CA2054196C - Device for preparing bone cement - Google Patents

Device for preparing bone cement

Info

Publication number
CA2054196C
CA2054196C CA002054196A CA2054196A CA2054196C CA 2054196 C CA2054196 C CA 2054196C CA 002054196 A CA002054196 A CA 002054196A CA 2054196 A CA2054196 A CA 2054196A CA 2054196 C CA2054196 C CA 2054196C
Authority
CA
Canada
Prior art keywords
agitator
mixing
bone cement
lid
rod
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 - Lifetime
Application number
CA002054196A
Other languages
French (fr)
Other versions
CA2054196A1 (en
Inventor
Thomas Nilsson
Jan Thorling
Staffan Smeds
Soren Jonsson
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.)
Cemvac System AB
Original Assignee
Cemvac System AB
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
Application filed by Cemvac System AB filed Critical Cemvac System AB
Publication of CA2054196A1 publication Critical patent/CA2054196A1/en
Application granted granted Critical
Publication of CA2054196C publication Critical patent/CA2054196C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/88—Osteosynthesis instruments; Methods or means for implanting or extracting internal or external fixation devices
    • A61B17/8802—Equipment for handling bone cement or other fluid fillers
    • A61B17/8805—Equipment for handling bone cement or other fluid fillers for introducing fluid filler into bone or extracting it
    • A61B17/8825—Equipment for handling bone cement or other fluid fillers for introducing fluid filler into bone or extracting it characterised by syringe details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/50—Mixing liquids with solids
    • B01F23/565—Mixing liquids with solids by introducing liquids in solid material, e.g. to obtain slurries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/44—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement
    • B01F31/441—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement performing a rectilinear reciprocating movement
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/50—Movable or transportable mixing devices or plants
    • B01F33/501—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use
    • B01F33/5011—Movable mixing devices, i.e. readily shifted or displaced from one place to another, e.g. portable during use portable during use, e.g. hand-held
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/50—Mixing receptacles
    • B01F35/514—Mixing receptacles the mixing receptacle or conduit being transparent or comprising transparent parts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/713—Feed mechanisms comprising breaking packages or parts thereof, e.g. piercing or opening sealing elements between compartments or cartridges
    • B01F35/7137—Piercing, perforating or melting membranes or closures which seal the compartments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/7173—Feed mechanisms characterised by the means for feeding the components to the mixer using gravity, e.g. from a hopper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71—Feed mechanisms
    • B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/7173—Feed mechanisms characterised by the means for feeding the components to the mixer using gravity, e.g. from a hopper
    • B01F35/71731—Feed mechanisms characterised by the means for feeding the components to the mixer using gravity, e.g. from a hopper using a hopper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/75—Discharge mechanisms
    • B01F35/754—Discharge mechanisms characterised by the means for discharging the components from the mixer
    • B01F35/75425—Discharge mechanisms characterised by the means for discharging the components from the mixer using pistons or plungers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/88—Osteosynthesis instruments; Methods or means for implanting or extracting internal or external fixation devices
    • A61B17/8802—Equipment for handling bone cement or other fluid fillers
    • A61B17/8833—Osteosynthesis tools specially adapted for handling bone cement or fluid fillers; Means for supplying bone cement or fluid fillers to introducing tools, e.g. cartridge handling means
    • A61B2017/8838—Osteosynthesis tools specially adapted for handling bone cement or fluid fillers; Means for supplying bone cement or fluid fillers to introducing tools, e.g. cartridge handling means for mixing bone cement or fluid fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30316—The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30535—Special structural features of bone or joint prostheses not otherwise provided for
    • A61F2002/30561—Special structural features of bone or joint prostheses not otherwise provided for breakable or frangible
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2002/4685—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor by means of vacuum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0071—Additional features; Implant or prostheses properties not otherwise provided for breakable or frangible
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/20—Mixing of ingredients for bone cement
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/70—Mixers specially adapted for working at sub- or super-atmospheric pressure, e.g. combined with de-foaming
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/75—Discharge mechanisms

