Abstrict Prefilled, disposable syringes for injecting preparations with
a fill volume of less than 5 ml are typically made of glass. The
disposable syringe in this invention avoids the use of glass as
a construction material. The body of the syringe with barrel, grip
and nozzle is made of transparent, glass-like plastic with a very
low gas permeability and is designed to be resistant to gamma rays
and/or ethylene oxide gas, whereby the hypodermic needle is directly
integrated within the plastic nozzle.
Claims What is claimed is:
1. A prefillable, low-particle, sterile, single use syringe for
the injection of preparations having a filling volume of less than
5 ml, the syringe comprising:
a syringe plunger;
a piston rod connected to the syringe plunger; and
a syringe body, the syringe body including:
a syringe cylinder having a first end and a second end and inner
walls defining a cylinder interior and an inner gliding surface,
the first end of the cylinder being open for reception of the syringe
plunger, the syringe cylinder and the syringe plunger together defining
a filling volume within the syringe cylinder of less than 5 ml,
the syringe plunger being movable within the syringe cylinder by
means of the piston rod;
a grip formed proximate the first end of the syringe cylinder;
a tapered syringe head having an outer surface and walls formed
integrally as an extension of the second end of the syringe cylinder,
the tapered syringe head being formed from the same material as
the syringe cylinder and including a conically tapered portion;
wherein the syringe body is formed of plastic that is gamma-sterilizable
and/or ethyleneoxide-sterilizable, without any change causing functional
deterioration of chemical and physical properties, in particular
brittleness and color;
wherein the walls of the syringe cylinder and the syringe head
are so formed with regard to water vapor permeability that they
have a permeability of less than 0.08 g/m.sup.2.times.d at the wall
thickness of 500 .mu.m, whereby the wall is transparent at least
in the area of the syringe cylinder; and
an injection needle having a first end extending through and integrated
directly into the tapered syringe head and indisconnectably fastened
therein and a second end extending out of the tapered syringe head
proximate the conically tapered portion of the syringe head; and
a protective cap of a soft material covering the injection needle
so that the needle pierces the protective cap and is thereby sealed,
the cap having an inner side that is in sealing abutment with the
outer surface of the tapered syringe head, so that the outer surface
of the needle is also sealed, whereby the protective cap is gamma-sterilizable
and/or ethyleneoxide-sterilizable, without any change causing functional
deterioration.
2. A single use syringe according to claim 1 wherein a portion
of the insertion needle is encased in the tapered syringe head.
3. A single use syringe according to claim 2 wherein the portion
of the insertion needle that is encased in the tapered syringe head
has a non-linear shape so as to provide a positive shape conforming
connection between the insertion needle and the tapered syringe
head.
4. A single use syringe according to claim 1 wherein a recess
is formed in the tapered syringe head and the insertion needle is
glued into the recess in the tapered syringe head.
5. A single use syringe according to claim 1 wherein tapered syringe
head includes support elements in the form of ridges molded into
the tapered syringe head.
6. A single use syringe according to claim 1 wherein the outer
surface of the tapered syringe head includes a collar portion, whereby
the inner side of the cap is in sealing abutment with the collar
portion of outer surface of the tapered syringe head, so that the
outer surface of the needle is also sealed.
7. A single use syringe according to claim 1 wherein the syringe
cylinder includes an inner and outer layer made of different plastics
and wherein one of the layers acts as a barrier to oxygen diffusion
and the other layer blocks diffusion of water vapor.
8. A single use syringe according to claim 7 wherein one of the
plastic layers consists of a cyclic olefin copolymer (COC).
9. A single use syringe according to claim 7 wherein a further
layer of metallic, ceramic or glassy material is provided between
the inner and outer layers made of different plastics.
10. A single use syringe according to claim 1 wherein the syringe
cylinder and the tapered syringe head are provided with an inner
layer made of a metallic, ceramic or glassy material.
11. A single use syringe according to claim 1 wherein the syringe
cylinder and the tapered syringe head are provided with an outer
layer made of a metallic, ceramic or glassy material.
