Classifications

• • D—TEXTILES; PAPER
  • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
  • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
  • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
  • D01F6/58—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products
  • D01F6/70—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from homopolycondensation products from polyurethanes
• • 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
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G18/00—Polymeric products of isocyanates or isothiocyanates
  • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
  • C08G18/08—Processes
  • C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G18/00—Polymeric products of isocyanates or isothiocyanates
  • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
  • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
  • C08G18/40—High-molecular-weight compounds
  • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
  • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
  • C08G18/4269—Lactones
  • C08G18/4277—Caprolactone and/or substituted caprolactone

Definitions

• the invention relates to a linear block polymer, to various preparations made from said linear block polymer, and to an implant comprising the linear block polymer.
• Certain injuries to soft tissue of the body do not heal by itself.
• One example of such an injury is injuries to the meniscus, injuries common to certain athletes. When such an injury happened, the injured part was often removed, resulting in reduced bodily functions. This often meant the end of the career of the athlete.
• a continued high load on a knee without a meniscus leads to wear of the skeleton on the bearing surfaces, with permanent pains as a probable outcome.
• ACL anterior cruciate ligament
• the materials used for the artificial ligaments were for instance polytetrafluor ethyiene, polyethylene terephtalate, polypropylene, polyethylene and carbon fibers.
• a material for use in implants disclosed that is biocompatible and biodegradable.
• the material disclosed is a linear block polymer comprising urea and urethane groups, which polymer exhibits a molecular weight of at least 10 4 Dalton.
• High initial strength of the implant is required to prevent rupture of the implant before the bodily tissue has been able to re-growth and take over the bodily function.
• a stepwise degradation of the material is essential to induce re- growth of the bodily tissue.
• Degradation speed should be balanced to get optimum re-growth of tissue.
• the mechanical properties of the implant should be corresponding to that of the bodily tissue it is replacing so as to achieve as normal bodily function as possible during healing.
• R1 is derived from a diamine, e.g. ethyiene diamine, 1 ,2-diamino propane or 1 ,3-diamino propane;
• R2 is derived from an aromatic diisocyanate
• R3 is derived from an esterdiol
• R4 is derived from dibutyl amine or ethanolamine
• the monomers from which R2 and R3 are derived from are added in such amounts that the molar ratio between R2 and R3 is larger than 2:1. That is, the number of molars of monomer added that R2 is derived from, is more than twice the number of molars of monomer added that R3 is derived from. As described in the examples below, more than twice the amount of isocyanate to that of esterdiol is added during the polymerisation process.
• a polymer is obtained that is more optimised as regarding the mechanical and degradation properties compared to that of prior art.
• the material obtained through the present invention can be made stiffer. It is also rendered a lower speed of degradation. That is, degradation is slower. In other words, the strength of the material decreases slower than would be the case for conventional materials. How fast or slow the degradation goes, depends on the monomers chosen as staring materials.
• R1 is derived from ethyiene diamine, 1 ,3-diamino propane, 1 ,2-diamino propane, 1 ,4-diamino butane, 1 ,5-diamino pentane, or 1 ,6-diamino hexane.
• R2 is derived from 4,4'diphenyl methane diisocyanate, naphthalene diisocyanate, or toluene diisocyanate.
• R3 is derived from polycaprolactone diol, polydiethylene glycol adipate or poly (pentane diolpimelate).
• R1 and R2 may be freely combined within the realms of the invention.
• the linear block polymer may be spun into a fibre.
• the fibres may be produced by a wet spinning process described in " Gisselfalt, K.; Flodin, P. Macromol. Symp. 1988, 130, 103-111 ".
• the fibres produced from the linear block polymer described above exhibits a specific strength of at least 0.1 N/Tex, more preferably above 0.2 N/Tex.
• the fibres exhibit high stiffness. Due to that fact, an implant made from the fibres may obtain a stiffness that makes the implant work very well as a replacement for the injured bodily tissue. For some implants, it is desirable that the elongation at break is not too high. Conventional polyurethane fibres of Spandex type, such as Lycra, often exhibit too high elongation at break.
• a fibre produced from the linear block polymer according to the invention preferably exhibits an elongation at break that is below 100 %.
• the linear block polymer according to the invention may be used in different forms, depending on the use.
• suitable forms are fibres, foams and films.
• Other examples are porous films or porous polymeric material. Porous films are described in Swedish patent No. SE, C2, 514 064, which is hereby incorporated in its entirety. Further, porous film materials are described in Swedish patent application No. SE, A, 0004856-1 , which is hereby incorporated in its entirety. SE, A, 0004856-1 describes a method for manufacturing an open porous polymeric material.
