CZ20003071A3 - Shape memory polymers - Google Patents

Abstract

Shape memory polymer blends having at least two shapes in memory comprise: a) at least one stable segment with a melting point or glass transition temperature Ttrans of 40 to 270 °C, b) a first conformable segment, bonded to at least one stable segment, with a temperature Ttrans at least 10 °C lower than that of the stable segment, c) a second conformable segment, bonded to at least one stable segment or first conformable segment with a temperature Ttrans at least 10 °C lower than that of the first conformable segment, wherein the shape memory polymer is selected from the group consisting of grafted polymers, linear polymers and dendrimeric polymers, e.g. polyetheresters, polyesters, polyamides, polyesteramides, polyurethanes, polysaccharides, and the molecular weight of at least one of the segments is 500 to 10,000. In the method of shaping objects, the object is shaped into a given shape at a temperature above the Ttrans of the conformable segment and below T,rans stable segment and cooled to a temperature below Ttrans of the conformable segment, if the object is subsequently formed into a second shape, it can be returned to its original shape by heating it above T,trans of the stable segment.

Description

Shape memory polymers

Technical area:

The invention relates to shape memory polymers

State of the art

This application is generally in the field of shape memory polymers and particularly shape memory polymers having improved characteristics and memory of more than one shape.

Shape memory is the ability of a material to remember its original shape after mechanical deformation (Figure 1), which is a “one-way” effect, or cooling or heating (Figure 2), which is a “two-way” effect. This phenomenon is based on a structural phase transformation.

The first known materials to possess these properties were shape memory alloys (SMAs), which included TiNi (Nitinol), CuZnAl, and FeNiAl. The structural phase transformation of these materials is known as the martensitic transformation. These materials have been designed for a variety of purposes, including vascular stents, medical catheters, dental wires, vibration dampers, pipe joints, electrical connectors, thermostats, actuators, spectacle frames, and bra underwires. These materials have not been widely used, in part because they are relatively expensive. Scientists are actively developing shape memory polymers (SMPs) to replace or extend the uses of SMAs, in part because polymers are lighter, have a higher ability to recover their original shape, are easy to handle, and are more economical than SMAs. In the literature, SMPs are generally characterized as phase-separated linear block copolymers having a stable [hard] segment and a compliant [soft] segment. The stable segment is typically crystalline with a defined melting point and the compliant segment is typically amorphous with a defined glass transition temperature. In some cases, the stable segment is amorphous and has a glass transition temperature rather than a melting point. In other cases, the compliant segment is crystalline and has a melting point rather than a glass transition temperature. ···· ·

- 2 transition temperature. The melting point or glass transition temperature of the compliant segment is significantly lower than the melting point or glass transition temperature of the stable segment.

If the SMP is heated above the melting point or glass transition temperature of the stable segment, the material can be shaped. This (original) shape can be stored in the material by cooling the SMP below the melting point or glass transition temperature of the stable segment. If the shaped SMP is cooled below the melting point or glass transition temperature of the compliant segment while deforming the shape, this (temporary) shape is fixed. The original shape is restored by heating the material above the melting point or glass transition temperature of the compliant segment, but below the melting point or glass transition temperature of the stable segment. In another way of preserving the temporary shape, the material is deformed at a temperature below the melting point or glass transition temperature of the compliant segment, resulting in stresses and strains that are absorbed by the compliant segment. If the material is heated above the melting point or glass transition temperature of the compliant segment, but below the melting point (or glass transition temperature) of the stable segment, the stresses and strains are released and the material returns to its original shape. The return to the original state caused by an increase in temperature is called thermal shape memory effect. The properties that describe the shape memory ability of a material are the restoration of the shape to the original state and the shape stability of the temporary shape.

In response to external changes in temperature and stress, many physical properties of SMPs other than shape memory change significantly, particularly at the melting point or glass transition temperature of the compliant segment. These properties include the elastic modulus, hardness, flexibility, vapor permeability, damping, refractive index, and dielectric constant. The elastic modulus (the ratio of stress in a body to the corresponding stress) of an SMP can change by a factor of up to 200 when heated above the melting point or glass transition temperature of the compliant segment. The hardness of the material also changes dramatically when the compliant segment is above or at the melting point or glass transition temperature. When the material is heated above the melting point or glass transition temperature of the compliant segment, the damping capacity can be up to five times higher than that of a conventional rubber product.

• ·

- 3 The material can quickly return to its original cast shape after many thermal cycles and can be heated above the melting point of the stable segment and reshaped and cooled to fix the new original shape.

In polymers, it is possible to influence the shape memory (e.g. heat shrinkable film). However, this is not the main specific property, but is based on the structure of the polymer and its morphology. The effect persists for many polymers, which can vary considerably in their chemical composition. However, only a few polymer systems with shape memory have been described in the literature (Kim, et al., “Polyurethanes having shape memory effect”, Polymer, 37, (26), 5781 - 93, (1996); Li, et al., “Crystallinity and morphology of segmented polyurethanes with different soft-segment length”, J. Applied Polymer, 62, 631 - 38, (1996); Takahashi, et al., “Structure and properties of shape-memory polyurethane block copolymers”, J. Applied Polymer Science, 60, 1061 - 69, (1996); Tobushi, H., et al., “Thermomechanical properties of shape memory polymers of polyurethane series and their applications”, J. Physique IV (Colloque C1), 6, 377 - 84, (1996)).

Examples of polymers used to prepare stable and conformable SMP segments include various polyethers, polyacrylates, polyamides, polysiloxanes, polyurethanes, polyetheramides, polyurethane-urea copolymers, polyetheresters, and urethane-butadiene copolymers. See, for example, U.S. Patent No. 5,506,300 to Ward, et al.; U.S. Patent No. 5,145,935 to Hayashi; U.S. Patent No. 5,665,822 to Bitler, et al.; and Gorgen: “Application of Shape Memory Polyurethanes,” Proceedings of the First International Conference on Shape Memory and Superelastic Technologies, SMST International Committee, pp. 115-19, (1994). SMPs developed, mostly limited to the ability to temporarily retain only one shape. It would be beneficial to provide SMPs capable of forming objects capable of retaining more than one shape.

The essence of the invention

The object of the present invention is therefore to provide SMPs that are capable of • · • · • ·

• ·

- 4 create objects that can hold more than one shape in memory.

Another object of the present invention is to provide SMPs with physical and chemical properties and chemical structure different from conventional SMPs.

Yet another object of the present invention is to provide a shape memory SMP that is triggered by a stimulus other than temperature.

Summary of the invention

The composition of the mixtures, the products made from them and the methods of their preparation and use are described here. A preferred solution has such compositions of mixtures of polymers with shape memory that can retain more than one shape in memory. It may, for example, be composed of a stable segment and at least two adaptive segments. The _Ttrans of the stable segment is at least 10 °C, preferably 20 °C higher than the Kans of one of the adaptive segments and the _Ttrans of each subsequent adaptive segment is at least 10 °C, preferably 20 °C lower than the Ttrans of the previous adaptive segment. A multiblock copolymer with a stable segment with a relatively high _Ttrans and an adaptive segment with a relatively low Kans can be mixed or blended with a second multiblock copolymer with a stable segment with a relatively low _Ttrans and the same adaptive segment as the first multiblock copolymer. If the conforming segments in both multiblock copolymers are identical, the polymers are miscible when the conforming segments are melted. The resulting mixture has three transition temperatures: one for the first stable segment, one for the second stable segment, and one for the conforming segment. This allows these materials to remember two shapes.

Any polymers that are crystalline or amorphous and that have a _Ttrans within the range defined herein can be used to form the stable and compliant segments. The melting point or glass transition temperature (hereinafter referred to _{as Ttrans} ) of the stable segment is at least 10°C, more preferably 20°C higher than the _Ttrans of the compliant segment. The _Ttrans of the stable segment is preferably between -30 and 270°C, and more preferably between 30 and 150°C. The weight ratio of the stable segment to the compliant segment is approximately between 5:95 and 95:5, preferably between 20:80 and 80:20.

• · • 9

- 5 Shape memory polymers in some cases have at least one physical crosslink (physical interactions of the stable segment) or contain covalent crosslinks instead of a stable segment. Shape memory polymers can also penetrate into the lattice or partially penetrate into the lattice. In addition to changes of state from solid to liquid (melting point or glass transition temperature), both stable and flexible segments can also undergo transitions from one solid state to another solid state and undergo ionic interactions, however, requiring polyelectrolyte segments or supramolecular influence through highly organized hydrogen bonds.

Articles can be prepared from blends of shape memory polymers by, for example, injection molding, blow molding, extrusion, and laser deposition. In preparing shape memory articles, the articles can be formed at a temperature above the _Ttrans of the stable segment and cooled below the _Ttrans of the compliant segment. If the article is subsequently formed into a second shape, it can be returned to its original shape by heating above the _Ttrans of the compliant segment and below the _Ttrans of the stable segment.