12. A prefillable, low-particle, sterile, single use syringe for
the injection of preparations having a filling volume of less than
5 ml, the syringe comprising:
a syringe plunger;
a piston rod connected to the syringe plunger; and
a one-piece plastic syringe body, the syringe body including:
a syringe cylinder portion having a first end and a second end
and inner walls defining a cylinder portion interior and an inner
gliding surface, the first end of the cylinder portion being open
for reception of the syringe plunger, the syringe cylinder portion
and the syringe plunger together defining a filling volume within
the syringe cylinder portion of less than 5 ml, the syringe plunger
being movable within the syringe cylinder portion by means of the
piston rod;
a grip portion formed proximate the first end of the syringe cylinder
portion;
a tapered syringe head portion having walls formed integrally as
an extension of the second end of the syringe cylinder portion,
the tapered syringe head portion being formed from the same plastic
material as the syringe cylinder portion;
an injection needle having a first end extending through and integrated
directly into the tapered syringe head portion and a second end
extending out of the tapered syringe head portion; and
a protective cap of a soft material covering the injection needle
so that the needle pierces the protective cap and is thereby sealed,
the cap having an inner side that is in sealing abutment with the
walls of the tapered syringe head portion, so that the outer surface
of the needle is also sealed.
13. A single use syringe according to claim 12 wherein a portion
of the insertion needle is encased in the tapered syringe head portion
and the portion of the insertion needle that is encased in the tapered
syringe head portion has a non-linear shape so as to provide a positive
shape conforming connection between the insertion needle and the
tapered syringe head portion.
14. A single use syringe according to claim 12 wherein the walls
of the syringe cylinder portion and the syringe head portion are
so formed with regard to water vapor permeability that they have
a permeability of less than 0.08 g/m.sup.2.times.d at the wall thickness
of 500 .mu.m, whereby the wall is transparent at least in the area
of the syringe cylinder portion.
15. A single use syringe according to claim 12 wherein the outer
surface of the tapered syringe head portion includes a collar portion,
whereby the inner side of the cap is in sealing abutment with the
collar portion of outer surface of the tapered syringe head portion,
so that the outer surface of the needle is also sealed.
16. A single use syringe according to claim 12 wherein the syringe
cylinder portion includes an inner and outer layer made of different
plastics and wherein one of the layers acts as a barrier to oxygen
diffusion and the other layer blocks diffusion of water vapor.
17. A single use syringe according to claim 16 wherein one of
the plastic layers consists of a cyclic olefin copolymer (COC).
18. A single use syringe according to claim 16 wherein a further
layer of metallic, ceramic or glassy material is provided between
the inner and outer layers made of different plastics.
19. A single use syringe according to claim 12 wherein the syringe
body is formed of plastic that is gamma-sterilizable and/or ethyleneoxide-sterilizable,
without any change causing any change in brittleness and color.
20. A single use syringe according to claim 12 wherein the protective
cap of a soft material covering the injection needle is formed of
a material that is gamma-sterilizable and/or ethyleneoxide-sterilizable,
without any change causing functional deterioration.
Description BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention generally relates to a prefilled, low particle,
sterile, disposable syringe for injecting preparations with a fill
volume of less than 5 ml. More particularly, the present invention
relates to a syringe comprising a main body and a hypodermic needle,
the body of the syringe being comprised of a grip, a nozzle, and
a barrel equipped with an interior lubricating layer and an open
end to accommodate a plunger that can be moved by means of a plunger
rod within the barrel, and the hypodermic needle being mounted firmly
within the nozzle, such that the needle penetrates the protective
cap, forming a seal, while at the same time the interior of the
cap sleeve fits tightly against the nozzle, also sealing the exterior
surface of the needle. Furthermore, the invention concerns a procedure
for the manufacture of such a syringe.
2. Description of the Prior Art
Prefilled, sterile, disposable syringes for medicinal purposes
combine two different functions. On the one hand, they are suitable
for storing highly effective preparations over a period of several
years; on the other hand, they are also the instrument used to administer
the preparations directly to the patient. Whereas in the case of
vials and ampoules, preparations can only be administered after
having first been drawn from the container by means of an empty
syringe. The use of a prefilled, disposable syringe eliminates this
filling process, i.e., pulling the plunger. In this way, the energy
expended and the risks of confusing and of contaminating preparations
are considerably reduced. In addition, when considering the "Total
Cost of Drug Delivery," administering preparations directly
from the container represents by far the most economical possibility.
