CA2426740C - Polyester urethanes - Google Patents
Polyester urethanes Download PDFInfo
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- CA2426740C CA2426740C CA002426740A CA2426740A CA2426740C CA 2426740 C CA2426740 C CA 2426740C CA 002426740 A CA002426740 A CA 002426740A CA 2426740 A CA2426740 A CA 2426740A CA 2426740 C CA2426740 C CA 2426740C
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- 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
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/73—Polyisocyanates or polyisothiocyanates acyclic
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- 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
- C08G18/4009—Two or more macromolecular compounds not provided for in one single group of groups C08G18/42 - C08G18/64
- C08G18/4018—Mixtures of compounds of group C08G18/42 with compounds of group C08G18/48
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- 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
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- 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
- C08G18/48—Polyethers
- C08G18/4854—Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
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- 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
- C08G2101/00—Manufacture of cellular products
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- 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
- C08G2280/00—Compositions for creating shape memory
Abstract
The present invention relates to polyester urethanes comprising polypentadecalactone segments. These polyester urethanes do show good properties which may be adjusted in a controlled manner. In preferred embodiments the polyester urethanes display additionally polycaprolactone segments. Such polymer may show shape memory effects.
Description
Polyester urethanes The present irivention relates to polyester urettianes cornprising a specific component of polypentadecatactone (PDL).
Plastic materials are valuable synthetic polymeric materials wt)ich have secured a prominent place in many applica6ons in the art. By varying the different components of polymers attempts are made to achieve optimum properties for the desired applications, in order to respond precisely and selectively to specific demands. A dass of in particular interesting products are polyurethanes since these materials may be produced by addition reactions of preformed segments, without producing undesired side products. A
known class of polyurethanes are polyurethanes comprising two different polyester components, namely a_ polycaprolactone segment and a polyparadioxanone segment.
These materials, described in WO-A-99-42528 and WO-A-99-42147, do show shape memory effects, wherein the polycaprolactone segment serves as trigger segment and the polyparadioxanone segment serves as so called hard segment. The use of polyparadioxanone segments however is problematic in some applications since this segment provides the polyester urettianes with a rather rapid biodegradability.
Furthermore a lot of the known polyester urethanes do not show the desired mechanical properties, so that the use of novel segments is necessary, in order to meet the ever increasing demands concerning the applications of polymeric materials. Finally polymeric materials should preferable enable the controlled adjustment of desired properties over a broad range, preferably by means of modifications with minor chemical amendments, only.
It is the object of the present invention to provide a novel polymeric material which is able to overcome the drawbacks cited above in connection with the known materials.
This object is achieved with a polyester urethane comprising as essential component, segments of polypentadecalactone.
The most basic form of the present invention may be seen in the use of polypentadecalactone segments in polyester urethanes. The polypentadecalactone segments may be the only polyestersegments in the polyester urethan or further segments, different from polypentadecalactone may be present in a preferred embodiment the polypentadecalactone segments are employed as hard segments in the polyester urethane, which, in addition to the poiypentadecaiactone segments, do comprise further polyester segments, preferably polycaprolactone segments, as soft segments. These further segments may be selected among a broad variety of chemically different components which are suitable as soft segment. Speciflc examples which may be named comprise partially crystalline segments, comprising polyester segments, polyether ester segments and polyether segments, such as polycaprolactone segments (PCL), poiycaprolactone-co-potytetrahydrofiarane segments (PCL-co-pTHF), tetrahydrofurane segments (pTHF), polypropyleneglycol segments (PPG) and polyethyleneglycol segments (PEG), as well as glassy segments, comprising polyester and copolyester, such as poly-L-lactid-co-glycolide (ran) (PLGA) and poty-DL-lactide (P-DL-LA). in particular a combination of polypentadecalactone segments and polyethyleneglycole segments enables intriguing- properties of the resulting material due to the combination of hydrophobic and hydrophilic segments.
The polypentadecalactone segment, contained in the polyester urethane used in accordance with the present invention, is usually introduced into the polyester urethane in the form of a macro diol, This segment may be obtained by ring opening polymerisation from m-pentadecalactone employing tin catalysis and using ethylene dioi as initiator. The ratio of initiator to monomer controls the tnolecular weight of the segment. The molecular weight of the polypentadecalactone segments in the polyester urethane used in accordance with the present invention is not criticai.
Usually the number average of the molecular weight is however in the range of from 1000 to 20,000 g/mol, preferably to 2000 to 11,000 g/mol, determined by GPC-analysis, The macrodiol from pentadecaiactone may be converted to a polyester urethane using those diisocyanates which are typically employed for the preparation of polyurethanes. Preferred diisocyanate are compounds having the formula O=C=N-R-N=C=O wherein R is aromatic or aliphatic. Preferably however R is aliphatic comprising a carbon chain of from I to 10, preferably 2 to 8 and in perticular preferably 4 to 7 carbon atoms. This carbon chain may be saturated with hydrogen or may show additional substituents. These substituents comprise short chain alkyl groups, in particular methyl groups. A preferred diisocyanate is trimethyl hexane-1,6-diisocyanate.
Plastic materials are valuable synthetic polymeric materials wt)ich have secured a prominent place in many applica6ons in the art. By varying the different components of polymers attempts are made to achieve optimum properties for the desired applications, in order to respond precisely and selectively to specific demands. A dass of in particular interesting products are polyurethanes since these materials may be produced by addition reactions of preformed segments, without producing undesired side products. A
known class of polyurethanes are polyurethanes comprising two different polyester components, namely a_ polycaprolactone segment and a polyparadioxanone segment.
These materials, described in WO-A-99-42528 and WO-A-99-42147, do show shape memory effects, wherein the polycaprolactone segment serves as trigger segment and the polyparadioxanone segment serves as so called hard segment. The use of polyparadioxanone segments however is problematic in some applications since this segment provides the polyester urettianes with a rather rapid biodegradability.
Furthermore a lot of the known polyester urethanes do not show the desired mechanical properties, so that the use of novel segments is necessary, in order to meet the ever increasing demands concerning the applications of polymeric materials. Finally polymeric materials should preferable enable the controlled adjustment of desired properties over a broad range, preferably by means of modifications with minor chemical amendments, only.
It is the object of the present invention to provide a novel polymeric material which is able to overcome the drawbacks cited above in connection with the known materials.
This object is achieved with a polyester urethane comprising as essential component, segments of polypentadecalactone.
The most basic form of the present invention may be seen in the use of polypentadecalactone segments in polyester urethanes. The polypentadecalactone segments may be the only polyestersegments in the polyester urethan or further segments, different from polypentadecalactone may be present in a preferred embodiment the polypentadecalactone segments are employed as hard segments in the polyester urethane, which, in addition to the poiypentadecaiactone segments, do comprise further polyester segments, preferably polycaprolactone segments, as soft segments. These further segments may be selected among a broad variety of chemically different components which are suitable as soft segment. Speciflc examples which may be named comprise partially crystalline segments, comprising polyester segments, polyether ester segments and polyether segments, such as polycaprolactone segments (PCL), poiycaprolactone-co-potytetrahydrofiarane segments (PCL-co-pTHF), tetrahydrofurane segments (pTHF), polypropyleneglycol segments (PPG) and polyethyleneglycol segments (PEG), as well as glassy segments, comprising polyester and copolyester, such as poly-L-lactid-co-glycolide (ran) (PLGA) and poty-DL-lactide (P-DL-LA). in particular a combination of polypentadecalactone segments and polyethyleneglycole segments enables intriguing- properties of the resulting material due to the combination of hydrophobic and hydrophilic segments.
The polypentadecalactone segment, contained in the polyester urethane used in accordance with the present invention, is usually introduced into the polyester urethane in the form of a macro diol, This segment may be obtained by ring opening polymerisation from m-pentadecalactone employing tin catalysis and using ethylene dioi as initiator. The ratio of initiator to monomer controls the tnolecular weight of the segment. The molecular weight of the polypentadecalactone segments in the polyester urethane used in accordance with the present invention is not criticai.
Usually the number average of the molecular weight is however in the range of from 1000 to 20,000 g/mol, preferably to 2000 to 11,000 g/mol, determined by GPC-analysis, The macrodiol from pentadecaiactone may be converted to a polyester urethane using those diisocyanates which are typically employed for the preparation of polyurethanes. Preferred diisocyanate are compounds having the formula O=C=N-R-N=C=O wherein R is aromatic or aliphatic. Preferably however R is aliphatic comprising a carbon chain of from I to 10, preferably 2 to 8 and in perticular preferably 4 to 7 carbon atoms. This carbon chain may be saturated with hydrogen or may show additional substituents. These substituents comprise short chain alkyl groups, in particular methyl groups. A preferred diisocyanate is trimethyl hexane-1,6-diisocyanate.
By varying the molecular weight of the polypentadecalactone segment the properties of the polyester urethane may be varied. The molecular weight of the polyester urethane is not critical and may be selected in accordance with the desired use. Typical molecular weights (number average, determined by GPC) are in the range of from 50,000 to 250,000 g/mol, preferably within the range of 80,000 to 200,000 g/mol and in particular within the range of 62,000 to 196,000 g/mol.
