Porous material

Abstract

The present invention provides porous material comprising or consisting of a least one polyester wherein the pores are filled with either air or a solvent, such as a carbonate solvent or water and a process for the preparation thereof.

Description

[0001] Porous Material

[0002] Field of the Invention

[0003] The present invention relates to the field concerning porous polyester materials, and the method of producing the same. The present invention also includes a porous polyester material wherein the pores are filled with an aqueous solution, such as water.

[0004] Background

[0005] Materials based on polyesters, such as polycaprolactone (PCL), are desirable in a range of applications due to the biodegradability and biocompatibility of the polymer. Polyester materials are able to biodegrade through hydrolysis of the ester moieties within the polymer backbone to form benign substances, such as water, carbon dioxide and biomass.

[0006] Porous materials are commonly prepared using solid porogens. A typical method for the preparation of a porous polymeric material involves a solvent casting and particulate leaching (SCPL) technique, wherein the polymer is dissolved in a suitable solvent and solid porogen particles (e.g. salts) are added to the solution. The solvent can be evaporated to produce a composite polymeric material and the solid porogen must be subsequently be dissolved from the composite polymeric material to leave a porous material.

[0007] The use of a solid porogen to prepare a porous polyester material using a SCPL technique is not new. US2017225405, for example, describes the preparation of a porous poly(lactide-co- glycolide) using N-methyl-2-pyrollidone (NMP) solvent and sugar as a porogen, wherein the sugar was leached from the solid composite material through dissolution in water over the course of two days.

[0008] Typically, when the porogen is notin the same phase as the host substrate, the pores which are formed lack uniformity (e.g. due to clumping of the porogen). Additionally, it is often difficult to control the dissolution of the solid porogen to enable the formation of the porous material, and this often must occur over extended periods of time (depending, for example on the size and solubility of the porogen). This also increases the risk of residual solid porogen remaining in the composite material, which is undesirable.

[0009] In view of the above, it would be an advantage to provide a bulk porous polyester material which was readily biodegradable. It would also be an advantage to provide a bulk porous polyester material with increased pore uniformity. It would be a further advantage to provide a bulk porous polyester material which is substantially free of residual solid porogen materials. It would be a further advantage to provide a bulk porous polyester material which was an "open cell” material having pores in fluid communication through the material (e.g. to allow access for solvents). It would be a further advantage to provide a facile method for generating porous polyester materials as described herein. Further advantages of the present disclosure will be evident from the following description and examples.

[0010] Moreover, the present inventors have found that the porogen solvent can be evaporated to remove any residual solvent, or displaced with an aqueous solvent such as water. The present inventors have provided a means to prepare a porous polycaprolactone material wherein the pores are filled with water, which is surprising due to the known hydrophobicity of this polymer. The present invention therefore provides a porous material comprising at least one polyester wherein the pores are filled with an aqueous fluid (e.g. water). Summary of the Invention

[0011] Viewed from one aspect, the present invention provides a method of producing a porous material comprising:

[0012] (i) Forming a homogenous solution of a) at least one polyester polymer and b) at least one solvent, by heating to a temperature above the melting point of component a); and

[0013] (ii) Cooling said homogenous solution of step (i) to a temperature at which the polymer solidifies, forming the porous material; wherein component b) has a melting point less than 60 °C and a boiling point higher than 80 °C.

[0014] In an important embodiment, the present invention provides a method of producing a porous material as defined herein wherein step (ii) comprises:

[0015] (ii-a) Cooling said homogenous solution of step (i) to form micro-scale phase separation between polymer component a) and solvent component b); and

[0016] (ii-b) Cooling further to a temperature at which the polymer component a) solidifies, forming the porous material.

[0017] In a further important embodiment, the present invention provides a method of producing a porous material as defined herein additionally comprising the step:

[0018] (iii) Closing the pores at the surface of the porous material.

[0019] In yet a further important embodiment, the present invention provides a method of producing a porous material as defined herein additionally comprising the steps:

[0020] (iv) Contacting the porous material with an aqueous solvent; and / or optionally

[0021] (v) Isolating and drying the porous material of step (iv).

[0022] Viewed from another aspect, the present invention provides a porous material comprising or consisting of a polyester, further comprising pores filled with air, wherein the polyester is polycaprolactone, the average pore size is 1 nm to 5 pm, such as 100 nm to 1 pm, the density of the porous material is less than 1.5 g cm3, such as 0.2 to 1.0 g cm3, such as 0.4 to 0.8 g cm3and optionally the porous material has been surface-treated so the pores at the surface are closed.

[0023] Viewed from a further aspect, the present invention provides a porous material comprising or consisting of a polyester, further comprising pores filled with a solvent, wherein the solvent comprises or consists of water and / or at least one carbonate solvent

[0024] Viewed from yet a further aspect, the present invention provides a porous material which is formed or formable by following any method defined herein.

[0025] Viewed from an alternative aspect, the present invention provides the use of a solvent, preferably a carbonate solvent, to produce a porous material in the absence of a solid porogen, wherein the porous material comprises at least one polyester polymer.

[0026] Viewed from a further aspect, the present invention provides a porous material as defined herein for the use in biotechnology and / or pharmaceutical fields. Brief Description of the Figures

[0027] Figure 1 shows a DSC trace from an upward temperature sweep on a sample with a 29.4 wt% concentration of b) (here propylene carbonate (PC])) where straight line extrapolations determine the onset and endset temperatures, which are 33.5 °C and 47.6 °C respectively.

[0028] Figure 2 shows the relationship between the onset (i.e. melt) temperature and the concentration of b).

[0029] Figure 3 shows a representative sample of the porous material in the form of a solid rod of PCL with a diameter of ca. 3 mm, a length of ca. 10 mm, and a weight ca. 80 mg. This sample was prepared by injecting a PCL / PC blend in the molten state into silicone tubing followed by cooling to room temperature.

[0030] Figures 4a-d show relative weight evolution with time for solid PCL / PC blends prepared as rods in line with Figure 3 and immersed in excess water (0-9810 minutes) then allowed to dry in air (9810-20145 minutes), immersed again in water (20145-21330 min), dried again (21330- 21690 min), immersed in propylene carbonate (21690-40050 mins) and finally drying in air (40050 mins onwards). The following concentrations of PC are used: 8.3 wt% (Figure 4a), 17 wt% (Figure 4b), 33 wt% (Figure 4c) and 50 wt% (Figure 4d). Each line represents a replicate.