Up to now only one example is known of a prefilled, disposable
syringe of the type described in the introduction: the SCF (Sterile
Clean Fill)--Staked Needle Injection by Becton Dickinson. The body
of the syringe, i.e., the barrel, the grip, and the nozzle, consists
of a single glass part, and for this reason the syringe is also
called a prefilled, disposable glass syringe. Certainly in all known
disposable syringes for injections of <5 ml, the barrel at the
very least is made of glass.
The needle of an SCF--Staked Needle Injection is glued into a corresponding
recess in the nozzle. Disposable glass syringes are also known (e.g.,
German Patent Nos. DE 2939180 C2 and DE 3916101) in which the
hypodermic needle is not directly integrated in the nozzle, but
rather, is glued into an additional piece that can be mechanically
connected to the nozzle. This increases the number of pieces and
introduces an additional seam which must be sealed.
A major disadvantage of the disposable glass syringe is the risk
of breakage and the related risks of injury and infection. Furthermore,
many types of glass are not suitable for gamma ray sterilization,
as the glass becomes permanently discolored. Gamma ray sterilization
is, however, a very simple, economical and harmless sterilization
procedure.
A further disadvantage of the disposable glass syringe is the costly
procedure necessary to manufacture the glass components and to transfer
them to a low particle, sterile environment. The manufacturing process
for the glass components is slow and only allows for computer control
and inspection in the beginning. The uncertainty of the process
is equally as large. In addition to this, the glass components are
continually in contact with equipment and lubricants, making a wash
step absolutely necessary. The corresponding wash equipment requires
a large capital investment and is expensive to operate.
Prefilled, disposable plastic syringes with total fill volumes
of at least 50 ml are also known. Mallinckrodt's disposable hypodermic
syringe, known under the brand name OPTIRAY, is not equipped with
a hypodermic needle. Instead, infusion tubing is mechanically mounted
on the nozzle. The plastic consists of (translucent) polypropylene.
The plastic barrel of the disposable syringe found in U.S. Pat.
No. 4861335 is equipped with a plastic cap on the side of the
barrel turned away from the plunger. The hypodermic needle is fastened
to the cap by means of a mounting method known under the brand name
LUER-LOCK. Therefore, the needle is not integrated with the nozzle.
For injections of considerably less than 50 ml, particularly for
fill volumes smaller than 5 ml, the surface of the syringe is so
large in comparison to the dispensed volume that the known prefilled
plastic syringes could not be stored for long periods of time. The
loss of preparation components from diffusion, particularly of water
as a solvent, would be so great that the change in composition would
be unacceptable. Furthermore, known plastic syringes are constructed
from a translucent plastic, permitting only limited visual inspection
of the syringe contents, which is an important step for low volume,
prefilled disposable syringes. For this reason, only prefilled,
disposable glass syringes are known for fill volumes under 5 ml.
SUMMARY OF THE INVENTION
The task underlying this invention is to create a prefilled, disposable
syringe that has a considerably lower risk of breakage and injury
as compared to glass models, is an effective barrier against water
vapor diffusion, permits the visual inspection of the dispensed
preparation, and is especially simple, controllable and economical
to manufacture as a preassembled unit consisting of a barrel with
an integrated needle and an attached protective cap, all in a low
particle, sterile package.
The solution to this task is successful in that the invention of
the low volume, prefilled disposable syringe described in the introduction
has the following properties: the body of the syringe is made of
plastic and can be sterilized by gamma rays and/or ethylene oxide
without affecting chemical or physical properties (particularly
brittleness and color in the case of the syringe body) in such a
way as to impair its function; the protective cap can be sterilized
by gamma rays and/or ethylene oxide without affecting chemical or
physical properties in such as way as to impair its function; the
walls of the barrel and nozzle are designed in such a way that their
permeability to water vapor is less than 0.08 g/(m.sup.2.times.d)
relative to a wall thickness of 500 .mu.m; the walls are, at least
in the barrel area, transparent like glass; and the hypodermic needle
is directly integrated in the nozzle.