The polyester urethanes in accordance with the present invention which comprise polypentadecalactone segments do show a melting temperature, depending from the molecular weight within the range of about 90 C (preferably 87 - 95 C).
Typical mechanical properties are sche E-Modulus of about 17 MPa, an eiongation at break at 70 C of about 1000% and a tensile strength of about 18 MPa. Polyester urethanes comprising polycaprolactone segments, which are known from the prior art do show values for E-Modulus and tensile strength of only 0.5 and 2 MPa, respeeuvely.
The material in accordance with the present invention, although differing with respect to their chemical composition only to a minor extend from the polycaprolactone urethanes, are therefore vaiuable materials having a great potentiat for a variety of applications. The slower biodegradability of polypentadecalactone segments, compared with poaycaprolactone segments enables the application in field:, where an increased stability within a physiological environrnent is desired, for example implants for long time application. The use of segments made from pentadecala+ctone further ' offers the advantage that this manomer is readily available at moderate costs due to its use within the cosmetic industry.
Preferably the polyester urethane comprises in addition to the polypentadecalactone segment at teast one further polyester segment, such as those named above. In particular this further segment is a polycaprolactone segment. These polyester urethanes are block copolymers comprising polypentadecalactone segments, linked with other polyester segments, preferably polycaprolactone segments. The further segments, in particular the polycaprolactone segments, may, as described above for the p lypentedecalactone segment, be introduced into the polyester urethane in the form of a macrodiol. This macrodiol may be prepared using the usual processes known to the skitled person, such as ring opening potymerisation of e--caprolactone, in accordance with the process described above.
The polyester urethanes in accordance with the present invention which comprise polypentadecalactone segments do show a melting temperature, depending from the molecular weight within the range of about 90 C (preferably 87 - 95 C).
Typical mechanical properties are sche E-Modulus of about 17 MPa, an eiongation at break at 70 C of about 1000% and a tensile strength of about 18 MPa. Polyester urethanes comprising polycaprolactone segments, which are known from the prior art do show values for E-Modulus and tensile strength of only 0.5 and 2 MPa, respeeuvely.
The material in accordance with the present invention, although differing with respect to their chemical composition only to a minor extend from the polycaprolactone urethanes, are therefore vaiuable materials having a great potentiat for a variety of applications. The slower biodegradability of polypentadecalactone segments, compared with poaycaprolactone segments enables the application in field:, where an increased stability within a physiological environrnent is desired, for example implants for long time application. The use of segments made from pentadecala+ctone further ' offers the advantage that this manomer is readily available at moderate costs due to its use within the cosmetic industry.
Preferably the polyester urethane comprises in addition to the polypentadecalactone segment at teast one further polyester segment, such as those named above. In particular this further segment is a polycaprolactone segment. These polyester urethanes are block copolymers comprising polypentadecalactone segments, linked with other polyester segments, preferably polycaprolactone segments. The further segments, in particular the polycaprolactone segments, may, as described above for the p lypentedecalactone segment, be introduced into the polyester urethane in the form of a macrodiol. This macrodiol may be prepared using the usual processes known to the skitled person, such as ring opening potymerisation of e--caprolactone, in accordance with the process described above.
The molecular weight of the additional segments, as described above for the polycaprolactone segments, is not crltical. Mowever, typically these segments do show a number average of the molecular weight, determined by GPC, of from 1000 to 20,000 g/mol preferably 2,000 to 11.000 g/mol, wherein the preferred range for the PEG
segments is from 2000 to 20,000 g/moi, for the PLGA segments from 4000 to 9000 g/mol and for P-DI.-tA from 5000 to 11,000 g/rnol. The polyester urethanes comprising additional segments, preferably polycaprolactone segments do show preferably a molecular weight of from 50,000 to 250,000 g/mol (number average, determined by GPC), more preferably of from 60,000 to 200,000 g/moi and in particular preferably from 62000 to 196,000 g/mol (and in some embodiments of from 55,000 to 100,000 gfmol).
The content of polypentadecatactone units may be varied over a broad range, prefierably the content of pentadecalactone units is in the range of from 10 to 80 wt Xo.
in particuiarly within the range of from 20 to 60 wt%.
When the above described polyester segments are converted by a polyaddition rection using the above disclosed diisocyanates to polyester urethanes in accordance with the present invention, a variation of the respective amounts and molecular weights of the polyester segments enables an acUustment of the profile of properties of the resulting polyester urethanes. This preferred embodiment of the present invention provides a polymeric system which enables, by modifying simple starting materials, a.control of the resulting properties.
The materials in accordance with the present invention may be used in the form of fibres, such as in wrinkle resistant textiles, in the form of different shaped articies, for example in the field of medicine, as slowiy degrading implants or In the form of coatings, for 'example on short term implants, such as cannulae or lead-wires_ The use as coating material may increase the bic compatability of the coated articies and may therefore protect the user from undesired side reactions during use of the coated arbcles.
The preferr-ed polyester urethanes of the present invention, which comprise in addition to th polypentadec.alactone segments further segments, preferabiy polycaprolatone segments, do display further preferred profiles of properties.
The introduction of further segments, preferably polycaprolactone segments, into the polyester urethanes of the present invention introduces a second melting temperature, which may be detected during DSC measurements, into the polyester urethane.
This second melting temperature usually lies in the range of above 50 C, depending from the molecular weight and = the proportion of the further segment, preferably the polycaprolactone segment, in the polyester urethane.
In addition the mechanical properties may be controlled over a broad range.
With increasing content of polypentadeclactone the value for i==-Modulus may be increased as well. The value for the elongation at break may be adjusted to 600 to 1200%
with increasing content of polypentadecalactone and in addition tensile strength may be adjusted in a range of from 4 to 10 MPa vvrith increasing content of the polypentadecaiactone segment (all values determined at 70 C). The reduced, i.e. slower biodegradability of the polypentadecalactone segments, compared to polyparadioxanone segments used so far in the prior art, the preferred polyester urethanes of the present invention may also be employed in applications for which the known polyester urethanes were not suitable due to their faster degradability and the therewith associated decreased mechanical stability. Compared with known polyester urethanes comprising polycaprolactone segments and polyparadioxanone segments, the polyester urethanes of the present invention furthermore do display an improved production atability and ability to be granulated, which simplifies the production and the processing of the polyester urethanes of the present invention_ The known polyester urethaneS
having poiy-p-dioxanone segments in particular undergo degradation reactions upon extrusion, while the polyester urethanes of the present invention do show an improved stability in this respect. The materials of the present invention do show a good biocompatability, which was proven with appropriate evaluations.
The more preferred polyester urethanes of the present invention which do comprise polypentadecalactone segments as well as further segments, preferably polycaprolactone segements furthermore do display shape memory properties, so that accordingly these preferred materials may be designated shape memory polymers (SMP).
Such materials are obtained in particular if, within the polyester urethane of the present invention, the polypentadecalactone segments and ttte further segments, preferably polycaproiactone segments, are present in specified amounts. These specified amounts may be adjusted by appropriate seiection of the molecular weight and content (wt.-%) of t)ie further segments, preferably caprolactone segments, and the pentadecalactone segments. Generally speaking, with similar or equal number average molecular weights, SMP materials may be preferably obtained if the content of further segments, preferably caproiactone segments, within the polyester urethane is higher than the content of pentadecalactone units. Is the molecular weight of the further segments, preferably polycaprolactone segments, within the polyester urethane however higher than the molecular weight of the polypentadecalactone units, the content of pentad cafactone units may be higher than the content of further segments, preferably caprolactone units.
Good SMP-materials may in particular be obtained using the foilowing compositions:
Polypentaclecafactone segment: Molecular weight 1000 to 10,000 g/mol (number average), preferably 1500 to 5000, in particufar 2000 to 3000 glmot.
Polycaprolactone segrnent Molecular -weight 3000 to 11,000 g/mol (number average), preferably 4000 to 10,000 g/mol. .
Poiycaproiactone-co-polytetranadrofurane segment: molecular weight 1000 to g/mol (number average), preferabty 1500 to 3500 g/mol.
Polytetrahydrofurane segment: Molecular weight 1000 to 5000 g/mol (number average), preferably 1500 to 3000 gimol.
Polypropyfeneglacoi segment: molecular weight 1000 to 8000 g/mol (number average), preferably 1200 to 4500 g/mol.
Polyethyleneglycol segments: Molecular weight 1000 to 25,000 g/mol (number average), -preferably 1500 to 20,0000 g/mol.
Poiy-L-lactide-co-giycoiide segment (ran): Molecular vveight 4000 to 10,000 gtmo6 (number average), preferably 5000 to 8000 g/mot.
Poly-DL-lactide segment: Molecular weight 4000 to 15,000 g/mol (number average), preferably 5000 to 11,000 g/mol.