• the invention further concerns an implant for the implantation into the human or animal body, which implant comprises a linear block polymer according to the invention.
• MDI 4,4'-diphenylmetandiisocyanate
• Example 2 A prepolymer was manufactured according to Example 1 , but with the modification that 1075.9 g (2.03 mol) PCL was mixed with 1035.2 g
• Example 5 27.18 g of the prepolymer obtained according to Example 1 was dissolved under nitrogen gas in 104 ml dimethyl formamide (DMF) and 1.23 g MDI was added.
• DMF dimethyl formamide
• Mp eak 86 000 g/mol compared to PEO in DMF + 0.5 % LiCI.
• the molecular weight of the polymers obtained from the above examples were measured by Size Exclusion Chromatography (SEC), with a Waters
• Detector and a Waters 2410 Refracive Index Detector Two Styragel colons, HT6E and HT3, were run consecutively with a flow rate of 1 ml/minute of dimethyl formamide (DMF) comprising 0.005 g LiCI/l. The retention time was transformed into average molar mass (M peak ), with the use of polyethylene oxide as a standard.
• DMF dimethyl formamide
• the fibre spinning process comprises the steps of: the polymeric solution being extruded through a spinneret into a coagulation bath containing warm water; in a second water bath, the fibre is stretched; the fibre is rolled up on a spool, which is allowed to dry.
• Example 2 DMF 0.28 + 0.01 62 ⁇ 4 40 ⁇ 3
• Example 3 DMF+LiCl 0.16 ⁇ 0.015 56 ⁇ 3 28 ⁇ 10
• Materials used for these prosthetic devices or reinforcement ligament bands were e.g. poly(tetrafluoroethylene), poly(ethylene terephtalate), 1,4 ' 6"9 polypropylene, polyethylene, carbon fibres 10 and polydioxanone.”
• the common properties of these materials are a too high elastic modulus compared to native ACL and permanent deformation after repeated loading due to non-elastic behaviour.
• PUUR Poly(urethane urea)s
• PUURs are made of soft segments based on polyether or polyester and hard segments based on the reaction of diisocyanate and diamine chain extender. Due to the thermodynamic incompatibility between the two segments, PUURs undergo micro-phase separation resulting in the phase-separated heterogeneous structure that can be considered as hard segment domains dispersed in a soft segment matrix.
• the various physical properties of the material such as strength, modulus, and elasticity are closely correlated with the domain structure and the interaction between the segments inside the domain. By adjusting the chemical nature and respective amounts of reagents, it is possible to obtain a wide range of materials with different properties. Thus, materials may be tailored for various applications.
• ACL anterior cruciate ligament
• a possible way to fulfil these requirements is to use a textile composition made of degradable PUUR fibres.
• the aim was to make PUUR fibres suitable for designing a degradable ACL device.
• PUUR fibres of the Spandex type e.g. Lycra
• their elastic modulus is too low and they are not degradable.
• wet spinning, mechanical properties and degradation of a number of PUUR fibres are presented.
• the effects of soft segment chemical composition and content and the kind of diamine chain extender on the material properties are investigated.
• EDA 1,2-diaminopropane
• 1,3-diaminopropane 1,3-diaminopropane
• 1,4-DAB 1,4- diaminobutane
• Polyester synthesis Hydroxytelechelic polyesters were synthesized from adipic acid and di(ethylene glycol) with acid catalyst until the acid number was ⁇ 2 as determined by titration of aliquots with 0.1 molar KOH in ethanol. The removal of water to drive the reaction at a reasonable rate was achieved by azeotropic distillation
• MDI 4'-diphenylmethane diisocyanate
• Fibre spinning Fibres were prepared by a wet spinning process 21 (equipment from Bradford University Research Limited, Bradford, England). The polymer solution was metered through a spinneret (120 holes, 0 80 ⁇ m) submersed in a coagulating
• fibres were rinsed in running tap water overnight and dried at room temperature. For each batch of fibres linear density, tensile strength, stiffness and elongation at break were determined.
• the wet spun multifilament fibres were by doubling and slight twisting converted to a coarse yarn, which was used as warp threads.
• the bands were woven on a narrow fabric needle loom (type FX2/65, Mageba Textilmaschinen
• Density measurements The density of the fibres was measured with a Micrometrics Multivolume Pycnometer 1305. Porosity measurements. Pore sizes and pore size distributions of the woven bands were measured by mercury porosimetry, Micromeretics AutoPore III 9410.
