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
  • A61F2/02—Prostheses implantable into the body
  • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
  • A61F2/06—Blood vessels
• • 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
• • 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
  • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
  • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
  • A61L27/3625—Vascular tissue, e.g. heart valves
• • 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
  • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
  • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
  • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure

Definitions

• This invention involves a venous graft involving a vein segment and a supportive sheath chosen to provide the graft with mechanical compliance properties which resemble those of a healthy native artery.
• vascular prostheses are known or available.
• Commercially available synthetic vascular grafts in use are commonly made from expanded polytetrafluoroethylene (e-PTFE), or woven, knitted, or velour design polyethylene terephthalate (PET) or Dacron®.
• e-PTFE expanded polytetrafluoroethylene
• PET polyethylene terephthalate
• Dacron® Dacron®
• These prosthetic vascular grafts may have various drawbacks. When used for repairing or replacing smaller diameter arteries, these grafts may fail due to occlusion by thrombosis or kinking, or due to an anastomotic or neointimal hyperplasia (exuberant cell growth at the interface between artery and graft).
• Another problem may involve expansion and contraction mismatches between the host artery and the synthetic vascular prosthesis, which may result in anastomotic rupture, stimulated exuberant cell responses, and disturbed flow patterns and increased stresses leading to
• a vein segment if externally supported by an appropriate , flexible, radially-resiliently tubular support, can function, in much the same fashion as the artery to be replaced. That is, it functions without undue bulging or aggravated mismatching phenomena leading to graft failure.
• the term "compliance" means the ratio of the diameter change of a vessel as it expands in the radial direction in response to a given change in vessel pressure, and the values for compliance referred to below result from dynamic, in vitro testing. As described in greater detail below, the compliance of venous graft is largely dependent upon the compliance of the external, radially resilient support.
• the invention in one embodiment, accordingly, relates to a flexible, resilient, generally tubular external support within which may be supported a vein segment to form a venous graft.
• the tubular support is capable of resilient radial expansion in a manner mimicking the compliance properties of an artery, and compliance figures in the range of 3 to 30%/100 mm Hg are appropriate.
• the tubular support may be formed of a knitted or woven fiber mesh that is so formed as to exhibit the needed compliance properties.
• the invention in certain embodiments provides a venous graft for replacement of a section of an artery.
• the graft comprises a flexible, resilient, generally tubular external support and a vein segment carried within and having an ablumenal surface in contact with and supported by the tubular support, the venous graft being capable of resilient radial expansion in a manner mimicking the compliance properties of an artery. Compliance figures in the range of 3 to 30%/100 mm Hg are appropriate.
• the tubular support may take the form of a fiber mesh, such as a knitted, braided or woven mesh, the fibers of which may, if desired, be appropriately crimped to provide the required resiliency and compliance.
• the invention relates to a method for producing a venous graft for use in replacing a section of an artery.
• a segment of a vein is provided, and is sheathed in a generally tubular support in supportive contact with the ablumenal surface of the vein segment.
• the support is sufficiently flexible and radially resilient as to provide the resulting graft with compliance properties mimicking the compliance properties of an artery.
• Sheathing of the vein segment within the tubular support may be accomplished by supporting the generally tubular support upon an exterior surface of an applicator having an internal passage within which is positioned the vein segment, and removing the applicator to permit the tubular support to come into supportive contact with the ablumenal surface of the vein segment.
• Axial dimensional changes in the tubular support may be controlled as necessary to provide the venous graft with the desired compliance properties mimicking arterial compliance properties.
• Other embodiments of the invention relate to venous grafts that include a flexible, resilient, generally tubular external support formed of a shape memory alloy, and a vein segment carried within and having an ablumenal surface in contact with and supported by the tubular support.
• the shape memory support may be placed around a vein segment when the shape memory material is in a first enlarged configuration.
• the tubular support comes into supportive contact with the ablumenal surface of the vein when the support is transformed, as by a temperature increase, into a second configuration different from the first configuration.
• the shape memory support in its second configuration may exhibit superelastic properties and in any event is sufficiently flexible and resilient as to provide the venous graft with compliance properties mimicking the compliance properties of an artery. Compliance figures in the range of 3 to 30%/100 mm Hg are appropriate.