[0031] Figure 5 shows relative weight evolution with time for a solid cube of PCL / PC comprising 33 wt% PCL and 67 wt% PC with dimensions of ca. 11.5 mm x 11 mm x 7 mm and a weight of ca. 0.9 g with the following regime: contact with water (0-8280 mins), drying in air (8280- 18360mins), contact with water again (18360-19710 mins), drying in air again (19710- 21195mins), immersion in propylene carbonate (21195-28590mins), contact with water again (28590-41430 mins) and finally drying in air again (41430 mins onwards).

[0032] Figure 6 shows a DSC trace from a sample formed with 50 wt% concentration of b) (here PC) but subsequently contacted with water to exchange water for the PC. The onset temperature is calculated from straight line extrapolation, and is determined to be 50 °C. There is a second endothermic peak with an onset temperature of 0 °C which corresponds to water. The area under the curve is proportional to the measured energy in melting process and can be used to determine the amount of water in each of the samples. The onset temperature of 50°C suggests that some softener (e.g. PC) remains in the matrix. This is probably around 5%.

[0033] Figure 7 shows a graphical representation of the amount of water from the DSC trace compared to the expected amount of water assuming full replacement of PC solvent with water.

[0034] Figures 8 shows nine scanning electron microscopy (SEM) micrographs labelled a-i, wherein a- c represent sample with PCL / PC concentration of 100 / 0; Figures d-f represent sample with PCL / PC concentration of 67 / 33; and Figures g-i represent sample with PCL / PC concentration of 50 / 50. Images a, d and g have a magnification of lOOx; images b, e and h have a magnification of 50 Ox; and images c, f and i have a magnification of 2500 Ox.

[0035] Figures 9a-b shows the degradation of PCL rods (3 mm diameter) prepared from a PCL / PC mixture of wt ratio 50 / 50 in different media wherein the weight, normalised against the same material held in water and against pure PCL rod under corresponding conditions is calculated at different times.

[0036] Figure 10 shows: a) an image of the rods after 1380 minutes for PCL / PC mixtures of 100 / 0 and 50 / 50 for exposure to NaOH (20 wt%) and b) Graph of weights is shown over time for this degradation. Weights in NaOH are normalised against the same material held in water. Detailed Description of the Invention

[0037] Preparation of Porous Material

[0038] Viewed from one aspect, the present invention refers to a method of producing a porous material, comprising:

[0039] (i) Forming a homogenous solution of a] at least one polyester polymer and b) at least one solvent, by heating to a temperature above the melting point of component a); and

[0040] (ii) Cooling said homogenous solution of step (i) to a temperature at which the polymer solidifies, forming the porous material; wherein component b) has a melting point less than 60 °C and a boiling point higher than 80 °C.

[0041] The term "porous” refers to the presence of a plurality of pores or holes present within the structure of a material. The porous material will have a porosity value which is larger than 0. In a preferred embodiment, the porous material will have a porosity value in the range of 0.3 to 0.8, especially in the range of 0.4 to 0.5. The porosity value refers to a measurement between the volume of voids over the total volume of the material.

[0042] The term "homogenous solution” refers to an even and consistent liquid mixture. Both components a) and b) will be in the liquid phase when the homogenous solution is formed. The term "homogenous” covers liquids which are completely miscible, but also covers immiscible liquid solutions, such as emulsions.

[0043] The porous material is preferably in the solid phase. The term "solid” refers to a material which is firm and stable in shape and is not fluid at room temperature (e.g. 25 °C). Materials which are mouldable fall under the definition of solid, however they should be capable of maintaining their shape ata certain temperature, such as room temperature (e.g.25 °C). The term "solid" does not refer to liquids or fluids which take the shape of a container.

[0044] Component a) (i.e. the polyester polymer as described herein) refers to any polymer which comprises at least one ester repeating unit (formed or formable from at least one suitable monomer). In certain cases, the term polymer also covers oligomers. Herein the term oligomer refers to a compound which comprise between 10 to 50 repeat units. The description of component a) below is appropriate for all aspects and embodiments of the invention including the methods, products and uses described herein.

[0045] In a preferred embodiment, component a) will have a number-average molecular weight (Mn) of at least 2000 gmol1. In an especially preferred embodiment, component a) will have a Mn between 5000 and 250,000 g mol1, such as 10,000 to 100,000 g mol1or 15,000 to 50,000 g mob i

[0046] In certain embodiments, component a) is bio-derived and is prepared from a renewable starting feedstock such as an extract from a previously living material (e.g. plant waste, algae, bacterium or bio-gases). In an alternative embodiment, component a) may be synthesised from a nonrenewable starting feedstock, such as petroleum.

[0047] In certain embodiments, component a) is biodegradable or compostable. Herein, the terms "biodegradable” and "compostable” can be used interchangeably and they refer to the ability of a polymer to broken down by bacterial decomposition into simple substances such as gases, biomass and water. Biodegradable polymers cover polymers which are able to decompose in ambient and / or controlled conditions with respect to the temperature, pressure and humidity. The structure of component a) is not particularly limited. Component a) can comprise repeating units formed or formable from acyclic and / or cyclic monomers. It is preferred if component a) comprises repeating units formed or formable from at least one of the following cyclic ester monomer units: c-caprolactone, lactide (rac-lactide, L-lactide, D-lactide or mixtures thereof), glycolide, p-propriolactone, p-butyrolactone, 6-valerolactone, co-pentadecalactone, or mixtures thereof. The polymer may thus comprise the corresponding repeating units: lactate, glycolate, p-propriolactate and so forth. In an alternative embodiment, component a) may comprise at least one of the following repeating units: ethylene terephthalate, propylene terephthalate, butylene terephthalate, hexamethylene terephthalate. Such repeating units are evidently formed or formable from monomers such as terephthalic acid or dimethyl terephthalate with a glycol such as ethylene glycol or propylene glycol. In certain embodiments, it is preferred that component a) comprises at least one aromatic group per repeat unit.

