CA1182444A - Method of accelerating the dissolution of a hard- soluble lyophilized medicament using a magnetic stirrer - Google Patents

Method of accelerating the dissolution of a hard- soluble lyophilized medicament using a magnetic stirrer

Info

Publication number
CA1182444A
CA1182444A CA 383132 CA383132A CA1182444A CA 1182444 A CA1182444 A CA 1182444A CA 383132 CA383132 CA 383132 CA 383132 A CA383132 A CA 383132A CA 1182444 A CA1182444 A CA 1182444A
Authority
CA
Grant status
Grant
Patent type
Prior art keywords
container
magnetic
lyophilized
method
magnetic body
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA 383132
Other languages
French (fr)
Inventor
Heinz Redl
Thomas Seelich
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Immuno AG
Original Assignee
Immuno AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING, DISPERSING
    • B01F13/00Other mixers; Mixing plant, including combinations of mixers, e.g. of dissimilar mixers
    • B01F13/08Magnetic mixers ; Mixers having magnetically driven stirrers
    • B01F13/0818Magnetic mixers ; Mixers having magnetically driven stirrers using independent floating stirring elements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING, DISPERSING
    • B01F1/00Dissolving
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING, DISPERSING
    • B01F15/00Accessories for mixers ; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F15/06Heating or cooling systems

Abstract

ABSTRACT OF THE DISCLOSURE:

In a method of accelerating the dissolution of hard-soluble lyophilized medicaments based on proteins, a magnetic body is introduced into an end container under sterile conditions prior to the lyophilization of the batch. The end container is brought into the region of a magnetic rotary field after addition of a solvent to the lyophilized batch, whereupon the magnetic body is set in motion. An arrangement for carrying out the method includes a heatable block of anti-magnetic material with one or more accommodation openings for the end containers. A rotating magnetic stirrer is installed below the accommodation openings.

Description

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;

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.

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.

Claims (5)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method of handling and accelerating the dissolution of hard to dissolve lyophilized medicament comprising human proteins, comprising the steps of, - introducing a sterile medicament in liquid form into a container containing a magnetic body under sterile conditions;
- lyophilizing the liquid in the container so as to obtain a solid lyophilized madicament;
- 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.
2. A method as set forth in claim 1, wherein said magnetic body is a little rod of stainless ferritic material.
3. A method as set forth in claim 1, wherein said magnetic body is a little rod of plastic-covered ferritic material.
4. A method as set forth in claim 1, 2 or 3 wherein said magnetic body and said container are sterilized separately.
5. A method of accelerating the dissolution of a human fibrin adhesive in an end container, which method comprises the steps or introducing a magnetic rod and the fibrin adhesive containing fibrinogen and Factor XIII in liquid form into said end container under sterile conditions, subsequently lyophilizing the fibrin adhesive in liquid form in said end container so as to obtain a lyophilized fibrin adhesive, storing said lyophilized fibrin adhesive, adding sterile distilled water to said end container with an injection syringe, bringing said end container into the region of a magnetic rotary field and heat, and thereby, setting said magnetic rod in motion and simultaneously heating said end container until said lyophilized fibrin adhesive has been dissolved.
CA 383132 1980-08-25 1981-08-04 Method of accelerating the dissolution of a hard- soluble lyophilized medicament using a magnetic stirrer Expired CA1182444A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ATA4289/80 1980-08-25
AT428980A AT371719B (en) 1980-08-25 1980-08-25 Method and apparatus for accelerating the dissolution of lyophilized drugs schwerloeslichen

Publications (1)

Publication Number Publication Date
CA1182444A true CA1182444A (en) 1985-02-12

Family

ID=3562079

Family Applications (1)

Application Number Title Priority Date Filing Date
CA 383132 Expired CA1182444A (en) 1980-08-25 1981-08-04 Method of accelerating the dissolution of a hard- soluble lyophilized medicament using a magnetic stirrer

Country Status (9)

