Note: Descriptions are shown in the official language in which they were submitted.
A device for the even application of a suspension to a collagen carrier
The invention relates to a device for the even application of a suspension to
a
collagen carrier for the production of a material for sealing and healing
wounds.
A material for sealing and healing wounds which comprises a collagen carrier
coated with a fibrin component, a thrombin component, such as calcium ions,
protease inhibitors or heparin antagonists, is known from US 4,453,939.
To prepare this material, the individual components or additives are suspended
in an organic solvent, e.g. ethanol, and subsequently applied to a collagen
carrier, e.g. by means of spraying.
In doing this several problems arise, because the suspension to be applied is
difficult to handle. For example, the nozzle used usually for these purposes
clog immediatly. Lingnial air nozzles permit the use of a larger diameter, but
even in this case, only nozzles with the largest diameter available enable
working with a sufficient lack of trouble. However these nozzles show a
decisive disadvantage. The indistinct definition of the exiting stream does
not
an even layer of the suspension but creates a trapezoidal coating profile on
the
collagen carrier. This leads to considerable losses of collagen carrier and
valuable suspension at the edges.
A device for applying a liquid film to a fabric web according to the pouring-
out
principle is known from EP-A 472 050. By means of individual partitions for
liquid which are located directly next to one another, this device achieves a
forced distribution of the liquid form a feed opening to a number of outflow
openings. The liquid is distributed in the form of a family tree, i.e step by
step
from one opening to two, four, eight, sixteen etc, outflow openings. This
device
is not suitable for the even distribution of a suspension comprsing fibrinogen
and thrombin components, as the several divisions of the liquid stream cause
conglutination and clogging of the partitions by the suspension; furthermore,
this conglutination and clogging occurs to a greater extent then when nozzles
are used.
The problem solved by the present invention was therefore to prevent the
disadvantages of the previosly known methods.
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Brief Description of the Drawing's
Further aspects and advantages of the present invention will
become apparent from the following description, taken together
with the accompanying drawings, in which:
Figure 1 is a top plan view illustrating a device according to
the present invention for the even application of a suspension
to a collagen carrier;
Figure 2 is a schematic diagram showing the size and positioning
of the flow-thorough holes in the device according to the present
invention of Example 1;
Figure 3 is a graph showing the profile of the fibrinogen
coating, at a right angle to the direction of transport, produced
by the device of Example 1; and
Figure 4 is a graph showing the profile of the fibrinogen
coating, at a right angle to the direction of transport, produced
by a previously known spraying technique.
CA 02120477 2001-02-16
2
The object of the invention is therefore a device for the even application of
a
suspension to a collagen carrier for the production of a material for sealing
and healing wound, comprising a container into which the suspension is filled
the bottom of said container consisting of a base frame (1) and a perforated
base plate (2) whereby a moveable perforated plate (3) is mounted directly
above the perforated base plate (2).
A further object of the invention is therefore a process for the production of
a
material for sealing and healing wounds, comprising: filling a suspension into
an elongated container, the elongated container having a base frame and two
perforated plates forming a bottom of the elongated container, the two
perforated plates including an upper plate and a lower plate, and the upper
plate being movable relative to the lower plate; transporting a collagen
carrier
below the elongated container in a transport direction; and continuously
moving the upper plate back and forth in a direction that is at a right angle
to
the transport direction so as to allow the suspension to drip on to the
collagen
carrier being transported below the elongated container, whereby the
suspension is evenly applied to the collagen carrier.
The container is provided with a rectangular perforated base plate (base plate
(2)) which is surrounded by the base frame (1) and upon which lateral
boundary walls rest. A second pertorated plate is mounted directly above the
perforated base plate (2) and this plate can be moved back and forth inside
the container: movable perforated plate (3).
The suspension to be filled into container comprises a fibrinogen component,
a thrombin component, aprotinin (which acts as protease inhibitor) and other
additives such as calcium ions or heparin antagonists in alcohol such as
ethanol, n- or I- propanol or n- or I-butanol. This suspension is used for the
production of a material for sealing and heating wounds and for other medical
uses. For this reason, the device, especially the perforated plates, must be
CA 02120477 2001-02-16
2a
constructed of a material which is abrasion-resistant and which cannot react
with the suspensions. Suitable materials would be for example high grade
steel or titanium. The lateral boundary walls can also be constructed of glass
or plexiglass, which makes it possible to easily observe the suspension in the
container.
Both perforated plates are provided with one or more rows of holes, whereby
the flow-through holes in the rows are arranged at equal distances.
Preferably the plates are provided with several rows of holes.
The diameter of the flow through holes chosen must be large enough to
prevent the suspension from clogging them.
The ratio of the flow-through holes' diameter to that of the largest particle
in
the suspension amounts to approximately 5 : 1 to 50 : 1, preferably 7.5 : 1 to
40 : 1 and most preferably 10 : 1 to 30 : 1.
The largest particles present in the suspension possesses a diameter of
approximately 0.1 mm to 0.2 mm.