Due to the measures taken in this invention, a prefilled, sterile,
disposable syringe of the type described in the introduction has
been created for a small volume which, despite the use of plastic
as construction material, can be stored for long periods of time
and allows for visual inspection of the syringe contents for precipitates,
impurities, etc. In other words, the syringe possesses all of the
advantages of the disposable glass syringe, yet without having to
tolerate the disadvantages in handling and preparation caused by
the use of glass as a construction material.
Handling of the syringe when dispensing the syringe contents is
significantly safer than when using a disposable glass syringe.
With regard to the manufacturing process for the prefilled, sterile
disposable syringe in this invention, the solution to the aforementioned
task is successful in that: the plastic body of the syringe is produced
in a clean room (low particle environment) by injection molding,
the needles and protective caps are brought into a clean environment
in the clean room and mounted on the body of the syringe in the
clean room, the lubricating layer within the barrel of the syringe
is applied inside the clean room, and the preassembled syringe unit,
stored in a container in the clean room, is sealed in particle and
bacteria-proof packaging. The body of the syringe does not undergo
a previous wash step, and the container, together with its contents,
is sterilized with gamma rays and ethylene oxide outside of the
clean room.
This manufacturing process for the preassembled unit (consisting
of the syringe body with integrated needle and attached protective
cap) in low particle, sterile packaging is especially simple, controllable
and economical. It is also easier to automate than the known process.
The preassembled unit is then delivered to the pharmacist, who fills
and finishes assembling the syringe barrel (inserts the plunger),
with no need for additional costly steps in the process.
One development of the disposable syringe in this invention lies
in the nozzle area where the hypodermic needle is fastened. The
nozzle is constructed to encase the needle, which has an advantage
over known finished glass syringes with a glued-in needle, so that
no adhesive can interact with the preparation. This is especially
important for highly sensitive preparations.
The closed linkage caused by friction between the needle and its
casing is generally sufficient to guarantee secure attachment of
the hypodermic needle. It is nevertheless advantageous for the hypodermic
needle to have a profiling or a distortion (s-shaped, for instance)
to produce a positive locking of the needle position. In this instance
there are numerous possibilities available for achieving a variation
of the straight, thin, cylindrical form, even to the point of effecting
a bulge in the needle.
As an alternative to encasing the needle in the nozzle, another
version of the invention has the needle glued into a recess in the
nozzle. This disposable syringe can be used for less sensitive preparations
and has the advantage of lower production costs. Injection molding
with no inserted components simplifies equipment set up and facilitates
possible shorter cycle times. Subsequent gluing of the needle is
achieved using high clock rates.
A further development of this invention lies in the nozzle area
where the hypodermic needle is fastened. Here, support elements
(more specifically, ridges) are molded onto the nozzle, a construction
which makes possible smaller accumulations of plastic around the
nozzle and thus shorter cycle times during injection molding.
It is also an advantage if the nozzle surface on which the sleeve
of the protective cap forms a seal is constructed as a collar. A
collar ensures that the protective cap seals cleanly. The ridges
mentioned previously not only serve as supports, but also guide
the rim of the protective cap over the collar.
One advancement of the invention is characterized by the body of
the syringe having at least a syringe barrel consisting of an inner
and outer layer of different types of plastic. Constructing the
barrel and, likewise, the nozzle out of two layers of plastic is
an advantage if the preparation is, for example, sensitive to oxygen
or carbon dioxide. In general, plastics acting as an effective water
vapor barrier have correspondingly poor resistance to gases such
as oxygen and carbon dioxide. A double-layer composite structure
may therefore be necessary.
According to a preferred design for this invention, the plastic
used in the production of the syringe body consists of a cyclic
olefin copolymer (COC). The use of a cyclic olefin copolymer is
advantageous because this material offers an excellent barrier against
water vapor and at the same time is transparent like glass.
According to further developments of this invention, it is also
an advantage to provide another layer of metallic, ceramic or glass-like
material, which forms a functional boundary between the plastic,
providing form and acting as a structural material, and the coating
material, which offers the properties of a barrier. For designs
with two plastic layers, this additional layer is embedded between
the plastic layers, protecting it from scratching or peeling. A
design with an inner layer has the advantage that the barrier effect
is obtained directly on the surface in contact with the preparation.
A design with an exterior layer ensures that, even in the event
that the layer peels, no particles from that layer will reach the
preparation.