[0048] In certain aspects, component a) may be a homopolymer (such as polycaprolactone). In an alternative aspect component a) may be a copolymer (such as polyethylene terephthalate). Suitable copolymers may have the same repeating unit or may comprise more than one repeating unit Copolymers will comprise at least one ester repeating unit.

[0049] In certain embodiments, component a) is a copolymer which is formed or formable from at least one monomer comprising functional groups which are not, or not solely ester, alcohol and / or carboxylic acid, such as any of the following monomer functional groups: alpha-olefin monomers, acrylate monomers, siloxane monomers, ether monomers, polyfunctional epoxide monomers, triethyl urea, 2,3-butanedione monoxide, CO2as or mixtures thereof.

[0050] In a preferred embodiment, component a) comprises polycaprolactone (PCL) in at least 50 wt%, such as between 50 wt% and 100 wt% (e.g. 75 to 95 wt%) of the total weight of component a). In an especially preferred embodiment, component a) will consist essentially of or consist of polycaprolactone (PCL homopolymer or essentially a PCL homopolymer).

[0051] Polycaprolactone, as referred to herein may be a polycaprolactone (PCL). Alternatively, polycaprolactone may be a copolymer of caprolactone with any other suitable monomer.

[0052] Suitable polymers for component a) include homopolymers and copolymers. Both may be formed or formable from caprolactone monomers. In particular, in one embodiment, the polymer component a) may comprise, comprise essentially of or consist of at least one polycaprolactone homopolymer. In another embodiment, component a) may comprise, comprise essentially of or consist of at least one polycaprolactone copolymer. Such a copolymer will generally be with another polyester material and / or be formed or formable from another ester or alcohol-functionalised organic acid. Suitable alcohol-functionalised organic acids which may form suitable comonomers include lactic acid and / or glycolic acid, or any acid of formula (II) below. Wherein each of R5 and R6 is independently selected from H; CH3; C2 to C8 branched or straight chain alkyl or alkenyl groups; and m is 1 to 8, preferably 1 to 5 lactic acid (m=l, R5=H, R6= CH3); and glycolic acid (m=l, R5=H, R6=H) are preferred examples.

[0053] Where a caprolactone copolymer is used, preferably at least 50% (e.g. 50 to 90% or 50 to 95%) by weight of the monomer will be caprolactone with the remainder being one or more other monomers of formula II. Preferably, the caprolactone content will be at least 60% or at least 75%, preferably at least 85%. Correspondingly, the non-caprolactone monomer of formula II may be present in around 2 to 50% by weight, preferably 4 to 30% or 5 to 20% by weight of the polymer.

[0054] A preferred homopolymer is caprolactone homopolymer. In one embodiment, component a) may comprise, consist essentially of or consist of at least one caprolactone homopolymer.

[0055] A preferred copolymer is a copolymer of caprolactone and lactide ( e.g. 60 to 95% caprolactone and 5 to 40% lactide by weight). In one embodiment, component a) may comprise, consist essentially of or consist of at one least copolymer of caprolactone and lactide.

[0056] The polyester homopolymer or copolymer for use as component a) in all aspect of the invention may have any suitable molecular weight Typical number average molecular weights may be 3,000 to 200,000, preferably 10,000 to 120,000 or 20,000 to 100,000. In one embodiment, a polymer of MW around 40,000 to 80,000 is used.

[0057] In an alternative embodiment, component a) comprises repeating units formed or formable from at least two different cyclic ester monomers. In an especially preferred embodiment component a) will be a copolymer formed or formable from lactide, caprolactone and / or glycolide. Component a) may thus comprise (-O-C5H10-CO-) repeating units, (-O-CHMe-CO-) repeating units and / or (-O-CH2-CO-) repeating units and may be a homopolymer of any such units or a copolymer of any combination of such units.

[0058] In a preferred embodiment, melting point of component a) is more than 30 °C, preferably more than 35 °C, such as in the range of 37 to 60 °C. In an alternative embodiment, the melting point of componenta) is atleast50 °C, preferably at least 60 °C, such as 50 to 100 °C or 60 to 80 °C.

[0059] It is especially preferred if component a) is hydrophobic. The term "hydrophobic” herein refers to materials which repel and / or expel water at temperatures between room temperature (e.g. 25 °C) and 100 °C and / or at ambient pressure. Such repulsion may be demonstrated, for example, by a water contact angle larger than 75° or 90° (e.g. 90 to 160°, preferably 110 to 145°) at a suitable temperature (e.g. 25°C) and ambient pressure.

[0060] In certain embodiments, component a) will comprise an additional compound selected from any of the following: an active agent (e.g. pharmaceutically active agent), a plasticiser, a flame retardant, a stabiliser, a slip agent, a curing agent, a biocide, a colourant, a pigment, a flavour, a filler or a mixture thereof.

[0061] The amount of component a) used in step (i) is not particularly limited. Component a) will typically be present in the range of 50 mg to 5 g, such as 60 to 100 mg. In an alternative embodiment, the method can be conducted on a much larger scale, wherein for example 5 g to 1 kg of component a) is used, such as 250 to 750 g. In a further embodiment, the method can be conducted on an industrial scale, using kilograms or tonnes of component a).

[0062] Component b] is not limited to a specific type of solvent. The description of component b] below is appropriate for all aspects and embodiments of the invention including the methods, products and uses described herein.

[0063] In a preferred embodiment, component b] comprises or consists of a green solvent. The term “green solvent” may include, for example oxygen-containing organic solvents. Typically “green solvents” will be non-halogenated solvents (e.g. will not contain chlorine and / or fluorine]. Examples of green solvents are not limited to, but include the following: carbonates (e.g. propylene carbonate, dimethyl carbonate, ethylene carbonate, glyceryl carbonate]; esters (e.g. methyl acetate, ethylene acetate, glycerol triacetate, ethyl lactate, dimethyl glutarate, valerolactone]; ethers (e.g. ethylene glycol methyl ether, 1,3- dioxoloane, cyclopentyl methyl ether, 2 -methyltetrahydrofuran, 2,5-dimethylfuran, 1,2,3-trimethoxypropane]; alcohols (e.g. ethanol, butanol, 2-methylbutan-2-ol, glycerol, ethylene glycol, polyethylene glycol]; limonene, benzotrifluoride, pentafluorobutane, dimethylsulfoxide; hexamethyl disiloxane; or mixtures thereof. In a preferred embodiment, component b] will comprise at least 50 wt% green solvents, such as atleast 75 wt%, especially at least 90 wt%. Componentb] preferably comprises 50 to 100 wt% of green solvent, such as 75 to 90 wt%.

