounted laterally to the
piston pump.
The amount of liquid required for an injection is sucked into the pump chamber
by way
of an inlet passage and a flap check valve when the piston is retracted. As
soon as the
piston is moved in the direction of the nozzle body the liquid is urged
through the outlet
passage to the nozzle and expelled. The piston of the piston pump is a solid
round
piston.
EP 0 133 471 describes a needle-less vaccination unit which is operated with
carbon dioxide under pressure, from a siphon cartridge by way of a special
valve.
EP 0 347 190 discloses a vacuum compressed gas injector in which the depth of
penetration of the injected drug can be adjusted by means of the gas pressure
and the
volume of the drug can be adjusted by way of the piston stroke.
EP 0 427 457 discloses a needle-less hypodermic syringe which is operated by
means of compressed gas by way of a two-stage valve. The injection agent is
disposed
CA 02404360 2002-08-30
2
in an ampoule which is fitted into a protective casing which is secured to the
injector
housing. The ampoule is fitted on to the end of the piston rod. Disposed at
the other end
of the ampoule is the nozzle whose diameter decreases towards the end of the
ampoule.
WO 89/08469 discloses a needle-less injector for one-off use. WO 92/08508
sets forth a needle-less injector which is designed for three injections. The
ampoule
containing the drug is screwed into one end of the drive unit, with the piston
rod being
fitted into the open end of the ampoule. At its one end, the ampoule contains
the nozzle
through which the drug is expelled. A displaceable closure plug is provided
approximately at the centre of the length of the ampoule. The dose to be
injected can be
adjusted by way of the screwing-in depth of the ampoule. The piston rod which
projects
from the drive unit after actuation of the injector is pushed back by hand.
Both units are
operated with compressed gas.
WO 93/03779 discloses a needle-less injector with a two-part housing and a
liquid container which is fitted laterally to the unit. The drive spring for
the piston is
stressed by means of a drive motor. The spring is released as soon as the two
parts of
the housing are displaced relative to each other by pressing the nozzle
against the
injection location. Respective valves are provided in the intake passage for
the liquid
and in the outlet of the metering chamber.
WO 95/03844 discloses a further needle-less injector. It includes a liquid-
filled
cartridge which at one end includes a nozzle through which the liquid is
expelled. At
the other end the cartridge is closed by a cap-type piston which can be pushed
into the
cartridge. A piston which is loaded by a prestressed spring, after release of
the spring,
displaces the cap-type piston into the cartridge by a predetermined distance,
with the
amount of liquid to be injected being expelled in that case. The spring is
triggered as
soon as the nozzle is pressed sufficiently firmly against the injection
location. This
injector is intended for one-off or repeated use. The cartridge is arranged in
front of the
spring-loaded piston and is a fixed component of the injector. The position of
the piston
of the injector which is intended for a plurality of uses is displaced after
each use by a
distance in a direction towards the nozzle. The piston and the drive spring
cannot be
reset. The prestressing of the spring is initially sufficiently great to expel
the entire
amount of liquid in the cartridge all at once. The spring can only be stressed
again if the
CA 02404360 2002-08-30
injector is dismantled and the drive portion of the injector assembled with a
fresh,
completely filled cartridge.
In FR-2 629 706, two embodiments of a needle-less injector for use in
dentistry
are described, with which a pre-determined amount of liquid can be injected
into the
gum. Both injectors are respectively composed of two portions that are
assembled
together coaxially and are releasably connected to one another. Compressed air
serves
as the operating medium, and is supplied from the outside to the injector.
When the
injector is triggered by means of a trigger button, an operating piston is
suddenly
pushed by a pre-determined arnount by means of a combination of compressed
air, coil
springs and locking mechanisms, wherein the amount of liquid to be injected is
expelled through a nozzle. At the same time, several coil springs are
tensioned which
push several axially displaceable parts within the injector back into their
original
position as soon as the compressed air applied is no longer effective. The
liquid to be
injected is housed within the injector in a tubular, rigid container that is
provided at one
end with a plug moveable within the container, which keeps the liquid in the
container
constantly under pressure by means of a spring-tensioned piston. When some of
the
liquid is pushed out of the container into the liquid chamber within the pump
cylinder,
the pressure spring pushes the plug, via the piston, by a corresponding amount
into the
liquid container.