Abstract

The present invention relates to an arrangement for the manufacture of bone cement by mixing together its constituent components comprising a mixing cylinder (1) in the form of a tube with a bottom (2) and a lid (3) and inside the mixing cylinder an axially movable agitator (4). The agitator consists of a piston-like agitatordisc (4a), which is perforated by channels (4a1), through which the components of the bone cement are caused to flow during the mixing procedure and an agitator rod (4b) resembling a piston rod operatively connected to the agitator disc (4a) andsupported in the lid (3) in such a way that it is free to slide. The invention is characterized in that the agitator rod (4b) has an axial channel (4b1), which is closed off atthe agitator disc (4a) in such a way that it is capable of being opened. The bottom (2) is so arranged, under the effect of an axial force, as to be displaced like a piston axially in the direction of the lid (3), in conjunction with which the bone cement flows out through the channel (4b1) after it has been opened.

Description

CA 020~4196 1998-04-17 ..

The present invention relates to a method and an arrangement for the manufacture of bone cement by mixing together its constituent components according to the preambles of claims 1 and 4 respectively.

Bone cement is used in hip-j-oint operations, for example.
When manufacturing bone cement, for which purpose a component in the form of a powder and a liquid component require to be mixed, it is important that the mixture should be as homogeneous as possible, and that gases which occur during the mixing procedure are removed to the greatest extent possible. Any lack of homogeneity and gas inclusions have the effect of reducing the strength of the bone cement, which can result in a shorter service life for the implanted prosthesis. Furthermore, the gases which occur during manufacture are unhealthy, for which reason steps must be taken to ensure that they do not escape into the operating theatre.

Swedish document SE, B, 447 785 (& US-A-4 758 096) discloses an arrangement for the manufacture of bone cement comprising a mixing cylinder which is placed in a vacuum chamber in order to create vacuum in the mixing cylinder during mixing to ensure that no bubbles are formed in the bone cement. The components are loaded into the mixing cylinder prior to the mixing process. Once mixing is finished, the cylinder is removed from the vacuum chamber, a discharge pipe is connected to the cylinder and the mixed bone cement is manually extruded from the mixing cylinder.

Patent application WO, A1, 8705492 relates to a device and a process for mixing bone cement and filling an application holder with said cement. The device has a mixer and a sealing ring which can be coupled to the application holder. The application holder is located in the mixing CA 020~4196 1998-04-17 receptacle and is movable in relation to the latter. In one embodiment, the mixer contains the substances to be mixed in separate chambers and as a result of relative movement between the application holder and the mixing receptacle, the substances are mixed and filled into the application holder.

In US-A-4 208 133, upon which the preambles of claims 1 and 4 are based, an injection cartridge with at least two separate chambers is disclosed, with each chamber holding a component which can be mixed with the other component in the cartridge prior to use. Such an injection cartridge is primarily intended for use in the building industry for the anchoring of plugs, tie bolts of the like. A disadvantage with such an arrangement is that the quantities of the components and the mixing ratio cannot be varied since the components are contained in sealed chambers.

An object of the present invention is to make available a method and a preparation arrangement for bone cement, which arrangement is intended to be disposable and capable of being manufactured efficiently and at a low cost, and which also contributes to meeting the requirements stipulated above in respect of the prepared bone cement, whilst being more flexible than the arrangement disclosed in US-A-4 208 133.

This object is met in accordance with the present invention by a method according to claim 1 and an arrangement according to claim 4.

Additional advantages of the invention can be appreciated from the accompanying respective dependent claims and from the following description with reference to the accompanying drawing which illustrates schematically a k~

CA 020~4196 1998-04-17 ., longitudinal section through an embodiment of the preparation arrangement in accordance with the invention The designation 1 is used in the drawing for a mixing cylinder, and 2 for a bottom which is inserted in a sealing fashion into one end of the mixing cylinder 1. The mixing cylinder 1 is preferably made from a transparent material, and the bottom 2 is made from a rubber-like elastic material.