Articles with two or more shape memory components can be prepared by molding a polymer blend with a stable segment, a first conforming segment, and a second conforming segment, wherein the first conforming segment has a _Ttran s at least 10°C below the stable segment and at least 10°C above the second conforming segment. After molding the blend at a temperature above the _Ttran s of the stable segment, it can be cooled to a temperature below the Ttran _s of the first conforming segment and above the temperature of the second conforming segment and molded into a second shape. The blend can be molded into a third shape after cooling below the Ttran _s of the second conforming segment. To return the blend to the second shape, the blend can be heated above the _{Ttran s} of the second conforming segment. To return the blend to the first shape, the blend can be heated above the _Ttran s of the first conforming segment. The blend can also be heated above the Ttran _s of the stable segment, where the blend loses the first and second shape memory and can be reshaped using the method described above. Thermosetting polymers can be prepared by preforming macromonomers, for example by extrusion, and stabilizing the original shape at a temperature above the Ttrans of the thermosetting polymer, for example by a photochemically excited reaction

- 6 reactive groups of the macromonomer. However, the original shape can only be programmed once.

In a preferred embodiment, the shape change occurs in response to a change in temperature. In another embodiment, however, the mixture may change shape in response to irradiation, changes in ion concentration and/or pH, an electric field, a magnetic field, or ultrasound. For example, the SMP may have at least one stable segment and at least one flexible segment, wherein at least two segments, preferably two flexible segments, are linked to each other via a functional group that is cleavable by irradiation, an electric field, a magnetic field, or ultrasound. The temporary shape is stabilized by crosslinking the linear polymers. By cleavage of these bonds, it can be restored to its original state. The stimuli for crosslinking and cleavage of these bonds may be either the same or different.

Image overview

Figure 1 is a depiction of the “one-way” influence of shape memory.

Figure 2 is a depiction of the “two-way” (thermal) influence of shape memory.

Figure 3 shows combinations of suitable groups of thermoplastics.

Figure 4 is a diagram of the subsequent reactions in the synthesis by photoreactive crosslinking, which is preferred.

Figure 5 is an illustration of the formation of shape memory excited by a photopath.

Figure 6 is an illustration of the mechanism of temperature influence on shape memory in a multiblock copolymer.

Figure 7 is a diagram showing the stress-elongation dependence of a shape memory polymer for a multiblock copolymer.

Figure 8 is a diagram showing the dependence of the melting point of diols, dimethacrylates and poly-ε-caprolactone thermosets on the molar mass M _n of the macromonomer.

Detailed description of the invention

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- 7 The composition of the shape memory polymer blends, articles made therefrom, and methods of their preparation and use are provided. The shape memory polymers may consist of at least one stable segment and at least one flexible segment, or may consist of at least one type of flexible segment, characterized in that at least one type of flexible segment is crosslinked, without the presence of a stable segment. In a preferred embodiment, the polymers may have two or more shape memories.

Definition of terms used

A polymer is considered to be a shape memory polymer if the original shape of the polymer is restored by heating it above the recovery temperature (defined as the T _trans of the conformable segment) even if the original molded shape of the polymer is mechanically broken at a temperature below the shape recovery temperature, or if the shape memory can be restored to its original state by applying another stimulus.

As used herein, the term "segment" refers to a block or sequence of groups in a polymer forming part of a shape memory polymer.

As used herein, the terms stable (hard) segment and flexible (soft) segment are relative terms relating to the T _tra ns segments. The stable segment(s) have a higher T _tra ns than the flexible segment(s). The weight ratio of the stable segment to the flexible segment is approximately between 5 : 95 and 95 : 5, more preferably between 20 : 80 and 80 : 20.

As used herein, the term "biodegradable" refers to substances that are bioresorbable and/or degradable and/or break down by mechanical disruption through interaction with the physiological environment into components that are metabolizable or excreted within a period of minutes to three years, preferably faster than one year, while maintaining the desired structural integrity. As used herein in reference to polymers, the term "degradation" refers to the cleavage of the polymer chain such that the molecular weight is brought to approximately a constant oligomer level and the polymer particle undergoes further degradation.

9

9

- 8 The term "complete degradation" refers to the breakdown of a polymer at the molecular level such that the complete decomposition of the material occurs. The term "degrade" as used herein includes "complete degradation" unless otherwise specified.

Composition of shape memory polymer blends

Shape memory polymers can be thermoplastics, thermosets, interpenetrated networks, semi-penetrated networks or mixed networks. The polymers can be single polymers or mixtures of polymers. The polymers can be linear, branched, thermoplastic elastomers with side chains, or any type of dendritic structural elements. The stimuli causing the shape changes can be temperature, change in ionic strength, pH, light, electric field, magnetic field or ultrasound.

Thermoplastic shape memory materials can be molded (e.g., cast) into a desired shape above the T _tra ns of the stable segment(s) and cooled to a temperature below the shape recovery temperature, where the polymer can undergo mechanical deformation and stress is generated in it. Deformed polymers can be restored to their original shape by heating them to a temperature above the shape recovery temperature. Above this temperature, the stress in the polymer is released, and the polymer returns to its original shape. Thermoset shape memory materials, on the other hand, are molded into the desired shape before the macromonomers used to form the thermoset polymers polymerize. After the shape is stabilized, the macromonomers are then polymerized.

Polymer blends must be compressible by at least one percent or expandable by at least five percent of their original thickness, especially at temperatures below the recovery temperature, with the ability to stabilize the deformation by applying stimuli such as heat, light, ultrasound, magnetic fields, or electric fields. In some cases, the materials show a recovery rate of up to 98% (compared to experimental samples).

If a significant stress resulting in mechanical deformation is introduced at a temperature lower than the shape recovery temperature, the stress in the compliant segments ··«·

- 9 or amorphous regions are preserved and the main shape change is maintained even after partial stress relaxation by the elasticity of the polymer. If the molecular chain configuration is disrupted by influencing the controlled arrangement of the molecular chains at a temperature lower than the glass transition temperature, a new arrangement of the molecular chain will arise due to the increase in volume and the decrease in free volume space. The original shape is restored by the contraction of the stable segment aggregates by increasing the temperature according to the rigidity of the controlling chain conformations, and the shape of the polymer is restored to the memorized shape. In addition, during changes of state from solid to liquid (melting point or glass transition temperature), stable or flexible segments can undergo ionic interactions including polyelectrolyte segments or supramolecular effects based on highly organized hydrogen bonds. SMPs can go from a solid state to a transitional solid state (e.g. morphological change). Transitions from a solid state to a transitional solid state are well known to those skilled in the art, for example in block polystyrene butadiene.

Objects formed using shape memory polymers can be engineered to control the change in direction during recovery. In other words, contraction and expansion can occur along one or more axes depending on how the polymer is shaped and stressed. For example, in an SMP fiber, the change in shape can be limited to one dimension, such as the longitudinal direction of the fiber.

In another case, the thermal and electrical conductivity of SMP materials can be changed in response to a change in temperature.

Blends can vary in moisture permeability, especially when the polymer is formed into a thin film (i.e., less than about 10 μm). Some polymer blends in their original state have sufficient permeability, for example, for water vapor molecules to penetrate the polymer film, while water molecules are not small enough to penetrate the polymer film. The resulting materials have low moisture permeability at temperatures below room temperature and high permeability at temperatures above room temperature.

I. Polymer segments

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949 949 999 9494 99 99

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- 10 The polymers contain "hard" and "soft" segments. The segments are preferably oligomers. As used herein, the term "oligomer" refers to a linear chain molecule with a molecular weight of up to 15,000 Daltons. The segments forming the polymers are selected according to the desired glass transition temperature(s) (if at least one segment is amorphous) or melting point(s) (if at least one segment is crystalline), which in turn depends on the desired use, taking into account the environment for which they are to be used. The average molecular weight of the polymer segment is preferably greater than 400 and most preferably in the range between 500 and 15,000.

The transition temperature at which the polymer suddenly becomes soft and the deformation can be controlled by changing the monomer composition and the type of monomer. This allows the shape memory effect to be adjusted at the desired temperature. The thermal properties of polymers can be determined, for example, by dynamic mechanical thermal analysis or differential scanning calorimetry (DSC). The melting point can also be determined using a standard melting point apparatus.

The polymers may be thermosets or thermoplastics, although thermoplastic polymers are preferred for ease of casting. For some applications, thermosets are still preferred because they are generally softer in their original shape at temperatures above T _Tran s than physically crosslinked polymers.

The degree of crystallinity of the polymer or polymer block(s) is preferably between 3 and 80%, more preferably between 3 and 60%. If the degree of crystallinity is higher than 80% while the conformable segments are amorphous, the resulting polymer composition has poor shape memory characteristics.