[0064] In certain cases, component b] will be bio-compatible. In a preferred embodiment, component b] will be free of any of the following solvents: tetrahydrofuran (THF]; dimethyl sulfoxide (DMSO]; methyl chloride, ethyl acetate, chloroform, n-heptane, n-hexane, n-pentane, dioxane, benzene, xylene, naphthalene, dimethylformamide, acetic acid, acetone and mixtures thereof.

[0065] In a preferred embodiment, componentb] will be free of alcohol and / or water. In one embodiment, component b] will be free of the solvents of the previous paragraph and also free of alcohol and / or water.

[0066] In a preferred embodiment, componentb] will be monophasic. It is thus preferred that component b] is not a biphasic solution. Preferably component b] will be a single phase at the temperature above the melting point of component a] (as described herein]. Preferably components a] and b] will form a single phase during step (i). Preferably, components a] and b] will form a single phase at the temperature above the melting point of component a] (as described herein].

[0067] In one embodiment, component b] will remain as a single liquid phase during cooling step (ii]. In a related embodiment, component b] may remain as a single liquid phase during all steps of the present invention. Polymer component a] may form a separate phase from solvent step b] during cooling step (ii] but the solvent component b] will preferably remain in a single liquid phase. For example, solvent componentb] maybe a single-phase liquid at all points over the temperature range 0°C to 200°C (or 0°C to the boiling point of the solvent, if that is lower than 200°C], This may apply even if polymer component a] forms a separate phase on cooling.

[0068] In one embodiment, solvent component b] will not be in the form of an emulsion or bi- or multi- phasic mixture during step i]. In another embodiment, solvent component b] will not be in the form of an emulsion or bi- or multi-phasic mixture during step (ii]. Preferably, solvent component b] will not be in the form of an emulsion or bi- or multi-phasic mixture during either of steps (i] or (ii]. More preferably solvent component b] will not be in the form of an emulsion or bi- or multi-phasic mixture at any point in the method of the invention. For example, solvent component b] will not be in the form of an emulsion or bi- or multi-phasic mixture at any point over the temperature range 0°C to 200°C (or 0°C to the boiling point of the solvent, if that is lower than 200°C).

[0069] In a further embodiment, all solvents forming greater than 5% (e.g. 5 to 100%) by weight of component b) will each individually be solvents for component a) at the temperature of step (i). This is preferably true of all solvents forming 1% or more of component b).

[0070] In a preferred embodiment component b) will comprise or consist of carbonate solvent, preferably at least one of propylene carbonate, dimethyl carbonate or ethylene carbonate, especially propylene carbonate. In a preferred embodiment, component b) will comprise at least 50 wt% of carbonate solvent, such as at least 75 wt%, especially at least 90 wt%. Component b) preferably comprises 50 to 100 wt% of carbonate solvent, such as 75 to 90 wt% of carbonate solvent In an especially preferred embodiment, component b) will consist of propylene carbonate.

[0071] In a preferred embodiment, component b) will have a boiling point higher than 80 °C, such as 81 to 270 °C. In an especially preferred embodiment, component b) will have a boiling point higher than 100 °C, such as 150 to 250 °C.

[0072] In a preferred embodiment, component b) will have a melting point less than 40 °C, such as -100 to 39 °C. It is especially preferred if component b) has a melting point in the range of -80 to 10 °C, such as - 50 to 0 °C.

[0073] In a preferred embodiment, componentb) will have a density which is greater than 1.00 g cm-3, such as 1.15 to 1.45 g cm3.

[0074] In a preferable embodiment, step (i) will comprise heating components a) and components b) together at a temperature above 50 °C, such as between 55 to 250 °C (especially 80 to 180 °C) to form a homogenous solution.

[0075] In a certain embodiment, the homogenous solution of step (i) may be moulded into a specific shape e.g. by transferring the homogenous solution to a mould or container.

[0076] In a preferred embodiment, the ratio of component a) to b) in step (i) of the method of producing the porous material will be between 9:1 and 1:9, preferably between 5:1 and 1:1 (w / w).

[0077] In certain embodiments, componentb) will make up more than 30 wt% of the total weight of the homogenous solution of step (i), such as between 35 to 90 wt%, preferably 40 to 75 wt%. In an alternative embodiment, componentb) will be present in less than 50 wt% of the total weight of the homogenous solution of step (i), such as between 5 and 45, especially between 10 to 35 wt% or 15 to 30 wt%.

[0078] Without being bound by theory, for cases wherein the solvent concentration is low (e.g. less than 50 wt%) the resulting porous material may form a solid molecular mixture of components a) and b).

[0079] The method of cooling the homogenous solution in step (ii) is not particularly limited, but refers to a change in temperature from a higher value to a lower value to form a solid material. In a typical embodiment, step (ii) comprises cooling the solution to a final temperature between 0 to 40 °C, such as to room temperature or to 18 to 25 °C.

[0080] In a preferable embodiment, step (ii) can be divided into the following two sub-steps: (ii-a) Cooling said homogenous solution of step (i) to form a micro-scale phase separation between polymer component a] and solvent component b); and

[0081] (ii-b) Cooling further to a temperature at which the polymer component a) solidifies to form the porous material.

[0082] The term "micro-phase separation” refers to a mixture forming wherein there is separation between component a) and component b). The micro-phase separation typically reflects the phase separation between solid and liquid phases or phase separation between two different liquid phases. Micro-phase separation will typically be first observed at temperatures which are higher than 40 °C, such as between 40 and 80 °C. Micro-phase separation between solid and liquid phases may also be observed at temperatures which are lower than 40 °C, such as between 0 and 40 °C.