In some known design configurations of the needle-less injector the supply
container for the liquid to be injected is arranged laterally beside the drive
unit. The
amount of liquid to be injected is sucked into the pump chamber when the solid
piston
of the piston pump is retracted. The inlet passage includes an inlet valve and
the outlet
passage includes an outlet valve. Both valves operate with an auxiliary force.
In other design configurations of the needle-less injector the supply
container
for the liquid to be injected serves directly as a pump chamber and is
subjected to the
sudden application of force which occurs upon expulsion of the amount of
liquid to be
injected.
CA 02404360 2002-08-30
3~
-i~}es~as dismantIed and the_
e wi a es,. sn
completely filled cartridge.
In some known design configurations of the needle-less-ifijector the supply
container for the liquid to be injected is arranged later eside the drive
unit. The
amount of liquid to be injected is sucked into th mp chamber when the solid
piston
of the piston pump is retracted. The inlet ssage includes an inlet valve and
the outlet
passage includes an outlet valve. valves operate with an auxiliary force.
In other design zgurations of the needle-less injector the supply container
for the liquid e injected serves directly as a pump chamber and is subjected
to the
sudd pplication of force which occurs upon expulsion of the amount of liquid
to be
In the case of the needle-less injectors which are operated with compressed
gas,
a part of the compressed gas escapes after each injection. The compressed gas
container
is possibly replaceable but it cannot be directly filled with compressed gas
again. With
such injectors, the drive unit has to be replaced as soon as the compressed
gas container
is empty.
Accordingly the object is that of providing a multi-use needle-less injector
of a
simple design, which is preferably suited for repeated expulsion of a
predetermined
amount of liquid. The amount of liquid which is expelled overall after many
uses
should preferably be greater than the amount of liquid contained in a supply
container.
It should be possible for either a plurality of partial amounts of the liquid
to be
successively dispensed from the supply container or for the amount of liquid
contained
in a supply container to be taken as a whole and expelled all at once. The
supply
container should be able to be replaced in a simple manner. A sufficiently
great
mechanical thrust force (impulse) is to be imparted to the predetermined
amount of
liquid so that the predetermined amount of liquid penetrates a membrane, a
foil or
biological tissue.
In accordance with the invention that object is attained by a needle-less
injector
for a liquid, which is arranged in the form of a hand-held unit in a
cylindrical housing
and which includes a supply container for the liquid. The housing
substantially
comprises two portions. The two portions are releasably or non-releasably
connected
together and are arranged rotatably relative to each other. The needle-less
injector
CA 02404360 2002-08-30
4
includes a locking stressing mechanism for a spring-actuated drive, which is
stressed
prior to the expulsion of a predetermined amount of the liquid and which is
provided
with a triggering device. Fixed in the sprung portion of the locking stressing
mechanism is a hollow plunger which is driven by the locking stressing
mechanism.
The hollow plunger is arranged slidably within a cylinder. It projects with
its one end
out of the cylinder. Preferably at its other end there is mounted a valve body
which is
the single valve body of the needle-less injector. A nozzle with at least one
opening is
disposed at the end of the cylinder. The space between the nozzle and the end
of the
hollow plunger is the pump chamber. A supply container for the liquid is
provided
within the housing. The supply container is in the form of a container which
is separate
from the needle-less injector and which - preferably by means of a press fit -
is
releasably connected to the end of the hollow plunger which projects out of
the
cylinder. The predetermined amount of the liquid which has been conveyed into
the
pump chamber upon retraction movement of the sprung portion and the hollow
plunger
connected thereto, through the hollow plunger, is determined by the stroke
movement
and the cross-section of the hollow plunger.
The locking stressing mechanism comprises a spring-loaded drive flange as the
sprung portion, a drive for stressing the spring, a locking member, two
abutments for
the drive flange, between which the drive flange can move with a reciprocating
movement, and a device for triggering the locking member. The travel of the
drive
portion is limited precisely by the two abutments. A force-transmitting
transmission
arrangement is disposed between the energy-storing spring and the drive for
stressing
the spring. The locking member is annular and has interengaging locking
surfaces. A
preferably cylindrical coil spring or a disk spring or a leaf spring, which
acts as a
tension spring or as a compression spring, can be used as the energy storage
means.
