EP0349566A1 - Prothese resorbable - Google Patents

Prothese resorbable

Info

Publication number
EP0349566A1
EP0349566A1 EP88902596A EP88902596A EP0349566A1 EP 0349566 A1 EP0349566 A1 EP 0349566A1 EP 88902596 A EP88902596 A EP 88902596A EP 88902596 A EP88902596 A EP 88902596A EP 0349566 A1 EP0349566 A1 EP 0349566A1
Authority
EP
European Patent Office
Prior art keywords
prosthesis according
acid
prosthesis
elongate elements
tissue
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.)
Ceased
Application number
EP88902596A
Other languages
German (de)
English (en)
Inventor
Staffan Folke Bowald
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.)
Astra Tech AB
Original Assignee
Astra Meditec AB
Astra Tech 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 Astra Meditec AB, Astra Tech AB filed Critical Astra Meditec AB
Publication of EP0349566A1 publication Critical patent/EP0349566A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61F2/08—Muscles; Tendons; Ligaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides

Definitions

  • a resorbabie prosthesis The present invention relates to an implantable prosthetic element for the reconstruction of tendons, ligaments and cruciate ligaments of a human or an animal.
  • the U.S. patent 3,463,158 discloses the use of composites of polyglycolic acid and non-absorbabie fibre materials as implantates for the repair or replacement of tissue, the composites being designed such that the new tissue will surround the non-absorbable fibre material.
  • WO 85/0511 discloses a ligament or tendon replacement of natural collagen treated with glutaraldehyde, the collagen being provided in the form of a weave with sufficient space between the strands thereof to permit the propagation of fibroblasts therethrough for regeneration of the tendon or ligament.
  • a sheet of the weave has been rolled into a coil to form a three-dimensional network structure.
  • collagen has proved to be an unsuitable material in these connections. Even if the treatment with glutaraldehyde reduces the antigenicity, a foreign body reaction is obtained, giving rise to scar tissue with reduced function of the regenerated tendon or ligament.
  • the object of the present invention is to provide an improved prosthetic element which completely or partially may replace a tendon, a ligament or a cruciate ligament and which has not the above mentioned disadvantages of the hitherto known prostheses.
  • the novel prosthetic element should thus stabilize the tendon, ligament or cruciate ligament during the whole healing process.
  • the structure of the prosthetic element should be such that it controls the reconstruction of collagen in the new tissue to resemble as much as possible the original tissue that it is to replace and have essentially the corresponding function. Concerning ligaments and cruciate ligaments also bone should be capable of growing into the new structure.
  • the prosthetic material as a whole should be capable of disappearing from the body without leaving any residues.
  • the prosthetic element completely consists of a substantially water-insoluble, non-toxic bioresorbable material without adverse tissue reaction, with the exception of proteins, poiy ⁇ peptides and derivatives thereof, which bioresorbable material can be degraded and resorbed completely in the body without giving rise to scar tissue or toxic degradation products, and additionally has a special structure which, on one hand, should be capable of providing the necessary strength (particularly important for cruciate ligaments) and, on the other hand, be capable of " promoting and controlling the ingrowth of new tissue in a suitable direction.
  • this structure is characterized in that it exhibits longitudinal grooves or channels intended to serve as initial propagation guides for new fibrous tissue.
  • the terms grooves and channels, respectively, are herein to be understood in a broad sense, and to comply with the objects of the invention the structure may be arranged in a great number of different ways as will appear from the following.
  • the prosthetic element may simply consist of a single, or possibly more, elongate element(s), each of which is provided with several longitudinal grooves or channels. These grooves or channels may be provided on the outside of the element or extend within the element, possibly in combination.
  • the prosthetic element may be provided with the necessary grooves already in the manufacture thereof, e.g. by extrusion, but it may also consist of an initially sheet-shaped piece of material which has been folded to a suitable configuration.
  • An example of such a prosthetic element having inner channels or cavities is a sheet that has been rolled to obtain a helical cross-section.