• the tubular support may take the form of a wire mesh made of shape memory alloy, such as a knitted or woven mesh, the wires of which may, if desired, be appropriately crimped to provide the required resiliency and compliance.
• Figure 1 is a pressure versus diameter graph typifying the characteristics of a native vein, native artery, a non-compliant stented vein, and a compliant stented vein;
• Figure 2 is a schematic cross-sectional view of an artery;
• Figure 3 is a representative pressure versus strain graph;
• Figure 5 is a photograph of a tubular support in a first configuration, shown in an axially compressed and radially expanded configuration and supported on a plastic tube;
• Figure 6 is a photograph of the tubular support of Figure 5 in an axially elongated and radially reduced configuration to conform to a vein outer diameter;
• Figure 7 is a side view of the graft of Figure 6, showing a length-governing element
• Figure 8 is a schematic view of braided elements
• Figure 9 is a perspective view of a braided tubular support
• Figure 10 is a schematic view of knitted elements
• Figure 11 is a side view of a section of a knitted tubular support
• Figure 12 is a view of angular pre-braiding crimped elements
• Figure 13 is a perspective, schematic view of an angular pre-braiding crimped tubular support
• Figure 14 is a view of rounded pre-braiding crimped elements
• Figure 16 is a view of rounded pre-knitting crimped elements
• Figure 17 is a broken-away, perspective view of a post-braiding crimped tubular support
• Figure 18 is a broken-away, perspective view of a venous graft showing a portion with anti-fraying element
• Figure 21 is a photographic, perspective view of a section of a knit tubular support.
• Intimal hyperplasia is believed to be a primary reason for vein graft failure, hi this context it is known that intact endothelium acts in a manner to protect against the proliferation of underlying vascular smooth muscle cells, known as VSMC, The intact endothelium also plays a role in VSMC contractile responses. The VSMC have also been shown to release factors with long term physiological effects on the endothelial cells, including maintenance of a non-proliferative state.
• intimal hyperplasia in a vein graft may follow the sequence of dilatation under arterial pressure; overstretching to maximum capacity; disruption of borders of endothelial cells; rupture of internal elastic membranes; migration of smooth muscle cells into the intimal layer and resultant unbalanced proliferation; atrophy of media and further consolidation of stiffness; and graft arteriosclerosis with traumatic media necrosis and atrophy, as well as pathological surface and wall stress and strain.
• Intimal hyperplasia may be observed in such grafts from about 16 months, while anastomotic intimal hyperplasia may occur at about 18 months, and arteriosclerosis may occur from about 45 months.
• Figure 1 graphs blood pressure against vessel diameter, with D 0 representing the vessel diameter at zero pressure.
• lines 16, 18 represent the normal diastolic, i.e. low (80 mm Hg) and normal systolic, i.e. high (120 mm Hg) physiological blood pressure range for humans.
• Point 21 may represent the diameter of an artery (D A ) at 100 mmHg, and point 23 may represent the diameter of a vein (Dv) at the same pressure of 100 mmHg.
• a further consideration is the influence of tensile stress/strain on the structure and organization of smooth muscle cells during development and remodeling, particularly as to the orientation of such cells.
• this may also relate to the role of blood flow in the formation of focal intimal hyperplasia in known vein grafts, including inducement of eddy blood flow at locations of graft-host diameter mismatch.
• compliance is the ratio of the diameter change of a vessel in the radial direction to a given change in vessel pressure, and the values for compliance referred to below result from dynamic, in vitro testing. Compliance values are reported here as percentage changes in the internal diameter of a vessel per a 100 mm Hg change in vessel pressure, as measured in the range of normal blood pressures, that is, from about 80 mm Hg to about 120 mm Hg. In the laboratory, it is convenient to measure compliance through the use of an elongated balloon structure over which a candidate tubular support is positioned.
• the compliance of an implanted venous graft may be measured in vivo through the use of ultrasound techniques in which the vein graft is visualized in a cross-sectional view and the dimensional change of the vessel with varying blood pressure is recorded for at least one and usually a number of cardiac cycles.
• the cross-sectional lumenal area of the vein graft is measured for the smallest cross-sectional configuration and the largest cross- sectional configuration for one cardiac cycle.
• the smallest cross-sectional configuration of the vein graft lumen is associated with diastolic blood pressure whereas the largest cross- sectional configuration is associated with systolic pressure.