[0083] Without being bound by theory, micro-phase separation may typically be observed for homogenous solutions which comprise more than 30 wt% of component b), such as between 35 to 90 wt%, such as 40 to 75 wt%. Different combinations of components a) and b) may result in micro-phase separation at different temperatures. Such micro phase separation (i.e. the transition from a homogeneous mixture to a mixture in which microscopic domains of solvent are separated from domains containing polymer) is believed to be a useful step in generating a porous material, irrespective of the temperature at which is occurs. This is believed to be due to the phase separation acting as a fluid "porogen” within the mixture.

[0084] In a preferred embodiment the porous material formed in step (ii) is isolated, such as isolation by filtration from any liquid which may be present. In a further preferred embodiment, the porous material may be isolated and dried, such as through the evaporation of any remaining liquid, optionally at a reduced pressure.

[0085] The present inventors have surprisingly found that an appropriately chosen solvent, specifically a carbonate solvent, can be used as a combined solvent and porogen to prepare a porous polyester substrate. The prior art, for example KR20150119527, reports the use of a solventas a porogen for the preparation of porous polyester microparticles using an electrospraying technique. Herein the application of a voltage is required to generate the porous particles of poly(lactide-co-glycolide) from a dimethylsulfoxide (DMSO) solution. This method is limited by the concentration of the polymer, and requires electricity of a specific voltage to allow adequate pore formation. The inherent nature of an electrospray method also means that this can also only generate microscopic particles (e.g. 50 pm in largest dimension or smaller). Porous particles cannot readily be formed into larger porous material by methods such as injection moulding because the porous nature will be affected [e.g. the "open cell” nature will exist only within each particle) . The present inventors report an advantageous method for the generation of porous polyester materials using benign conditions based on phase transitions of the polymer and the solvent. The method reported herein is simple, and does not require electricity. The method is also not particularly limited by the concentration of the polymer for the preparation of a porous material and can be used to generate articles of any chosen size (e.g. by moulding and / or machining). Therefore, In a preferred embodiment, the method of preparing a porous material as defined herein does not involve the use of electricity or the application of a voltage.

[0086] One advantage of the materials of the present invention is that they may be porous but may also be made to any chosen size or shape by moulding the homogeneous mixture prior to cooling (e.g. before step ii) or before step ii-b as appropriate). The material may also be shaped by any suitable subtractive manufacturing method, such as cutting and / or machining. Previously known methods for forming porous polyester materials may use techniques such as electrospraying, which results in particles of a maximum of a few micrometers in largest dimension. It is assumed that the solvent is substantially lost in the electrospraying process or from the surface of the very small particles and thus this previously disclosed material cannot readily be melted for forming into larger pieces (e.g. by injection moulding) because this would risk collapse of the pores in the material.

[0087] In one embodiment, applicable to all aspects of the present invention, the material of the invention (and the materials formed by the methods of the invention as appropriate) may have a largest dimension of at least 100pm (e.g. 100pm to 1000m). In a further embodiment, the smallest dimension may be at least 50pm (e.g. 50pm to Im, preferably 100pm to 1 cm). Such materials cannot be made by known methods and would be structurally distinct from aggregates of sprayed particles since the pores within such aggregates will be limited to the individual particles from which it was created and will not be continuous through the structure.

[0088] In one embodiment, the materials of the present invention (and those formed by the methods described herein) have an "open” structure in which the pores are in fluid communication throughout the structure. This provides advantages for the materials, as discussed herein, and in particular allows for fluids to penetrate into and even through the material and to be exchanged with other fluids as necessary. The structure of an "open cell foam” porous material, which can be provided by the methods of the present invention and correspondingly embodied by the products, allows for such fluid communication and / or transfer within and / or through the materials.

[0089] In a certain embodiment, the method may comprise an additional step:

[0090] (iii) Closing the pores at the surface of the porous material.

[0091] Typically step (iii) refers to closing the pores at the surface of the material (i.e. on the outermost layer of the material). Step (iii) does not refer to the pores in the core of the material, which typically remains an "open foam” type material with intercommunicating pores. Step (iii) when present will typically be a physical method using techniques such as pressure or heating. Optional step (iii) is not limited to, but includes any of the following: closing the pores through contact with a mould surface, closing the pores through mechanical force (e.g.. cutting), or closing the pores through melting, such as flash heating the surface of the solid material and / or of mould containing said porous material.

[0092] Step iii) may occur at any appropriate stage in manufacture but will generally occur after step ii). Where optional step iv) is present, step iii) will generally occur after step iv). Where optional step v) is present, step iii) will generally occur after step v).

[0093] The method of producing a porous material as reported herein preferably does not include the use of a solid porogen. The term "porogen" refers to a material additive which can disperse throughout a composition and then leach out to allow the formation of pores. The present invention does not involve the use of a solid porogen, such as an inorganic porogen (e.g. SiO2, TiO2, A12O3, Fe304, CaCO3, graphene oxide, carbon nanotubes, zeolites), an organic porogen (e.g. polysaccharides, monosaccharides) a polymeric porogen (e.g. polystyrene, water-soluble polymers, polymeric microspheres) or a ceramic porogen. The present invention preferably does not involve the use of an ionic liquid or a deep eutectic solvents (DES) as a porogen. Without being bound by theory, the solvent component b) of the present invention is considered to act as a porogen by dispersing throughout the composition of component a). In one embodiment, the homogeneous solution formed in step i) of the methods of the present invention and / or the materials of the present invention will contain no more than 10 wt% (e.g. 0 to 10 wt%) of any material which is solid at room temperature, other than component a]. This will preferably be no more than 5 wt% or no more than 1 wt% and more preferably 0 to 0.5 wt%. In one embodiment, such material which is solid at room temperature may optionally exclude any of the following: an active agent, a plasticiser, a flame retardant, a stabiliser, a slip agent, a curing agent, a biocide, a colourant, a pigment, a flavour, a filler or a mixture thereof. In one embodiment, the homogeneous solution formed in step i) of the methods of the present invention and / or the materials of the present invention will contain no more than 10 wt% (e.g. 0 to 10 wt%) of any material which is solid at room temperature, other than component a] and optionally an active agent (e.g. an active pharmaceutical ingredient). This will preferably be no more than 5 wt% or no more than 1 wt% and more preferably 0 to 0.5 wt%.

