SK281644B6 - Device for uniform suspension application on collagen carrier - Google Patents

Abstract

The invention relates to a method and apparatus for uniformly applying a suspension to a suspension carrier for the production of a material for dressing and healing wounds. The method comprises the following steps: a) filling the suspension into an elongate container having a base frame and two surfaces with openings comprising an upper surface and a lower surface, the upper surface being movable relative to the lower surface, b) sliding the suspension carrier under the elongate container ; and c) a continuous movement of the upper surface back and forth and the suspension can drip onto the suspension carrier, which slides under the elongate container and is evenly applied to the suspension carrier. The device consists of a suspension container having a base frame (1) and two surfaces with openings forming the bottom of the container, the two surfaces with openings comprising an upper surface (3) and a lower surface (2), the upper surface (3) being movable with respect to to the lower surface (2) so as to allow continuous movement of the upper (3) surface here and there.ŕ

Description

Technical field

The invention relates to a method and apparatus for uniformly applying a suspension to a suspension carrier for the manufacture of wound dressing and wound healing material.

BACKGROUND OF THE INVENTION

EP 0 059 265 discloses a wound dressing and healing material consisting of a single collagen carrier which is coated with one fibrinogen component, one thrombin component and additions such as calcium ions, protease inhibitors or heparin antagonists.

For the manufacture of this material, individual components or additions suspended in an organic solvent such as ethanol are used and subsequently applied, for example by spraying, to the collagen carrier.

However, some problems arise because the coating suspension is difficult to process. For example, nozzles used for liquids of this kind are immediately blocked. It is possible to use liquid-air nozzles with a larger diameter, but only the nozzles with the largest diameters offered allow for trouble-free operation. However, these nozzles have one decisive disadvantage. A fuzzy delimitation of the outlet stream does not produce the desired uniform suspension layer, but a trapezoidal applied profile on the collagen support. This leads to considerable losses at the edges of the collagen carrier or to the loss of valuable suspension.

EP-A 472 050 discloses a device for applying a liquid film to a casting belt, which causes the liquid to be distributed from the inflow opening up to a plurality of outflow openings through the individual liquid distribution spaces immediately adjacent to each other.

The liquid distribution takes place in the form of a strain, namely from one hole to two, four, eight, sixteen, and so on. outlets. This device is not suitable for the uniform application of any suspension that contains fibrinogen components and one thrombin component, since by multiple separation of the liquid streams, the fluid spaces become clogged and clogged by the suspension, and this is more pronounced than when using nozzles.

It is therefore an object of the present invention to avoid the aforementioned drawbacks of the prior art methods.

This object can now be solved by the device according to the invention.

SUMMARY OF THE INVENTION

The present invention provides a method of manufacturing a wound dressing and healing material comprising the following steps:

(a) filling the suspension into an elongated container having a base frame and two aperture surfaces comprising an upper surface and a lower surface, the upper surface being movable relative to the lower surface;

b) moving the suspension carrier under the elongated container in the transport direction; and

c) continuously moving the top surface back and forth so that the suspension can drip onto the suspension carrier that slides under the elongate container, thereby uniformly applying the suspension to the suspension carrier.

In step c), the continuous back and forth movement is performed in a direction transverse to the sliding direction of the suspension carrier. Preferably, this movement is substantially perpendicular to the sliding direction of the suspension carrier.

In step c), it is possible to control the suspension flow by adjusting the extent of the upper surface deflection. The suspension is pumped into the container at a constant rate, the openings in the surfaces having the openings displaced relative to each other such that the container is closed. Steps b) and c) begin when the suspension in the elongated vessel reaches a steady state level corresponding to a given pumping rate. The suspension level is kept constant during steps b) and c).

Another object of the invention is an apparatus for uniformly applying a suspension to a suspension carrier for producing a wound dressing and wound healing material comprising a container that is filled with the suspension. The container comprises a base frame and two surfaces with openings forming the bottom of the container. The apertured surfaces include an upper surface and a lower surface, the upper surface movable relative to the lower surface so as to allow continuous movement of the upper surface back and forth so that the suspension can be uniformly applied to the suspension carrier while the suspension carrier moves under the device in the direction transport.

The device according to the invention consists of a vessel equipped with a rectangular bottom surface in the form of a plate with openings, bounded by a base frame on which the side delimiting walls of the vessel are located. Immediately above the bottom surface with openings there is a second surface with openings that can be moved inside the container - a movable surface in the form of a plate with openings.

The suspension that is fed into the vessel consists of one fibrinogen component, one thrombin component, as well as aprotinin as a protease inhibitor and other additions such as calcium ions or heparin antagonists in an alcohol such as ethanol, n- or ipro-panol, or n- or i-butanol. It is used for the production of wound dressing and healing material and is thus used for medical purposes.

For this reason, the device, especially the areas with openings, must be made of non-abrasive material which does not react in contact with the suspension. Suitable materials are, for example, stainless steel or titanium. The side boundary walls may also be of glass or plexiglass, which makes it possible to observe the suspension in the container well.

The two aperture surfaces each have one or more rows of apertures, the flow apertures in the rows of apertures always being equidistant. Preferably, a plurality of holes are provided on the aperture surfaces.