The preparation arrangement in accordance with the invention also includes a lid 3 with an agitator 4 capable of axial movement therein. This comprises a piston-like agitator disc 4a and an agitator rod lb supported in the lid 3 in such a way that it is free to slide. The mixing cylinder 1 and lid 3 are manufactured in a single piece and the lid 3 has an evacuation channel 3a and a seal 5 against the agitator rod 4b. The bottom 2 is formed as an outwardly open cup with annular flange-like seals 2b in contact with the inner wall of the mixing cylinder 1.

The agitator disc 4a is perforated by channels 4al, through which the bone cement components are caused to flow during agitation in order to make this as effective as possible.
The agitator rod 4b exhibits in accordance with the invention an axial channel 4bl. With the help of the agitator rod 4b, the agitator disc 4a is caused to move up and down inside the mixing cylinder 1. Since the cylinder wall is transparent, a person skilled in the art can easily decide when the preparation of the bone cement is complete.

A funnel 19 is removably attached to the outer end of the agitator rod 4b and a rod 20 is introduced into the axial channel 4bl of the agitator rod 4b, together with a tubular holder 21 into which the mixing cylinder 1 is introduced.
The narrow opening of the funnel 19 is in close contact CA 020~4196 1998-04-17 .

with the agitator rod 4b, and its purpose is to facilitate the introduction of the bone cement components into the mixing cylinder 1, for which purpose the rod 20 must have been pulled from the channel 4bl. The rod 20 is of a length such that, when introduced fully into the channel 4bl, it reaches into the vicinity of the agitator disc 4a and is in this area executed with a seal 20a in contact with the inner wall of the channel 4b. The rod 20 with the seal 20a sealingly closes one end of the channel 4bl. At its opposite end the rod 20 is executed with a draw ring 20b or similar. The mixing cylinder 1 and the piston 2 are fixed relative to the holder 21 by means of a removable cotter pin 22.

The preparation arrangement is used as follows: The rod 20 is first removed so that the bone cement components can be introduced into the mixing cylinder 1 via the channel 4bl.
The funnel 19 is then removed, and the rod 20 is introduced into the channel 4bl. The bone cement components are now mixed together; any gases which occur are removed via the channel 3a. During the mixing procedure the arrangement is placed in the holder 21. Once the mixing procedure is complete, the cotter pin 22 is withdrawn from its position, thereby enabling the preparation arrangement to be removed freely from its holder 21. The preparation arrangement is now placed in a syringe mechanism of the kind which is customarily used for the extrusion of sealing compound or similar in the form of a bead. Once the cotter pin 22 has been removed, the piston 2 can be displaced axially under the effect of e.g. a compression piston known per se. Once the rod 20 has been removed from the channel 4bl, bone cement can be forced out through it for the intended use

Claims (5)