The energy-storing spring can be stressed by means of a direct drive. For that
purpose the drive flange is displaced by an axially acting external force.
When a high
level of spring force is involved, a force-stepup transmission arrangement is
advantageous, for example a worm-thrust transmission arrangement, by means of
which the spring is stressed by an external torque. A transmission arrangement
of that
kind is a single-speed or multi-speed transmission arrangement which is
disposed
between the spring and the drive for stressing the spring.
CA 02404360 2002-08-30
The drive flange can be of a cup-shaped configuration. The collar of the drive
flange may include for example two sawtooth-shaped openings, against which two
sawteeth in the upper part of the housing slide.
The average spring force can be between 10 N and 150 N. Between the two
positions of the sprung portion of the locking stressing mechanism the spring
force
changes approximately by 10% of the average spring force.
The locking member can be a ring which in itself is radially elastically
deformable or a rigid ring with displacement projections or a rigid ring with
leaf
springs formed thereon or a ring which is subjected to prestressing by one or
more
metal springs. The ring can be closed or open; it can comprise a plurality of
portions.
The locking member is arranged displaceably in a plane perpendicular to the
axis of the
housing, or it is deformable in that plane.
Further details relating to the locking stressing mechanism for a spring-
actuated
drive are described in DE 195 45 226.
Fixed in the sprung portion of the locking stressing mechanism is a hollow
plunger which is driven by the locking stressing mechanism. The hollow plunger
engages into the cylinder and projects with a part of its length out of the
cylinder; it is
arranged slidably within the cylinder.
A nozzle is fitted to the end of the cylinder. The nozzle opening can have a
hydraulic diameter of 10 m to 500 m, preferably 50 m to 150 m. The nozzle
opening can have a length of 50 m to 500 m, preferably 100 m to 300 m.
When the nozzle has a plurality of openings, the longitudinal axes of the
nozzle
openings can run parallel to one another, or they can be inclined divergently
with
respect to one another. When the nozzle has a plurality of openings, the
hydraulic
diameters thereof can be different.
The nozzle can comprise a parallelepiped which is composed of two silicon
plates and which for example is 1.1 mm wide, 1.5 mm long and 2.0 mm high. In
the
contact surface between the plates the parallelepiped can have a shallow
triangular
opening which is about 400 m thick and which terminates in a single nozzle
opening
which is 50 m wide, 50 m thick and 200 m long. It may be desirable for the
nozzle
to be surrounded over its entire periphery with an accurately fitting
elastomer shaped
portion. The internal contour of the elastomer shaped portion is matched to
the external
CA 02404360 2002-08-30
6
contour of the nozzle and the external contour of the elastomer shaped portion
is
matched to the internal contour of a nozzle holder which preferably comprises
metal. A
'floating mounting' of that kind means that the nozzle which is of brittle
material is
insensitive to loadings which act in a shock-like fashion and which occur in
regular use
of the needle-less injector.
A valve body which preferably consists of one piece is mounted preferably to
the end of the hollow plunger which is disposed within the cylinder, which
valve body
is guided by the hollow plunger and is arranged axially displaceably with
respect to the
hollow plunger. The valve body moves substantially with the hollow body. The
valve
body is preferably of a shape which is rotationally symmetrical about a single
axis,
such as for example a circular cylinder or a truncated cone. Its diameter can
be smaller
than the diameter of the space in which the valve body is displaceably
arranged. The
valve body can rotate about its axis. The axis of the valve body always
remains parallel
to the axis of the hollow plunger. That therefore affords a defined sealing
surface on the
inlet side of the valve body. The distance over which the valve body can be
displaced
relative to the hollow plunger is limited by an abutment. The valve is closed
in the
position in which the valve body bears against the defined sealing surface.
The space between the nozzle and the valve body mounted to the hollow
plunger is the pump chamber. It is possible to arrange a filter which is
preferably in the
form of a depth filter in front of the nozzle end of the pump chamber, that is
to say in
the expulsion passage for the liquid. If the liquid to be injected contains
suspended
particles, the pore width of the filter has to be matched to the size of the
particles.