The diameter of the flow orifices should be chosen sufficiently large to prevent the flow orifices from clogging with the suspension.

The ratio of the flow orifice diameters to the diameter of the largest particles of the suspension is about 5: 1 to 50: 1, preferably 7.5: 1 to 40: 1 and particularly preferably 10: 1 to 30: 1.

The largest particles present in the suspension have a diameter of about 0.1 mm to 0.2 mm.

In a preferred embodiment of the device according to the invention, the flow openings have a diameter of about 2 to 3 mm.

The centers of the flow openings preferably lie at a distance of between 2 and 8 mm, particularly preferably at a distance of 3 to 4.5 mm, transverse to the application face.

Depending on the number of rows of holes, the distance between two adjacent holes in one row of holes may be up to 16 mm or more.

To apply the suspension to the suspension carrier, a pre-homogenized suspension is pumped into the container at a constant rate pump, initially the movable surface with the openings lies on the bottom surface with the openings so that the flow openings are closed. The seal should be as efficient as possible and may be supported by loading the weight on a movable area with openings if necessary.

SK 281644 Β6

When the suspension in the container reaches a stationary level corresponding to a predetermined pumping rate, the application apparatus is set in motion. As a result, the movable surface with the openings starts to move back and forth above the stationary bottom plate with the openings. In one position - preferably in the middle between the two turning points at which the change of direction of the movable plate with the holes occurs - both plates overlap and the suspension can drip onto the suspension carrier which is guided on the conveyor belt under the application apparatus.

The level of suspension in the deposition apparatus remains constant as long as a new suspension is added by the pump.

By varying large oscillations of the movable surface in the form of a plate with openings, the ratio of open time intervals to closed time intervals can be adjusted over a wide range. In this way, it is also possible to select hole diameters in which there are no more complications and at the same time the drip rate is limited.

Taking into account the alignment of the rows of holes and the speed of the treadmill, a droplet distribution pattern can be obtained in which the droplets form the tips of equilateral triangles, corresponding to the tightest spherical layer.

The movement of the plate with the openings preferably takes place at a right angle to the conveying direction of the treadmill. At the same time, the slurry is kept constant by moving the movable plate back and forth so that a uniform distribution of the components on the suspension carrier is achieved. Alternatively, it is possible to stir by an additional device on a movable surface with openings or by means of a mixer.

Another embodiment is designed so that instead of the plates, two moving tubes, one tube and one half tube, respectively, are used. The outer tube or the half tube is preferably stationary and is provided with outlet openings at the bottom. Into this tube is inserted an inner tube which is provided with rows of openings that can coincide with the openings of the outer tube. By periodically rotating the inner tube or the semi-tube back and forth, the outlets open and close periodically to achieve the desired effect.

By means of the device according to the invention, it is possible to apply the suspension evenly at a precisely defined width to the suspension carrier without causing marginal loss on the suspension or on the suspension carrier. The coating profile obtained after evaporation of the suspension medium is not, as in the spraying techniques known to date, trapezoidal, but rectangular.

A comparative experiment in which the edge loss achieved with the liquid-air nozzle technique used to date has been compared with the loss achieved with the apparatus of the present invention shows that with the liquid-air nozzle, more than 5 impacts are greater on the side of the suspension liquid. than with the device according to the invention.

This is a relatively low productivity effort. The ratio is all the greater the larger the deployments.

The loss of suspension when applied by means of the device according to the invention is only conditional upon the remaining content remaining in the container when the suspension is pumped.

BRIEF DESCRIPTION OF THE DRAWINGS

In FIG. 1 shows the bottom of the device according to the invention, FIG. 2 shows an exemplary layout of the openings of the bottom surface, and FIG. Figures 3 and 4 show slurry application profiles transversely to the conveying direction of a conveyor belt according to the invention and a comparative example.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

In a container with a bottom plate with holes and a movable plate with holes having the following dimensions: Width: 450 mm Depth: 12 mm

Number of rows of holes: 2

Outlet diameter: 2 mm

Distance between centers of two outlets in one row: 8 mm

Spacing between rows of orifices: 6.9 mm (alignment of the outflow orifices is shown in Fig. 2), with open plates 2, 3, a suspension of 55 mg / ml fibrinogen 20 IU / ml thrombin and 0.71 Ph was pumped. Eur. U / ml aprotinin in ethanol at a rate of 450 ml / min until a stationary liquid height of 50 mm was reached. At this point, a movable plate was set in motion with holes of 400 cycles / min, with a 6 mm swing in both directions. The suspension dripped at 450 mm width onto the collagen sponge from a 5 mm height which was transported by means of a treadmill at a speed of 1 m / min. at right angles to the movement of the movable plate under the container. After evaporation of the suspension liquid, the collagen carrier was coated with about 5.5 mg / cm ^{2 of} fibrinogen 2 IU / cm ^{2 of} thrombin and 0.071 Ph.EUr.U./cm ² aprotinin.

The marginal loss was below 1%.