  • the prosthetic element structure according to the invention is built-up from a plurality of elongate members, which define longitudinal channels or cavities between them.
  • these elongate members are arranged to be substantially individuaily load absorbing when the prosthesis is applied.
  • they may consist of threads or fibres, in which case the assembly thereof may be straight, or braided, twined or rotated. They may also consist of a plurality of parallel laminar, leaf- or strip- ' shaped members.
  • Another alternative is a plurality of concentrically disposed cylinders or tubes.
  • the individual members may in these cases be whole, optionally perforated material pieces, but may, e.g., also consist of net or be knitted, woven or braided structures, etc.
  • a folded structure may be comprised by this embodiment, in the case of, e.g., a weave the load absorbing members corresponding to the warp-threads.
  • the cavities of a perforated, net- shaped or knitted structure must, of course, not be so large that the propagation guiding function of the longitudinal grooves or channels is. influenced to any considerable extent.
  • the design and dimensions of said grooves or channels of the prosthetic element structure may vary considerably, but for the desired penetration of cells into, e.g. inner channels or cavities to take place, the latter should have a minimum cross-sectional dimension of about 10 ⁇ m.
  • the resorption period of the prosthetic element structure according to the invention should be sufficiently long for the structure to be a stabilizing replacement until the new tissue has been sufficiently regenerated to absorb loads itself. This period will, of course, depend on the type and the extension of tissue to be replaced but may generally be said to be about six months to about two years.
  • the strength requirements vary according to the tissue to be replaced, and therefore the strength requirements are relatively high in case of a cruciate ligament, while they, of course, may be relatively low for, for example, a finger tendon.
  • the cross-sectional dimensions of the actual prosthetic element may, as examples, be mentioned about 1 to 2 mm for minor tendons up to two centimeters (the Achilles tendon), and, e.g., for cruciate tendons about 4-5 millimeters.
  • the prosthetic elements according to the invention will function as a load absorbing replacement for the tendon, ligament or cruciate ligament that they are to replace, such that loading of the body part in question may take place almost immediately after the surgical operation. Such immediate loading has proved to accelerate the healing process and favourably influence the cell differentiation. Concurrently with the growth of the new tissue the prosthetic material is slowly degraded and resorbed in the body, the new tissue successively taking over the load absorption.
  • special structure according to the invention has proved to function as an efficient scaffold for the new tissue while successively guiding the same along the elongate elements, such that the eventually formed new tissue at least to a very large extent will resemble the original tissue.
  • the different individual members have two or more different resorption periods, which, for example, easily may be achieved by varying the thickness of the members and/or by the choice of material.
  • each individual member of the prosthetic structure may consist of a single material, but to obtain the desired resorbability and strength of the prosthesis as a whole it may be necessary to utilize a combination of different materials.
  • each individual member may have a core of a material with high strength but which is relatively quickly resorbabie and an outer covering of a material with low strength but with a longer resorption period.
  • the prosthetic element structure is surrounded by a porous outer covering of bioresorbable material, for one thing, when necessary, for the purpose of holding the inner structure together, but above all to reduce the entry of body fluids to the inner structure and thereby to adequately delay the chemical attack thereon to prolong the resorption period, which may be of importance depending on the resorbabie material chosen.
  • the outer covering will advantageously serve as a scaffold for blood vessels and fibroblasts penetrating from the outside.
  • the porosity of the outer layer should, however, be sufficient to permit the penetration of blood cells and fluids and is suitably such that at least half of the pores are in the range of between about 10 and about 200 ⁇ m, the pores preferably, however, not being larger than 150 ⁇ m.