The tensile modulus of polymers below _T trans is typically between 50 MPa and 2 GPa (gigapascals), while the tensile modulus of polymers above _T trans is typically between 1 and 500 MPa. The ratio of the elastic modulus above and below T trans is 20 or higher. The higher the ratio, the better the memory of the resulting polymer blend.

The polymer segments may be natural or synthetic, although synthetic polymers are preferred. The polymer segments may be biodegradable or non-biodegradable, although biodegradable polymers are preferred for in vivo medical use. Generally, these materials are degraded by hydrolysis, exposure to water or enzymes

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- 11 9 9 9

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9 9 • 4 4 9 under physiological conditions, by surface erosion, total erosion, or a combination thereof. Non-biodegradable polymers used for medical purposes should preferably not contain aromatic groups other than those found in natural amino acids.

The polymers are selected based on their glass transition temperature (if at least one segment is amorphous) or melting point(s) (if at least one segment is crystalline), which actually requires the method of application and at the same time takes into account the environment in which they will be used. The average molecular weight of the polymer block is preferably higher than 400 and most preferably in the range between 500 and 15,000.

The polymer may be in the form of a hydrogel (typically absorbing up to 90% by weight of water) and may optionally be cross-linked with multivalent ions or polymers. Ionic cross-linking between the compliant segments can be used to maintain a structure that can be reshaped upon deformation by breaking the ionic cross-linking between the compliant segments. The polymer may also be in the form of a gel in solvents other than water or aqueous solutions. In these polymers, the temporary shape can be fixed by hydrophilic interactions between the compliant segments.

Representatives of natural polymer blocks or polymers include proteins such as zein, modified zein, casein, gelatin, gluten, serum albumin and collagen and polysaccharides such as alginate, celluloses, dextrans, pullulan and polyhyaluronic acid, as well as chitin, poly-3-hydroxyalkanoates, especially poly-β-hydroxybutyrate, poly-3-hydroxyoctanoate and poly-3-hydroxyfatty acids. Representatives of natural biodegradable polymer blocks or polymers include polysaccharides such as alginate, dextran, cellulose, collagen and their derivatives (substituted, with added groups, for example alkyl, alkylene, hydroxylated, oxidized and other modifications commonly prepared by those skilled in the art) and proteins such as albumin, zein and their copolymers and mixtures, alone or in combination with synthetic polymers.

Representatives of synthetic polymer blocks or polymers include polyphosphazenes, polyvinyl alcohols, polyamides, polyesteramides, polyamino acids, synthetic polyamino acids, polyanhydrides, polycarbonates, polyacrylates,

polyalkylenes, polyacrylamides, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyorthoesters, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinyl pyrrolidone, polyesters, polylactides, polyglycolides, polysiloxanes, polyurethanes and copolymers thereof. Examples of suitable polyacrylates include polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, polyisobutyl methacrylate, polyhexyl methacrylate, polyisodecyl methacrylate, polylauryl methacrylate, polyphenyl methacrylate, polymethyl acrylate, polyisopropyl acrylate, polyisobutyl acrylate and polyoctadecyl acrylate.

Synthetically modified natural polymers include cellulose derivatives such as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitrocelluloses and chitosan. Examples of suitable cellulose derivatives are methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxybutyl methyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose, cellulose triacetate and sodium sulfate cellulose. These are collectively referred to herein as "celluloses".

Representatives of the synthetic degradable polymer segments include polyhydroxy acids such as polylactides, polyglycolides and their copolymers; polyethylene terephthalate; polyanhydrides; polyhydroxybutyric acid; polyhydroxyvaleric acid; polylactide-poly-s-caprolactone copolymer; polyglycolide-poly-c-caprolactone copolymer; polycarbonates, polypseudoamino acids; polyamino acids, polyhydroxyalkanoates, polyanhydrides, polyorthoesters; and mixtures and copolymers thereof. Polymers containing labile bonds such as polyanhydrides and polyesters are well known for their hydrolytic reactivity. The rate of their hydrolytic degradation can be altered by simple changes in the polymer backbone and structural sequence.

Examples of non-biodegradable synthetic polymer segments include ethylene vinyl acetate, polymethacrylic acid, polyamides, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyvinylphenol, and copolymers and blends thereof.

Polymers can be obtained from commercial sources such as Sigma Chemical Co., St. Louis,

MO; Polysciences, Warrenton, PA; Aldrich Chemical Co., Milwaukee, WI; Fluke, • ·

- 13 Ronkonkoma, NY; and BioRad, Richmond, CA. Alternatively, polymers can be synthesized from monomers obtained from commercial sources using standard techniques.

Hydrogels

Hydrogels can be formed from polyethylene glycols, polyethylene oxide, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylates, polyethylene terephthalate, polyvinyl acetate, and copolymers and mixtures thereof. Many polymer blocks, such as acrylic acid, are elastomers only when the polymer is hydrated and hydrogels are formed. Other polymer blocks, such as methacrylic acid, are crystalline and meltable even when the polymers are not hydrated. Depending on the application and conditions of use, any type of polymer block can be used.

For example, shape memory is observed in acrylic acid copolymers only in the hydrogel state, because the acrylic acid units are mainly hydrated and behave as a compliant elastomer with a very low glass transition temperature. Dry polymers are not shape memory polymers. When the acrylic acid units are dry, they behave as a hard plastic even above the glass transition temperature and do not show any sudden change in mechanical properties upon heating.

In contrast, copolymers containing methyl methacrylate polymer blocks as conformable segments exhibit shape memory properties even when dry.

Certain polymers, such as block copolymers of polyethylene oxide and polypropylene oxide (PLURONICS™, BASF), are water-soluble at temperatures below body temperature and become hydrogels at temperatures above body temperature. By incorporating these polymers as blocks into shape memory polymers, shape memory polymers are created with a temperature response that is completely opposite to that of conventional shape memory polymers. These materials recover their shape when cooled below their shape recovery temperature instead of being heated above their shape recovery temperature. This effect is called the inverse thermal shape memory effect. Shape memory polymer blends including these polymer blocks are suitable for a variety of biomedical applications.

- 14 applications where the polymer can be inserted as a liquid and cooled in situ to recover the intended shape. The inverse thermal shape memory effect can be obtained by placing two different blocks miscible at temperatures below T _misc but immiscible at higher temperatures into the polymer. Phase separation at higher temperatures stabilizes the temporary shape.

Conductive polymers include various polymers such as polyacetylenes and polypyrroles. These materials are particularly preferred for applications where electrical conductivity is important. Examples of applications include tissue engineering and any biomedical application where cell growth is supported. These materials may find particular application in the computer field, as they are better able to absorb heat without increasing temperature than SMA. Conductive shape memory polymers are useful in the field of tissue engineering to support tissue growth, such as neural tissue.

II. Joining of polymer segments

Blends of shape memory polymers are preferred in which more than one shape memory can be formed. The blend may include, for example, a stable segment and at least two conformable segments, wherein the _Ttrans of the stable segment is between 30 and 270°C and is at least 10°C, but preferably 20°C higher than the _Ttrans of one of the conformable segments, and the _Ttrans of each subsequent conformable segment is at least 10°C, preferably 20°C lower than the _Ttrans of the preceding conformable segment.

One or more segments may optionally be biodegradable or linked to another segment via a biodegradable linkage such as an ester, amide, anhydride, carbonate or orthoester linkage.

The shape memory effect is based on the morphology of the polymer. In the case of thermoplastic elastomers, the original shape of the object is fixed by physical crosslinking caused by the stable segment. In the case of thermoset polymers, the flexible segments are covalently crosslinked instead of having stable segments. The original shape is given by the crosslinking process.

Compared to the previous method, segmented polyurethane SMPs do not have to • ·

- 15 the mixtures of segments described herein may be linear. The segments may be partially grafted or attached to dendrimeric side groups.

Thermoplastic and thermosetting polymers

The polymers may be in the form of diblock, triblock, tetrablock or multiblock copolymers, branched or grafted polymers, thermoplastic elastomers containing dendritic structures and mixtures thereof. Figure 3 illustrates some combinations of suitable groups of thermoplastic materials forming stable and conformable segments. Thermoplastic shape memory polymers may also be a blend of one or more homo- or copolymers with one or more diblock, triblock, tetrablock or multiblock copolymers, branched or grafted polymers. These types of polymers are well known to those skilled in the art.

The polymers can also be thermosetting polymers. There are four different types of thermosetting polymers with shape memory properties. These include polymers with polymer networks, semi-interpenetrated networks, interpenetrated networks, and mixed interpenetrated networks.

i. Polymer grids

The polymer network is prepared by covalent crosslinking of macromonomers, i.e. polymers containing polymerizable end groups such as carbon-carbon double bonds. The polymerization process can be induced by light- or heat-sensitive initiators, or by irradiation with ultraviolet light (“UV”) without an initiator. Shape memory polymer networks are prepared by crosslinking one or more conformable segments corresponding to one or more thermal transitions. For biomedical applications, crosslinking is performed using a radiation crosslinking stimulus and does not require any chemical initiator. The radiation crosslinking agent advantageously eliminates the need for initiator molecules, which can be toxic. Figure 4 is a diagram of the reaction sequence for the synthesis of a preferred radiation crosslinking agent, with an overall yield of about 65%.