Polyesterurethane: Molecular weight 50,000 to 200,000 g/mol (number average), preferably 60,000 to 190,000 glmol; content of the additional segment 20 to 80 wt%, preferably 45 o 70 wt~o, more preferably 50 to 60 wt%, content polypentadecalactone segment 80 to 20 wtoh, preferably 55 to 30 wt%, more pneferably 40 to 50 wt ,b.
The polymers of the present invention may be blended with further components, which further widens their range of application. Fillers, such as silica, barium sulfate and simiiar materials, medicinal active compounds, such as anti bactericides, funguzides and similar materials of organic or inorganic nature, such as nano-silver, and colorants may be blended with the polymers of the present invention. The valuable properties of the polymers are usually not affected if the addition an--ount is within the range up to 25%
(based on the weight of the total blend) , preferably within the range of from I to 10%.
It is furthermore possible to blend the polymers of the present invenfion with other commercially available poiymers, such as polyolefins, in particular polyethylene and polypropylene, or vinyl polymers, such as pofysfyrene and PVC. It could be shown that with an content of from 50 to 90 wt.-% of the polymer in accordance with the present invention, the shape memory properties could be retained. This enables in particular the preparation of low cost SMP materials since the commercially available blend components are, compared with the polymers of the present invention, relativeiy cheap and may be blended in an amount of up to 50 wt.-%. , The blending of the above named additional components may be accomplished in a usual manner known to the skilled person, for example by compounding using sultable kneadars or extruders.
The polyester urethanes of the present invention which comprise only pentadecalactone units in the polyester segments furtherrnore show the surprising property that these polyester urethanes, blended with other polyesters, preferably PCL and a polyester urethane based on PCL yield a blend showing shape memory properties, although the single blend components do not show such proper6ies. The blend ratio preferably is selected in such a way, so that the polyester urethane of the pentadecalactone segments is present in the blend in an amount of from 20 to 80 wt.-%, preferably 40 to 60 wt-%. Without being bound to this theory it is assunied that a compatabilisation is achieved through the urethane segments which yields a mixture, which corresponds, as far as macroscopic properties are concemed to the covalently crossiinked shape memory materials.
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Such blends may be prepared by coprecipitation from a solution or by compounding.
Coprecipitation results in a superior maing_ However coprecipitation has drawbacks due to the use of solvents, in particular regarding costs as well as regarding working safety.
The materials in accordance with the present invention furthermore may be processed in order to obtain interesting products, such as foams (porous structures) as well as micro carriers (micro beads), which may be employed over a broad range of applications. Due to the properties of the materials valuable products in particular in the medlcinal field may be obtained.
Production of a foam may be carried out in the usual way, such as compourtcling with a foaming agent and exbruding or by thermally induced phase separation of a polymer solution. The type of foaming agent is not critical and it has been proven that usual foaming agents may be employed using master batch technology.
The foams which may be obtained generate, due to their shape ' memory properties which are not lost due to foam preparation, controlled forces upon recovery of the permanent shape, which opens up further applicafion'fields.
During the production of the foam the pore size as well as the pore size distribution may be controlled in the manner known to the skilled person, by adjusting the geometric configuration of the screw, processing temperature and torque The micro carriers of the present invention, which may for exxampfe be employed for Tissue Engineering, may be produced from the materials of the present invention using usual processes, such as soivent evaporation of an emulsion or by thermally induced phase separation of a solution, in each case comprising at least one polyester urethane of the present invention. The size of the micro carriers (av. Diameter) may vary within the range of frorn 100 nm to 800 pm, preferably 100 to 200 pm, depending from the desired field of application. The particles substantially show a spherical shape and often do show an inner hollow cavity. The surface is predominantly smooth with some structures within the nanometer region.
The present invention is further illustrated with the t'ollowing examples.
Preparation of polyester macrodiols Caproiactone and pentadecalactone, respectively were polyrnerised under ring opening using ethylene glycol as initiator and dibutyl tin as catatyst without addition of any solvent, at 130 C. The typical reaction time was 5 hours. Selecting the amount of initiator adjusts the molecular weight.
in this manner difFerent macrodiols were prepared having molecular weights (number average) of 10000, 2000 and 3000 g/mol for nnacrodiols form pentadecalactone and 10000 and 4000 glmol for makrodiols from caprolactone.
Further polyester urethanes, in which the segments of PCL had molecular weights of 2000, 3000, 4000 and 10000 g/moi and in which the segments of PDL has molecular weights of 2000 and 3000 g/mol were evaluated and it was found that the rriateriais showed a melting point of the PCL'segments in the range of from 30 to 55 C, which is preferred in particular for many apptications in the medicinal frefd.
Preparation of polyester urethanes These macrodiois were reacted using a mixture=of 2,2,4- and 2,4,4-trimethylhexane-1,6-diisocyanate to obtain polyester urethanes. This reaction was carried out at 3 C using dioctyl tin as catalyst and 1,2-dichloroethyne as solvent. The average reacdon time was two days.
In this manner different polyester urethanes were prepared which are summarized in the foUowing table. PDL describes the amount of pentydecalactone within the polyester urethane (neglecting the diisocyanate linkers) as well as the molecular weight of the poiypentadecalaCtone segments. PCL provides, the =corresponding vaiues - for the caprolactone units. The materials of examples 6, 7 and 8 do show pronounced shape memory properties. It should be noted in this connection that the elongation at break, for the materials exemplified here, increases with increasing PDL content of from 700 to 1200 k. This cleariy demonstrates the influence, concerning the mechanical properties, exerted by the type of composition. Generally speaking these illustrative examples show that the present invention provides a polymeric system enabling the controlled adjustment of desired properties.
Exampie PDL PCl M lecuiar E-Module Tensile weight of the (70 C I MPa) strength polyester (MPa) urethane 100 wt.-% / Mn = 192000 17 18 10000 gimol 2 22 wt. %/ 78 wt.-% / Mn = 120000 '{ ,4 5 10000 g/moI 10000 g/mol 3 41 wt.-% / 59 wt.-% / Mn =196000 3 10 10000 gimoi 10000 g/mol 4 60 wt.-0/6 / 40 wt.% / Mn =176000 7 8 10000 g/mot 10000 g/mol 5 80 wt-% / 20 wt_-% I Mn =185000 8,5 7 10000 g/mot 10000 g/mot 6 40 wt.-% 1 60 wt.% / Mn = 86000 3,5 4,5 2000 g/mol 4000 g/mol 35 (RT) 23 (RT) 7 50 wt-% / 50 wt.- /o I Mn = 75000 1.5 1,6 3000 g/mol 10000 g/moi 70 (R7) 24 (RT) 8 40 wt_-% / 60 wt-% / Mn = 62000 3 9 3000 g/mol 10000 g/moi 45 (FtT) 30 (RT) In order to evaluate the temperature dependence of the mechanical properties experiments were conducted with the material of. example B. The results of these experiments are given in the foitowing table and demonstrate that the tensile stretch remains almost without change even when heating the material to a temperatum close to the melting temperature of the polypentadecalactone segments while E-modulus and tensile strength decrease. Comparable polyester urethanes comprising polyparadioxanone segments in place of th polypentadecalactone segments do show a signiFcantly lower tensile stretch.
FC. Ten sile E-Modulus Tensile ) stretch (Mpa) strength (%) (MPa) 80 1000 1,5 3 Furthermore the material was subjected to experiments for the determination of the shape memory properties. Thenno-cyclic expenments were carried out (for an explanation of such experiments see for example the International Patent Applications described in the introductory part of the present application). Values for shape fixity (Rf) and shape recovery after the course of several cycles (Rr) were determined.
The results are shown in the following table.
Number of Rf (%) Rr (%) cycles The above shown experiments were conducted in such a manner that the shape merriory effect was initiated at a temperature of 80 C. Similar results may be obtained if the shape memory effect is initiated at temperatures within the range of from 50 to 90 C.
In addition the following copolyester urethanes were produced and several mechanical properties were tested.