  • the outer layer which substantially is not load absorbing, may consist of a separate cover structure, e.g., net-shaped, but it may also be a layer that has been deposited or coated on the inner structure in any suitable manner.
  • a suitable resorption period of the outer layer may be mentioned about 3 to about 12 weeks, which depending on the material choice usually will give a layer of the order of 0.1-0.5 mm.
  • the outer shape of the prosthetic element is not critical per se and is adapted to the structure to be replaced.
  • Suitable bioresorbable materials for the purposes of the present invention and corresponding to the above given definition may readily be selected by the person skilled in the art, e.g., among those materials which are either commercially available or have been described in the literature or will be available in the future. Particularly useful are aliphatic polyesters.
  • specific bioresorbable materials may be mentioned polymers based upon polyglycolic acid (PGA), copolymers of glycolic acid and lactic acid, copolymers of lactic acid and £-aminocaproic acid, and various iactide polymers.
  • PGA esters are, e.g., described in the U.S.
  • growth factors may be incorporated in the prosthetic structure, either deposited in the mentioned cavities or incorporated into the resorbabie material for slow release of growth factor.
  • growth factors may be incorporated in the prosthetic structure, either deposited in the mentioned cavities or incorporated into the resorbabie material for slow release of growth factor.
  • Fig. 1 is a schematic perspective view of an embodiment of a prosthetic element according to the invention
  • Fig. 2 schematically illustrates the application, as a cruciate ligament replacement, of three prosthetic elements according to Fig. 1 in a knee joint,
  • Fig. 3 to 10 show schematic cross-sections of alternative embodiments of the prosthetic element according to the invention.
  • Fig. 11 schematically illustrates a piece of a helical structure according to Fig. 10 before coiling.
  • the prosthetic element of of Fig. 1 which is generally designated by the reference numeral 1, comprises an inner structure in the form of a plurality of threads 2 of a suitable bioresorbable material or material combination, which have been twined to form a multi-filament strand of a desired thickness and been provided with an, in the illustrated case, net-shaped outer covering or coating 3 of a suitable bioresorbable material.
  • the threads 2 may be composites consisting of a core of Vicryf ⁇ and an outer layer of PHB, which have been bundled and twined and then been provided with a coating of PHB and PHV.
  • the coating may, e.g., be applied by dipping the twined filament bundle first into a solution of PHB and PHV in dimethylacetamide (DMA), and then into water.
  • DMA dimethylacetamide
  • a suitable porous outer layer of PHB-PHV is then precipitated onto the twined structure.
  • the prosthetic element 1 is, in the illustrated case, intended to be used as a cruciate ligament replacement, in which case three such elements are used, but the structure as such may generally be used for all kinds of tendons and ligaments.
  • the threads 2 and the outer covering 3 are attached to an externally threaded end cap 4 at the lower end of the prosthetic element 1, to which end cap each thread 2 is individually fixed.
  • An internally threaded lower fixing sleeve 5 with an end flange 6 is arranged to be screwn onto the end cap 4.
  • An upper fixing sleeve 7 is slidably arranged on the prosthetic element 1 and has an end flange 8 provided with inwardly facing pointed projections or spikes 9.
  • the end cap 4 as well as the fixing sleeves 5, 7 may consist of a bioresorbable material or of a suitable non-resorbable material without adverse tissue reaction, such as titanium.
  • a guide wire 10 extends from the lower end of the prosthetic element 1.
  • Fig. 2 schematically illustrates the application' of three prosthetic or cruciate ligament elements 1 in a knee joint which has been provided with suitably disposed bores 11 in the two joint portions 12, 13.
  • the arrangement of cruciate ligament elements 1 shown in the figure is intended to be isometric, i.e. the cruciate ligament elements 1, on the basis of the known movement pattern of the joint, having been placed with their fibre or thread directions such that loads are absorbed and the joint is stabilized in three different main directions during the joint movement.
  • each cruciate ligament 1 is introduced into its respective bore 11 by means of the guide wire 10.
  • the length of the cruciate ligament is then adjusted with the upper fixing sleeve 7, which is fixed to the cruciate ligament, e.g., by clamping, and simultaneously in the bore opening via the projections 9.