- 16 ii. Interpenetrated grids

Interpenetrated lattices ("IPN") are defined as lattices in which two components are crosslinked, but not to each other. The original shape is determined by the lattice with the highest crosslink density and the highest mechanical strength. The material has at least two T _tran s corresponding to different adaptive segments of the two lattices.

iii. Mixed interpenetrated grids

The IPN blend has at least one physically crosslinked polymer lattice (thermoplastic polymer) and at least one covalently crosslinked polymer lattice (thermosetting polymer) that cannot be separated by any physical means. The initial shape is given by the covalently crosslinked lattice. The temporary shape corresponds to the Tt _{ran s} of the compliant segments and the T _tra ns of the stable segment of the thermoplastic elastomer component.

The interpenetrated network is preferably prepared by polymerization of a reactive macromonomer in the presence of a thermoplastic polymer, for example by photopolymerization of carbon-carbon double bonds. In this embodiment, the weight ratio of thermoset polymer to thermoplastic polymer is preferably between 5:95 and 95:5, more preferably between 20:80 and 80:20.

iv. Semi-interpenetrated lattices

Semi-interpenetrated networks ("semi-IPNs") are defined as two independent components, where one component is a crosslinked polymer (polymer network) and the other component is an uncrosslinked polymer (homopolymer or copolymer), where the components cannot be separated by physical means. A semi-IPN has at least one thermal transition corresponding to the compliant segment(s) and the homo- or copolymer components. The crosslinked polymer preferably has between about 10 and 90% by weight of the component with the semi-interpenetrated network.

v. Polymer blends

Shape memory polymers can exist as physical mixtures of thermoplastic polymers. In one case, a shape memory polymer mixture can be prepared by the interaction or mixing of two thermoplastic polymers. Polymers • · · · • ·· • ·

- 17 may be semi-crystalline homopolymers, semi-crystalline copolymers, thermoplastic elastomers with linear chains, thermoplastic elastomers with side chains or any kind of dendritic structural elements, and branched copolymers, and these may be blended with each other in any combination.

For example, multiblock copolymers with a stable segment with a relatively high Ttrans and a compliant segment with a relatively low _Ttrans can be blended or mixed with a second multiblock copolymer with a stable segment with a relatively low T^ans and the same compliant segment as the first multiblock copolymer. The compliant segments in both multiblock copolymers are identical, so that when the compliant segments melt, the polymers are miscible with each other. In the resulting blend, there are three transition temperatures, one in the first stable segment, another in the second stable segment, and another in the compliant segment. These materials can also remember two different shapes. The mechanical properties of these polymers can be tuned by varying the weight ratio of the two polymers.

Other types of blends of at least two multiblock copolymers can be prepared, in which at least one of the segments is miscible with at least one of the segments of other multiblock copolymers. If two different segments are miscible and together build a domain, then the thermal transition of this domain depends on the mass content of these two segments. The maximum number of memory shapes is based on the number of thermal transitions of the blend.

Shape memory blends may have better shape memory capability than the blend component alone. Shape memory blends consist of at least one multiblock copolymer and at least one homo- or copolymer. Di-, tri- or tetrablock copolymers may be suitable substitutes for multiblock copolymers.

Shape memory blends are very suitable for industrial applications as a wide range of mechanical, thermal and shape memory properties can be obtained from just two or three basic polymers by blending them in different weight ratios. A twin screw extruder is an example of a standard process that can be used for the mixing of the ingredients and the blending process.

• ·

- 18 Polymers with functional groups that respond to stimuli other than temperature

In a preferred embodiment, the shape memory polymer blend comprises at least one stable segment and at least one flexible segment, or more flexible segments, which are covalently crosslinked, and wherein at least two of the segments are bonded via a functional group that is cleavable by light, ion concentration, pH, electric field, magnetic field and/or ultrasound. In addition to changing shape in response to temperature changes, the blend can also change shape in response to light, ion concentration, pH, electric field, magnetic field and/or ultrasound. The temporary shape of these polymers is fixed by covalent crosslinking.

i. Photochemical stimuli

Photoreversible reactions can be used to bond the conformable segments together and hold the polymer in a temporary shape. The original shape of the material is given by the stable segment. By photochemically cleaving these bonds, the material returns to its original shape. Since these reactions are photoreversible, bonds can be formed and broken in cycles. Each time the bonds are broken, they must be re-formed to create a memory shape. Examples of such functional groups capable of undergoing photoreversible reactions are derivatives of cinnamic acid and cinnamylidene acid. Bonding and cleavage can be induced by different wavelengths of UV radiation. Cleavage can also occur by thermal treatment.

For another solution, polymers can contain side chains with chromophores such as azo groups that absorb light. Chromophores can also be incorporated into the main chain. Stable and/or flexible segments can also contain double bonds that shift from the cis to the trans position when the chromophore isomers absorb light. Light can also be used to isomerize the segments, which dramatically affects the Ttrans of the segment. The initial shape of such polymers is determined by the stable segment. The polymers can then deform into an intermediate shape. The intermediate shape is

- 19 is fixed by the action of light on the polymer, causing photoisomerization. In this process, the polymer is prevented from returning to its original shape because the thermal transition temperature has been increased. In this way, a transition from one solid phase to another can also be induced.

ii. Changes in ionic strength and/or pH

Various functional groups are known to crosslink in the presence of certain ions or in response to a change in pH. For example, calcium ions are known to crosslink amine and alcohol groups, i.e. the amine groups on alginate can be crosslinked by calcium ions. Carboxylate and amine groups are also charged at certain pH values. If these groups are charged, they can crosslink with ions of opposite charge. The presence of groups that respond to changes in the concentration of certain types of ions and/or changes in pH will result in reversible crosslinking between these segments in stable or adaptable segments. When segments are crosslinked, the shape of the object can be fixed. After deformation of the shape, a change in ionic concentration or pH can result in the cleavage of the ionic interactions that formed the crosslink between the segments and therefore release the chain formed by the deformation and thereby return the object to its original shape. Since ionic bonds are formed and broken in this process, this can only happen once. However, the bonds can be re-formed by changing the ion concentration or pH, so the process can be repeated as desired.

iii. Electric and magnetic fields

Various moieties such as chromophores with a large number of delocalized electrons increase in temperature upon application of electric or magnetic fields as a result of the increased electron flow caused by the field. Upon increasing the temperature of these materials, heat-induced shape memory can occur in the same way as if the material were heated directly. Such mixtures are particularly suitable for biomedical applications where direct application of heat to the implanted material could cause problems, but the applied magnetic or electric field only has an effect on those molecules that contain the chromophore and does not heat the surrounding tissue.

• * • ·

- 20 iV. Ultrasound

Various materials contain reactive groups that fragment in response to ultrasound. Examples of such groups are those that form stable radicals such as nitroso and triphenylmethane groups. The shape of the object is fixed by forming bonds between two or more conformable segments, for example by using heat or light. After the shape is deformed, ultrasound can break the bonds between the conformable segments and release the chain causing the deformation. The object then returns to its original shape. Since covalent bonds are formed and broken during this process, it can only occur once.

III. Polymer production methods

The polymers used to form the segments in the SMPs described above are both commercially available and can be synthesized by routine chemical procedures. Those skilled in the art can readily prepare the polymers using known chemical procedures.

IV. Methods of shaping polymer blends

The mixtures can be formed into a first shape under appropriate conditions, for example at a temperature above the _Ttrans of the stable segments and allowed to cool below the Ttrans of the compliant segment(s). Standard technologies are extrusion and injection molding. The article can optionally be reshaped into a second shape. By applying heat or another set of conditions, the article returns to its original shape.

Thermosetting polymers can be prepared by extrusion of prepolymerized material (macromonomers) and the initial shape fixed at a temperature above the T _tra ns of the thermosetting polymer, for example by irradiation of reactive groups on the monomer. The transitional shape is fixed by cooling the material below T _tra ns after deformation of the material.

Crosslinking can also be carried out in a solution of macromonomers. The solvent is

- 21 of the formed gel is removed in a subsequent step.

Such blends formed from thermoplastic polymers can be blown, extruded into sheets, or injection molded, for example to form fibers. The blends can also be molded by other methods known to those skilled in the art of solid-state machining, such as laser machining, micromachining, hot wire machining, and CAD/CAM (computer-aided design/computer-aided manufacturing) processes. These processes are preferred for molding thermosetting polymers.