• the cross-sectional lumenal area values for diastolic and systolic blood pressure are used to calculate the lumenal diameter values and the vein graft compliance.
• Compliance values of a venous graft measured in vivo often are slightly larger that the compliance values measured in the laboratory, and the compliance values referred to herein are laboratory values resulting from the in vitro measurements described above
• FIG. 2 is a sectional representation of vascular tissue useful for illustrating the relation of the natural arterial structure with the prosthetic venous graft structure of the invention.
• the natural adventitial layer 95 of an artery 98 is comprised of two main tissue types that contribute to the mechanical properties of the natural artery, namely elastin and collagen. The mechanical properties of these two soft tissue components are described in Table I below:
• stiffness index ( ⁇ )
• ⁇ stiffness index
• Figure 4 shows that the Elastic Modulus (K), as defined in above equations, is proportional to the secant Si of the pressure-diameter curve PDi , plotted on a linear scale (left y-axis in Figure 4), between diastolic and systolic pressure.
• the slope, (P syst - Pdiast)/(D sy st - Ddiast), of the secant Si is a good approximation to the slope of the pressure- diameter curve PDi in that pressure range.
• the stiffness index ( ⁇ ) is proportional to the secant S of the pressure-diameter curve PD between diastolic and systolic blood pressure when the pressure-diameter curve is plotted on a logarithmic pressure scale (right y-axis in Figure 4).
• the slope of the secant S 2 is (In P S yst - In Pdiast)/(D sy st - D iast) and is a good approximation to the slope of the pressure-diameter curve PD 2 in that pressure range. It can be again appreciated, from the above equations for the Stiffness Index ( ⁇ ) that the Stiffness Index ( ⁇ ) is not equal to the slope of the secant S 2 but is proportional to the slope by a factor Ddiastoiic-
• Polymeric fibers may be employed, such as polyurethanes, polyethylene terephthalate, polypropylene, and polytetraflouroethylene, and good results may be obtained through the use of wires of such metals as stainless steel and cobalt- chromium alloys. Wires made of shape memory alloys such as nitinol may be used to advantage. Shape memory elements or filaments may be made of one or more shape memory materials as exemplified in the following table, it being understood that this is not to be considered an exhaustive list. Also, any metal or metal alloy may be coated with a polymer for improved biocompatibility, recognizing that the polymer may or may not be biodegradable.
• shape memory alloys other design considerations include temperatures, different diameters and radial compliance, shape transformation dimensional changes, and wire thicknesses.
• shape memory alloys and shape memory polymers may have transformation temperatures which are below physiological temperatures, i.e., 37° C, to ensure self-righting responses.
• transformation temperatures will also be above room temperature to ensure that the shape memory material reinforcing does not need to be refrigerated for storage purposes.
• the ideal shape memory transformation temperatures will likely be between 21° and 37° C.
• This transition may either be a two-way or a one-way directional transition, with a currently preferred embodiment including a two-way directional transition.
• the transition temperature range can either be a short, i.e.
• a long transition temperature range i.e. 10° C, where the shape is proportionally regained over this temperature range.
• a desired temperature transition to be 100% complete at 25° C but with it starting at 20° C, then this would yield a temperature range of 5° C.
• the changes in radial diameter due to the shape memory material experiencing transformation dimensional changes is preferably in a range of from 5% to 30%.
• FIG. 5 shows an arterial reinforcement tubular support 77 formed of one or more shape memory material elements 165. These elements are braided, but may also be knitted, into a generally tubular structure designed for placement around a portion of a vein to produce an arterial graft.
• a shape memory alloy is employed because of its so-called "superelastic" properties rather than its ability to undergo temperature-induced phase changes, although some phase change from austenite to stress- induced martensite may occur
• the braided tube is positioned on a hollow plastic straw as representing a vein segment, and has been compressed axially to produce an increase in diameter. By extending the braided tube axially, as shown in Figure 6, the tube becomes reduced in diameter to provide support to the vein segment.
• shape memory materials can be controlled by altering compositions, tempering procedures, wire diameters, etc., so that a tubular support fashioned from this material may mimic (when combined with the minimal mechanical values of a vein segment) the compliance values of a host artery in order to optimize the venous graft- artery interaction.