  • the application is completed by screwing the lower fixing sleeve 5 onto the end cap 4 while simultaneously adjusting the tension of the cruciate ligament.
  • the illustrated cruciate ligament prosthesis is ready to absorb loads. New ligament tissue will grow into the interspaces between the threads 2 and obtain an advantageous successive orientation in the longitudinal direction.
  • the prosthetic material will slowly be subjected to hydrolysis and/or enzymatic degradation, which at least during the Initial period of the healing process is suitably delayed by the outer structure 3, which additionally will serve as a scaffold for inter alia blood vessels.
  • the possibility of loading the knee joint already from the beginning will contribute to an efficient regeneration of the ligament tissue owing to the fact that the natural movements promote the differentiation of the new " cells.
  • a successive regenera ⁇ tion of the ligament tissue will take place to ultimately result in a collagen-rich tissue oriented In parallel bundles and very like a normal cruciate ligament.
  • Fig. 3 and 4 relate to prosthetic elements which in conformity with that of Fig. 1 are built up from a plurality of subeiements, while Fig. 5 to 11 show prosthetic elements based upon one single element.
  • the prosthetic element structure of Fig. 3 consists of a schematically illustrated assembly of a plurality of concentrically arranged tubular or cylindri ⁇ cal members 14 of a bioresorbable material, the outermost tubular member 14a being surrounded by or coated with an outer covering or layer 15, also of a bioresorbable material.
  • the members 14 define annular channels or cavities between them which in the figure are very exaggerated; in practice, however, the members 14 may contact each other and still leave the necessary interspaces.
  • the inner structure consists of a plurality of laminae or bands 17 of a bioresorbable material which are kept together by an outer covering or layer 18 of a bioresorbable material.
  • the bands 17 define channel-shaped passages or cavities 19 between them which are very exaggerated in the figure. Also in this case the bands 17 may in practice contact each other.
  • Fig. 5-8 all consist of a solid elongate element 20 shaped into different configurations exhibiting external grooves or channels 21 which are to serve as propagation guides for the new tissue.
  • the prosthetic element is formed from a film or foil 22, which in Fig. 9 has been folded and in Fig. 10, 11 coiled.
  • Propagation guiding grooves or channels 23 are in Fig. 9 formed by the folds, while in Fig. 10, 11 they are formed between adjacent coil layers.
  • the film or foil 22 is provided with a plurality of longitudinal slits 24 to increase the penetration of cells and fluids from the sides thereof.
  • the prosthetic elements of Fig. 5-11 may in conformity with the 5 embodiments according to Fig. 1-4 be provided with a covering or coating of a porous bioresorbable material (not shown).
  • Example A cruciate ligament prosthesis according to Fig. 1 was made of bundles of PHB-PHV-coated Vicryr ⁇ thread, which were twined to strands of about 3 mm thickness and were provided with a knitted hose of Vicry ⁇ to keep the strands together.
  • the Vicryf ⁇ material has a high strength with a relatively rapid resorption, which is balanced by the outer layer of PHB-PHV -5 with a long resorption but a lower strength.
  • the anterior cruciate ligament was recessed on 10 adult sheep, anaesthetized with sodium pentothal, oxygen/laughing gas and Fluothane.
  • Two or three above described cruciate ligament prostheses were inserted either isometrically via bore channels or anti-isometrically. The latter attachment was 0 made to determine the sensitivity to incorrect insertion. After reconstruction all knees were stable. Four months later half of the animals were killed and after another two months the rest of the animals were killed. A microscopic photo documentation was performed, whereupon the preparations were fixed in 4% formalin.
  • the bone attachment was sawn out, whereupon the bone substance was 5 decalcified and the cruciate ligaments were section-cut for macroscopic analysis. A regenerate was taken for strength test.
  • the microscopic analysis showed excellent regeneration of collagen-rich tissue oriented in parallel bundles and very like the picture of a normal cruciate ligament.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rehabilitation Therapy (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Vascular Medicine (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Chemical And Physical Treatments For Wood And The Like (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)