[0094] In one embodiment, the homogeneous solution formed in step i) of the methods of the present invention will contain no more than 10 wt% (e.g. 0 to 10 wt%) of any material which is solid at room temperature, other than component a). This will preferably be no more than 5 wt% or no more than 1 wt% and more preferably 0 to 0.5 wt%.

[0095] In one embodiment, the homogeneous solution formed in step i) of the methods of the present invention and / or the materials of the present invention will contain no more than 10 wt% (e.g. 0 to 10 wt%) of any inorganic solid material, ionic liquid or deep eutectic solvent. This will preferably be no more than 5 wt% or no more than 1 wt% and more preferably 0 to 0.5 wt%.

[0096] In a further embodiment, the homogenous solution formed in step i) of the methods of the present invention and / or the materials of the present invention will contain no more than 10 wt% (e.g. 0 to 10 wt%) of any polysaccharide or monosaccharide solid particles. This will preferably be no more than 5 wt% or no more than 1 wt% and more preferably 0 to 0.5 wt%.

[0097] Viewed from another aspect, the present invention refers to a method of producing a porous material as defined herein, additionally comprising:

[0098] (iv) Contacting the porous material with an aqueous solvent; and / or optionally

[0099] (v) Isolating and drying the porous material of step ii) or step (iv).

[0100] The term "contacting” as used herein refers to the exposure of at least one surface of the solid porous material to the aqueous solvent, for example by submersion of the solid porous material in the aqueous solvent or application of the aqueous solvent to a top and / or bottom surface of the material. This may be floating of the material on the solvent and / or by addition of the solvent to the top surface of the material.

[0101] The aqueous solvent comprises at least 50 wt% water. In a preferable embodiment the aqueous solvent consists essentially of or consists of water. Water as used herein may refer to either deionised water and water comprising minerals. In a preferable embodiment, the water will be deionised water and will be free or substantially free of any mineral or salt (e.g. the aqueous solvent may be free or substantially free or phosphate). In certain embodiments, the aqueous solution will comprise an additional compound selected from any of the following: an active agent, a plasticiser, a flame retardant, a stabiliser, a slip agent, a curing agent, a biocide, a colourant, a pigment, a flavour, a filler or a mixture thereof.

[0102] Without being bound by theory, it is believed that the presence of component b) within the polymer matrix serves to facilitate the entry of the aqueous solvent into that material. It is observed that (in at least some cases) the porous material does not readily incorporate water once the solvent is removed, butthat component b) may be displaced by water (see Examples). In one embodiment, component b) will thus be at least partially miscible with water at a temperature at which the porous material (of any embodiment of the invention) is solid (e.g. at at least one temperature between 25 and 40’C). Partially miscible liquids herein are considered to be liquids which can mix to form a single phase at some ratio between 1:100 and 100:1 by weight, at the relevant temperature. The incorporation of water into the matrix by displacement of component b) may be used to transport water-soluble materials (e.g. catalysts, degradation agents or active agents such as APIs) into the interior of the material. The water may then be removed by drying as discussed herein, which may leave the water-soluble material (e.g. solid water soluble material) in the pores of the porous material (as described in any embodiment herein).

[0103] In a specific embodiment, the aqueous solution will comprise an additional compound as defined herein, and thus the active agent (e.g. API) can be loaded into the porous material. ‘Loaded’ as defined herein refers to the active agent (at least partially) filling the pores of the porous material in the form of an aqueous solution which can undergo subsequently drying to remove the aqueous solvent through evaporation. At least some (e.g. more than 90 %, preferably more than 99 %) of the active agent will remain on the surface or in the pores of the porous material following drying.

[0104] In a preferred embodiment, the aqueous solvent of step (iv) has a density lower than the density of component b). In an especially preferred embodiment, the density of the aqueous solution will be about 1.00 g cm3.

[0105] In certain embodiments, step (iv) will result in the displacement of remaining component b) which is present in the pores of the porous material. Even when component a) is hydrophobic, the displacement of component b) from the porous material can occur upon contact with an aqueous solution, leading to the surprising effect of the pores being (at least partially or substantially) filled with the aqueous solution.

[0106] In a certain embodiment, step (iv) of the method of producing a porous material will be conducted in ambient conditions. For example, step (iv) may be conducted at around atmospheric pressure (e.g. around 1 atm or 101325 Pa) and / or room temperature (e.g. 25 °C). Without being bound by theory, when step (iv) is conducted at atmospheric pressure, displacement of component b) from the porous material by the aqueous solvent may occur via diffusion or osmosis.

[0107] In a certain embodiment, step (iv) is carried out for at least 30 minutes, preferably at least one hour. In a preferable embodiment step (iv) is carried out between 1 and 200 hours, such as 2 to 8 hours. It is preferred is step (iv) can reach completion within 10 days, such as within 7 days. It is further preferred if step (iv) can reach completion within 24 hours. Without being bound by theory, completion of step (iv) is assessed by monitoring the mass of the porous material at room temperature. Once the mass of the material plateaus within the range of the error bars, it is assumed that step (iv) is complete.

[0108] In an alternative embodiment, step (iv) of the method for producing a porous material may be conducted under reduced and / or increased pressure. For example, in step (iv) a hydrostatic pressure gradient may be applied across the shortest dimension of the porous material with aqueous solvent positioned (at least) on the side of higher pressure.

[0109] In a certain embodiment, step (iv) is carried out for at least 3 seconds, such as 10 seconds to 30 minutes. It is preferred if step (iv) is complete within 24 hours, such as within 5 hours or within 1 to 4 hours. The properties of the porous material from any of steps (ii) to (v) are typically influenced by the end use of the material or the application thereof.

[0110] The mass of porous material from any of steps (ii) to (v) is not particularly limited. The porous material will typically be produced in an amount of 50 mg to 5 g, such as 60 to 100 mg . In an alternative embodiment, the method can be conducted on a much larger scale, wherein for example 5 g to 1 kg of porous material is produced per unit, such as 250 to 750 g. In a further embodiment, the method can be conducted on an industrial scale, using kilograms or tonnes of component a).