1. Transitions between shapes

In some applications, it is advantageous to proceed in small steps from a temporary shape to another temporary shape or to the original shape. Under operator control, it is possible to proceed backward and forward between shapes as needed.

A. Wide thermal transitions

Typically, the _Tt of a shape memory polymer is sharp, so that the polymer returns to its original shape simply by heating the material by only a few degrees Celsius. Other times, however, shape memory polymers have a broad thermal transition, so that the original shape is fully restored only when the polymer is heated above the upper limit of the thermal transition. Partial recovery occurs when heated to a temperature between the lower and upper limits of the thermal transition. In this case, the trigger is temperature, and the effect is necessarily independent of the time interval of heat application.

B. Gradual energy transfer

To restore the memory shape, a certain amount of energy is required to transfer the shape memory polymer. To achieve thermal shape memory, the amount of energy required to completely restore the memory shape depends on the heat capacity of the material. For very sensitive materials, the amount of energy therefore depends on the radiation dose. In the preferred solution, the polymer for thermal shape memory should have a sharp thermal transition and its initiation should be based on a time of exposure to a temperature higher than Tt _ran s. Other factors affecting the transition include the mass or dimensions of the material and the temperature and heat transfer coefficient of the medium. ···· • 4

• · • ·

- 22 or the environment (and used to heat it) that is in contact with the material. For example, the higher the temperature of the environment, the faster the shape memory is restored.

C. Selective energy transfer and alternative mechanisms

In the case of the classical method of influencing thermal shape memory, the entire polymer must be heated to restore its original shape by the action (and transfer) of thermal energy from an external source. In an alternative solution, the polymer is heated by an energy source other than thermal. By using this technique, it is possible to heat not only the entire object with shape memory, but also certain parts of it (another way of starting and improving the control to restore the original shape).

i. Light energy

Polymers absorb light of different wavelengths depending on their chemical structure. Polymers commonly exhibit strong absorption in the infrared (IR) and near-infrared (NIR) regions. The strongest and most suitable absorption regions for a given application can be found using IR or NIR spectroscopy. Shape memory polymers may also exhibit strong absorption in the ultraviolet (UV) region. Polymers can be exposed to light having at least one specific frequency in their spectrum so that they absorb the light energy and heat up. The absorption characteristics of shape memory polymers can be modified by adding chromophores, which are fragments, functional groups, or molecules exhibiting strong absorption in specific regions of the UV/visible/IR/NIR/microwave spectrum. The chromophore may be covalently bound to the polymer, combined as a physical mixture with the polymer, or both.

In preferred biomedical applications, non-invasive control of the implantation of SMC objects may be used. For example, the implanted object may be exposed to a specific external light source that does not simultaneously heat the tissue, serum, or other parts of the physiological environment surrounding the SMC implant. Such a light source (e.g., a light bulb) must emit one or more frequencies (e.g., near infrared, “NIR”) that are not absorbed <*·>»·

• · • · · • · · • · ♦ • · ·

- 23 physiological environment, but is absorbed by the shape memory material. The use of NIR light is known in the diagnostic field.

In an alternative approach, interference techniques are used to control the frequency of the light incident on the SMP implant. Interference provides three-dimensional (3D) control over the area to be affected, as the specific frequency absorbed by the shape memory object is created at a specific location by the interference of two or more beams crossing at that specific location. The sources of these beams are external to the body and the frequencies of the beams are generally modulated by a radio frequency selected to produce the desired frequency upon interference.

ii. Ultrasound

In an alternative solution, bubbles of gas or a bubble-containing liquid, preferably fluorocarbons, are incorporated into the shape memory object.

Using standard ultrasound technology, a cavitation effect can be induced in the gas/liquid mixture to heat the SMP. The technology of controlled 3-D ultrasound application is known to those skilled in biomedical diagnostics.

iii. General

It is also possible to influence the energy transfer based on the interaction of the shape memory polymer with electromagnetic fields. The use of magnetic fields to induce heating or localized thermal changes is well known. In yet another approach, the energy transfer is generated by non-radiative effects, such as Foerster-Perrin energy transfer.

2. "Two-way influence on shape memory"

Objects made of shape memory polymers can be prepared to have two original (permanent) shapes, i.e. two-way shape memory effect. These systems always consist of at least two components. The components are combined using layered technology (similar to bimetals) or lattices are interwoven. By changing the temperature, the shape memory object changes its shape towards permanent shape 1 or permanent shape 2. Each of the permanent shapes belongs to one component of the object. The resulting shapes are always in

- 24 equilibrium between the two shapes. The temperature dependence of the shape is due to the fact that the mechanical properties of one component (“component A”) are almost independent of temperature in the desired temperature range. The mechanical properties of the other component (“component B”) are temperature dependent. In one case, component B is stronger at lower temperatures compared to component A, while component A is stronger at higher temperatures and determines the current shape. An object with a “two-way” memory can be prepared by (a) establishing the original shape of component A; (b) deforming the object to the original shape of component B; and (c) fixing the original shape of component B when a stress is applied to the component.

3. Initiation of restoration of the original shape by polymer degradation

The recovery of the original shape of a shape memory polymer can be initiated by a hydrolytic degradation process. In a preferred embodiment, this characteristic is incorporated into a system comprising a thermoplastic polymer composed of a stable segment and at least one compliant segment or a thermoset comprising at least one compliant segment (one-component systems). In these polymers, the two compliant segments can be linked by a readily hydrolyzable bond. The term “readily hydrolyzable bond” is used herein to refer to groups having a hydrolytic rate greater than that of other functional groups of the polymer. The original shape of these polymers is determined by the stable segments (thermoplastic material) or by covalent crosslinking (thermoset). The temporary shape is fixed by crosslinking between the two compliant segments after deformation of the object. When the crosslinking between the compliant segments is hydrolyzed, the original shape is recovered. Rapidly hydrolyzable functional groups include activated ester bonds such as the glycolyl glycolate and anhydride bond.

In another preferred embodiment, the polymer is a two-component system in which at least one component is a covalent lattice, such as an IPN, a mixed IPN or a semi-IPN. The covalent lattice is an amorphous lattice having a very low Tt _ran s. The covalent lattice determines the initial shape of the system and the second component deforms the system to fix the intermediate shape. The second component is another lattice in the case of an IPN, a homo- or copolymer in the case of a semi-IPN and a thermoplastic elastomer in the case of a mixed IPN. The first component (the covalent lattice) hydrolyzes more slowly than the second

- 25 component, so the polymer will restore its original shape when the second component degrades.

φ this·· this · · • thisthis • this • · this this ·· ·· ··♦· ·«·« • this · · · · • this « this this · this this · · · · ><· ♦··· ··

V. Application

These materials have a huge number of applications.

1. Therapeutic, prophylactic and diagnostic applications

These materials are particularly suitable for medical and biological applications.

For example, any of a variety of therapeutic, prophylactic, and/or diagnostic agents may be incorporated into a polymer composition that can deliver the introduced agents locally or systemically upon administration to a patient. Examples include synthetic inorganic or organic compounds or molecules, proteins and peptides, polysaccharides and other sugars, lipids, and nucleic acid molecules having therapeutic, prophylactic, or diagnostic effects. Nucleic acid molecules include genes, plasmid DNA, DNA itself, transcription inhibitors, molecules that bind complementary DNA to inhibit transcription, ribozymes, and accompanying ribozyme sequences. Agents such as vasoactive agents, neuroactive agents, hormones, growth factors, cytokines, anesthetics, steroids, anticoagulants, anti-inflammatory agents, immunomodulatory agents, cytotoxic agents, prophylactic agents, antibiotics, antiviral agents, inhibitors, antigens, and antibodies that are introduced can have a variety of biological effects. In some cases, the proteins may be antibodies or antigens that would otherwise be administered by injection to elicit an appropriate response. Proteins are defined as substances containing 100 amino acid residues or more; peptides have fewer than 100 amino acid residues. Unless otherwise specified, the term protein refers to both proteins and peptides. Polysaccharides such as heparin may also be administered. Compounds with a wide range of molecular weights, for example between 10 and 500,000 grams per mole, may be encapsulated.

Diagnostic or imaging agents that may be used include commercially available agents used in positron emission tomography (PET), computer-controlled

- 26 tomography (CAT), single-photon emission computed tomography, radiography, fluoroscopy, magnetic resonance imaging (MRI) and contrast agents for ultrasound.

2. Objects and devices for biomedical applications

Polymer blends can be used to prepare objects with potential use in biomedical applications. For example, sutures, orthodontic materials, bone screws, nails, plates, meshes, prosthetics, pumps, catheters, tubes, foils, stents, orthopedic clips, splints, tapes for preparing casts and skeletons for tissue engineering, contact lenses, drug delivery devices, implants, and thermal indicators can be prepared.

