WO2002019944A2 - Flexible implant - Google Patents
Flexible implant Download PDFInfo
- Publication number
- WO2002019944A2 WO2002019944A2 PCT/EP2001/009299 EP0109299W WO0219944A2 WO 2002019944 A2 WO2002019944 A2 WO 2002019944A2 EP 0109299 W EP0109299 W EP 0109299W WO 0219944 A2 WO0219944 A2 WO 0219944A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- basic structure
- monofilaments
- implant
- implant according
- bending
- Prior art date
Links
- 239000007943 implant Substances 0.000 title claims abstract description 65
- 238000005452 bending Methods 0.000 claims abstract description 49
- 239000011148 porous material Substances 0.000 claims abstract description 18
- 238000012360 testing method Methods 0.000 claims abstract description 18
- 238000013001 point bending Methods 0.000 claims abstract description 12
- 229920001577 copolymer Polymers 0.000 claims description 20
- 239000000463 material Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- 239000002033 PVDF binder Substances 0.000 claims description 9
- 229920001519 homopolymer Polymers 0.000 claims description 9
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 9
- BQCIDUSAKPWEOX-UHFFFAOYSA-N 1,1-Difluoroethene Chemical compound FC(F)=C BQCIDUSAKPWEOX-UHFFFAOYSA-N 0.000 claims description 7
- HCDGVLDPFQMKDK-UHFFFAOYSA-N hexafluoropropylene Chemical compound FC(F)=C(F)C(F)(F)F HCDGVLDPFQMKDK-UHFFFAOYSA-N 0.000 claims description 6
- 229920000117 poly(dioxanone) Polymers 0.000 claims description 5
- 229920000098 polyolefin Polymers 0.000 claims description 3
- -1 polyethylene Polymers 0.000 description 15
- 239000004743 Polypropylene Substances 0.000 description 14
- 229920001155 polypropylene Polymers 0.000 description 14
- 238000010586 diagram Methods 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 4
- 230000007794 irritation Effects 0.000 description 4
- 229920000339 Marlex Polymers 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 210000002837 heart atrium Anatomy 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 229920006373 Solef Polymers 0.000 description 2
- 210000003815 abdominal wall Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000004303 peritoneum Anatomy 0.000 description 2
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- VVOLVFOSOPJKED-UHFFFAOYSA-N copper phthalocyanine Chemical compound [Cu].N=1C2=NC(C3=CC=CC=C33)=NC3=NC(C3=CC=CC=C33)=NC3=NC(C3=CC=CC=C33)=NC3=NC=1C1=CC=CC=C12 VVOLVFOSOPJKED-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- 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
- A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
-
- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04B—KNITTING
- D04B21/00—Warp knitting processes for the production of fabrics or articles not dependent on the use of particular machines; Fabrics or articles defined by such processes
- D04B21/10—Open-work fabrics
- D04B21/12—Open-work fabrics characterised by thread material
-
- 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
- A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
- A61F2002/0068—Implantable repair or support meshes, e.g. hernia meshes having a special mesh pattern
-
- D—TEXTILES; PAPER
- D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
- D10B2509/00—Medical; Hygiene
- D10B2509/08—Hernia repair mesh
Definitions
- the invention relates to a flexible implant with a meshlike basic structure.
- Implant meshes Flexible implants with a mesh-like basic structure are widespread, e.g., in the form of implant meshes. They are inserted into the patient's body during a surgical procedure, e.g. at the abdominal wall, in order to reinforce the body tissue at least temporarily and to prevent complications such as e.g. hernias.
- Such implant meshes are frequently produced from mono- filaments, e.g., from polyethylene and in particular from polypropylene.
- US 3 124 136 A shows an implant mesh of polyethylene with a pore size of less than 1 mm.
- US 4 452 245 A a double-laid implant of polypropylene mono- filaments is described in which the pores of the mesh structure are greater than 1 mm.
- Implant meshes of multifilament yarns e.g. polyester or polypropylene.
- Resorbable materials can be used here.