• This aspect of compliance mimicking has components of expansion, recoil, timing, and tissue remodeling, hi this example, the vein-stent compliance values are chosen to closely mimic those of a healthy native artery.
• shape memory wires are shown as braided in these figures, they may also be knit, and in fact the knit configuration appears to be offer certain advantages.
• the knitted or braided tubular support may then be subjected to crimping to provide crimps extending, for example, about the circumference of the tubular support (that is, in the manner shown in Figure 17) .
• crimping to provide crimps extending, for example, about the circumference of the tubular support (that is, in the manner shown in Figure 17) .
• One way of doing this is through the use of an axially fluted mandrel that is inserted into the tube and is pressed outwardly against a wall of the tube to force the wall against a complementary shaped outer female mold to bend the knitted or braided wires and to form a circumferential crimp, the crimp resulting from each flute or raised ridge of the mandrel extending axially of the support.
• a compliant venous graft using various metals or polymers for the tubular support may be provided in several ways.
• Embodiments may be advantageously provided in knitted form.
• Figures 8 and 9 show material 165 in a braided configuration
• Figures 10 and 11 show material 165 in a knitted configuration.
• Mechanical characteristics of the tubular support may be enabled by the type of shaping and relational structures formed on the elements making up the knit or braided structures. It is contemplated that a technique involving crimping of the material 165 to achieve angular crimps (shown in Figures 12 and 13), formed prior to the braid or knit construction, and rounded crimps (shown in Figure 14) may provide acceptable results. Crimping techniques that may be appropriate with pre-knit configurations, are shown in Figure 15 (angular crimps) and Figure 16 (rounded crimps).
• FIG. 17 shows one embodiment of material 165 formed in a braided configuration and having a post-braided crimping operation applied to form a crowned pattern to achieve desired crimp characteristics.
• Crimp angle and pitch density may be important variables in certain embodiments of the current design of the tubular supports. It is understood, however, that certain advantages of this invention may still be achieved without use of crimping. Ranges of crimp angle are preferably from about 10° to 85° to the line of lay of the reinforcing wire or braid. The crimp size may vary from 0.01 to 5 mm in length. It is desired that the braid or helical wires have a pitch angle that may vary from about 5-85° to the axial length of the vein graft. Applicants have identified certain crimping techniques that relate to crimping either before or after braiding or knitting.
• adjustable rings 210 of bioabsorbable or biodegradable material are placed generally circumferentially around a portion of the material 165, and in contact with external surfaces 217, as shown in Figure 18.
• the number of rings may be varied as needed.
• the location of the rings may be adjusted to the position of anastomoses where vein and tubular support need to be cut.
• the cut or suture may be carried out through the ring, and the ring may be absorbed or degraded over a predetermined time, as desired.
• Another embodiment of a structure to prevent fraying of a knit or braided tubular support when it is cut is the use of polymer coating for the fiber mesh. This feature may also provide the benefit of preventing gluing of joints and contact zones of elements of the stent.
• use of the radially compliant tubular support as a reinforcing structure may advantageously involve bonding of the ablumenal surface of a vein segment to confronting internal surfaces of the support. This attachment or connection may be accomplished through the use of a glue or other material having adhesive or connecting characteristics.
• a fibrin glue or other material having adhesive or connective characteristics may be sprayed on designated portions of the yein (as exemplified at 283 in Figure 20) and/or the tubular support.
• Another embodiment includes placement of a material on designated portions of the lumenal surfaces of the tubular support so as to provide the characteristics of contact adhesion and/or bonding when these portions contact the vein.
• the glue or other material must not inhibit the function of the tubular support. It is desirable that the contact of the tubular support with the ablumenal vein segment surface be reasonably uniform along the length of the support, and that regions of much higher force of the support against the ablumenal wall of the vein be avoided.
• This applicator may also facilitate placement of anti- fraying rings 210.
• the method of using the applicator comprises the steps of: providing the means of longitudinally contracting a stent; holding the stent in the contracted position with increased stent diameter resulting; inserting a vein into the stent lumen; and distending the stent longitudinally while the vein is inserted simultaneously until the stent is slipped over the desired portion of the vein. Further design considerations must ensure that the stent will not be fixed to the vein in a longitudinally over-distended or contracted state, so as to ensure that the predetermined mechanical stent properties remain viable.