Implantable polymer blends are preferably prepared from biocompatible polymers and, for most applications, from biodegradable polymers. Biodegradable polymers degrade at a controlled rate depending on the composition and crosslinking of the polymer. Degradable polymer implants eliminate the need for implant repairs and can be used simultaneously with the introduction of therapeutic agents. The materials can be used in many applications requiring load and controlled degradation. Polymer blends can be formed into the shape of an implant that can be implanted into the body to perform a mechanical function. Examples of such implants include rods, pins, screws, plates, and anatomical shapes. Blends are particularly preferred for preparing suture material that is stiff enough to be easily handled, but softens when body temperature is reached to form a second shape that is more tolerable for the patient and still allows for healing.

Another preferred application is in the catheter field. Catheters generally require high stiffness during insertion, but once inserted, it is better if they are soft and flexible. In the preferred solution, the SMP catheter is stiff below body temperature for easy insertion and softens upon warming to body temperature, reducing patient discomfort and complications.

The polymer blend may be combined with fillers, reinforcing materials, radioimaging materials, excipients, or other materials necessary for the appropriate implant application. Those skilled in the art will readily determine the amounts of such substances to be included in the blend.

- 27 • · • · • · • ·

The articles may introduce various therapeutic and/or diagnostic agents, as discussed above.

3. Non-medical applications

There are many other applications for shape memory polymer compositions than just biomedical ones. These applications include: shape memory polymer foams, parts requiring recovery from impact such as bumpers and other car body parts, food packaging, automatic chokes for internal combustion engines, polymer composites, textiles, moisture permeable materials such as sportswear, diaper material and shoe linings, pipe joints, mold core materials, heat shrink tubing, rewritable compact discs (CDs) and connecting pins, temperature sensors, damping materials, pads and protectors, toys, connecting materials for individual tubes for internal encapsulation, connecting pins, materials for medical devices used in plaster casting, etc., office and educational materials, artificial flowers, dolls, internal lamination of dot matrix printer cylinders for computers, soundproofing materials, parts requiring recovery from impact such as car bumpers and other parts, building filler materials in divided parts of buildings, portable containers that can be folded when not in use and that return to their original state when used, mechanical devices such as couplings, etc., various heat-shrinkable hoses, materials for human cosmetic use, polymer foams with shape memory, fibers, polymer composites, seals and gaskets, choke valves, soundproofing and oil filters.

Shape memory foams have a deformed shape and an apparent cast shape. They have their deformed shape when compressed at a temperature above T _tra ns and retain this compressed shape at a temperature below T _tra ns as it is compressed and the compressed polymer returns to its original cast shape when heated above the temperature to restore the original shape. Foams can be prepared by polymerizing materials in the presence of a blowing agent (e.g., a gas or a low-boiling solvent).

VII. Methods of use

Some specific objects are intended to maintain a desired shape if ·

- 28 does not treat them in a manner inconsistent with their normal use. For example, car bumpers maintain their desired shape until impact. A product containing SMP can be used in its desired shape, but can be repaired, for example by heat, after damage (e.g. deformation).

Other objects are intended to be used in their first intended form and a second form for a second intended use. Examples of such objects include biomedical objects that can form a second form upon reaching body temperature or upon application of external stimuli that heat the object above body temperature.

Other objects are for intended use, so they change shape in response to changes in temperature by triggering some action, such as turning on a mechanical or electrical switch. For example, a switch can be used to regulate the temperature of the SMP environment, as in temperature sensors and automatic car chokes.

The present invention will be better understood by reference to the following examples, which, however, are not intended to limit it in any way.

Design examples

Example 1: Shape memory polymers from ester urethane copolymer

A group of biocompatible and biodegradable multiblock copolymers exhibiting shape memory with a thermal effect was synthesized. These polymers were composed of a crystallizable stable segment (T _m ) and a conformable segment having a thermal transition temperature T _tran s between laboratory temperature and body temperature. In contrast to previous segmented polyurethanes, the stable segment was an oligoester or oligoetherester and did not contain an aromatic component.

The mechanism for programming the temporary shape and restoring the permanent shape of a multiblock copolymer is shown in Figure 6. The permanent shape of the materials was created by melting the polymer and cooling it above _Ttrans (Fig. 6 - top position). The polymer was then formed into a temporary shape (Fig. 6 - right position), which was fixed by cooling below _Ttrans (Fig. 6 - bottom position). After the pressure was removed, the • ·

- 29 restored its original shape by reheating above T _tr ans· • · • · · · · · · · · 0 1 • 0 0

Synthesis of telechelates, oligomers with functional groups at both ends

Telechelate macrodiol was synthesized by ring-opening polymerization of cyclic monomers with di(n-butyl)tin oxide as a transesterification catalyst under a nitrogen atmosphere.

The stable segment α,ω-dihydroxy[oligo(ethylene glycol glycolate)ethylene oligo(ethylene glycol glycolate)] (PDS1200 and PDS1300) was prepared as follows: The monomeric p-dioxan-2-one was obtained before its further use by distillation (thermal depolymerization) of the oligomers. 57 g (0.63 mol) of monomer, 0.673 g (10.9 mmol) of ethylene glycol and 0.192 g (0.773 mmol) of di(n-butyl)tin oxide were heated for 24 hours at 80 °C. The end of the reaction (equilibrium) was determined by GPC. The product was dissolved in hot 1,2-dichloroethane and filtered through a hot Buchner funnel filled with silica gel. The product was obtained by precipitation in hexane and drying in vacuo for 6 hours.

Adaptive segment

i. Crystalline

Poly-ε-caprolactonediols with various M _n are commercially available, for example from Aldrich and Polysciences. PCL-2000 was used here.

ii. Amorphous a,c)-dihydroxy[oligo(L-lactate-co-glycolate)ethyleneoligo(L-lactate-co-glycolate)] - (abbr.: PLGA2000-15) was prepared as follows: In a 1000 ml two-necked round-bottomed flask, 300 g (2.08 mol) of L,L-dilactide, 45 g (0.34 mol) of diglycolide and 4.94 g (0.80 mol) of ethylene glycol were heated to melting at 40 °C with stirring. Next, 0.614 g (2.5 mmol) of di(n-butyl)tin oxide was added. After 7 hours, the reaction reached equilibrium as determined by GPC. The reaction mixture was dissolved in 1,2-dichloroethane and

9 • 9

- 30 purified on a silica gel column. The product was obtained by precipitation in hexane and dried for 6 hours under vacuum.

Properties of telechelates

As shown in Table 1 below, the molecular weight M _n and thermal properties of the macrodiols were determined.

Table 1: Molecular weight and thermal properties of macrodiols

Marking M _n GPC [g.rnor ¹ ] M _n VPO [g.rnor ¹ ] _Tm [°C] ΔΗ [Jg ¹ ] Tg [°C] ΔΟ _Ρ [Jg ¹ ] PCL2000 1980 1690 43 73.5 <-40 PDS1300 1540 1340 97 74.5 <-20 - PDS1200 2880 1230 95 75.0 <-20 - PLGA200 0 2020 1960 - - 29.0 0.62

Synthesis of thermoplastic elastomers (multiblock copolymers)

In a 100 mL two-necked round-bottom flask connected to a Soxhlet extractor filled with 0.4 nm molecular sieves, two different macrodiols (one stable segment and one flexible segment) as described in Table 2 below were dissolved in 80 mL of 1,2-dichloroethane. The mixture was refluxed to dryness by azeotropic solvent extraction. Freshly distilled trimethylhexane-1,6-diisocyanate was added via syringe and the reaction mixture was heated to 80 °C for at least 10 days. Samples of the mixture were taken at regular intervals to determine the molecular weight of the polymer by GPC. At the end of the reaction, the product was obtained by precipitation of the polymer in hexanes and purified by repeated dissolution in 1,2-dichloroethane and precipitation in hexanes.

Multiblock copolymers were prepared from the following two types of polymers.

(i) PDC polymers contained poly-s-caprolactone. The T _tr ans of the adaptive segment is the melting point.

(ii) PDL polymers contain a,ro-dihydroxy[oligo(L-lactate-co-glycolate)ethyleneoligo(L-lactate-co-glycolate)]. The Tt _ra ns of the compliant segment is the glass transition point.

- 31 » ·· · »

»··

I · ·«

Table 2: Synthesis of multiblock copolymers

Polymer 1. diol m [g] , n [mmol] 2. diol m [g] n [mmol] TMDI [mmol] time [d] PDC22 PDS1200 3.0245 2,653 PCL2k 6.0485 3,024 5,738 10 PDL23 PDS1200 2.2787 2,000 PLGA2k 6.1443 3,070 5,163 10 PDC27 PDS1300 2.5859 1,724 PCL2k 5.3611 2,681 4,368 14 PDC40 PDS1300 3.6502 2,433 PCL2k 3.9147 1,957 4,510 13 PDC31 PDS1300 3.2906 2,194 PCL2k 4.8619 2,431 4,500 16 PDL30 PDS1300 3.7115 2,474 PLGA2k 4.0205 2,011 4,480 16

Properties of thermoplastic elastomers

The determined physical, mechanical and degradation properties of the mixtures are given in the following tables 3 - 9.