- partly resorbable meshes are known in which, apart from polypropylene, polyglactin 910, a copolymerisate of 9 parts glycolide and 1 part lactide, is used.
- implant meshes of multifilament yarns are relatively soft, the multifilament yarns have a large surface and show a capillary effect, which can lead to undesired tissue reactions and is associated with a danger of infection for the patient.
- the object of the invention is to provide a flexible implant which is tissue-friendly and relatively soft and behaves largely inertly.
- the flexible implant according to the invention contains a mesh-like basic structure of monofilaments, the diameter of which is in the range from 0.02 mm to 0.30 mm (preferably in the range from 0.05 mm to 0.30 mm) and the bending elasticity modulus of which is smaller than 3500 N/mm 2 .
- the basic structure contains pores the size of which lies in the range from 1.5 mm to 8.0 mm over more than 90% of the total area of the pores.
- the bending force of the basic structure measured in a three-point bending test with a span of 11 mm and normalized to a sample width of 10 mm, is at most 30 mJSL
- the mesh-like basic structure is preferably the only component of the implant according to the invention. Additional components can also be provided, however, e.g. a coating of the basic structure or additional threads in- serted into the basic structure with other properties than the monofilaments of the basic structure have.
- the mesh-like basic structure of the implant according to the invention consists of monofilaments.
- the monofilaments which as a rule have a smooth surface, behave essentially inertly.
- the implant according to the invention thus has the good properties of implant meshes which are produced from monofilaments .
- a soft implant can be made which causes, at most, slight mechanical irritation of the tissue (e.g. of the peritoneum) and causes no, or only slight, adhesions.
- the implant according to the invention thus also has the advantages of the implant meshes of multifilaments .
- the bending elasticity modulus of the monofilaments is a material property which corresponds to the Young's modulus (measured in a bending test) .
- the bending elasticity modulus depends inter alia somewhat on the production conditions (in particular the stretching conditions and the thermal post-treatments) and dimensions of the monofilaments.
- the value of 3500 N/mm 2 is lower than the bending elasticity modulus of usual polypropylene monofilaments for mesh production, which is of the order of 5000 to 9000 N/mm 2 .
- the monofilaments of the mesh-like basic structure are thus relatively soft and have a high flexibility with a diameter in the range from 0.02 mm to 0.30 mm.
- the predominant share of the pores i.e. the proportion of the pores which accounts for more than 90% of the total area of the pores in the basic structure
- Individual pores of the basic structure may (e.g. for production reasons) be smaller than 1.5 mm, but this has no noteworthy effect on the overall properties of the implant.
- the flexibility or softness of the implant depends not only on the monofilaments used as material and the size of the pores as such, but e.g. also on the weft-knitted or warp-knitted structure of the basic structure and the matching of the parameters to each other.
- an upper limit for the bending force of the basic structure is stated as a further parameter which characterizes the implant according to the invention. This bending force emerges from the evaluation of a force-path diagram in which the deflection (i.e. the path) of a sample of the basic structure is plotted as a function of the force acting on the sample.
- a sample of the basic structure is placed on two supports, 11 mm apart, the force acting perpendicular to the sample and in the middle between the two supports.
- the deflection increases as the force grows, until the force reaches a maximum and falls again as the deflection continues to increase.
- This maximum force is called bending force and is normalized to a sample width of 10 mm.
- the bending force is there- fore a measure of the elasticity behaviour of the implant as a whole.
- Suitable as materials for the monofilaments of the basic structure are, e.g., thermoplastically workable fluori- nated homopolymers, thermoplastically workable fluori- nated copolymers, polyolefins and mixtures of such materials.
- the basic structure preferably contains monofilaments of polyvinylidene fluoride, copolymers of vinylidene fluoride and hexafluoropropene and/or mixtures of such materials.
- Mixtures of polyvinylidene fluoride (PVDF; thus a homopolymer of vinylidene fluoride) and a copolymer of 95 wt.-% vinylidene fluoride and 5 wt.-% hexafluoropropene are particularly suitable.
- the mixture ratio of the homo- polymer to the copolymer can be, e.g., 50 : 50 or 80 : 20; the weight ratio is stated each time.