Further details relating to the hollow plunger and the valve body are set
forth in
DE 195 36 902.
The locking stressing mechanism and the energy-storing spring are preferably
stressed relative to each other by rotation of the two housing portions,
preferably by
way of a worm-thrust transmission arrangement. The torque can be produced by
hand
or by means of a motor.
The cylinder diameter is preferably practically identical over its entire
length to
the outside diameter of the hollow plunger. The cylinder can be fixedly
mounted in the
one portion of the housing. In addition the cylinder can be axially
displaceably mounted
CA 02404360 2002-08-30
7
in the one portion of the housing. The displaceable cylinder is held in its
rest position
by a return spring.
The two abutments for the sprung portion can be fixedly positioned in the
housing. Furthermore the position of one of those abutments can be variable in
the axial
direction. In that way it is possible to alter the volume of the pump chamber
while the
outside diameter of the hollow plunger is constant. In an otherwise unaltered
design
configuration of the needle-less injector the amount of expelled liquid can be
altered by
varying the position of an abutment.
The position of the travel movement of the sprung portion and thus the stroke
movement of the hollow plunger within the needle-less injector is delimited by
the two
abutments. With a given position for the abutments the position of the travel
movement
of the sprung portion and therewith the stroke travel of the hollow plunger is
constant
for each injection.
The locking member is displaced parallel to the plane of the ring or is
radially
deformed in the plane of the ring, by means of a triggering device. When the
cylinder is
fixedly mounted in the housing the triggering device is actuated by means of a
triggering button which can be depressed with a finger and the locking member
is
released. When the cylinder is mounted slidably in the housing the triggering
device is
actuated when the cylinder is pressed in against the force of the return
spring and the
locking member is disengaged.
A supply container for the liquid is provided within the housing. That supply
container is in the form of a container which is separate from the needle-less
injector; it
is connected to the end of the hollow plunger which is in opposite
relationship to the
pump chamber. The end of the hollow plunger is covered by the liquid which is
disposed in the supply container.
The supply container which is connected to the hollow plunger can additionally
be connected to the sprung portion. That connection can be a releasable or non-
releasable push-in connection in which the sprung portion is provided with a
plurality
of snap hooks which engage into a peripherally extending groove in the supply
container after the supply container has been pushed into the needle-less
injector.
CA 02404360 2002-08-30
8
The predetermined amount of the liquid to be expelled is determined by the
stroke movement and the cross-section of the hollow plunger. The stroke
movement of
the hollow plunger is delimited by the two abutments for the drive flange.
It is desirable to provide in front of the nozzle a removable closure cap for
protecting the nozzle opening during storage of the needle-less injector prior
to and
during the period of use thereof from contamination and evaporation of the
liquid.
The two portions of the housing, the locking stressing mechanism, the cylinder
and the supply container preferably comprise plastics material, for example
polybutyleneterephthalate. The hollow plunger preferably comprises metal, for
example
high-quality steel.
The valve body can comprise metal, ceramic, glass, precious stone, plastics
material or elastomer.
The nozzle can comprise metal, plastics material, glass, silicon or precious
stone
such as sapphire, ruby or corundum.
The filter preferably comprises sintered metal or sintered plastics material.
The needle-less injector is preferably produced in the form of a hand-held
unit.
It can be held and operated with one hand in the injection procedure. The
cylinder, the
hollow plunger, the valve body, the nozzle and possibly the filter are
miniaturised
components.
The mode of operation of the needle-less injector is described hereinafter.
During storage of the needle-less injector which has not been used or which
has
already been put to use and between two injections, the needle-less injector
is in the rest
condition. The energy-storing spring is in a prestressed condition. The sprung
portion
bears against the abutment which limits the travel of the sprung portion in
the rest
condition. The hollow plunger engages deeply into the cylinder. There is only
a small
spacing between the end of the hollow plunger and the inside of the nozzle.
The locking
member is in the disengaged position.