Country Link
JP (1) JPS6353823B2 (en)
BE (1) BE890002A (en)
CA (1) CA1182444A (en)
DE (1) DE3129995C2 (en)
DK (1) DK157331C (en)
ES (1) ES8303111A1 (en)
FR (1) FR2488802B1 (en)
GB (1) GB2082929B (en)
NL (1) NL189799C (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4735616A (en) * 1985-06-20 1988-04-05 Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte Arrangement for applying a tissue adhesive
US4909251A (en) * 1988-05-31 1990-03-20 Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte Tissue adhesive
WO2008117746A1 (en) 2007-03-22 2008-10-02 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Solid fibrinogen preparation

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3308892A1 (en) * 1983-03-12 1984-09-13 Vaw Ver Aluminium Werke Ag Heatable magnetic stirrer for hochtemperaturaufschluesse
DE3439654C2 (en) * 1984-10-30 1987-02-26 Brauerei Beck Gmbh & Co, 2800 Bremen, De
DE4017868A1 (en) * 1990-06-02 1990-10-31 Siegfried Dipl Phys Stiller Mixing chamber - for dilution and haemolysis of blood free from air bubbles
DE4406217C2 (en) * 1994-02-25 1997-04-17 Janke & Kunkel Kg Magnetic stirrer with a housing
US5529391A (en) * 1994-09-22 1996-06-25 Duke University Magnetic stirring and heating/cooling apparatus
US5549382A (en) * 1995-04-27 1996-08-27 Correia, Ii; Bernard A. Stirrer for food preparation
DE19617369A1 (en) * 1996-04-30 1997-11-06 Immuno Ag Storage-stable fibrinogen preparations
US5899567A (en) * 1997-09-23 1999-05-04 Morris, Jr.; Joseph E. Magnetic synchronized stirring and heating test apparatus
US6382827B1 (en) * 2000-11-01 2002-05-07 Dade Behring Inc. Method and apparatus for mixing liquid solutions using a rotating magnet to generate a stirring vortex action
US6467946B1 (en) * 2001-04-24 2002-10-22 Dade Microscan Inc. Method and apparatus for mixing liquid samples in a container using rotating magnetic fields
WO2003014732A1 (en) 2001-08-10 2003-02-20 Symyx Technologies, Inc. Apparatuses and methods for creating and testing pre-formulations and systems for same

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE498056A (en) * 1949-03-25
FR1200467A (en) * 1958-06-25 1959-12-22 Rech S Et De Controle Du Caout Device for stirring and thermal control, particularly applicable in laboratories
GB921719A (en) * 1960-05-06 1963-03-20 Nat Res Dev Improvement in magnetic stirrers
US3356346A (en) * 1966-01-03 1967-12-05 Landsberger Kurt Test tube stirring support
CA1072538A (en) * 1975-07-03 1980-02-26 Leonard E. Brown Bottom supported magnetic stirring element
US3997272A (en) * 1975-12-15 1976-12-14 Varian Associates Magnetic stirrer improvement

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4735616A (en) * 1985-06-20 1988-04-05 Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte Arrangement for applying a tissue adhesive
US4909251A (en) * 1988-05-31 1990-03-20 Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte Tissue adhesive
WO2008117746A1 (en) 2007-03-22 2008-10-02 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Solid fibrinogen preparation
US9775884B2 (en) 2007-03-22 2017-10-03 The Chemo-Sero-Therapeutic Research Institute Solid fibrinogen preparation

Also Published As

Publication number Publication date Type
NL189799C (en) 1993-08-02 grant
DK157331C (en) 1990-05-14 grant
FR2488802B1 (en) 1985-01-04 grant
ES8303111A1 (en) 1983-02-01 application
DK157331B (en) 1989-12-18 grant
ES504858A0 (en) 1983-02-01 application
BE890002A (en) 1981-12-16 grant
DE3129995C2 (en) 1987-01-15 grant
DE3129995A1 (en) 1982-05-27 application
JPS5789863A (en) 1982-06-04 application
GB2082929A (en) 1982-03-17 application
GB2082929B (en) 1985-02-27 grant
NL8103695A (en) 1982-03-16 application
NL189799B (en) 1993-03-01 application
JPS6353823B2 (en) 1988-10-25 grant
DK351481A (en) 1982-02-26 application
FR2488802A1 (en) 1982-02-26 application
ES504858D0 (en) grant
CA1182444A1 (en) grant
BE890002A1 (en) grant

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