- Such polymers can be coloured in the melt, e.g.
- polyethylene or polypropylene for example are suitable according to selected production conditions.
- the basic structure can also contain monofilaments of a resorbable material, e.g. of poly-p-dioxanone or of a copolymer of glycolides and caprolactones. Such a copolymer is marketed for example by Ethicon under the name "Mono- cryl”. If resorbable monofilaments are used, the basic structure can be made completely, but also only partly, from resorbable material.
- a resorbable material e.g. of poly-p-dioxanone or of a copolymer of glycolides and caprolactones.
- a copolymer is marketed for example by Ethicon under the name "Mono- cryl”. If resorbable monofilaments are used, the basic structure can be made completely, but also only partly, from resorbable material.
- the tensile strength of at least a part of the monofilaments is at least 400 N/mm 2 .
- Such tensile strengths can be achieved, e.g., with the above-mentioned mixtures of polyvinylidene fluoride and a copolymer of vinylidene fluoride and hexafluoropropene.
- the basic structure preferably contains a weft-knitted product or warp-knitted product, warp-knitted products preferably being made as crochet galloon ware.
- Weft- knitted products and warp-knitted products have proved suitable for flexible implants and can be made in a plurality of patterns.
- Figure 1 the typical shape of a force-path diagram which is measured in a three-point bending test on a monofilament or on the basic structure of a flexible implant
- Figure 2 a schematic illustration of the warp-knitted structure in the case of the implant according to the invention according to example 1,
- Figure 3 a schematic illustration of the warp-knitted structure in the case of the implant according to the invention according to examples 2 and 3 and
- Figure 4 a schematic illustration of the warp-knitted structure in the case of the implant according to the invention according to examples 4 and 5.
- FIG. 1 The shape of a typical force-path diagram is shown in Figure 1 as results when carrying out a three-point bending test on a monofilament or on the mesh-like basic structure of a flexible implant.
- the force maximum in the force-path diagram of a given sample is called the bending force .of the sample.
- the bending force is a measure of the flexibility behaviour of the sample, thus the monofilament here. The greater the bending force, the more rigid the monofilament.
- the bending force is given in N and depends on the test conditions, essentially on the distance between the two support points (span) . In the three-point bending tests which led to the numerical values given below for the monofilaments, the span was 4 mm.
- the test speed i.e. the speed at which the deflection of the sample is increased, was 50 mm/minute.
- the bending rigidity of the sample can also be measured from the force-path diagram.
- the bending rigidity is the slope in the linear range of the measurement curve.
- the unit of measurement is N/mm.
- the bending elasticity modulus of a monofilament can be calculated from a force-path diagram, taking the diameter of the monofilament into account.
- the bending elasticity modulus corresponds to the Young' s modulus and is given in N/mm 2 . This variable is largely independent of the test conditions, but depends not only on the material as such (like, e.g., in the case of metals), but also somewhat on the production conditions and the dimensions of the monofilaments .
- a three-point bending test can be carried out in an analogous manner on an areal flexible implant or on its mesh-like basic structure.
- the sample is supported along two lines which run parallel to each other the distance of the span apart .
- the span was 11 mm and the test speed (as for the monofilaments) was 50 mm/minute.
- samples with a width of at least 25 mm were used.
- the bending rigidity (in N/mm) of the mesh-like basic structure results from the force-path diagram as the slope in the linear range of the curve.
- a normalisation to the width of the sample took place. The numerical values given below relate to a sample width of 10 mm. If for example the sample width was actually 25 mm, this standardization took place by dividing the slope read off directly from the force-path diagram by 2.5.
- the bending force is obtained by evaluation of the force- path diagram as force maximum of the curve. The numerical values given below were standardized to a sample width of 10 mm.
- the bending force is a measure of the rigidity of the implant or of the mesh-like basic structure as a whole. The greater the bending force, the more rigid and less flexible the implant.
- Tables 1, 2 and 3 show respectively, for monofilaments of various materials and with various diameters, the bending elasticity modulus, the bending rigidity and the bending force. These variables were each established using three- point bending tests, as explained.