• Size Exclusion Chromatography was conducted with a Waters 2690 Separations Module equipped with a Waters 996 Photodiode Array Detector and a Waters 2410 Refractive Index Detector. Two Styragel columns, HT6E and HT3, were operated in series at a flow rate of 1 ml/min in DMF containing 0.5%(w/v) LiCI to prevent aggregation. The retention times were converted to apparent molar masses using poly(ethylene oxide) standards. Linear density measurements. The linear density of the fibres was determined by weighing of a known length of fibre, typical 100 m, and is presented in tex. The tex unit is defined as g/ 1000 m.
• the constant rate of extension was 900 mm minute and the sample lengths were 100 mm for fibres and 30 mm for the woven bands.
• DSC Differential Scanning Calorimetry
• PUURs were synthesized using poly(di(ethylene glycol) adipate) (PDEA) or polycaprolactone diol (PCL), with different molar masses as soft segments, MDI and EDA as chain extender (Table 1).
• the length of the soft segment was altered by changing the molar mass of the polyesterdiol while the length of the hard block was unchanged.
• there was a distribution of hard block lengths as a consequence of the stoichiometric ratio in the prepolymerization step. 23 As the soft segment was shortened from 2000 g/mol to 500 g/mol the hard block content increased from 23 % by weight to 55%.
• a requirement for spinnability is that the polymer is soluble.
• the solvent, DMF should prevent gelation due to hard segment interaction before spinning, but the solubility of PUUR in DMF is poor.
• LiCI 0.07 g LiCI /g polymer solution
• turbidity could be removed and gelation could be prevented.
• the increased solubility is based on the destruction of the hydrogen bonds between chains and on a simultaneous blocking of the acceptor positions owing to the favoured complex formation between Li and carbonyl oxygen.
• 27 Fibre spinning. The fibres are formed in a wet spinning process. In the first step precipitation occurs and the solvent diffuses out of the extrudate into the bath, and non-solvent diffuses from the bath into the extrudate. The rate of the coagulation has a profound effect on the yarn properties. Important process variables are for example concentration and temperature of the spinning solution, composition and temperature of the coagulation bath.
• the temperature of the spinning solutions was kept within 20-25 °C and the
• polymer concentration was 18 wt.-%. No correlation between polymer content and tensile properties could be seen. However, a spinning solution viscosity of more than 1 Pas was needed to be able to get a stable spinning process.
• the temperature of the coagulation bath was found to be of great importance.
• the rate of PUUR coagulation occurring when the polymer solution was extruded into the water depends on the coagulation temperature and influences both the morphology of the undrawn fibre and the ultimate fibre properties.
• the suitable spin bath temperature for PDEA based PUURs was about 20°C (Table 2). At higher
• Figure 1 Tensile test diagrams for PUUR fibre of PCL530-3 showing changes produced by increasing orientation and improving structure. Draw ratio D 3.5, D 3.8 and D 5.4.
• the draw ratio of the fibres is dependent on the temperature not only in the coagulation bath but also in the stretching bath. It was found that the best processability and draw ratio were achieved when the baths had the same temperature.
• the spinning conditions are shown in Table 2. Three different groups are identified. The first group contains PDEA based PUURs, described earlier, which have best processability and draw ratio at 20°C. The second group contains PCL
• This group contains PCL- based PUUR with chain extenders with more than two methylene groups and are spun from DMF+LiCl. Even though the highest draw ratio was achieved at the same temperature within each group, the temperature dependence of draw ratio of the fibres differed (Table 2 and Figure 2 a, b).
• PCL530-4 and PCL530-6 were constant at temperatures below 60°C and 70°C, respectively. At these temperatures
• the yarn radius can be calculated. From the calculations it is given that the tenacity of the fibres should be at least 0.2 N/tex to meet the criteria of strength and size.
• the multifilament fibres made from wet spinning have a high void content. Furthermore, when fibres are processed into woven structures, varying degrees of porosity can be provided.
• the pore sizes and pore size distribution of two woven bands made of 1500 multifilament PCL530-3 fibres are presented in Table 3. The smallest pores, ⁇ 8 ⁇ m,
• the tensile properties of the fibres are shown in Table 4.
• the length and composition of the esterdiol was varied and the hard block was formed from MDI and EDA.
• the effects upon shortening the soft segment were seen in increased stiffness and decreased elongation of the fibres. The largest effect is seen when comparing polymers made from soft segments of molar masses of -1000 g/mol and -500 g/mol. As a consequence of the shortening of the soft segment the hard/ soft ratio increases.