The locking stressing mechanism is stressed when the two housing portions are
rotated relative to each other. The sprung portion is displaced in the axial
direction
away from the cylinder, in which case the stressing of the energy-storing
spring is
increased. At the same time the hollow plunger is pulled a distance out of the
cylinder
and the pump chamber is increased in size. The hollow plunger still projects
with a part
CA 02404360 2002-08-30
9
of its length into the cylinder. At the same time a part of the liquid
contained in the
storage container is conveyed through the hollow plunger and past the valve
body into
the pump chamber and the pump chamber is filled with liquid. The amount of
liquid in
the pump chamber is practically the same as the amount of liquid expelled upon
an
injection being administered. The sprung portion is displaced until the
locking member
jumps into its engaged position. In the case of a needle-less injector with a
triggering
button that button protrudes somewhat out of the housing.
The nozzle end of the needle-less injector is applied to and pressed against
the
injection location. In the case of a needle-less injector with triggering
button the
triggering button is actuated with a finger and pressed into the housing. In
that way the
locking member is pushed into the disengaged position and the injection is
triggered. In
the case of a needle-less injector with slidably arranged cylinder the
injector is pressed
with its nozzle end by hand with increasing force against the force of the
return spring,
against the injection location. In that situation the cylinder is pushed into
the housing,
the locking member is pushed into its disengaged position and the injection is
triggered.
When the needle-less injector is lifted off the injection location the return
spring urges
the cylinder back into its rest position.
As soon as the locking member has assumed the disengaged position the force
K of the stressed energy-storing spring acts by way of the sprung portion, the
hollow
plunger and the closed valve at the end of the hollow plunger, during the
period of time
At, on the liquid in the pump chamber, whereby the mass of liquid m has
imparted
thereto the speed Av and thus a mechanical impulse K' At = m* Av, and it
issues from
the nozzle at high speed and intracutaneously penetrates into the tissue. The
needle-less
injector is in the rest condition again after the injection.
The needle-less injector according to the invention can serve in human
medicine
and in veterinary medicine for intracutaneous injection of an active substance
in liquid
form, for example, a medicinal preparation, into human or animal tissue.
Examples of
suitable pharmaceutical preparations are inter alia analgesics, vaccines, anti-
diabetic
agents, horrnones, contraceptives, vitamins, antibiotics, sedatives,
antimicrobial
substances, amino acids and coronary agents.
CA 02404360 2002-08-30
The preparation of the drug can be in the form of a solution, a s spension or
an
emulsion. In the case of suspensions the mean particle size should not exceed
15 m,
preferably 10 m.
Suitable agents for dissolving, suspending or emulsifying active substances
and
possibly required additives are for example water, alcohols, alcohol-wa er
mixtures and
emulsions of oil in water or water in oil. They include purified, terilised
water,
ethanol, propane diol, benzyl alcohols, ethanol-water mixtures, oils ( uch as
coconut
oil, peanut oil, soya oil, castor oil, sunflower oil), fatty acid esters (s ch
as isopropyl
myristate, isopropyl palmitate and ethyloleate), triglycerides, triaceti ,
solketal, and
propylene glycol. The formulations may also contain additives such as for
example
preserving agents as well as acids or bases for adjusting the pH-value.
The predetermined amount of a liquid can be injected by me s of the needle-
less injector into a leaf or the stalk of a plant through a membrane into he
space behind
the membrane.
The needle-less injector according to the invention enjoy~ the following
advantages:
= It is of an easily manageable shape. The supply container for the liquid is
disposed in the injector housing.
= It can be used for many - up to several hundred - injections which can be
taken from one or more supply containers.
= Besides the valve at the end of the hollow plunger it does not have any
further valves.
= The locking stressing mechanism can be easily handled, even when high
spring forces are involved, even by unskilled persons, and can be stressed
with the application of a relatively small amount of force by way of a worm-
thrust transmission arrangement.
= The locking stressing mechanism is triggered by hand by pressing the
trigger button with a finger or when the needle-less injector is pressed
against the injection location.
= The drive unit is not replaced but only the supply container for the liquid.
= The valve mounted at the end of the hollow plunger operates without
ancillary force and closes very quickly.
CA 02404360 2006-09-26
25771-751
11
= The volume of the pump chamber can be varied by
varying the position of one of the two
abutments.
= The mechanical impulse of the amount of liquid
to be injected can be adapted to the desired
depth of penetration into the tissue or to the
thickness of the membrane to be penetrated.