[0111] In one embodiment, the porous material may also be divided into smaller fragments through any appropriate processing method in the art Example methods of processing include, but are not limited to mechanical techniques such as cutting, extruding, stamping, drilling and blasting. In such an embodiment, the mass of the porous material produced may therefore be less than 100 pg, such as 10 pg to 90 pg. This may be, for example, where the porous material comprises an active agent (e.g. API). This will, however, generally be a less favoured embodiment for most other applications.

[0112] The dimensions of the porous material from any of steps (ii) to (v) are not particularly limited. In a certain embodiment, the average thickness [e.g. the smallest dimension) of the porous material is in the range of 0.1 mm to 5.0 cm, such as 1.0 mm to 5.0 mm. In an alternative embodiment, the average thickness of the porous material can be larger than 50 cm, such as 1 to 5 m. Herein the terms "thickness” and "diameter” can be used interchangeably where context allows. In a certain embodiment, the average length of the porous material is in the range of 1.0 mm to 50 cm, such as 5.0 mm to 5.0 cm. In an alternative embodiment, the average length can be larger than 100 cm, such as 1 to 10 m.

[0113] In a certain embodiment, the porous material from any of steps (ii) to (v) may be a particle on the micro-scale. For example, the average particle size of the porous material particle may be less than 900 pm, such as between 100 and 500 pm.

[0114] The shape of the porous material from any of steps (ii) to (v) is also not particularly limited. In certain embodiments, the shape of the porous material may be controlled or influenced by moulding or shaping the homogenous solution in step (i) and / or by shaping the solid material after cooling. In a typical embodiment, the porous material has a cylindrical rod shape, a film, plate or bar shape but may be any shape formable by moulding and / or physical shaping.

[0115] Product

[0116] Viewed from another aspect, the present invention covers a porous material comprising or consisting of a polyester, further comprising pores filled with a gas such as air, wherein the largest dimension is at least 100p.m.

[0117] The gas which fills the pores in the porous material is typically air, but in certain cases it may comprise or consist of any other suitable gas. Other suitable gases include, but are not limited to: inert gases (such as nitrogen, argon, helium), carbon dioxide and oxygen, as well as mixtures thereof.

[0118] In a preferred embodiment, the porous material is biodegradable and / or compostable. In a further preferred embodiment, the porous material is biocompatible and non-toxic.

[0119] The polyester may be any polyester homopolymer or copolymer as described herein (e.g. as described above and / or below).

[0120] The polyester can be any polymer which comprises at least one ester repeating unit. In certain cases, the term polyester also covers oligomers comprising less than 50 repeat units.

[0121] In a preferred embodiment, the polyester will have a number-average molecular weight (Mn) of at least 2000 g mol1. In an especially preferred embodiment, the polyester will have a Mn between 5000 and 250,000 g mol1, such as 10,000 to 100,000 g mol-'or 15,000 to 50,000 g mol- i,

[0122] In certain embodiments, the polyester is bio-derived and is prepared from a renewable starting feedstock such as plant waste, algae, bacterium or gases. In an alternative embodiment, the polyester may be synthesised from a non-renewable starting feedstock, such as petroleum.

[0123] In certain embodiments, the polyester is biodegradable or compostable.

[0124] The structure of the polyester is not particularly limited. The polyester can have any of the compositions and / or properties described herein for any embodiment, and in particular for the aspects described above in relation to component a).

[0125] In certain embodiments, the porous material will comprise an additional compound selected from any of the following: an active agent, a plasticiser, a flame retardant, a stabiliser, a slip agent, a curing agent, a biocide, a colourant, a pigment, a flavour, a filler or a mixture thereof.

[0126] In a preferable embodiment, the pores will not be visible by the naked eye, and will only be visualised using microscopy. The pores of the porous material typically refer to holes within the structure of the material which have an average size of 1 nm to 5 pm, such as 2.0 nm to 50 nm or 50 to 500 nm. In a preferred embodiment, the average size of the pores is 100 nm to 1 pm. In an alternative embodiment, the average size of the pores maybe less than 2.0 nm, such as 0.5 to 2.0 nm. The average size herein refers to the average diameter across the longest dimension of the pore.

[0127] In addition to the pores, the porous material may comprise larger voids of a size in the range of 1 pm to 500 pm, such as 20 to 200 pm. The larger voids and pores for a certain embodiment are illustrated in Figure 8, for example in images d and g. A porous material comprising both larger voids and pores is believed to typically form from following the method reported herein.

[0128] The shape of the pores is not particularly limited, and includes cylindrical, spherical, slit-shaped, conical, rhomboid, elliptical and square shaped pores. In a preferable embodiment, the pores will be uniformly distributed or substantially uniformly distributed across the entire structure of the porous material. In an alternative embodiment, the porous material will be a "closed surface material”. The term "closed surface material” as defined herein refers to a material wherein the pores will be uniformly distributed or substantially uniformly distributed across the internal area (i.e. core) of the material, but wherein the surface of the material is sealed and thus is non-porous.

[0129] It is generally preferred that the pores are free from any inorganic materials, such any metal salts. Examples include alkali metal or alkaline earth metal salts, such as hydroxyapatite and / or sodium chloride.

[0130] Viewed from another aspect, the present invention covers a porous material comprising or consisting of a polyester, further comprising pores filled with a solvent, wherein the solvent comprises or consists of water or at least one solvent described herein for component b) (particularly a carbonate solvent).

[0131] The solvent which is used to fill the pores may comprise an additional solvent, such as any of the following: an aromatic solvent, an additional aqueous solvent, a hydrocarbon solvent or a mixture thereof. In a certain embodiment, the solvent may comprise a green solvent. The term "green solvent” is used as described above.

[0132] In an especially preferred embodiment, the solvent comprises or consists, especially consists of water or propylene carbonate. In a preferable embodiment the solvent consists of water.

[0133] In a preferred embodiment the solvent will comprise or consist of carbonate solvent, preferably at least one of propylene carbonate, dimethyl carbonate or ethylene carbonate, especially propylene carbonate. In a preferred embodiment, the solvent will comprise at least 50 wt% of carbonate solvent, such as at least 75 wt%, especially at least 90 wt%. The solvent preferably comprises 50 to 100 wt% of carbonate solvent, such as 75 to 90 wt% of carbonate solvent.