PDLypolyre#hane comprising partially- crystalline soft segments Composition of polyester urethane comprising POL
PDL= polypentadecadolactone, polyester + PCL = polycaprolactone, polyester + PCL-cv-pTHF = potycaprolactone-co-potytetrahydrofuran , potyetherester + pTHF= polyfietrahydrofuran, poiyether + PPG= polypropyleneglycol, polyether + PEG= Polyethyleneglycol, polyether ( novel combination hydrophobic (PPDL) hydrophilic (PEG) Combination with PDL 3000 aImo1 Material % % Mn PDL 3000 g/mol 9 00 69.000 PDL 3000 glmol 50 PCL 1000 g/mol 50 72.000 PDL 3000 g/mol 50 PCL 1250 g/mol 50 105.000 PDL 3000 g/mol 50 PCL 2000 g/moi 50 83_000 PDL 3000 g/mol 40 PCL 2000 g/rnol 60 76.000 PDL 3000 g/mol 50 PCL 3000 gfmol 50 75.000 PDL 3000 g/mol 40 PCL 3000 g/moi 60 89.000 PDL 3000 g/mol 50 PCL 4000 g/mol 50 85.000 PDL 3000 g/mol 40 PCL 4000 g/mol 60 95.000 PDL 3000 9/mol 50 PCL 10000 g/mo6 50 87.000 PDL 3000 9/mol 40 PCL 10000 g/mol 60 103.000 PDL 3000 g/mol 30 PCL 10000 g/mol 70 89.000 POL 3000 g/mol 60 PCL 10000 g/mol 40 73.000 PDL 3000 g/mol 40 PCL-co-pTHF 60 79.000 2000g/mol 13' PtOL 3000 glrnol 40 PTHF 2500 g/mol 60 4S=000 PDL 3000 g/mol 40 PPG 1200 g/m61 60 65.000 PDL 3000 g/mo! 40 PPG 4000 g/mol 60 53.000 PDL 3000 g/mol 40 PEG 2000 g/mol 60 28.000 PDL 3000 g/mol 40 PEG 4000 gimof 60 32.000 PDL 3000 g/mol 40 PEG 6000 g/mol 60 40.000 PDL 3000 glmol 40 :::# 8000 g/mot 60 42.000 PDL 3000 g/mot 40 10000 g/mol 60 43.000 PDL 3000 g/moi 40 20000 g/mol 60 50.000 Combination with pDL 2000 o/mol Material 0/0 % Mn PDL 2000 g/mol 30 PCL 2000 g/mol 70 75.000 PDL 2000 g/mol 40 PCL 2000 gimoi 60 95.000 P L 2000 g/mol 5o PCL 2000 g/mol 50 65.000 PDL 2000 glmol 60 PCL 2000 g/mol 40 73_000 PDL 2000 g/mol 70 PCL 2000 g/mol 30 46.000 PDL 2000 g/mol 30 PCL 3000 glmol 70 99_000 PDL 2000 g/moi 40 PCL 3000 g/mol 60 72.000 PDL 2000 g/mol 50 PCL 3000 g/moi 50 78_000 PDL 2000 glmol 60 PCL 3000 glmol 40 73.000 PDL 2000 g/mol 70 PCL 3000 g/mol 30 65.000 PDL 2000 g/mol 30 PCL 4000 g/mol 70 49.000 PDL 2000 g/mol 40 PCL 4000 g/mol 60 62_000 PDL 2000 g/mol 50 PCL 4000 g/mol 50 85.000 PDL 2000 g/mol 60 PCL 4000 g/mol 40 83.000 PDL 2000 g/mot 70 PCL 4000 g/mol 30 56_000 PDL 2000 g/mol 30 PCL 10000 g/mol 70 85_000 PDL 2000 g/mol 40 PCL 10000 g/mol 60 1 09.000 PDL 2000 g/mol 50 PCL 10000 g/mol 50 130.000 PDL 2000 g/mo1 60 PCL 10000 g/rnol 40 121 _000 PDL 2000 g/mo! 70 PCL 10000 g/mo! 30 1 _ 000 PDL 2000 g/mol 30 PCI.-co-pTHF 70 60_0 0 2000g1mol 14=
PC?L 2000 g/mol 40 PCL-co-pTHF 60 78.000 2000g/mol PDL 2000 g/mo1 50 PCL-co-pTHF 50 89.000 2000g/mo{
PDL 2000 g/mol 60 PCL-co-pl'HF 40 59.000 2000g/mo8 PDL 2000 g/mol 70 PCL-co-p'1=HF 30 55.000 2000g/ma6 P L 2000 g/mol 40 PPG 1200 gfmo( 60 65.000 PDL 2000 g/mol 40 PPG 4000 gIm i 60 63.000 PDL 2000 glmol 40 PEG 2000 g/mol 60 28.000 PDL 2000 9/mol 40 PEG 4000 g/mol 60 32.000 PDL 2000 glmoi 40 IPEG 6000 g/ma! 60 40.000 PDL 3000 9/mof. 40 PEG 8000 g/mol 60 42.000 PDL 3000 g/mol 40 PEG 10000 g/mol 60 43.000 PDL 3000 g/mol 40 PEG 20000 g/mo! 60 50.000 Mechanical oronerties=
Material Temp. E-Modulus Ternsile stretch PDL 2k-rA-PCL1 Ok 40/60 20 C 35 1350%
PDL-2k-co-PCL1 Ok 40160 70 C 5 1000%
PDL-3k-cA-PCL1 Qk 40/60 20 C 145 1500%
PDL polyuretharie comprising glassy components Composition of pt>I iyester urethanes with POL
PDL= polypentadcscadolacton, polyester PI.GA= poly-L-lactide-e:o-glycolide (ran), polyester P-DL-LA = poly-D L-iactide, polyester Material % Mn PDL 3000 g/moI 50 PLGA 7000 g/mol 50 65.000 PDL 3000 g/rno! 40 PLGA 7000 g/mol 60 55.000 PDL 2000 g/mol 50 P-DL-LA 6000 g/moi 50 87.000 PDL 2000 glmcl 40 P-DL-LA 6000 g/mol 60 72.000 PDL 2000 g/mol 50 P-DL-LA 10000 g/mol 50 63.000 Mechanical rgperties:
Material Temp. E-Modulus MPa Tensile stretch PDL-3k-co-P-DL-LAEk 50150 20 C 279 453 %
PDL-3k-co-P-DL-LA6k 60150 50 C 31 303 %
PDL-3k-co-P-DL-LA6k 50/50 55 C 25 276 %
PDL-3k-co-P-DL-LA6k 50/50: copolyester urethane, comprising segments of PDL
and P-DL-LA having an Mn of 3000 and 6000 g/mol, respectively, and comprising 50 et.-% of each of the segments PDL and P-DL-LA, respectively Shape Memory Pronertles:
Materiai Number of Recovery % Fixity %
cycles PDL-3k-co-P-DL-.I..A6k 50/50 1 46,5 98.4 PDL-3k-co-P-DL-LA6k 50/50 2 87,3 98,8 PDL-3k co-P-DL-LA6k 50/50 3 96,8 99.1 PDL-3k-co-P-DL-LA6k 50/50 4 97,9 98,5 PDL-3k-co-P-DL-LA6k 50/50 5 98,2 98,5 Blends The following biends were prepared and evaluated:
Blends comprisirjg PDL, Additives were mixed with a PDL polyester urethane having the composition PDL-3k-co-PCL-10k 40/60.
The following addifive components were added in amounts of from 0.5 to 25 wt.
o:
Colorant (master batch comprising PDL-3k-c:o-PCL-1 k 40160 and about 5 to 10 wt.%
colorant) ~ nano-silver ~ barium sutfate For a blend comprising 10 wt.-% of the colored master batch the following shape memory properfiies were obtained:
Shape Memorv Pronert#es:
Material Number of Recovery % Fixity %
cycles 90% PDL-3k-co-PCL-1 k 40/60 1 30,5 98,3 10% master batch blue 90 !a PDL-3k-Co-PCL-10k 40/60 2 93,3 98,5 10% master batch blue 90% PDL-3k-CO-PCL-10k 40/60 3 96,5 99,5 10% master batch blue 90% PDL-3k-co-PCL-10k 40/60 4 98,6 98,6 10% master batch blue 900/6 PDL-3k-co-PCL-10k 40/60 5 99,2 98,9 10% master batch blue Also blends with commercially available polymers, such as PE or PVC, when using of from 50% to 90% PDL-polyurethane satisfactory shape memory properties, which correspond to those given above.
SlraPe MemorY 411ends These blends are mixtures of pure PDL-polyurethanes with PCL and PCL-potyurethanene, respect'svely. Only after a combination of the two materiats yields a shape memory material. For preparing those blends both materials. the PDL-polyurethane and PCL or PCL-polyurethane are dissolved together and are subsequently precipitated (co-precipitation). In addition blends were prepared in the melt using a compounder (twin smw extruder).
Components emplMd:
A: PDL-3k-polyurethane, Mn 95.000 B: PCL-10k-polyurethane, Mn 102.000 C: PCL; Mn 80.000 With a content of the PDL-component of from 20% - 80 % good shape memory praperties were obtained. In par6cular using blend compositions with blend ratios o'f 40/60; 50/50; 60/40 correspond, as far as shape memory properties are concemed, to PDL-co-PCL-polyurethanes, Material - Number of Recovery % Fixity %
cycles 40% PDL-3k-polyurethane 55,5 98,2 60% PCL-10k-polyurethane 40% PDL-3k-polyurethane 2 97,3 98,2 60% PCL-10k-polyurethane 40% PDL-3k-potyurethane 3 98,5 99,1 60% PCL-10k-poiyurethane 40% PDL-Jk-polyurethane 4 98,6 98,8 60% PCL-10k-polyurethane 40% PDL-3k-po1yUrethane 5 99,1 98,9 60% PCL-10k-polyurethane Pi]L-Polvester urethanes= bio comaatabiiitylde4 cla ation behaviour~
is Experiments were carried out regarding the degradation behaviour of the resorbable materials. Degradation studies were condu4ted at body temperature (37 C) in aqueous buffered solutions (phosphate buffer, pH 7, comprising NazHPOa, ICziiPOa and NaN3). In order to obtain estimates above long term behaviour so called accelerated degradation studies were carried out at 70 C. For the purpose of this evaluation samples are taken at defined times and molecular weight (Mn) as well as relative weight loss (%) are determined.