= The supply container for the liquid is adapted
to the conditions involved upon storage of the
container - possibly for years - and to the
connection thereof to the injector. Its design
configuration is independent of the demands
which are made on the pump chamber in front of
the nozzle.
= The supply container for the liquid is not
exposed to the thrust force upon injection.
= The supply container for the liquid can be
replaced in a simple manner.
= The amount of liquid to be delivered that is
necessary for a given application can be
injected in a simple manner consecutively in
several partial amounts in different places in
the area of injection.
= Needle-less injection affects the place injected
considerably less than injection by means of a
hypodermic syringe.
In one broad aspect, there is provided a needle-
less injector for a liquid, which is in the form of a hand
unit, comprising a housing and a supply container for the
CA 02404360 2006-09-26
25771-751
12
liquid, wherein the housing includes two portions which are
connected together and are arranged rotatably relative to
each other, and the needle-less injector includes a locking
stressing mechanism with a sprung portion which is
displaceable between two abutments and which is provided
with a triggering device, and a hollow plunger which is
fixed in the sprung portion and which is driven by the
locking stressing mechanism, wherein the hollow plunger is
arranged slidably within a cylinder and includes a single
valve body and mounted at the end of the cylinder is a
nozzle with at least one opening and the space between the
nozzle and the valve body forms a pump chamber, and the
supply container for the liquid is arranged within the
housing and is in the form of a container separate from the
needle-less injector and is connected to the end of the
hollow plunger which projects out of the cylinder, and the
amount of liquid which has been conveyed through the hollow
plunger into the pump chamber when the hollow plunger is
pulled out of the cylinder is determined by the stroke
travel a and the cross-section of the hollow plunger, and
the position of the hollow plunger stroke travel a within
the needle-less injector is determined by the position of
the two abutments.
The invention will now be described in greater
detail with reference to the Figures.
Figure 1 is a view in longitudinal section through
a needle-less injector with triggering button in the rest
condition, in which the cylinder is fixedly arranged in the
one housing portion.
Figure 2 is a view in longitudinal section through
a needle-less injector without triggering button in the
stressed condition of the energy-storing spring, in which
CA 02404360 2006-09-26
25771-751
13
the cylinder is arranged displaceably in the one housing
portion.
Figures 3 and 4 show one end of the supply
container and the sprung portion in a further embodiment.
In Figure 3 the hollow plunger has been introduced into the
supply container but not yet connected to the hollow
plunger.
Referring to Figure 1 shown therein are the two
housing portions (1) and (2) which are releasably connected
together and which are arranged rotatably relative to each
other. Of the locking stressing arrangement which is in the
rest condition, the Figure shows the sprung portion (3), the
locking member (4) in the disengaged condition, the
triggering button (5) which acts on the locking member, and
the energy-storing coil spring (6) in the form of a
compression spring. Fixed in the sprung portion (3) is the
hollow plunger (7) which engages into the cylinder (8).
Mounted to the end of the cylinder is the nozzle (9) with
the nozzle opening (10). The filter (11) is disposed in
front of the nozzle. The nozzle end of the hollow plunger
is provided with the valve body (12). The pump chamber (13)
is disposed between the valve body and the filter. The
supply container (14) is arranged in the otherwise free
space within the coil spring; it is fitted in the flange
(15) on to the hollow plunger and is held on the hollow
plunger by the press fit (19). The cage (16) which
surrounds the coil spring is connected in positively locking
relationship to the housing portion (1). The sprung portion
(3) bears against the abutment (17). The nozzle is
protected by the removable closure cap (18).