These various designs, as well as other advantages of the invention,
will be described in conjunction with the sample designs presented
in the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a longitudinal section of a fully assembled, prefilled,
disposable syringe for medicinal purposes;
FIG. 2 shows a longitudinal section of a preassembled unit consisting
of the body of the syringe, integrated needle and attached protective
cap;
FIG. 3 shows a longitudinal section of a further design for the
syringe body with the needle encased in the nozzle;
FIG. 3A shows a longitudinal section of the design of FIG. 3 further
including a middle layer.
FIG. 4 shows a longitudinal section of a design for a distorted
needle encased in the nozzle;
FIG. 5 shows a longitudinal section of a design for a needle glued
into the nozzle; and
FIG. 6 shows a schematic representation of the manufacturing process
for the disposable syringe in this invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows a longitudinal section of a prefilled, sterile, disposable
syringe for medicinal purposes having a fill volume of less than
5 ml. According to one design, the fill volume of the prefilled,
sterile, disposable syringe in this invention lies preferably within
the range of 0.2-1 ml. There is a high demand in the medical community
for syringes in this range. They are needed, for example, for the
administration of heparin solutions. The body of the syringe consists
of a barrel (1) with a grip (2) at one end. Within the barrel (1)
is a plunger (4) which can be pulled through the barrel by means
of a plunger rod (3). When the syringe is prefilled and fully assembled,
the plunger (4) is located near the grip (2). After dosing, the
plunger (4) is located at the other end of the syringe barrel, as
shown in FIG. 1.
At this end of the syringe, the barrel turns into the nozzle (5),
at which point, as will be explained, a hypodermic needle (6) is
firmly fastened, i.e., not removable without damage. This hypodermic
needle (6) can be covered by a protective cap (7). The nozzle (5)
has, in addition, a collar (8), which can be more clearly discerned
from FIG. 3. The sleeve of the protective cap (7) seals onto the
cylindrical surface of the collar (8).
There are a number of alternatives available for the construction
of the protective cap (7). This cap can, for instance, be made from
an elastomer, primarily rubber, and the wall thickness then selected
so that, when the cap is put in place, the tip of the cannula (6)
penetrates the cap material, forming a seal. It is also conceivable
to make a plastic cap out of relatively hard elastic material, which
is then, at least in the interior area around the tip of the needle,
coated with a soft elastic material that would form a seal. In this
way, the soft elastic material can be selected on the basis of optimum
sealing properties (sealing function), while the hard elastic material
is better suited to counteract external, physical damage (protective
function).
The barrel of the syringe (1) with the integrated grip (2) and
nozzle (5), as well as the plunger rod (3) are made of plastic,
whereas the hypodermic needle (6), as usual, is made of a metallic
material and the plunger (4) of a soft elastic material. The walls
of the barrel (1) and the nozzle (5) have a permeability to water
vapor of less than 0.08 g/(m.sup.2.times.d) relative to a wall thickness
of 500 .mu.m. This low permeability to gas can be achieved by selecting
an appropriate type of plastic. Depending on demand, a multilayer
construction is also possible as shown, for example, in FIG. 3.
This multilayer construction will be explained later in more detail.
The walls of the syringe have, at least in the barrel area, a transparent,
glass-like section, so that the contents of the prefilled syringe
can be visually inspected at any time for possible contamination
or precipitates. Furthermore, for the body of the syringe and the
protective cap, a material is selected that can be sterilized by
gamma rays and/or ethylene oxide, without affecting chemical or
physical properties in such a way as to impair their function.
The hypodermic needle (6) in the sample design in FIG. 1 (and FIG.
3) is held in place by only the surrounding nozzle, without the
use of additional adhesives. The collar (8) shape of the nozzle
surface, which forms a seal with the protective cap (7), only leads
to small accumulations of material in the area surrounding the needle.
The plastic encasing the needle is therefore designed to be thin,
allowing it to shrink after molding around the needle. In this way,
a sufficient sealing and bonding effect can be achieved while the
plastic cools after injection into the mold. This effect becomes
particularly noticeable in the design shown in FIG. 3 where the
area surrounding the needle is relatively thin and has support ribs
(11).