In the following table the results of evaluations for the material PDL-2k-co-PCL-10k are listed.
T = 70 C T = 37 C
Week Mn Weight loss [%] week Mn Weight loss [%l tg/moi1 t9omov]
0 185.000 0 185_000 1 0.08 175.000 2 184.000 0,06 2 6 183,000 0,12 011 152.000 3 10 184.000 0,15 0.16 134.000 4 18 182.000 0,17 0,'t9 76.314 6 29 180.000 0,20 0,24 27.054 0 29 8.769 590 2.178 22,65 2.469 41,61 25 2.123 4936 3.061 53, 6 2.976 In the foflowing table the results of the degradation experiment using the jrnateriat PDL-3k-co-PCL-10k are listed.
T = 700C T = 3T C
week Mn Weight loss [ I week Mn Weight iloss [%j [9/moll~ (g/mol]
0 185.000 0 0 185.000 0 1 182.000 0,05 2 184.000 0,08 2 160_000 0,11 6 183,000 0,15 3 123.000 0,15 10 184.000 0,18 4 112.000 0,18 18 182.000 0,20 6 49.000 0,21 29 180.000 0,22 8 17.500 0,41 12 10.000 6.47 16 7.300 23,98 21 4.200 43,54 25 3.500 50,46 29 2.500 54,15 In addition the sarnples were evaluated under a microscope regarding possible surPace modifications. A distinct change in the morphology of the surface coutd be detected.
Sio compatability studies:
For selected matariais (PDL-3k-co-PCt.-10k; PDL.-2k-co-PCL-10k) experiments were camed out regarding the biological evaluation for medicinal products in accordance with tS4/EN/f01N 10993-5 (cytotoxicity). Samples were sterilised, prior to these experiments with ethylene oxid e (EO).
Cytotoxicity evali-eatioras were carried out using direct contact with the murine ~tforoblast cell line L929 (f3ic~Withaker Bi=71-131F). Contr ( of membrane integrrty was carried out by PA 17 vital coloration (vital cells are cotored green). Morphology of the cells after 24h incubation was evaluated using Pa 13 hamalaun coloration.
1=valuation_ For bith samples membrane integrity was not affected by the materials of the present invention.
The morphology of the cells on the samples is, compared with the negative control, not changed. Cell apparence of the culture and the seeding eff+cience on the material corrrespond to that of the negative t+ontrol.
Processina of Pbi.-aolvesterurethanes Foam extrusiort=
After extruding and pelletazing the polymer, the polymer, in a second work up, is mixed with a master batch in a double arew extruder (chemical foaming agent Hydrocerol CT
572, product of Ctariant), in order to obtain a foam (5% foaming agent, 95%
PPDL-3k-co-PCL10k)..Yhe material, in the form of the rod in the temporary shape is comprssed to 25 % of the initial diameter. Subsequently the rod is expanded again by heating the compressed rod. The initial (permanent) shape is recovered, during this recovery a force of 5 N is exerted by the material.
Foams b y TIPS
A further methocd for producing porous structures is the thermaliy [ndiced phase separation" (TIPS) eingesetzt. A polymer solution (dioxan, I to 25 wt.- /
polymer) is cooled at a defined gradient (from 60 C to 3 C). During cooling a liquid-liquid separation occurs first. Further cooling solidifies the formed phase struCture. Using the material PDL-3k-co-PCl.1 k a foam could be produced. The solvent was removed using a high vacuum_ Praaration of micr0carriers,(d 100 Elm - 800 um) Preparation of microbeads from PDL-3k-ca-PCL1ok. Using an emulgator (PVA) an oil-in-water emulsion was prepared_ By carfully removing the solvent spherical micro carriers were obtained. iJsing SEM a broad distribution of the particle size was found, as well as a non-uniformity regarding the particle shape. On average the particle size was in the range of from 100 to 200 Nm, with the most part of the carriers showing a sperical shape.
SEM evaluations furthermore showed that most of the carriers were hollow an Collapsing under the electron beam. Evaluations of single carriers revealed that they showed a smooth surface having some sort of structure within the nanometer range.
The present invention provides novel polyester urethanes, which enable a controlled adjustment of desired profile of properties. The starting materials to be used are usual compounds, which are available without to much efFort. The reactions to be used for preparing the prepoiymers (macrodiols) are typical operations in the field of polymer chemistry, so that the polyester urethanes of the present invention may be obtained in a simple and efficient manner. The present invention enables to overcome the drawbacks of the known materials described above.
segments is from 2000 to 20,000 g/moi, for the PLGA segments from 4000 to 9000 g/mol and for P-DI.-tA from 5000 to 11,000 g/rnol. The polyester urethanes comprising additional segments, preferably polycaprolactone segments do show preferably a molecular weight of from 50,000 to 250,000 g/mol (number average, determined by GPC), more preferably of from 60,000 to 200,000 g/moi and in particular preferably from 62000 to 196,000 g/mol (and in some embodiments of from 55,000 to 100,000 gfmol).
The content of polypentadecatactone units may be varied over a broad range, prefierably the content of pentadecalactone units is in the range of from 10 to 80 wt Xo.
in particuiarly within the range of from 20 to 60 wt%.
When the above described polyester segments are converted by a polyaddition rection using the above disclosed diisocyanates to polyester urethanes in accordance with the present invention, a variation of the respective amounts and molecular weights of the polyester segments enables an acUustment of the profile of properties of the resulting polyester urethanes. This preferred embodiment of the present invention provides a polymeric system which enables, by modifying simple starting materials, a.control of the resulting properties.
The materials in accordance with the present invention may be used in the form of fibres, such as in wrinkle resistant textiles, in the form of different shaped articies, for example in the field of medicine, as slowiy degrading implants or In the form of coatings, for 'example on short term implants, such as cannulae or lead-wires_ The use as coating material may increase the bic compatability of the coated articies and may therefore protect the user from undesired side reactions during use of the coated arbcles.
The preferr-ed polyester urethanes of the present invention, which comprise in addition to th polypentadec.alactone segments further segments, preferabiy polycaprolatone segments, do display further preferred profiles of properties.
The introduction of further segments, preferably polycaprolactone segments, into the polyester urethanes of the present invention introduces a second melting temperature, which may be detected during DSC measurements, into the polyester urethane.
This second melting temperature usually lies in the range of above 50 C, depending from the molecular weight and = the proportion of the further segment, preferably the polycaprolactone segment, in the polyester urethane.
In addition the mechanical properties may be controlled over a broad range.
With increasing content of polypentadeclactone the value for i==-Modulus may be increased as well. The value for the elongation at break may be adjusted to 600 to 1200%
with increasing content of polypentadecalactone and in addition tensile strength may be adjusted in a range of from 4 to 10 MPa vvrith increasing content of the polypentadecaiactone segment (all values determined at 70 C). The reduced, i.e. slower biodegradability of the polypentadecalactone segments, compared to polyparadioxanone segments used so far in the prior art, the preferred polyester urethanes of the present invention may also be employed in applications for which the known polyester urethanes were not suitable due to their faster degradability and the therewith associated decreased mechanical stability. Compared with known polyester urethanes comprising polycaprolactone segments and polyparadioxanone segments, the polyester urethanes of the present invention furthermore do display an improved production atability and ability to be granulated, which simplifies the production and the processing of the polyester urethanes of the present invention_ The known polyester urethaneS
having poiy-p-dioxanone segments in particular undergo degradation reactions upon extrusion, while the polyester urethanes of the present invention do show an improved stability in this respect. The materials of the present invention do show a good biocompatability, which was proven with appropriate evaluations.
The more preferred polyester urethanes of the present invention which do comprise polypentadecalactone segments as well as further segments, preferably polycaprolactone segements furthermore do display shape memory properties, so that accordingly these preferred materials may be designated shape memory polymers (SMP).
Such materials are obtained in particular if, within the polyester urethane of the present invention, the polypentadecalactone segments and ttte further segments, preferably polycaproiactone segments, are present in specified amounts. These specified amounts may be adjusted by appropriate seiection of the molecular weight and content (wt.-%) of t)ie further segments, preferably caprolactone segments, and the pentadecalactone segments. Generally speaking, with similar or equal number average molecular weights, SMP materials may be preferably obtained if the content of further segments, preferably caproiactone segments, within the polyester urethane is higher than the content of pentadecalactone units. Is the molecular weight of the further segments, preferably polycaprolactone segments, within the polyester urethane however higher than the molecular weight of the polypentadecalactone units, the content of pentad cafactone units may be higher than the content of further segments, preferably caprolactone units.
Good SMP-materials may in particular be obtained using the foilowing compositions:
Polypentaclecafactone segment: Molecular weight 1000 to 10,000 g/mol (number average), preferably 1500 to 5000, in particufar 2000 to 3000 glmot.