• the hard blocks which are extensively hydrogen bonded, mainly affect the stiffness and serve as both cross-links and filler particles in the soft segment matrix.
• Figure 4 Typical tensile test diagrams for a PUUR band of PCL530-3 fibres. Differential Scanning Calorimetry. The glass transition temperatures of the soft blocks for the different PUURs are presented in Table 5. As the molar mass of the soft segments decreased the T g increased from -30.7 to -5.5°C and from -48.3 to -
• the effect of soft segment length on its T g is related to the limitation of the soft segment mobility imposed by the attached hard segment. Beside the molar mass of the soft segment, the chain extender affected the T g so some extent. PCL530- 2Me and PCL530-3 showed the highest T g . For chain extenders with three or more methylene groups there was a movement towards higher T g the longer the diamine. All PUUR fibres but PCL530-2Me and PCL530-3 were spun from DMF+LiCl. PCL530-3 spun from DMF+LiCl showed no change in T g compared to PCL530-3 spun from DMF. The phase mixing of soft and hard segments makes thermal molecular motion in soft segment phase restricted. Therefore, the shifts of T g to higher temperatures are attributed to the interaction between hard and soft segments. Table 5. DSC data
• PDEA2000 and PCL2000 display lower hydrolytically stability than PCL530 and PDEA500, respectively. The reason is a higher fraction of soft segments and, consequently, of ester groups exposed to hydrolysis.
• the chemical composition of the ester affects the degradation rate of the different
• PUURs PUURs with soft segments made of PDEA degrade faster than those based on PCL.
• the superior resistance to hydrolysis is ascribed to the hydrophobicity of
• PCL poly(oxyethylene) blocks
• PDEA 500 contains about three diethylene glycols whereas the PCL diols initiated with diethylene glycol contain one.
• the initial molar mass of the different PUURs varied to a small extent (Table 1).
• the rate of the decrease in tensile strength was not affected, but the time to complete degradation became somewhat shorter the lower the initial molar mass.
• the molar mass decreases after an induction period of about 10 days for PCL530-2 and-3 and about 3 days for PCL1250-2 ( Figure 6). No induction period was seen for the other samples. During the induction period a decrease in SEC retention time was seen. The phenomenon has been occasionally reported by some researchers using both in vitro and in vivo systems, 34"36 but no unanimous conclusions on the reasons for the increase were drawn.
• the size of the formed aggregates is to some extent independent of the molar mass of the molecules that take part in the aggregate formation. It is obvious that the degradation proceeds since after 500 days the SEC retention time has increased accompanied by a the loss in tensile strength of 5-10%. Thus, the degradation rate at 37°C seems to be about 1/20 lower than of the degradation rate at
• Fibres made of PUUR based on PCL 530 have superior strength and stiffness compared to other polyesterdiols used in the study and keep at least 50 per cent of its original tensile strength more than nine months at body temperature. Furthermore, chain extension of PCL530:MDI with 1,3-DAP produces a polymer solution from which strong fibres can be spun without additives. A porous band with appropriate strength and size can be woven of the fibres.
• fibres of PCL530-3, ARTELONTM are suitable for designing a degradable ACL device.
• Human clinical trials with ACL reconstruction using the PUUR band are in progress. Acknowledgement. The Knowledge Foundation via the Material Research School at Chalmers University of Technology is gratefully acknowledged for financial support.

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicinal Chemistry (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Epidemiology (AREA)
• General Health & Medical Sciences (AREA)
• Textile Engineering (AREA)
• Dermatology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Transplantation (AREA)
• General Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Engineering & Computer Science (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Polyurethanes Or Polyureas (AREA)
• Artificial Filaments (AREA)
• Materials For Medical Uses (AREA)
• Prostheses (AREA)
• Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
• Ceramic Products (AREA)
• Graft Or Block Polymers (AREA)

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• 2002
  • 2002-06-20 SE SE0201948A patent/SE526106C2/sv not_active IP Right Cessation
• 2003
  • 2003-06-23 AT AT03733793T patent/ATE359308T1/de not_active IP Right Cessation
  • 2003-06-23 AU AU2003239077A patent/AU2003239077B2/en not_active Ceased
  • 2003-06-23 US US10/518,428 patent/US20060063909A1/en not_active Abandoned
  • 2003-06-23 CN CNB038167190A patent/CN1289563C/zh not_active Expired - Fee Related
  • 2003-06-23 WO PCT/SE2003/001085 patent/WO2004000904A1/en not_active Ceased
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  • 2003-06-23 DE DE60313169T patent/DE60313169T2/de not_active Expired - Lifetime
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