The prefilled, fully assembled, disposable syringe in FIG. 1 consists
of a preassembled unit with a syringe body (125), an integrated
needle (6), and a protective cap (7) on the one hand, as well as
the plunger (4) and plunger rod (3) on the other hand. For the sake
of clarity, the preassembled unit is shown again separately in FIG.
2. The syringe manufacturer delivers it in an opened state (i.e.,
plunger and plunger rod separate) to the pharmacist, who fills the
preassembled syringe and finishes the assembly.
As shown in FIG. 1 the wall of the syringe barrel (1) and nozzle
(5) can be homogeneous, i.e., constructed as a single layer. The
corresponding plastic must then demonstrate all of the properties
required to keep the prefilled, sterile, disposable syringe fully
functional. It must be compatible with the prefilled medication
as well as have the necessary strength and impermeability to water
vapor. The wall of the barrel and, likewise, the nozzle can nevertheless
be constructed of several layers of various types of plastic. In
the sample design in FIG. 3 the syringe barrel (1) consists of
two different layers of plastic (9 and 10).
To better bring out details, a larger scale was chosen for FIG.
3 whereby, the barrel (1) is drawn with a break in the scale for
presentation reasons. In the area where the needle is fastened in
the nozzle (5), four ridges (11) are provided, distributed symmetrically
around the perimeter. Two of these ridges are shown uncut in FIG.
3. In each case the supports extend outward from above the collar
(8) up to the conical tip. These ridges or ribs (11) serve on the
one hand to strengthen the area surrounding the needle and, on the
other hand, to guide the edge of the protective cap (not shown)
when it is set in place.
The double layer construction of the syringe barrel (FIG. 3) has
the advantage that the barrier properties of the wall can be easily
tailored according to the requirements of the preparation to be
dispensed. In this way, for example, a type of plastic that acts
as a good barrier to oxygen diffusion can be combined with one that
blocks diffusion of water vapor.
Plastics that act as good barriers to water vapor diffusion are,
for example, cyclic olefin copolymers, polyethylenepentene and glass-clear
polypropylene; plastics that counteract oxygen diffusion are PET,
EVOH and PVDC.
A middle layer 14 made of a metallic, ceramic or glassy material,
such as SiO.sub.x, SiO.sub.x C.sub.y, and TiO.sub.x C.sub.y, can
also be placed between the two layers of plastic as shown in FIG.
3A to act as a diffusion barrier. With a typical thickness of 50-300
nm, this type of layer has a greater resistance to diffusion than
all known plastics and is substantially stronger. In this way, prefilled,
disposable syringes with an inorganic middle layer between two plastic
layers meet high demands with respect to their properties as diffusion
barriers, and thus allow for the consideration of a larger selection
of plastics.
A syringe body consisting of several layers of plastic can be manufactured
using multi-component injection molding. This is itself a familiar
process in which the inner layer is injected first, followed by
a second step in which the first layer is coated with another plastic.
Between steps it is also conceivable to plasma-treat the outer surface
of the first layer in order to effect changes in the plastic surface
aimed at enhancing the diffusion barrier. Adhesion-promoting layers
can also be applied to the outer layer of the first body.
Furthermore, a syringe barrel and nozzle consisting of a single
plastic layer construction can also be provided with an inner layer
made of a metallic, ceramic or glassy material. This prevents the
active substance from depositing on or migrating into the plastic.
This inner layer can also be designed to enhance the ability of
the plunger (4) to slide within the barrel (1). In this case, it
is conceivable to construct the metallic, ceramic or glass layer
in such a way that it gradually merges with a fluoropolymer layer,
such as PTFE, PFA or FEP, so that the otherwise standard siliconization
of the interior of the syringe barrel can be eliminated.
The aforementioned metallic, ceramic and glass layers, as well
as the fluoropolymer layers can be applied by a chemical vapor deposition
process (i.e., CVD, PVD, particularly plasma-CVD). This could ideally
be done using injection molding equipment. Plasma polymerization
layers or modifications to plastics are also possible using a plasma
treatment.