CA 02404360 2006-09-26
25771-751
13a
Referring to Figure 2, shown therein are the two
housing portions (31) and (32) which are releasably
connected together and which are arranged rotatably relative
to each other. Of the locking stressing mechanism in the
stressed condition, the Figure shows the sprung portion
(33), the locking member (34) in the engaged condition and
the energy-storing coil spring (36) in the stressed
condition. Fixed in the sprung portion (33) is the hollow
plunger (37) which engages into the cylinder (38). Mounted
at the end of the cylinder is the nozzle (39) having the
nozzle opening (40). The nozzle end of the hollow plunger
is provided with the valve body (42). The pump chamber (43)
is disposed between the valve body and the nozzle. The
supply container (44) is arranged in the otherwise free
space within the coil spring; it is fitted in the flange
(45) on to the hollow plunger and is held on the hollow
plunger by the press fit 49. The cage (46) which surrounds
the coil spring is connected in positively locking
relationship to the housing portion (31). The sprung
portion (33) bears against the abutment (47) on the engaged
locking member (34). The cylinder (38) is arranged axially
slidably in the housing portion (31); it is held in its rest
position by the helical return spring (48) which acts as a
compression spring. The cylinder (38) is provided with a
triggering device (not shown) which disengages the locking
member (34) as soon as the cylinder (38) is pushed into the
housing portion (31) against the force of the return spring
when the needle-less injector is pressed against the
injection location. Reference (a) denotes the travel of the
drive portion between the two abutments. The stroke
movement of the hollow plunger is identical to that travel.
Figure 2 shows the needle-less injector used for
injection. The nozzle (39) is pressed against the
CA 02404360 2006-09-26
25771-751
13b
schematically shown tightly stretched skin (35); with
further pressure on the point of injection, the needle-less
injector is triggered and the liquid is injected from the
pump chamber (43) into the skin.
Figure 3 is a view in longitudinal section of part
of the (triple-shell) supply container (54). The outer
shell of the supply container is a stiff casing (55) which
is provided with a peripherally extending groove (52). The
supply container is closed by the plug (56) which goes into
the immersion connection portion (58) with a press fit (59).
A part of the sprung portion (53) with the hollow plunger
(57) fixed therein is shown in longitudinal section. On its
side towards the supply container the sprung portion is
provided with a plurality of snap hooks (51).
In Figure 4 the supply container is connected to
the hollow plunger and the sprung portion, more specifically
to the hollow plunger by the press fit (59) and to the
sprung portion by way of the snap hooks (51) which engage
into the peripherally extending groove (52) in the supply
container.
The connection between the supply container and
the sprung portion, which is shown in Figures 3 and 4,
comprises snap hooks (51) with round shoulders and a
peripherally extending groove (52) of semicircular cross-
section. That connection is a releasable plug-in
connection.
To provide a non-releasable plug-in connection, it
is possible to adopt snap hooks with sawtooth-shaped
shoulders and a peripherally extending groove of triangular
cross-section.
CA 02404360 2006-09-26
25771-751
13c
Example 1: Structure of a needle-less injector according to
the invention.
A needle-less injector for intracutaneous
injection into biological tissue has the following features:
The housing is of an outside diameter of about
20 mm and a length of about 70 mm. Both portions of the
housing, the locking stressing mechanism and the spring
cage, are made from polybutyleneterephthalate. The cylinder
also comprises polybutyleneterephthalate; it is of an
outside diameter of 5 mm and an inside diameter of 1.60 mm.
The nozzle comprises quartz. The nozzle opening is of a
diameter of 140 m and a length of 220 m. The hollow
plunger of high-quality steel is of an outside diameter of
1.59 mm and an inside diameter of 0.35 mm. The piston
stroke travel is 12 mm. The valve body comprises elastomer;
it is in the form of a 2 mm thick disc with
CA 02404360 2002-08-30
14
an outside diameter of 1.60 mm. The disc is provided on its peripheral surface
with
axial openings through which the liquid can flow past the valve body into the
pump
chamber. The end of the hollow plunger is provided with a groove into which
the valve
body engages. The amount of liquid expelled is about 23 mm3. The
interchangeable
supply container is of a volume of about 11 cm3.
Example 2: Intracutaneous application of a liquid
An injection solution comprising 20g of dextran fluorescein (UW 3000) per
litre
of distilled water was injected through the skin of two dogs under anaesthetic
using the
needle-less injector according to the invention. For that purpose 4.5 ml of
the dextran
fluorescein solution was introduced into the supply container of the needle-
less injector
and the supply container was connected to the hollow plunger of the injector.
The
injector was actuated by stressing and triggering the locking stressing
mechanism a
plurality of times in order to expel the air from the hollow plunger, the pump
chamber
and the nozzle. The needle-less injector was then applied to a previously
shaved part of
the skin in the region of the stomach of the dogs and triggered. That
procedure was
repeated a plurality of times.