Claims:
1. A method for manufacturing bone cement by mixing together its constituent components, said method comprising the steps of:
providing a mixing arrangement comprising a mixing cylinder (1) in the form of a tube with a bottom (2) and a lid (3), and an axially movable agitator (4) inside the mixing cylinder (1), which agitator consists of an agitator disc (4a) which is perforated by channels (4a1) through which the components of the bone cement are caused to flow during the mixing procedure, and an agitator rod (4b) that is operatively connected to the agitator disc and supported in the lid (3) in such a manner that it is free to slide, said agitator rod (4b) presenting an axial channel (4b1) having an opening at the end of the agitator rod attached to the agitator disc (4a), which opening is closed off during mixing of the constituent components and opened to allow discharge of the bone cement, the bottom (2) being so arranged that, under the effect of an axial force, it is displaceable like a piston axially in the direction of the lid (3);
providing the mixing arrangement with the constituent components;
mixing together the constituent components by sliding the agitator (4) within the mixing cylinder (1);
opening the opening to the axial channel (4b1) in said agitator rod (4b), and displacing the bottom (2) towards the lid (3) to thereby discharge the bone cement from the mixing cylinder (1), characterized by providing the mixing arrangement with the constituent components by introducing the components into the mixing cylinder (1) via said axial channel (4b1) in the agitator rod (4b).
2. The method as claimed in claim 1, characterized by connecting a vacuum source to cooperate with the interior of the mixing cylinder (1).
3. The method as claimed in claim 1 or claim 2, characterized by introducing the components into the mixing cylinder (1) via a funnel (19) removably attached to the outer end of the agitator rod (4b).
4. An arrangement for manufacturing bone cement by mixing together its constituent components, comprising a mixing cylinder (1) in the form of a tube with a bottom (2) and a lid (3), and an axially movable agitator (4) inside the mixing cylinder (1), which agitator consists of an agitator disc (4a) which is perforated by channels (4a1) through which the components of the bone cement are caused to flow during the mixing procedure, and an agitator rod (4b) that is operatively connected to the agitator disc and supported in the lid (3) in such a manner that it is free to slide, said agitator rod (4b) presenting an axial channel (4b1) having an opening at the end of the agitator rod attached to the agitator disc (4a), which opening is closed off during mixing of the constituent components and opened to allow discharge of the bone cement, the bottom (2) being so arranged that, under the effect of an axial force, it is displaceable like a piston axially in the direction of the lid (3), characterized in that said mixing vessel (1) is provided with an evacuation channel (3a) to which an evacuation source is connectable, and in that said arrangement further comprises a funnel (19) removably attached to the outer end of the agitator rod (4b) to facilitate the introduction of the bone cement components into the mixing cylinder (1).
5. The arrangement as claimed in claim 5, characterized in that said evacuation channel (3a) is provided in the lid (3) of the mixing cylinder (1).
CA002054196A 1989-05-03 1990-01-11 Device for preparing bone cement Expired - Lifetime CA2054196C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8901599-4 1989-05-03
SE8901599A SE462315B (en) 1989-05-03 1989-05-03 DEVICE FOR MANUFACTURING BENCEMENT

Publications (2)

Publication Number Publication Date
CA2054196A1 CA2054196A1 (en) 1990-11-04
CA2054196C true CA2054196C (en) 1999-01-19

Family

ID=20375858

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002054196A Expired - Lifetime CA2054196C (en) 1989-05-03 1990-01-11 Device for preparing bone cement

Country Status (13)

Country Link
US (1) US5252301A (en)
EP (1) EP0470959B1 (en)
JP (1) JP2915567B2 (en)
KR (1) KR0131143B1 (en)
AT (1) ATE126993T1 (en)
AU (1) AU633058B2 (en)
CA (1) CA2054196C (en)
DE (1) DE69022047T2 (en)
DK (1) DK0470959T3 (en)
ES (1) ES2078336T3 (en)
NO (1) NO314923B1 (en)
SE (1) SE462315B (en)
WO (1) WO1990013264A1 (en)

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US5252301A (en) 1993-10-12
AU5155190A (en) 1990-11-29
ES2078336T3 (en) 1995-12-16
KR920700587A (en) 1992-08-10
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NO314923B1 (en) 2003-06-16
EP0470959B1 (en) 1995-08-30
AU633058B2 (en) 1993-01-21
DE69022047D1 (en) 1995-10-05
SE462315B (en) 1990-06-11
DK0470959T3 (en) 1995-12-18
NO914245L (en) 1991-10-30
JPH04507200A (en) 1992-12-17
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JP2915567B2 (en) 1999-07-05
WO1990013264A1 (en) 1990-11-15
ATE126993T1 (en) 1995-09-15
DE69022047T2 (en) 1996-04-11
SE8901599D0 (en) 1989-05-03
KR0131143B1 (en) 1998-04-14
EP0470959A1 (en) 1992-02-19

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