The selection of layer combinations must be optimized according
to the requirements of the entire packaging. Typical requirements
are high resistance to diffusion of gases (H.sub.2 O.sub.2 CO.sub.2)
both into and out of the syringe, resistance to diffusion of plastic
components or label adhesive into the syringe, as well as resistance
to sterilization by .gamma.-radiation, ethylene oxide gas, or to
autoclaving for longer than 20 minutes at a temperature of 121.degree.
C. When determining the sequence of layers, it must be taken into
consideration that the interior layer needs to be compatible with
the filling material (inertness, no adsorption or absorption of
preparation components) and that the exterior layer be as scratch
resistant as possible.
FIG. 4 shows a nozzle (5) design with an encased needle (6). Here
the needle is distorted (12), providing a positive shape-conforming
connection between the needle and nozzle, which ensures that the
needle is not pulled out or pushed in. Other forms are possible
(such as a bulge in the needle) instead of the distortion shown.
FIG. 5 shows a design of the nozzle (5) with a recess (13) for
adhesive used to secure the needle (6) in the nozzle. The adhesive
area lies, as shown, only in the front section of the nozzle, maintaining
a desirable distance from the syringe barrel (1). In this way, contact
between the adhesive and the contents of the syringe is largely
avoided.
The prefilled, disposable syringe in this invention can be manufactured,
sterilized and the low particle content maintained with relative
ease when compared with the state-of-the-art technology in European
Patent No. 0 227 401 B1 which describes a manufacturing (and filling)
process for the Mallinckrodt large volume, finished polypropylene
syringe. This technology is analogous to that described for this
invention.
In this familiar case, the next step is a mechanical removal of
waste particles and other contaminants, as well as a sterilization
step for the cap and the plunger.
The syringe barrel, with the nozzle, is washed after its production
to remove waste particles and pyrogens. Then it is dried. Afterward,
a lubricant is applied to the interior of the barrel.
Following this, the protective cap is set in place, the barrel
is filled with the liquid to be dispensed, the plunger is inserted
in the open end of the syringe body, and the entire disposable syringe
is sterilized in an autoclave. These process steps are performed
predominantly in the pharmacy, making the actual filling process
relatively expensive.
In contrast, the production of the prefilled, sterile disposable
syringe in this invention is as follows (FIG. 6):
1. The syringe body (1 and 5) with the integrated hypodermic needle
(6) is produced in clean room conditions (low particle environment).
The needles and protective caps are brought in a clean environment
into the clean room and mounted on the body of the syringe. For
designs in which the needle is encased in the nozzle, the body of
the syringe with the inserted needle is produced by injection molding.
If the syringe body has a double layer construction, production
is undertaken using two component injection molding.
2. In the next step, a lubricating layer is applied to the interior
of the syringe body under clean room conditions. Preferably, silicon
oil is applied as a lubricant onto the interior of the syringe barrel
by spraying, brushing, dipping or a similar process immediately
after production of the barrel. It is advantageous to heat-fix the
lubricant (air convection or radiation). A possible alternative
is the use of a UV-polymerizing silicon oil or similar silicon emulsion.
3. This is followed by the placement of the protective needle cap
(7).
4. Finally, while in the clean room, the body of the syringe is
placed in a closed storage container, sealed from particles or bacteria
and sterilized by gamma rays or, alternatively, by ethylene oxide
gas outside of the clean room.
Afterwards--at the pharmacy--the preassembled syringe unit is filled
with the preparation material to complete the assembly, i.e., the
plunger and plunger rod are inserted, followed by, if necessary,
autoclaving and inspection, as well as labeling and secondary packaging.
Preparatory steps prior to filling, inserting the plunger and plunger
rod, and further packaging are principally carried out according
to the state of the art.
The advantages of the process in this invention over the known
process are:
a) The complicated washing and drying of the syringe body have
been eliminated, because the plastic components can be produced
under clean room conditions (low particle environment). For small
volume containers, it is therefore not necessary to remove pyrogens
when using the present invention.
b) The silicon lubricant is coated immediately after the plastic
has been molded. In this way, the heightened surface activity, which
is still available shortly after production of the plastic, can
be utilized to improve the adhesion of the lubricant.
c) Sterilization can be simply carried out even before the syringe
is filled with the preparation. In this way, preassembled syringe
units that have already been sterilized can be made available to
pharmacists, substantially simplifying the process steps at the
pharmacy. |