Note: Descriptions are shown in the official language in which they were submitted.
The invention relates to a method of accelerating the
dissolution of hard-soluble lyophilized medicaments based on
proteins, in particular human proteins.
Various protein preparations to be used as medicaments
are stored in solid Eorm, preferably in lyophilized form, in
end containers; they have to be dissolved under sterile con-
ditions prior to their applieation, the dissolution having to
take place rapidly and the preparation having to be protected.
So far, this proeedure has involved difficulties,
since with the frequently applied manual shaking of the con-
tainer with the dissolution medium foam forms, which does
hardly, or not at all, subside. This foam formation is also
detrimental to the structure of the proteins; for, it is known
that thereby changes in the protein structure or a partial
decomposition may occur. The foam formation also has the dis-
advantage that the solution to be applied can be dosed only
inaccurately, and air in the preparation can render the injec-
tion completely impossible. In the directions for the dissolu-
tion a cautious pivoting of the con-tainer with the dissolution
medium is therefore mostly recommended, which is accordingly
time-consuming.
The invention aims at a~oiding these disadvantages
and difficulties and has as its object to provide a method by
which a gentle and quick dissolution of hard-soluble solid pro-
tein preparations under sterile conditions is facilitated whilst
avoiding foam formation involving the disadvantageous conse-
~uences describecl.
The invention provides a method of handling and
accelerating the dissolution of hard to dissolve lyophilized
medicament comprising human proteins, comprising the steps of,
-introduciny a sterile medicament in liquid form into
a container containing a magnetic body under sterile conditions;
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4~
-lyophilizing the liquid in the container so as to
obtain a solid lyophilized medicament;
-storing the sterile container containing the
lyophilized medicament and magnetic body;
-adding a sterile solvent to said container;
-subjecting the container to a rotating magnetic
field to set the magnetic body in motion; and
-maintaining the magnetic body in motion by means of
said magnetic field until the lyophilized medicament is
dissolved.
The invention thus also covers an end container fox
the hard-soluble lyophilized medicament, wherein a sterile
magnetic body, advantageously a little rod of stainless or
plastic-covered ferritic material, is enclosed in the batch.
The invention furthermore relates to an arrangement
for carrying out the method of the invention, which arrangement
comprises a heatable block of antimagnetic material having one
or more accommodation openings for accommodating end containers
containing a lyophilized batch and is characterized in that
below the accommodation openings a rotating magnetic stirrer is
installed.
A prefe~red embodiment consists in that insert rings
of antimagnetic material are insertable into the ac~ommodation
openings of the block, whose inner diameters are adapted to the
dimensions of standardized end containers, wherein fixing means
for the containers, preferably spring-loaded catches, are pro-
vided in the inner walls of the insert rings.
The invention will now be explained in more detail by
way of one embodiment with reference to the accompanying draw-
ings, wherein:
Figure 1 is a vertical section of the arrangement
according to the invention, and
, i
~L829~
Fig. 2 is a top view of the arrangement of the inven-
tion.
In a casing 1 a heatable block 2 of antimagnetic ma-
terial, preferably aluminium, is enclosed and secured by a
seal ledge 1'. The block has several accommodation openings
3, 3', 3", ~... with closed bottoms 4, 4', 4", ....
The accommodation openings have different diameters acco~na
to the sizes of the containers or end containers in question.
One or more accommodation openings, in the Example that de-
noted by 3, lie in the region of a magnetic rotary field.Into this accommodation opening 3 an insert ring 5 is inser-
table, whose inner diameter corresponds to the outer diameter
o~ a standardized end container. An end container 6 is in-
serted into the insert ring 5.
According to an advantageous embodiment a fixing means
7, preferably a spring-loaded catch, is incorporated in the
inner wall of the insert ring, preventing a rotation of the
end container 6. ~elow the block 2 a permanent magnet 8 is
fastened on a shaft 9, which is driven by a motor 10
fastened on rods 11. By driving the shaft the magnetic ro-
tary field is formed within the accommodation opening 3 and
the end container 6. In the end container there is the
lyophilized pro-tein preparation 12, into which a magnetiz-
able body, in particular a little rod 13 of stainless or
plastic-covered ferritic material, was introduced during
~illing of the container under sterile conditions. The
heating of the block 2 ~s effected by a heating rod 14. Part
of the accommodation openings designed by 3', 3", ... may
also be equipped with stirring means as described, another
part may be used for dissolving less sensible preparations.
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The following Example serves for illustrating the
invention:
A fibrin adhesive destined for the sealing of wounds,
based on human proteins and having a con-tent oE fibrinogen
and factor XIII is prepared in liquid form, sterile filtered
and filled into a sterilized end container into which a
sterilized rod of ferritic material had previously been in-
serted. Then the preparation present in the end con-tainer
is freeze-dried with the rod being enclosed in the solid
mass. After storage and prior to the application of the
preparation, sterile distilled water is introduced into the
end container with an injection syringe and the container
is inserted into the insert ring, as described in Fig. 1.
Then the permanent magnet 8 is set in motion by starting the
motor, with a rotary field forming which reaches into the
end container and sets the steel rod 13 in motion. By simul-
taneous heating, the dissolution takes place rapidly and
without foam formation. During the whole dissolution pro-
cess sterile conditions are maintained.