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In a perferable embodiment of the device according to the invention the
diameter of the flow-through holes is approximately 2 to 3 mm.
The center of the flow-through holes are preferably located at a distance or
approximately 2 to 8 mm, especially perferabyl at a distance of 3- 4.5 mm from
the face of the coating and at right angle to it.
Depending on the number of rows, the distance between the neighboring holes
in a row can measure up th 16 mm and more.
In applying the suspension to a collagen carrier, the previously homogenized
suspension is pumped into the container at a constant speed, whereby the
movable perforated plate lies on top of the perforated base plate in the
beginning in such a way as to close the flow-through holes. The seal should be
as efficient as possible and can optionally be assisted by bearing weights
being
placed on top of the movable perforated plate.
As soon as the suspension in the container has reached the stationary level
corresponding to the given pumping speed the coating apparatus is put into
operation. This causes the movable perforated plate to move back and forth
over the stationary perforated plate. The two perforated plates coincide at a
certain position (preferably in the middle between the two stationary points
at
which the movably perforated plate changes direction) and the suspension can
drip onto the collagen carrier, which is passed under the coating apparatus on
a conveyer belt.
The level of the suspension in the coating apparatus remains constant during
this process provided that additional suspension is pumped in.
The varying excursional distances of the movable perforated plate allows a
wide range for setting the ratio of the intervalls of closure and opening.
This
makes it possible th choose hole diameters of a size with which no
complications result and, at the same time, limit the drip speed.
In consideration of the arrangement of the holes and the speed of the conveyor
belt, a distribution pattern of the holes can be achieved with which the drops
form the corners of equilateral triangles, which correspond to layer of
spheres
packed as tightly as possible.
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The perforated plate preferably moves at a right angle to the direction of the
conveyor belt.
The back and forth movement of the movable perforated plate simultaneously
ensures that the suspension remains homogenous, so that an even distribution
of the components is achieved on the collagen carrier.. Mixing can be assisted
optionally by means of additional arrangements on the movable perforated
plate or by a mixer.
Another embodiment of the invention is that the container into which the
suspension is filled is constructed as a tube or semi-tube provided with holes
into which a movable perforated tube or semi-tube is mounted. Moving the
inner tube causes periodically opening and closing of the holes, thus
achieving
the desired effect.
With the aid of the device according to the invention, applying an exactly
defined breadth of the suspension is possible without loss of suspension or
collagen carrier at the edge.
The profile of the coating achieved after evaporation of the suspension medium
is not trapezoidal (as it is using known spraying techniques) bit rectangular.
A comparative test, in which the loss at the edge resulting when using
previously known spraying technique, in which an lignial air nozzle is used,
is
compared to the loss resulting with the device according to the invention,
shows that more than five times more suspension is lost with the ligniai air
nozzle than with the device according to the invention.
A relatively small batch was used in this test. The ratio increases
correspondingly as the batch size increases. A loss of suspension during
application with the device according to the invention occurs only with the
residual volume of suspension remaining in the container after pumping
ceases.
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Example 1:
In a container provided with a perforated base plate and a movable perforated
plate with the following dimensions:
Breadth: 450 mm
Depth: 12 mm
Number of rows of holes: 2
Diameter of flow through holes: 2 mm
Distance between the centers of the two flow through holes located in one row:
8mm
Distance between the rows of holes: 6.9 mm
(The arrangement of the flow-through holes is shown in fig. 2).
in which the perforated plates were closed, a suspension of 55 mg/ml of
fibrinogen 20 IU/ml of thrombin and 0.71 Ph. Eur. U/ml of aprotinin in ethanol
was pumped at a speed of 450 ml/min until the stationary level of the liquid
of
50 mm was reached. At that point, the movable perforated plate was put into
motion at 400 cycles/min, whereby the excursion measured 6 mm in both
directions.
A breadth of 450 mm of the suspension was then dripped onto a collagen
sponge measuring 5 mm in height which was being transported underneath the
container by a conveyor belt at a speed of 1 m/min and at a right angle to the
movement of the movable perforated plate. After evaporation of the suspension
liquid the collagen carrier was coated with approximately 5.5 mg/cm2 of
fibrinogen, 2 IU/cm2 of thrombin and 0,071 Ph.Eur.U./cm2 of aprotinin.
The loss at the edge was less than 1 %.
The profile of the coating at a right angle to the direction of transport is
shown
in flg.3.
Comparative Example:
A breadth of 450 mm of a suspension with the same composition was again
applied to a collagen carrier which was transported on a conveyor belt. Fig 4
shows the best result achieved in numerous tests with various lignial air
nozzles.
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In this example, a nozzle combination from Spraying systems Inc., which
features a turnaround surface, was used. The best sample was chosen from
numerous examples of the same model.
The profile of the coating at a right angle to the direction of transport is
shown
in fig. 4 , in which the distribution of fibrinogen at a right angle to the
direction
of the conveyor belt is shown. Even under these conditions, the loss of
suspension falling from both sides still amounts to approximately 20 %.