The hydrolytic degradation behavior of the new materials was tested in a solution buffered to pH 7 at 37 °C. It was shown that the polymers are completely degradable and their degradation rate can be adjusted by the concentration of easily hydrolyzable ester bonds. The values of the relative mass loss m _r = m(t ₀ )/m(t) are in % at 37 °C and the relative molecular mass loss M _r = M _w (t)/M _w (t ₀ ) is in % at 37 °C.

The toxicity of two different multiblock copolymers was investigated in a test on chick embryos. It was shown that the embryos developed normally and their condition was not affected by the polymer samples.

Table 3: Composition of copolyesterurethanes determined by 400 MHz ¹ H-NMR spectroscopy

Marking Stable segment Weight content [%]* Adaptive segment Weight content [%]* PDL23 PDS 23.0 PLGA 54.2 PDL30 PDS 30.0 PLGA 52.1

PDC22 PDS 22.0 PCL 64.5 PDC27 PDS 27.0 PCL 61.1 PDC31 PDS 31.1 PCL 55.4 PDC40 PDS 40.4 PCL 46.2

*The remainder to 100% is the urethane content.

Table 4: Molecular weight M _w of urethane copolymer films determined by multidetector GPC

Marking Polymer foil M _W (LS) M _w (Visc) day/week [g.mor] [g.mor ¹ ] [ml.g- ¹ ] PDL23 161,500 149,000 0.065 PDL30 79,100 83,600 0.057 PDC22 119,900 78,500 0.078 PDC27 72,700 61,100 0.080 PDC31 110,600 108,600 0.065 PDC40 93,200 86,300 0.084

Table 5: Transition temperatures T _m and T _g , heat of fusion AH _m and changes in heat capacity

Ac _p of polymer films from DSC measurements (values are from the second heating)

Marking Tm1 [°C] ΔΗγπ1 [J-g' ¹ ] ,"O 1 o AC _P [Jg ¹ ] Tm2 [°C] AHm2 [J-g' ¹ ] PDL23 - 34.5 0.38 - PDL30 - - 33.5 0.25 85.0 8.5 PDC22 35.0 26.0 - - - - PDC27 37.0 25.0 - - 75.5 3.5 PDC31 36.5 28.5 - - 76.5 5.5 PDC40 35.0 7.0 - - 77.5' 7.0

Table 6: Mechanical properties of polymer films at 50 °C from strength test

Code modulus E [MPa] £r [%] _σΓ [MPa] Smax [%] Cmax [MPa] PDC27 1.5 1350 2.1 1300 2.3 PDC31 1.5 1400 4.9 1300 5.4 PDC40 4.0 1250 5.8 1300 5.9 PDL30 2.0 1400 2.1 1250 2.3

• ·

- 33 Table 7: Degradability of PDL22

Degradation time [d] M _r (viscometric) [%] M _r (light scattering) [%] 14 81.3 85.7 21 67.1 74.6 29 62.9 65.6 42 43.6 47.7 56 54.4 41.9

Table 7: Degradability of PDL23

Degradation time [d] M _r (viscometric) [%] M _r (light scattering) [%] 14 61.1 87.3 21 40.7 76.7 29 32.8 62.2 42 17.4 46.7 56 16.9 18.5

Table 9: Relative weight loss

PDC22 PDL23 Degradation time m _r m _r [%] [%] [%] 14 99.2 98.1 21 99.3 97.5 29 98.6 97.2 42 98.3 96.9 56 97.3 93.3

Shape memory properties

Figure 7 shows the results of tensile strength tests performed on multiblock copolymers as a function of the number of thermolysis cycles. The average dimensional stability of the polymers subjected to thermal cycling and the dependence of the stress recovery rate as a function of the number of cycles are shown in the following tables 10 and 11. The polymers have high dimensional stability and an equilibrium state is reached after only two cycles.

4 4 4

- 34 4 444 • 44

Table 10: Average speed of shape constancy Rf

Marking Rf [%] PDC27 97.9 PDC40 96.2 PDL30 97.7

Table 11: Dependence of the number of cycles on the voltage recovery rate R _r

PDC27 PDC40 PDL23 Number of cycles Rr [%] Rr [%] Rr [%] 2 77.3 73.7 93.8 3 93.2 96.3 98.8 4 98.5 98.7 98.9 5 98.5 98.7 98.8

Example 2: Degradable shape memory thermoset with crystallizable conformal segment

A large number of poly-ε(caprolactone)dimethacrylates and thermosets have been evaluated for mechanical properties and shape memory.

Macromonomer synthesis

Poly-s-caprolactone dimethacrylates (PCLDMA) were prepared as follows: To a solution of polys-(caprolactone)diol with M _n = 2000 g.mol' ¹ (20.0 g, 10 mmol) and triethylamine (5.3 g, 38 mmol) in 200 ml of dry THF, methacryloyl chloride (3.7 ml, 38 mmol) was added dropwise at 0 °C. The solution was stirred for 3 days at 0 °C and the precipitated salt was filtered off. After concentrating the mixture at room temperature under reduced pressure, 200 ml of ethyl acetate was added and the solution was filtered again and precipitated with a tenfold excess of a mixture of hexanes, ethyl ether and methanol (18

• · • · <··· • ··

- 35:1:1). The colorless precipitate was separated, dissolved in 200 ml of dichloroethane, re-precipitated and carefully dried at room temperature under reduced pressure.

Synthesis of thermosets

The macromonomer (or monomer mixture) was heated to 10 °C above its melting point (T _m ) and filled into a casting mold consisting of two glass plates (25 mm x 75 mm) and a Teflon insert with a thickness of 0.60 mm. To achieve good homogeneity, the melt was kept at T _m for another hour. Light exposure was performed on a heated plate at T _m for 15 min. The distance between the front of the heating lamp and the sample was 5.0 cm. After cooling to room temperature, the sample was extracted overnight and carefully washed with 100 times the amount of dichloromethane. Finally, the sample was dried at room temperature under reduced pressure.

Properties of macromonomers and thermosets

The following Table 12 lists the poly-ε-(caprolactone)dimethacrylates that were prepared, together with the corresponding degree of acrylate (D _a ) (%). The number after PCLDMA is the molecular weight M _n of the poly-ε-(caprolactone)diol used for the synthesis as determined by ¹ H-NMR and GPC, rounded to 500.

Table 12: Poly-s-(caprolactone)diol and degree of acrylate

Name Yes [%] PCLDMA1500 87 PCLDMA2000 92 PCLDMA3500 96 PCLDMA4500 87 PCLDMA6500 93 PCLDMA7000 85 PCLDMA10000 86

Figure 8 shows the melting point (T _m ) of diols, dimethacrylates and thermosets of polyy-ε-

- 36 caprolactone as a function of the molecular weight M _n of the macromonomers. In the diagram, macrodiols are represented by macromonomers ...· and thermosets _ Δ

The strength properties of poly-ε-caprolactone thermosets C1 to C7 at laboratory temperature are given in Table 13, where E is the modulus of elasticity (Young's modulus), s _s is the elongation and as is the stress at the permanent deformation limit, and _max is the maximum stress, emax is the elongation at a _max , sr is the elongation at break and _R is the stress at break. Table 14 below gives the tensile strength values of the same polyε-caprolactone thermosets at 70 °C.

Table 13: Strength properties of thermosets at laboratory temperature

Marking E [MPa] es [%] in [MPa] Smax [%] Omax [MPa] Wed [%] Or [MPa] C1 2.4±0.6 - - 16.1±2.0 0.4±0.1 16.1±2.3 0.38±0.02 C2 35±3 - - 20.6±0.3 4.7±0.1 20.6±0.3 4.7±0.1 C3 38±1 48±1 11.2±0.1 180±20 12.1±1.2 190±20 11.7±1.6 C4 58±4 54±1 12.2±0.1 247±4 13.6±1.9 248±13 15.5±2.7 C5 72±1 56±2 15.5±0.2 275±10 15.6±1.7 276±6 15.0±1.0 C6 71±3 43±2 14.2±0.1 296±14 15.5±0.2 305±8 13.8±2.7 C7 71 ±2 42±5 13.6±0.2 290±30 16.2±0.5 290±30 15.7±0.9

Table 14: Strength properties of thermosets at 70 °C

Marking E [MPa] Omax [MPa] Wed [%] C1 1.84±0.03 0.40±0.08 24±6 C2 2.20±0.12 0.38±0.05 18±2 C3 6.01±0.12 2.05±0.21 43±9 C4 2.30±0.16 0.96±0.01 61±3 C5 1.25±0.08 0.97±0.15 114±13 C6 1.91±0.11 1.18±0.06 105±11 C7 0.70±0.09 0.79±0.10 210±7

- 37 Shape memory

The thermomechanical properties of the thermosets were determined as shown in Table 15. The values of the average molecular weights (M _n ) are for the macromonomer. The lower limit temperature T ₍ is 0 °C and the upper limit temperature Th is 70 °C. The elongation of the temporary shape is 50%. Rf(2) is the stress recovery rate at the second cycle, R _f>to t is the total stress recovery rate after 5 cycles, Rf is the average set rate.