Polycaprolactone segrnent Molecular -weight 3000 to 11,000 g/mol (number average), preferably 4000 to 10,000 g/mol. .
Poiycaproiactone-co-polytetranadrofurane segment: molecular weight 1000 to g/mol (number average), preferabty 1500 to 3500 g/mol.
Polytetrahydrofurane segment: Molecular weight 1000 to 5000 g/mol (number average), preferably 1500 to 3000 gimol.
Polypropyfeneglacoi segment: molecular weight 1000 to 8000 g/mol (number average), preferably 1200 to 4500 g/mol.
Polyethyleneglycol segments: Molecular weight 1000 to 25,000 g/mol (number average), -preferably 1500 to 20,0000 g/mol.
Poiy-L-lactide-co-giycoiide segment (ran): Molecular vveight 4000 to 10,000 gtmo6 (number average), preferably 5000 to 8000 g/mot.
Poly-DL-lactide segment: Molecular weight 4000 to 15,000 g/mol (number average), preferably 5000 to 11,000 g/mol.
Polyesterurethane: Molecular weight 50,000 to 200,000 g/mol (number average), preferably 60,000 to 190,000 glmol; content of the additional segment 20 to 80 wt%, preferably 45 o 70 wt~o, more preferably 50 to 60 wt%, content polypentadecalactone segment 80 to 20 wtoh, preferably 55 to 30 wt%, more pneferably 40 to 50 wt ,b.
The polymers of the present invention may be blended with further components, which further widens their range of application. Fillers, such as silica, barium sulfate and simiiar materials, medicinal active compounds, such as anti bactericides, funguzides and similar materials of organic or inorganic nature, such as nano-silver, and colorants may be blended with the polymers of the present invention. The valuable properties of the polymers are usually not affected if the addition an--ount is within the range up to 25%
(based on the weight of the total blend) , preferably within the range of from I to 10%.
It is furthermore possible to blend the polymers of the present invenfion with other commercially available poiymers, such as polyolefins, in particular polyethylene and polypropylene, or vinyl polymers, such as pofysfyrene and PVC. It could be shown that with an content of from 50 to 90 wt.-% of the polymer in accordance with the present invention, the shape memory properties could be retained. This enables in particular the preparation of low cost SMP materials since the commercially available blend components are, compared with the polymers of the present invention, relativeiy cheap and may be blended in an amount of up to 50 wt.-%. , The blending of the above named additional components may be accomplished in a usual manner known to the skilled person, for example by compounding using sultable kneadars or extruders.
The polyester urethanes of the present invention which comprise only pentadecalactone units in the polyester segments furtherrnore show the surprising property that these polyester urethanes, blended with other polyesters, preferably PCL and a polyester urethane based on PCL yield a blend showing shape memory properties, although the single blend components do not show such proper6ies. The blend ratio preferably is selected in such a way, so that the polyester urethane of the pentadecalactone segments is present in the blend in an amount of from 20 to 80 wt.-%, preferably 40 to 60 wt-%. Without being bound to this theory it is assunied that a compatabilisation is achieved through the urethane segments which yields a mixture, which corresponds, as far as macroscopic properties are concemed to the covalently crossiinked shape memory materials.
$
Such blends may be prepared by coprecipitation from a solution or by compounding.
Coprecipitation results in a superior maing_ However coprecipitation has drawbacks due to the use of solvents, in particular regarding costs as well as regarding working safety.
The materials in accordance with the present invention furthermore may be processed in order to obtain interesting products, such as foams (porous structures) as well as micro carriers (micro beads), which may be employed over a broad range of applications. Due to the properties of the materials valuable products in particular in the medlcinal field may be obtained.
Production of a foam may be carried out in the usual way, such as compourtcling with a foaming agent and exbruding or by thermally induced phase separation of a polymer solution. The type of foaming agent is not critical and it has been proven that usual foaming agents may be employed using master batch technology.
The foams which may be obtained generate, due to their shape ' memory properties which are not lost due to foam preparation, controlled forces upon recovery of the permanent shape, which opens up further applicafion'fields.
During the production of the foam the pore size as well as the pore size distribution may be controlled in the manner known to the skilled person, by adjusting the geometric configuration of the screw, processing temperature and torque The micro carriers of the present invention, which may for exxampfe be employed for Tissue Engineering, may be produced from the materials of the present invention using usual processes, such as soivent evaporation of an emulsion or by thermally induced phase separation of a solution, in each case comprising at least one polyester urethane of the present invention. The size of the micro carriers (av. Diameter) may vary within the range of frorn 100 nm to 800 pm, preferably 100 to 200 pm, depending from the desired field of application. The particles substantially show a spherical shape and often do show an inner hollow cavity. The surface is predominantly smooth with some structures within the nanometer region.
The present invention is further illustrated with the t'ollowing examples.
Preparation of polyester macrodiols Caproiactone and pentadecalactone, respectively were polyrnerised under ring opening using ethylene glycol as initiator and dibutyl tin as catatyst without addition of any solvent, at 130 C. The typical reaction time was 5 hours. Selecting the amount of initiator adjusts the molecular weight.
in this manner difFerent macrodiols were prepared having molecular weights (number average) of 10000, 2000 and 3000 g/mol for nnacrodiols form pentadecalactone and 10000 and 4000 glmol for makrodiols from caprolactone.
Further polyester urethanes, in which the segments of PCL had molecular weights of 2000, 3000, 4000 and 10000 g/moi and in which the segments of PDL has molecular weights of 2000 and 3000 g/mol were evaluated and it was found that the rriateriais showed a melting point of the PCL'segments in the range of from 30 to 55 C, which is preferred in particular for many apptications in the medicinal frefd.
Preparation of polyester urethanes These macrodiois were reacted using a mixture=of 2,2,4- and 2,4,4-trimethylhexane-1,6-diisocyanate to obtain polyester urethanes. This reaction was carried out at 3 C using dioctyl tin as catalyst and 1,2-dichloroethyne as solvent. The average reacdon time was two days.
In this manner different polyester urethanes were prepared which are summarized in the foUowing table. PDL describes the amount of pentydecalactone within the polyester urethane (neglecting the diisocyanate linkers) as well as the molecular weight of the poiypentadecalaCtone segments. PCL provides, the =corresponding vaiues - for the caprolactone units. The materials of examples 6, 7 and 8 do show pronounced shape memory properties. It should be noted in this connection that the elongation at break, for the materials exemplified here, increases with increasing PDL content of from 700 to 1200 k. This cleariy demonstrates the influence, concerning the mechanical properties, exerted by the type of composition. Generally speaking these illustrative examples show that the present invention provides a polymeric system enabling the controlled adjustment of desired properties.
Exampie PDL PCl M lecuiar E-Module Tensile weight of the (70 C I MPa) strength polyester (MPa) urethane 100 wt.-% / Mn = 192000 17 18 10000 gimol 2 22 wt. %/ 78 wt.-% / Mn = 120000 '{ ,4 5 10000 g/moI 10000 g/mol 3 41 wt.-% / 59 wt.-% / Mn =196000 3 10 10000 gimoi 10000 g/mol 4 60 wt.-0/6 / 40 wt.% / Mn =176000 7 8 10000 g/mot 10000 g/mol 5 80 wt-% / 20 wt_-% I Mn =185000 8,5 7 10000 g/mot 10000 g/mot 6 40 wt.-% 1 60 wt.% / Mn = 86000 3,5 4,5 2000 g/mol 4000 g/mol 35 (RT) 23 (RT) 7 50 wt-% / 50 wt.- /o I Mn = 75000 1.5 1,6 3000 g/mol 10000 g/moi 70 (R7) 24 (RT) 8 40 wt_-% / 60 wt-% / Mn = 62000 3 9 3000 g/mol 10000 g/moi 45 (FtT) 30 (RT) In order to evaluate the temperature dependence of the mechanical properties experiments were conducted with the material of. example B. The results of these experiments are given in the foitowing table and demonstrate that the tensile stretch remains almost without change even when heating the material to a temperatum close to the melting temperature of the polypentadecalactone segments while E-modulus and tensile strength decrease. Comparable polyester urethanes comprising polyparadioxanone segments in place of th polypentadecalactone segments do show a signiFcantly lower tensile stretch.
FC. Ten sile E-Modulus Tensile ) stretch (Mpa) strength (%) (MPa) 80 1000 1,5 3 Furthermore the material was subjected to experiments for the determination of the shape memory properties. Thenno-cyclic expenments were carried out (for an explanation of such experiments see for example the International Patent Applications described in the introductory part of the present application). Values for shape fixity (Rf) and shape recovery after the course of several cycles (Rr) were determined.
The results are shown in the following table.
Number of Rf (%) Rr (%) cycles The above shown experiments were conducted in such a manner that the shape merriory effect was initiated at a temperature of 80 C. Similar results may be obtained if the shape memory effect is initiated at temperatures within the range of from 50 to 90 C.
In addition the following copolyester urethanes were produced and several mechanical properties were tested.