- PDS is an abbreviation for poly-p-dioxanone, a resorbable material.
- “Monocryl” is an Ethicon trade name for a resorbable copolymer of glycolides and caprolactones.
- “Pronova” is an Ethicon trade name for monofilaments of a mixture of polyvinylidene fluoride (PVDF) and a copolymer of 95 wt.-% vinylidene fluoride • and 5 wt.-% hexafluoropropene.
- PVDF polyvinylidene fluoride
- copolymer of 95 wt.-% vinylidene fluoride • and 5 wt.-% hexafluoropropene.
- Polyvinylidene fluoride and the copolymer are marketed for example by Solvay Advanced Polymers under the trade name "Solef 1008" and “Solef 11010", respectively.
- Surgical filaments of such materials are de- scribed in US 4 564 013 A.
- the mixture ratio of the homopolymer to the copolymer is 50 : 50 (in wt.-%) .
- the monofilaments of PDS, "Monocryl” and “Pronova” are suitable for building up the mesh-like basic structure of an implant according to the invention.
- the numerical values for monofilaments of various thicknesses of polypropylene (PP) are given in Tables 1 to 3.
- the bending elasticity modulus of polypropylene is greater than 4000 N/mm 2 .
- the bending rigidity should preferably be approx 0.08 N/mm at most for a diameter of 0.15 mm and approx 0.5 N/mm at most for a diameter of 0.25 mm.
- the bending force should preferably be smaller than approx 30 mN for a diameter of 0.15 mm and smaller than approx 150 mN for a diameter of 0.25 mm.
- the mesh-like basic structure was washed and subsequently stretched on a frame and thermofixed at temperatures between 80 °C and 130 °C. Afterwards the mesh-like basic structure was cut to size as a flexible implant, packed and subjected to a gas sterilisation with ethylene oxide.
- Crochet galloon ware was made from a "Pronova" monofilament (see above) of 0.079 mm diameter with a mixture ratio of homopolymer to copolymer of 80/20 (in wt.-%) similarly to Example 1.
- the production specification as well as the pattern template emerge from Figure 3. Subsequently the mesh-like basic structure was washed as in Example 1, thermofixed, packed as a flexible implant and sterilized.
- IPOM-technique "Intraperitoneal Onlay Mesh”
- IPOM-technique "Intraperitoneal Onlay Mesh”
- a commercial implant mesh of polypropylene (“Marlex”, see below) was implanted in an analogous way. Directly after the surgery the implant according to Example 2 lay flat, and the edges had not rolled up. On the other hand, the implant of polypropylene was lying incorrectly, the edges having slightly rolled up and sticking out from the bottom layer.
- the conventional implant mesh had caused very marked adhesions over the whole surface, which was attributable inter alia to a mechanical irritation of the peritoneum.
- the implant according to the invention was covered by a thin, transparent, smooth mesothelium cell layer. Surprisingly, there were no adhesions.
- Example 4 A mesh-like basic structure was warp-knitted as crochet galloon ware as in Example 2 and further processed, the only difference being that in this case a "Pronova" monofilament (see above) with a diameter of 0.093 mm and a mixture ratio of homopolymer to copolymer of 50/50 (in wt.-%) was used.
- the production specification and the pattern template again result from Figure 3.
- Example 4
- Crochet galloon ware was produced in a similar way to Example 1 from a "Pronova" monofilament (see above) of 0.079 mm diameter with a mixture ratio of homopolymer to copolymer of 80/20 (in wt.-%).
- Example 2 the mesh-like basic structure was washed as in Example 1, thermofixed, packed as a flexible implant and sterilized.
- a mesh-like basic structure was warp-knitted as crochet galloon ware as in Example 4 and further processed, the only difference being that in this case "Pronova" monofilament (see above) with a diameter of 0.093 mm and a mixture ratio of homopolymer to copolymer of 50/50 (in wt.-%) was used.
- the production specification and the pattern template again result from Figure 4.
- the pore size is the greatest pore width of the mesh-like basic structure and was determined with a measuring magnifier.