The cross-sectional profile of the conveyor belt is shown in FIG. Third

COMPARATIVE EXAMPLE Again, a suspension of the same composition was applied at a width of 450 mm on a collagen carrier that had been transplanted on a conveyor belt. Figure 4 shows the best result in several experiments with different liquid-air nozzles.

In this example, a combination of Spraying Systems Inc. nozzles was used. with a change of plate. Of the many specimens of the same type, the best specimen was chosen.

The cross-sectional application profile of the conveyor belt is shown in FIG. 4 and shows the distribution of fibrinogen transversely to the transport direction of the treadmill. The loss on both sides of the dropping amount was still about 20% under these conditions.

Claims (17)

PATENT CLAIMS A method for producing wound dressing and healing material, comprising the steps of: a) filling the suspension into an elongated container having a base frame and two aperture surfaces comprising a top surface and a bottom surface, the top surface being movable relative to the bottom surface, b) moving the suspension carrier under the elongated container in the transport direction; and c) continuously moving the top surface back and forth and the suspension can drip onto the suspension carrier, which slides under the elongated container, and is uniformly applied to the suspension carrier. A method according to claim 1, comprising the step of carrying out any one of the claims in step c), wherein steps b) to c) 3, any of the claims, wherein step c) further comprises up to 4, a continuous back and forth movement in a direction that is transverse to the sliding direction of the suspension carrier. The method of claim 2, wherein the transverse direction is substantially perpendicular to the sliding direction of the suspension carrier. 4. The method of claim 1 carrying out simultaneously. 5. A method according to the step of regulating the suspension flow by adjusting the extent of the upper surface deflection. Method according to any one of claims 1 to 5, characterized in that step a) comprises the step of pumping the suspension into the container at a predetermined constant speed, wherein the openings in the surfaces with the openings are displaced relative to each other such that the container is closed; (b) and (c) begin when the suspension in the elongated vessel reaches a steady-state level corresponding to a given pumping rate. 7. The method of claim 6, further comprising the step of maintaining a constant level of the suspension during steps b) and c). The method of any one of claims 1 to 7, wherein the suspension is a low viscosity suspension comprising a fibrinogen component and a thrombin component, wherein during step c) a single layer comprising the fibrinogen component and the thrombin component is formed on the suspension carrier. The method of any one of claims 1 to 8, wherein the suspension comprises aprotinin. Process according to any one of claims 1 to 9, characterized in that the suspension comprises an organic solvent. Process according to claim 8 or 9, characterized in that the suspension is an alcohol. The method of any one of claims 1 to 11, wherein the two orifice surfaces comprise corresponding rows of evenly spaced flow orifices, the method comprising the step of arranging the flow orifices to align and not align with each other in two surfaces with holes during step c). The method of any one of claims 1 to 12, further comprising the step of stirring the suspension during step c). A method according to any one of claims 1 to 13, characterized in that the suspension carrier is a collagen carrier. Apparatus for uniformly applying a suspension to a suspension carrier for producing wound dressing and healing material, comprising a container that is filled and having a base frame (1) and two surfaces with openings forming the bottom of the container, the two surfaces with the apertures comprising an upper surface (3) and a lower surface (2), the upper surface (3) being movable relative to the lower surface (2) so as to allow continuous movement of the upper (3) surface back and forth so that the suspension can be uniform applied to the suspension carrier, wherein the suspension carrier moves under the device in the transport direction. Device according to claim 15, characterized in that the upper surface (3) is movable in a direction transverse to the sliding direction of the suspension carrier. Apparatus according to any one of claims 15 to 17, characterized in that the lower surface with the openings (2) and the upper movable surface with the openings (3) are provided with at least one series of flow openings which are equidistantly spaced from one another. Device according to claim 18, characterized in that the lower surface with the openings (2) and the upper movable surface with the openings (3) are provided with more than one series of flow openings, the distance between adjacent openings in the row being up to 16 mm or greater. Apparatus according to claim 18 or 19, characterized in that the distance between the centers of the holes is approximately 2 to 8 mm, preferably 3 to 4.5 mm. A device according to any one of claims 18 to 21 20, characterized in that the suspension comprises particles, and the ratio of the diameter of the flow openings in the two surfaces with the openings (2, 3) and the diameter of the largest particles is 5: 1 to 50: 1, preferably 7.5; 1 to 40: 1, and most preferably 10: 1 to 30: 1. A device according to any one of claims 15 to 22 21, characterized in that the flow rate of the suspension can be controlled by adjusting the deviation of the movable surface with the apertures. A device according to any one of claims 15 to 15 22, characterized in that it is formed as a rectangular elongated container with a perforated bottom and a base frame (1) inside the container which holds the movable surface with the openings (3). Apparatus according to any one of claims 15 to 22, characterized in that the container which is filled with the suspension is constructed as a tube or a half-tube, provided with openings on its bottom, in which a movable tube or a half-tube with openings fits. Apparatus according to any one of claims 15 to 22, characterized in that the movable vessel which is filled with the suspension is constructed as a tube or a half-tube equipped with openings on its bottom which fits into the movable tube or the half-tube with openings. 2 drawings 17. The apparatus of claim 16, wherein the transverse direction is substantially perpendicular to the sliding direction of the suspension carrier.