• Figure 20 shows an embodiment in which a tubular support 185 is received along the outer surface of surface of an applicator 281 having an internal passage, and, while passing the vein segment 86 from within the applicator passage, the tubular support is drawn onto the ablumenal surface of the vein segment.
• the applicator here may be a thin walled tube resembling a soda straw.
• a length-defining support feature or system should ensure a predetermined support length. This is particularly true with respect to braided supports, and perhaps less important with knit supports in which radial resilience is less dependent upon the amount to which the support is extended axially.
• axial support length may be controlled, for example, through the use of an axially extending, relatively inextensible element, (as for example the thread 78 in Figure 7), that restrains the tubular support from unwanted axial extension.
• the tliread may be woven through the support mesh and may be fastened, as by welding, to the various wires that the thread encounters along the length of the support so that as the support is stretched axially, the extent of axial elongation is controlled by the thread as the thread is drawn taut.
• this feature may enable a length of the tubular support to be divided into portions of appropriate length, with the permitted axial extension of each portion controlled by the section of thread within it.
• a vein segment may be sheathed in a tubular support as discussed in detail above, with the intent of cutting out a smaller segment of the resulting venous graft for use in the surgical replacement of an artery, and the venous graft that is thus used will have vein and tubular support ends that are coextensive.
• Various generally tubular external wire mesh supports were fabricated from metal wires by braiding and by knitting, some being crimped and others not, and the diametrical compliance of each was measured using the in vitro diametrical compliance testing outlined above. The measured compliance values were dependent upon many variables, including wire size, tightness of braid or knit, etc. The following values were obtained:
• the external tubular support cannot be applied yet because leaks in the vein wall need to be freely accessible for repair. Therefore, no over-distention protection is placed around the vein yet, necessitating the limitation of the inflation pressure to a level suitable for detecting any leaks of concern but less than a level deemed to cause unacceptable damage, such as, for example, in one embodiment, 15 mm of Hg, the pre-maximal dilatation pressure for veins.
• the tissue remodeling functions of applicants' invention become more critical in view of the importance of leak testing and the reality of possible damage to the intimal layer in the vein during even the most carefully performed leak testing.
• the next step involves assembling the harvested vein segment and an external tubular support of this invention.
• the tubular support (typified here as a knit support) is mounted on a tube or straw-like applicator within which is positioned the vein segment. See Figure 20.
• the straw is then removed axially, leaving the support and vein in contact to form the venous graft. Over-extension of the tubular support is prevented using a length-limiting central thread or other means, as described above.
• the vein segment is then inflated under arterial blood pressures of 120 mm of Hg, causing it to contact the tubular support inner lumenal surfaces.
• an adhesive securing the tubular support to the vein will ensure that the vein does not collapse during the surgical procedure when no internal pressure is applied. Again, it should be recognized (without limitation) that this is one of several ways to accomplish the above objectives. ⁇
• One of the external anti-fraying rings or cuffs is slid to the end of the vein, and a typical double-S-cutting line is used to prepare the end for the first anastomoses.
• the thin cuff prevents fraying of the tubular support and also gives the vein tissue and tubular support a uniformity which makes the surgical process of stitching the vein to the host artery in an end-to-side fashion much easier.
• Another thin anti-fraying ring is then slid down from the applicator to a position where either a side-to-side anastomoses for a sequential graft is being performed, or where the vein is being cut at an appropriate graft length.
• the half of the sliding cuff which remains on the original vein will make the process of the anastomoses to the proximal host artery much easier.
• the end of the remaining vein protected by the other half of the cuff is used for the next distal graft anastomoses.

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• Health & Medical Sciences (AREA)
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• Veterinary Medicine (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Transplantation (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
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• Medicinal Chemistry (AREA)
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• Chemical Kinetics & Catalysis (AREA)
• Prostheses (AREA)
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• Graft Or Block Polymers (AREA)
• Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

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• 2004
  • 2004-04-28 EP EP04760409A patent/EP1626679B1/en not_active Expired - Lifetime
  • 2004-04-28 US US10/834,360 patent/US8057537B2/en active Active
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  • 2004-04-28 EP EP10015780A patent/EP2335648A1/en not_active Withdrawn
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• 2012
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