Blood samples were taken from the dogs at regular intervals and the content of
dextran fluorescein in the blood plasma was determined. The results
demonstrate the
operability of the needle-less injector according to the invention.
Example 3: In-vitro examination of a viral suspension
In laboratory experiments using the needle-less injector, it was determined
whether the viability of suspended live viruses was decreased when the
suspension was
expelled through the valve of the needle-less injector.
From the viral suspension obtained after expulsion from the needle-less
injector,
a yield of only approximately 1 logio PFU (plaque forming units) in the case
of
relatively large DNA viruses (test virus: vaccinia virus) and less
(approximately 0.5
logio PFU) with small RNA viruses (test virus: bovine viral diarrhoea virus)
was
determined.
Example 4: In-vivo application of a vaccine with modified live viruses
In an animal experiment, the applicability of the needle-less injector for
delivering a vaccine suspension with modified live viruses was tested. In this
CA 02404360 2002-08-30
experiment, both the safety and the tolerability of vaccination by means of
the needle-
less injector, as well as the effectiveness of this method of delivery were
determined.
Six healthy dogs of the same age were assigned to two groups. Group 1
comprised two dogs, group 2 comprised four dogs. The animals in both groups
were
each vaccinated three times, in each case at an interval of three weeks, with
a modified
live vaccine for canine adenovirus.
In group 1, in each case 1 millilitre of the canine adenovirus vaccine (CAV-1)
(Galaxy DA2ppvL+Cv, SNo 610041; Solvay Animal Health Inc.) was delivered
intramuscularly in accordance with the manufacturer's recommendations by means
of a
hypodermic syringe. In group 2, an experimental canine adenovirus was
delivered by
means of the needle-less injector.
The experimental vaccine (CAV-2) used for vaccinating the animals in group 2
was manufactured from a weakened strain of the canine adenovirus. The titre
was 7.2
logio TCID50 per 60 microlitres (TCID = tissue culture infective dose). At
each
injection site, six individual shots were administered (six times 10
microlitres = 60
microlitres for each vaccination). The injection area on the back of the dogs
was
shaved and the respective six injection sites were marked with a ball-point
pen.
The effectiveness of the vaccination was established by determining the number
of virus neutralising antibodies in the serum of the dogs, in each case three
weeks after
each vaccination.
Tolerability was determined by observation of the injection sites six seconds
after the vaccination and subsequently daily until the end of the animal
experiment.
The injection sites were photographed and the results after palpating the
injection sites
were noted.
This experiment showed:
In the animals in group 2 a very slight reddening of the injection sites was
evident during the first 2 to 3 days. A temporary swelling lasting 1 to 2 days
could be
determined only by palpation. This slight and entirely tolerable local
reaction is very
probably connected with the local amplification of the depleted modified live
virus, and
is therefore viewed as necessary for the proper effectiveness of the vaccine.
This
explanation is supported by the fact that after the injection of physiological
common
CA 02404360 2002-08-30
16
salt solution, using the needle-less injector, absolutely no colouration and
also not even
a slight, temporary swelling was to be noted.
Effectiveness is determined by the virus neutralisation test. The results are
shown in Table 1. The largest titres are still capable of neutralising canine
adenoviruses.
In the serum of all the animals from the two groups, virus neutralising
antibodies were evident three weeks after the first vaccination. After the
second and
third vaccination, a small intensification effect was shown.
The vaccination with the experimental canine adenovirus vaccine by means of
the needle-less injector is exactly as effective as intramuscular vaccination
with the
conventional vaccination by means of a hypodermic syringe.
CA 02404360 2002-08-30
17
Table 1: Canine adenovirus neutralisation titres of canine serum
Dog VN titre of canine serum
Test number Reference 21days after first 21 days after second 21 days after
third
vaccination vaccination vaccination
CAV-1 conventional vaccine
intramuscular by means of hypodermic syringe
1496 ------ 1024 1024 4096
1498 ------ 1024 1024 512
CAV-2 experimental vaccine
Subcutaneous by means of needle-less injector
1494 TTK9 4096 4096 8192
1495 USK9 4096 4096 8192
1497 UVL9 4096 8192 4096
1499 TVL9 2048 2048 2048