Table 15: Thermomechanical properties of thermosets

Marking M _n [g.mol' ¹ ] Rf(2) [%] Rf.tot [%] Rf [%] C4 4500 93.3 93.0 93.9±0.2 C5 6500 96.3 94.5 93.9±0.2 C6 7000 93.8 92.1 92.5±0.1 C7 10000 98.6 96.8 86.3±0.5

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Claims (40)

Patent claims A blend of shape memory polymers, characterized in that it has at least two shapes in memory. 2. A composition according to claim 1 comprising: a) at least one hard segment which has a Tt _wounds between -40 and 270 ° C, (b) a first adaptive segment having a T _tra ns of at least 10 ° C lower than that of the stable segment (s) and which is bound to at least one stable segment; c) a second adaptive segment bound to at least one of the stable segments or a first adaptive segment having a T _tra ns at least 10 ° C lower than the Tt _{rans of the} first adaptive segment, 3. The composition according to claim 2, characterized in that T _tra ns hard segment is in the range between 30 and 150 ° C. The composition according to claim 3, wherein the T _tran of the stable segment is in the range between 30 and 100 ° C. 5. The composition according to claim 2, characterized in that Tt _wounds first soft segment (s) is at least 20 ° C below Tm _trans of the hard segment (s). 6. The composition of claim 2 wherein the T _trans of the second soft segment (s) is at least 20 ° C below the Tm _{of wounds} with the first soft segment (s). 7. The composition of claim 1 wherein the shape memory polymer comprises a thermoplastic polymer. The composition of claim 1 wherein the polymer comprises multiple segments and has a molecular weight M _{n of} at least one of the segments being between about 500 and 10,000. 9. The composition of claim 1 wherein the shape memory polymer is selected from the group consisting of graft polymers, linear polymers, and dendrimeric polymers. 10. The composition of claim 1 wherein the polymer comprises stable and conformable segments and the stable segment comprises cyclic fragments. - 39 11. The composition of claim 10 wherein said fragments are selected from the group consisting of crown ethers and cyclic oligopeptides. 12. The composition of claim 1 wherein the shape memory polymer is biodegradable. 13. The composition of claim 12 wherein the polymer comprises stable and adaptable segments and at least one of the stable and adaptable segments is selected from the group consisting of polyhydroxy acids, polyorthoesters, polyetheresters, polyesters, polyamides, polyesteramides, polydepsipetides, aliphatic polyurethanes, polysaccharides, polyhydroxyalkanoates and copolymers thereof. 14. The composition of claim 11 wherein the polyether ester is selected from the group consisting of oligo (p-dioxanone) and copolymers thereof. 15. The composition of claim 1, wherein the polymer comprises at least two adaptive segments, and the segments are attached via a bond that is cleavable by stimuli selected from the group consisting of ultrasound, electric field, magnetic field, and radiation. The composition of claim 1, wherein the polymer comprises at least one stable segment and two adaptive segments, and wherein the ratio between the weight of the stable segment to the first adaptive segment with the second adaptive segment is between about 5: 95 to 95: 5. 17. A composition according to claim 1 comprising a thermoset polymer having at least two covalently crosslinked crystallizable soft segments, characterized in that the first soft segment has a Tt _wounds between 250 ° C and -40 ° C; and the second adaptable segment attached to the first adaptive segment has a T _tr ans at least 10 ° C lower than the Ttrans of the first adaptive segment. The composition of claim 17, wherein the first adaptable segment has a Ttrans of between 200 ° C and 0 ° C. The composition of claim 17, wherein at least one of the stable and adaptable segments comprises a cross-linkable group and further comprises at least one of the stable and adaptable segments, which is bound by forming an interpenetrated grid or a semi-interpenetrated grid. - 40 · <♦ · • · 4 20. The composition of claim 17 wherein the stable and conformable segments form a mixed interpenetrated grid. 21. The composition of claim 17, wherein the stable and conformable segments form a shape memory semi-IPM consisting of a thermoset polymer having at least one conformable segment and a homo- or copolymer. 22. The composition of claim 21, wherein the resulting semi-IPN has a highest Ttrans in the range between 200 ° C and -40 ° C. 23. The composition of claim 21 wherein the thermoset polymer is degradable. 24. The composition of claim 21 wherein the homo- or copolymer is degradable. 25. The composition of claim 21 having a multiple shape memory wherein the number of shapes in the memory is equal to the number of polymer thermal transitions. 26. The composition of claim 1, comprising a shape memory IPN comprising interpenetrated crosslinking of thermoset polymers. 27. The composition of claim 1 comprising a shape memory mixed IPN consisting of a thermoplastic elastomer comprising at least one stable segment and at least one conformable segment and a thermoset comprising at least one conformable segment. 28. A shape memory polymer composition comprising: (a) at least one stable segment having a T _tra ns between -30 ° C and 270 ° C; (b) at least one adaptable segment having a T _tra ns of at least 10 ° C lower than that of the stable segment (s) and which is bound to at least one stable segment, wherein at least one of the stable or adaptable segments comprises a functional group that is capable of forming a crosslink which can be cleaved by stimuli selected from the group consisting of radiation, electric field, magnetic field and ultrasound. A shape memory polymer blend, characterized in that at least one of the stable or adaptable segments undergoes transitions between two solid states and / or interactions related to flfl. - 41 polyelectrolytic segments or supramolecular influences based on bonds of highly organized hydrogen bridges. 30. The composition of claim 29, wherein the polycationic metal salt binds at least two segments in which the formed bond can be cleaved by an aqueous solvent. 31. A method of shaping shape memory articles with two or more shapes in memory, comprising: (a) preparing a shape memory polymer blend consisting of: (i) at least one stable segment having a T _tr ans of between -30 ° C and 270 ° C; (ii) a first adaptable segment having a T _tra ns at least 10 ° C lower than the Ttrans of the stable segment (s) and which is bound to at least one stable segment, iii) a second adaptable segment bound to at least one stable segment and a first adaptable segment having a Tt _wound with at least 10 ° C lower than a Tt _wound from the first adaptable segment; b) heating the mixture over Tt _wounds with a stable segment; c) shaping the mixture into a desired first shape; d) cooling the mixture to a temperature below the Tt _wound from the stable segment and above the Tt _{rans of the} first adaptive segment to cure the stable segment while maintaining the first and second adaptive segments in a molten or amorphous state; e) shaping the mixtures into a desired second shape; f) shaping the mixtures into a desired third shape; and g) cooling the mixture below the T _{rans of the} second adaptive segment to fix the second shape. 32. The method of claim 31, wherein the mixture is extruded or injection molded. 33. The method of claim 32, further comprising heating the mixture over the Ttrans of the second adaptive segment to return the mixture to the second shape. 34. The method of claim 33, further comprising heating the mixtures above the Tn ns of the first adaptive segment to return the mixture to the first. - 42 ♦ 4 44 shape. 35. The method of claim 34, further comprising heating the mixture above the stable segment to lose memory of the first and second shapes. 36. A method of forming a shape memory composition comprising: (a) preparing a polymer blend containing: (i) at least one stable segment having a T _trans between -30 ° C and 270 ° C; (ii) at least one adaptable segment having a Tt _{rans of} at least 10 ° C lower than the T _tr ans of the stable segment (s) which is bound to at least one stable segment, wherein at least one of the stable or adaptable segments comprises a functional group capable of forming a crosslinking which can be cleaved using stimuli selected from the group consisting of radiation, electric field, magnetic field and ultrasound; b) heating the mixture above the T _tra ns of the stable segment; c) shaping the mixture into a desired first shape; d) cooling the mixture to a temperature below the Tt _wound from the stable segment and above the T _tra ns of the adaptive segment; e) shaping the mixture into a desired second shape; and f) fixing the second shape by binding the adaptive segments. 37. The method of claim 36, further comprising: g) forming the mixture into a third shape and cooling under a Tt _wound with an adaptive segment. 38. The method of claim 37, further comprising returning the mixture to a second shape by heating over a Tt _wound from the adaptive segment, but lower than the Tn ns of the stable segment. 39. The method of claim 38 further comprising returning the mixture to the first shape using stimuli selected from the group consisting of radiation, electric field, magnetic field, and ultrasound. A composition according to any one of claims 1, 28 or 29, comprising blends of polymers.