PDLypolyre#hane comprising partially- crystalline soft segments Composition of polyester urethane comprising POL
PDL= polypentadecadolactone, polyester + PCL = polycaprolactone, polyester + PCL-cv-pTHF = potycaprolactone-co-potytetrahydrofuran , potyetherester + pTHF= polyfietrahydrofuran, poiyether + PPG= polypropyleneglycol, polyether + PEG= Polyethyleneglycol, polyether ( novel combination hydrophobic (PPDL) hydrophilic (PEG) Combination with PDL 3000 aImo1 Material % % Mn PDL 3000 g/mol 9 00 69.000 PDL 3000 glmol 50 PCL 1000 g/mol 50 72.000 PDL 3000 g/mol 50 PCL 1250 g/mol 50 105.000 PDL 3000 g/mol 50 PCL 2000 g/moi 50 83_000 PDL 3000 g/mol 40 PCL 2000 g/rnol 60 76.000 PDL 3000 g/mol 50 PCL 3000 gfmol 50 75.000 PDL 3000 g/mol 40 PCL 3000 g/moi 60 89.000 PDL 3000 g/mol 50 PCL 4000 g/mol 50 85.000 PDL 3000 g/mol 40 PCL 4000 g/mol 60 95.000 PDL 3000 9/mol 50 PCL 10000 g/mo6 50 87.000 PDL 3000 9/mol 40 PCL 10000 g/mol 60 103.000 PDL 3000 g/mol 30 PCL 10000 g/mol 70 89.000 POL 3000 g/mol 60 PCL 10000 g/mol 40 73.000 PDL 3000 g/mol 40 PCL-co-pTHF 60 79.000 2000g/mol 13' PtOL 3000 glrnol 40 PTHF 2500 g/mol 60 4S=000 PDL 3000 g/mol 40 PPG 1200 g/m61 60 65.000 PDL 3000 g/mo! 40 PPG 4000 g/mol 60 53.000 PDL 3000 g/mol 40 PEG 2000 g/mol 60 28.000 PDL 3000 g/mol 40 PEG 4000 gimof 60 32.000 PDL 3000 g/mol 40 PEG 6000 g/mol 60 40.000 PDL 3000 glmol 40 :::# 8000 g/mot 60 42.000 PDL 3000 g/mot 40 10000 g/mol 60 43.000 PDL 3000 g/moi 40 20000 g/mol 60 50.000 Combination with pDL 2000 o/mol Material 0/0 % Mn PDL 2000 g/mol 30 PCL 2000 g/mol 70 75.000 PDL 2000 g/mol 40 PCL 2000 gimoi 60 95.000 P L 2000 g/mol 5o PCL 2000 g/mol 50 65.000 PDL 2000 glmol 60 PCL 2000 g/mol 40 73_000 PDL 2000 g/mol 70 PCL 2000 g/mol 30 46.000 PDL 2000 g/mol 30 PCL 3000 glmol 70 99_000 PDL 2000 g/moi 40 PCL 3000 g/mol 60 72.000 PDL 2000 g/mol 50 PCL 3000 g/moi 50 78_000 PDL 2000 glmol 60 PCL 3000 glmol 40 73.000 PDL 2000 g/mol 70 PCL 3000 g/mol 30 65.000 PDL 2000 g/mol 30 PCL 4000 g/mol 70 49.000 PDL 2000 g/mol 40 PCL 4000 g/mol 60 62_000 PDL 2000 g/mol 50 PCL 4000 g/mol 50 85.000 PDL 2000 g/mol 60 PCL 4000 g/mol 40 83.000 PDL 2000 g/mot 70 PCL 4000 g/mol 30 56_000 PDL 2000 g/mol 30 PCL 10000 g/mol 70 85_000 PDL 2000 g/mol 40 PCL 10000 g/mol 60 1 09.000 PDL 2000 g/mol 50 PCL 10000 g/mol 50 130.000 PDL 2000 g/mo1 60 PCL 10000 g/rnol 40 121 _000 PDL 2000 g/mo! 70 PCL 10000 g/mo! 30 1 _ 000 PDL 2000 g/mol 30 PCI.-co-pTHF 70 60_0 0 2000g1mol 14=
PC?L 2000 g/mol 40 PCL-co-pTHF 60 78.000 2000g/mol PDL 2000 g/mo1 50 PCL-co-pTHF 50 89.000 2000g/mo{
PDL 2000 g/mol 60 PCL-co-pl'HF 40 59.000 2000g/mo8 PDL 2000 g/mol 70 PCL-co-p'1=HF 30 55.000 2000g/ma6 P L 2000 g/mol 40 PPG 1200 gfmo( 60 65.000 PDL 2000 g/mol 40 PPG 4000 gIm i 60 63.000 PDL 2000 glmol 40 PEG 2000 g/mol 60 28.000 PDL 2000 9/mol 40 PEG 4000 g/mol 60 32.000 PDL 2000 glmoi 40 IPEG 6000 g/ma! 60 40.000 PDL 3000 9/mof. 40 PEG 8000 g/mol 60 42.000 PDL 3000 g/mol 40 PEG 10000 g/mol 60 43.000 PDL 3000 g/mol 40 PEG 20000 g/mo! 60 50.000 Mechanical oronerties=
Material Temp. E-Modulus Ternsile stretch PDL 2k-rA-PCL1 Ok 40/60 20 C 35 1350%
PDL-2k-co-PCL1 Ok 40160 70 C 5 1000%
PDL-3k-cA-PCL1 Qk 40/60 20 C 145 1500%
PDL polyuretharie comprising glassy components Composition of pt>I iyester urethanes with POL
PDL= polypentadcscadolacton, polyester PI.GA= poly-L-lactide-e:o-glycolide (ran), polyester P-DL-LA = poly-D L-iactide, polyester Material % Mn PDL 3000 g/moI 50 PLGA 7000 g/mol 50 65.000 PDL 3000 g/rno! 40 PLGA 7000 g/mol 60 55.000 PDL 2000 g/mol 50 P-DL-LA 6000 g/moi 50 87.000 PDL 2000 glmcl 40 P-DL-LA 6000 g/mol 60 72.000 PDL 2000 g/mol 50 P-DL-LA 10000 g/mol 50 63.000 Mechanical rgperties:
Material Temp. E-Modulus MPa Tensile stretch PDL-3k-co-P-DL-LAEk 50150 20 C 279 453 %
PDL-3k-co-P-DL-LA6k 60150 50 C 31 303 %
PDL-3k-co-P-DL-LA6k 50/50 55 C 25 276 %
PDL-3k-co-P-DL-LA6k 50/50: copolyester urethane, comprising segments of PDL
and P-DL-LA having an Mn of 3000 and 6000 g/mol, respectively, and comprising 50 et.-% of each of the segments PDL and P-DL-LA, respectively Shape Memory Pronertles:
Materiai Number of Recovery % Fixity %
cycles PDL-3k-co-P-DL-.I..A6k 50/50 1 46,5 98.4 PDL-3k-co-P-DL-LA6k 50/50 2 87,3 98,8 PDL-3k co-P-DL-LA6k 50/50 3 96,8 99.1 PDL-3k-co-P-DL-LA6k 50/50 4 97,9 98,5 PDL-3k-co-P-DL-LA6k 50/50 5 98,2 98,5 Blends The following biends were prepared and evaluated:
Blends comprisirjg PDL, Additives were mixed with a PDL polyester urethane having the composition PDL-3k-co-PCL-10k 40/60.
The following addifive components were added in amounts of from 0.5 to 25 wt.
o:
Colorant (master batch comprising PDL-3k-c:o-PCL-1 k 40160 and about 5 to 10 wt.%
colorant) ~ nano-silver ~ barium sutfate For a blend comprising 10 wt.-% of the colored master batch the following shape memory properfiies were obtained:
Shape Memorv Pronert#es:
Material Number of Recovery % Fixity %
cycles 90% PDL-3k-co-PCL-1 k 40/60 1 30,5 98,3 10% master batch blue 90 !a PDL-3k-Co-PCL-10k 40/60 2 93,3 98,5 10% master batch blue 90% PDL-3k-CO-PCL-10k 40/60 3 96,5 99,5 10% master batch blue 90% PDL-3k-co-PCL-10k 40/60 4 98,6 98,6 10% master batch blue 900/6 PDL-3k-co-PCL-10k 40/60 5 99,2 98,9 10% master batch blue Also blends with commercially available polymers, such as PE or PVC, when using of from 50% to 90% PDL-polyurethane satisfactory shape memory properties, which correspond to those given above.
SlraPe MemorY 411ends These blends are mixtures of pure PDL-polyurethanes with PCL and PCL-potyurethanene, respect'svely. Only after a combination of the two materiats yields a shape memory material. For preparing those blends both materials. the PDL-polyurethane and PCL or PCL-polyurethane are dissolved together and are subsequently precipitated (co-precipitation). In addition blends were prepared in the melt using a compounder (twin smw extruder).