- the bending force and the bending rigidity were measured using three-point bending tests, as explained above. These variables were normalized to a sample width of 10 mm.
- the bending elasticity modulus is calculated from the shape of the curve, taking into account the thickness and width of the sample.
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001291758A AU2001291758B2 (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
US10/363,196 US20040034373A1 (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
JP2002524430A JP4772267B2 (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
CA2421243A CA2421243C (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
EP01971904A EP1315468B1 (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
DE60111242T DE60111242T2 (en) | 2000-09-04 | 2001-08-10 | BENDING IMPLANT |
AU9175801A AU9175801A (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10043396.0 | 2000-09-04 | ||
DE10043396A DE10043396C1 (en) | 2000-09-04 | 2000-09-04 | Flexible implant |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002019944A2 true WO2002019944A2 (en) | 2002-03-14 |
WO2002019944A3 WO2002019944A3 (en) | 2002-07-25 |
Family
ID=7654832
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2001/009299 WO2002019944A2 (en) | 2000-09-04 | 2001-08-10 | Flexible implant |
Country Status (8)
Country | Link |
---|---|
US (1) | US20040034373A1 (en) |
EP (1) | EP1315468B1 (en) |
JP (1) | JP4772267B2 (en) |
AU (2) | AU9175801A (en) |
CA (1) | CA2421243C (en) |
DE (2) | DE10043396C1 (en) |
ES (1) | ES2243551T3 (en) |
WO (1) | WO2002019944A2 (en) |
Cited By (8)
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US7087065B2 (en) | 2001-10-04 | 2006-08-08 | Ethicon, Inc. | Mesh for pelvic floor repair |
US7993261B2 (en) | 2004-05-07 | 2011-08-09 | Ams Research Corporation | Method and apparatus for cystocele repair |
US8038594B2 (en) | 2003-09-22 | 2011-10-18 | Ams Research Corporation | Prolapse repair |
US8047982B2 (en) | 2004-05-07 | 2011-11-01 | Ethicon, Inc. | Mesh tape with wing-like extensions for treating female urinary incontinence |
US8147478B2 (en) | 2000-09-07 | 2012-04-03 | Ams Research Corporation | Coated sling material |
US8206281B2 (en) | 2004-04-30 | 2012-06-26 | Ams Research Corporation | Method and apparatus for treating pelvic organ prolapse |
US8211005B2 (en) | 2004-04-30 | 2012-07-03 | Ams Research Corporation | Method and apparatus for treating pelvic organ prolapse |
EP1411997B2 (en) † | 2001-06-26 | 2019-03-27 | FEG Textiltechnik Forschungs- und Entwicklungsgesellschaft MbH | Textile implant made of monofil threads from polyvinyl fluoride |
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US20060205995A1 (en) | 2000-10-12 | 2006-09-14 | Gyne Ideas Limited | Apparatus and method for treating female urinary incontinence |
GB0025068D0 (en) | 2000-10-12 | 2000-11-29 | Browning Healthcare Ltd | Apparatus and method for treating female urinary incontinence |
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- 2001-08-10 DE DE60111242T patent/DE60111242T2/en not_active Expired - Lifetime
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US8147478B2 (en) | 2000-09-07 | 2012-04-03 | Ams Research Corporation | Coated sling material |
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Also Published As
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US20040034373A1 (en) | 2004-02-19 |
JP2004508100A (en) | 2004-03-18 |
EP1315468A2 (en) | 2003-06-04 |
DE60111242T2 (en) | 2005-12-15 |
JP4772267B2 (en) | 2011-09-14 |
CA2421243A1 (en) | 2002-03-14 |
WO2002019944A3 (en) | 2002-07-25 |
AU9175801A (en) | 2002-03-22 |
EP1315468B1 (en) | 2005-06-01 |
ES2243551T3 (en) | 2005-12-01 |
AU2001291758B2 (en) | 2007-03-15 |
DE60111242D1 (en) | 2005-07-07 |
DE10043396C1 (en) | 2002-06-20 |
CA2421243C (en) | 2010-06-08 |
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