Abstract

Une prothèse, pouvant faire l'objet d'une implantation et servant à remplacer complètement ou partiellement un tendon, un ligament ou un ligament croisé, se caractérise par une structure (1) constituée par une substance bio-résorbable autre que des protéines, des polypéptides et leurs dérivés, structure qui présente des fentes ou des canaux longitudinaux destinés à servir de guide de propagation initiale pour les nouveaux tissus fibreux.
EP88902596A 1987-03-09 1988-03-08 Prothese resorbable Ceased EP0349566A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8700969 1987-03-09
SE8700969A SE457692B (sv) 1987-03-09 1987-03-09 Implanterbar protes foer att helt eller delvis ersaetta en sena, ett ligament eller ett korsband

Publications (1)

Publication Number Publication Date
EP0349566A1 true EP0349566A1 (fr) 1990-01-10

Family

ID=20367798

Family Applications (1)

Application Number Title Priority Date Filing Date
EP88902596A Ceased EP0349566A1 (fr) 1987-03-09 1988-03-08 Prothese resorbable

Country Status (6)

Country Link
EP (1) EP0349566A1 (fr)
JP (1) JPH02502431A (fr)
AU (1) AU1487388A (fr)
NO (1) NO173485C (fr)
SE (1) SE457692B (fr)
WO (1) WO1988006872A1 (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5425766A (en) * 1987-03-09 1995-06-20 Astra Tech Aktiebolag Resorbable prosthesis
US5263984A (en) * 1987-07-20 1993-11-23 Regen Biologics, Inc. Prosthetic ligaments
EP0336148A3 (fr) * 1988-04-02 1991-04-17 Beiersdorf Aktiengesellschaft Implants chirurgicaux
FI85223C (fi) * 1988-11-10 1992-03-25 Biocon Oy Biodegraderande kirurgiska implant och medel.
US6171338B1 (en) 1988-11-10 2001-01-09 Biocon, Oy Biodegradable surgical implants and devices
FI88111C (fi) * 1989-04-26 1993-04-13 Biocon Oy Sjaelvfoerstaerkande kirurgiska material och medel
DE4012602C2 (de) * 1990-04-20 1994-06-09 Ethicon Gmbh Implantat-Kordel
ATE131373T1 (de) * 1991-05-24 1995-12-15 Synthes Ag Resorbierbare sehnen- und knochenverstärkungseinrichtung
FR2704421B1 (fr) * 1993-04-30 1995-06-16 Lahille Michel Prothèse ligamentaire.
GB2282328B (en) * 1993-09-29 1997-10-08 Johnson & Johnson Medical Absorbable structures for ligament and tendon repair
US6017366A (en) * 1997-04-18 2000-01-25 W. L. Gore & Associates, Inc. Resorbable interposition arthroplasty implant
SE513491C2 (sv) 1998-12-15 2000-09-18 Artimplant Dev Artdev Ab Implantat för insättning i människor eller djur innefattande böjliga trådformiga element
ATE296069T1 (de) * 2000-03-10 2005-06-15 Macropore Biosurgery Inc Resorbierbare mikromembrane zur verminderung von narbengewebe
DE10046119A1 (de) 2000-09-15 2002-03-28 Inst Textil & Faserforschung Medizintechnisches bioresorbierbares Implantat, Verfahren zur Herstellung und Verwendung
SE525131C2 (sv) * 2001-01-15 2004-12-07 Artimplant Ab Implantat för rekonstruktion av leder
US7344539B2 (en) * 2001-03-30 2008-03-18 Depuy Acromed, Inc. Intervertebral connection system
GB2464952A (en) * 2008-10-30 2010-05-05 Xiros Plc Surgical cord

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4400833A (en) * 1981-06-10 1983-08-30 Kurland Kenneth Z Means and method of implanting bioprosthetics
FI78393C (fi) * 1982-09-10 1989-08-10 Gore & Ass Syntetiskt protes foer ersaettning eller reparation av ligament eller senor.
US4467478A (en) * 1982-09-20 1984-08-28 Jurgutis John A Human ligament replacement
FR2541888B1 (fr) * 1983-03-04 1989-04-21 Sgro Jean Claude Prothese vasculaire partiellement resorbable
WO1985000511A1 (fr) * 1983-07-25 1985-02-14 Medlen John C Procede et materiau de regeneration du collagene des ligaments et des tendons
US4792336A (en) * 1986-03-03 1988-12-20 American Cyanamid Company Flat braided ligament or tendon implant device having texturized yarns

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8806872A1 *

Also Published As

Publication number Publication date
NO884959L (no) 1988-11-07
SE8700969D0 (sv) 1987-03-09
JPH02502431A (ja) 1990-08-09
NO173485C (no) 1993-12-22
AU1487388A (en) 1988-10-10
SE457692B (sv) 1989-01-23
WO1988006872A1 (fr) 1988-09-22
NO173485B (no) 1993-09-13
NO884959D0 (no) 1988-11-07
SE8700969L (sv) 1988-09-10

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