Components emplMd:
A: PDL-3k-polyurethane, Mn 95.000 B: PCL-10k-polyurethane, Mn 102.000 C: PCL; Mn 80.000 With a content of the PDL-component of from 20% - 80 % good shape memory praperties were obtained. In par6cular using blend compositions with blend ratios o'f 40/60; 50/50; 60/40 correspond, as far as shape memory properties are concemed, to PDL-co-PCL-polyurethanes, Material - Number of Recovery % Fixity %
cycles 40% PDL-3k-polyurethane 55,5 98,2 60% PCL-10k-polyurethane 40% PDL-3k-polyurethane 2 97,3 98,2 60% PCL-10k-polyurethane 40% PDL-3k-potyurethane 3 98,5 99,1 60% PCL-10k-poiyurethane 40% PDL-Jk-polyurethane 4 98,6 98,8 60% PCL-10k-polyurethane 40% PDL-3k-po1yUrethane 5 99,1 98,9 60% PCL-10k-polyurethane Pi]L-Polvester urethanes= bio comaatabiiitylde4 cla ation behaviour~
is Experiments were carried out regarding the degradation behaviour of the resorbable materials. Degradation studies were condu4ted at body temperature (37 C) in aqueous buffered solutions (phosphate buffer, pH 7, comprising NazHPOa, ICziiPOa and NaN3). In order to obtain estimates above long term behaviour so called accelerated degradation studies were carried out at 70 C. For the purpose of this evaluation samples are taken at defined times and molecular weight (Mn) as well as relative weight loss (%) are determined.
In the following table the results of evaluations for the material PDL-2k-co-PCL-10k are listed.
T = 70 C T = 37 C
Week Mn Weight loss [%] week Mn Weight loss [%l tg/moi1 t9omov]
0 185.000 0 185_000 1 0.08 175.000 2 184.000 0,06 2 6 183,000 0,12 011 152.000 3 10 184.000 0,15 0.16 134.000 4 18 182.000 0,17 0,'t9 76.314 6 29 180.000 0,20 0,24 27.054 0 29 8.769 590 2.178 22,65 2.469 41,61 25 2.123 4936 3.061 53, 6 2.976 In the foflowing table the results of the degradation experiment using the jrnateriat PDL-3k-co-PCL-10k are listed.
T = 700C T = 3T C
week Mn Weight loss [ I week Mn Weight iloss [%j [9/moll~ (g/mol]
0 185.000 0 0 185.000 0 1 182.000 0,05 2 184.000 0,08 2 160_000 0,11 6 183,000 0,15 3 123.000 0,15 10 184.000 0,18 4 112.000 0,18 18 182.000 0,20 6 49.000 0,21 29 180.000 0,22 8 17.500 0,41 12 10.000 6.47 16 7.300 23,98 21 4.200 43,54 25 3.500 50,46 29 2.500 54,15 In addition the sarnples were evaluated under a microscope regarding possible surPace modifications. A distinct change in the morphology of the surface coutd be detected.
Sio compatability studies:
For selected matariais (PDL-3k-co-PCt.-10k; PDL.-2k-co-PCL-10k) experiments were camed out regarding the biological evaluation for medicinal products in accordance with tS4/EN/f01N 10993-5 (cytotoxicity). Samples were sterilised, prior to these experiments with ethylene oxid e (EO).
Cytotoxicity evali-eatioras were carried out using direct contact with the murine ~tforoblast cell line L929 (f3ic~Withaker Bi=71-131F). Contr ( of membrane integrrty was carried out by PA 17 vital coloration (vital cells are cotored green). Morphology of the cells after 24h incubation was evaluated using Pa 13 hamalaun coloration.
1=valuation_ For bith samples membrane integrity was not affected by the materials of the present invention.
The morphology of the cells on the samples is, compared with the negative control, not changed. Cell apparence of the culture and the seeding eff+cience on the material corrrespond to that of the negative t+ontrol.
Processina of Pbi.-aolvesterurethanes Foam extrusiort=
After extruding and pelletazing the polymer, the polymer, in a second work up, is mixed with a master batch in a double arew extruder (chemical foaming agent Hydrocerol CT
572, product of Ctariant), in order to obtain a foam (5% foaming agent, 95%
PPDL-3k-co-PCL10k)..Yhe material, in the form of the rod in the temporary shape is comprssed to 25 % of the initial diameter. Subsequently the rod is expanded again by heating the compressed rod. The initial (permanent) shape is recovered, during this recovery a force of 5 N is exerted by the material.
Foams b y TIPS
A further methocd for producing porous structures is the thermaliy [ndiced phase separation" (TIPS) eingesetzt. A polymer solution (dioxan, I to 25 wt.- /
polymer) is cooled at a defined gradient (from 60 C to 3 C). During cooling a liquid-liquid separation occurs first. Further cooling solidifies the formed phase struCture. Using the material PDL-3k-co-PCl.1 k a foam could be produced. The solvent was removed using a high vacuum_ Praaration of micr0carriers,(d 100 Elm - 800 um) Preparation of microbeads from PDL-3k-ca-PCL1ok. Using an emulgator (PVA) an oil-in-water emulsion was prepared_ By carfully removing the solvent spherical micro carriers were obtained. iJsing SEM a broad distribution of the particle size was found, as well as a non-uniformity regarding the particle shape. On average the particle size was in the range of from 100 to 200 Nm, with the most part of the carriers showing a sperical shape.
SEM evaluations furthermore showed that most of the carriers were hollow an Collapsing under the electron beam. Evaluations of single carriers revealed that they showed a smooth surface having some sort of structure within the nanometer range.
The present invention provides novel polyester urethanes, which enable a controlled adjustment of desired profile of properties. The starting materials to be used are usual compounds, which are available without to much efFort. The reactions to be used for preparing the prepoiymers (macrodiols) are typical operations in the field of polymer chemistry, so that the polyester urethanes of the present invention may be obtained in a simple and efficient manner. The present invention enables to overcome the drawbacks of the known materials described above.
Claims (14)
1. Polyester urethane comprising segments of pentadecalactone units.
2. Polyester urethane according to claim 1, comprising at least one further segment comprising ester units and/or ether units different from pentadecalactone units.
3. Polyester urethane according to claim 2, wherein the at least one further segment is selected from the group consisting of partially crystalline segments comprising poyestersegments, polyetherestersegments and polyethersegments, and of glassy segments comprising polyester.
4. Polyester urethane according to claim 2, wherein the at least one further segment is selected from the group consisting of polycaprolactone segments (PCL), polycaprotacton-co-polytetrahydrofuran segments (PCL-copTHF), tetrahydrofuran segments (pTHF), polypropyleneglycol segments (PPG) and polyethyleneglycol segments (PEG).
5. Polyester urethane according to claim 2, wherein the at least one further segment is selected from the group consisting of poly-L-lactide-co-glycolide(ran) (PLGA) and poly-DL-lactide (P-DL-LA).
6. Polyester urethane according to any one of claims 2 to 5, wherein the at least one further segment comprising ester units and/or ether units show a number average molecular weight of from 1000 to 20000 g/mol.
7. Polyester urethane according to any one of claims 1 to 6, wherein the segments of the pentadecalactone units show a number average molecular weight of from 1000 to 20000 g/mol.
8. Polyester urethane according to any one of claims 1 to 7, having a number average molecular weight in the range of from 50000 to 250000 g/mol.
9. Polyester urethane according to any one of claims 1 to 8, obtained by reacting macrodiols with an aliphatic diisocyanate.
10. Polyester urethane according to any one of claims 1 to 9, comprising 10 to 80 wt.-% pentadecalactone units.
11. Polyester urethane having shape memory properties according to any one of claims 1 to 10.
12. Polyester urethane according to claim 11, comprising 20 to 80 wt.-%
caprolactone units and 80 to 20 wt.-% pentadecalactone units, wherein the polycaprolactone segments have a number average molecular weight of from number average molecular weight of from 1000 to 10000 g/mol.
caprolactone units and 80 to 20 wt.-% pentadecalactone units, wherein the polycaprolactone segments have a number average molecular weight of from number average molecular weight of from 1000 to 10000 g/mol.
13. A blend comprising at least one polyester urethane according to any one of claims 1 to 12, comprising at least one further components selected among polyethylene, polypropylene, polystyrene, PVC, fillers, colorants and medicaments.
14. Process for preparing a foam comprising at least one polyester urethane according to any one of claims 1 to 12, comprising the steps:
compounding at least one polyester urethane according to any one of claims 1 to 12 with a foaming agent and extruding foam; or dissolving at least one polyester urethane according to any one of claims 1 to 12 in a solvent and subjecting the solution to a thermally induced phase separation in order to prepare porous structures.
compounding at least one polyester urethane according to any one of claims 1 to 12 with a foaming agent and extruding foam; or dissolving at least one polyester urethane according to any one of claims 1 to 12 in a solvent and subjecting the solution to a thermally induced phase separation in order to prepare porous structures.
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DE10217350A DE10217350C1 (en) | 2002-04-18 | 2002-04-18 | polyesterurethanes |
DE10217350.8 | 2002-04-18 |
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EP (1) | EP1362872B1 (en) |
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