[0134] In a further preferred embodiment, the solvent is non-toxic to humans or aquatic life, and / or is considered to be a biocompatible solvent

[0135] In a preferable embodiment, the solvent is miscible with water at room temperature. Alternatively, the solvent is miscible with water at a temperature which is lower than the melting point of the polyester, such as lower than 100 °C, preferably lower than 80 °C. In certain embodiments the solvent is miscible with water at temperature between room temperature (e.g. 25 °C) and 60 °C.

[0136] In an alternative embodiment, the solvent will comprise an additional compound selected from any of the following: an active agent, a plasticiser, a flame retardant, a stabiliser, a slip agent, a curing agent, a biocide, a colourant, a pigment, a flavour, a filler or a mixture thereof. It is preferred if any additional component is soluble in the solvent In a preferable embodiment, the solvent will comprise an active agent which is water-soluble.

[0137] The porous material is not particularly limited in its shape or size and may be as described in any of the aspects and embodiments herein.

[0138] The dimensions of the porous material are not particularly limited and may be as described in any of the aspects or embodiments herein.

[0139] The shape of the porous material is also not particularly limited and includes any of the shapes described herein. In a typical embodiment, the porous material has a cylindrical rod shape. In certain embodiments, the porous material may comprise a coating. The coating which may be applied to the porous material is not particularly limited, but is preferably biocompatible. In a preferable embodiment, the porous material will comprise a polysaccharide coating.

[0140] In a preferable embodiment, the porous material will comprise a non-porous coating. The term "non-porous” used herein refers to having a porosity of less than 5 %, preferably 0 to 4 %. In certain embodiments, the coating will be a layer with an average thickness of 50 nm to 1 mm, such as 500 nm to 10 pm.

[0141] In a preferred embodiment, the porous material is hydrophobic (e.g. as described above).

[0142] In a preferred embodiment, the density of the porous material is less than 1.5 g cm3, preferably between 0.2 and 1.0 g cm3, such as 0.4 to 0.8 g cm3?

[0143] In a preferred embodiment, the porous material has a porosity of at least 5 %, preferably at least 10 %, especially at least 20 %. It is preferred if the porous material has a porosity in the range of 5 to 90 %, such as 10 to 75 %, especially 15 to 50 %. Herein porosity is defined as the volume percentage of pores (i.e. voids) present in the total volume of the porous material.

[0144] In a preferable embodiment, the porous material (e.g. a 3mm rod of the porous material) will be able to full decompose in acidic and / or basic solution at room temperature (e.g. 25 °C) within a period of 200 hours(e.g. 1 to 200 hours), such as 170 hours or less or 120 hours or less. In an alternative embodiment, the porous material will suffer from substantial degradation (i.e. loss of original shape and original mass) within a period of 24 hours when exposed to an acidic or basic solution.

[0145] The acidic or basic solutions may be neat solutions consisting of concentrated acid and / or base. In a preferable embodiment, the acidic or basic solutions do not refer to neat acid or base. The acidic or basic solutions preferably are aqueous solutions comprising 5 to 20 wt% of the relevant acid or base.

[0146] The acid is not particularly limited, but may be selected from any of the following: hydrochloric acid, hydrogen peroxide, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, formic acid or mixtures thereof. The pH of the acidic solution may be in the range of 0 to 6, such as 2 to 4. In a preferable embodiment, the acid is not a superacid.

[0147] The base is not particularly limited, but may be selected from any of the following: sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, ammonia or sodium carbonate. The pH of the basic solution may be in the range of 8 to 14, such as 10 to 12. In a preferable embodiment, the base is not a superbase.

[0148] Viewed from another aspect, the present invention covers a porous material which is formed of formable by any method described herein.

[0149] Use

[0150] Viewed from another aspect, the present invention provides the use of a porous material as described herein in biotechnology and pharmaceutical fields. For example, the porous material may be used for drug delivery, tissue engineering, or as a stent, graft or implant or a part thereof. In a further embodiment, the porous material of the present invention may be used to treat or prevent an illness or condition, for example by administering a specific active ingredient to a human or animal in need thereof.

[0151] Because the material of the present invention is porous, the material may encourage in-growth of cells, which may promote growth and healing. Furthermore, the porous material may be used to contain an active pharmaceutical ingredient, either in solid form or in the form of a solution in any compatible solvent (e.g. any suitable solvent or aqueous liquid described herein]. The material of the present invention may then act as a "sponge” retaining API and protecting the active agent from degradative processes in the body. The API will then be released by diffusion or dissolution into body tissues where it may have a local or systemic effect

[0152] In an alternative embodiment, the porous material of the present invention may be used as a substitute for plastic, irrespective of the application thereof. The porous material of the present invention may be used as a material in a variety of applications where enhanced degradability / compostability is an advantage. Where appropriate for the application, the material may be "closed” at the surface, as described herein.

[0153] In an alternative embodiment, the porous material of the present invention may be used or implemented in packaging means. The type and nature of packaging for which the porous material can be used is not particularly limited, and may include food packaging.

[0154] In many uses, particularly for consumer products and packaging, it is an advantage to have more rapid degradation. The porous nature of the various embodiments of the present invention is believed to allow for more rapid degradation by chemical and / or biological means, both in recycling or waste facilities and in the environment. Some such degradation mechanisms are illustrated herein but others will be evident to the skilled worker since degradation typically occurs at the surface and the materials of the present invention typically have enhanced surface area and fluid access to the interior of the material.

[0155] In yet a further alternative embodiment, the porous material of the present invention may be used in industry, for example as a catalyst support, an adsorbent or as a filtration membrane.

[0156] In yet a further alternative embodiment, the porous material of the present invention may be used as an insulation material or in the field of thermal energy.

[0157] Viewed from another aspect, the present invention covers the use of a solvent, preferably a carbonate solvent, to produce a porous material in the absence of a solid porogen, wherein the porous material comprises at least one polyester as herein described. The use of the solvent to produce a porous material in the absence of a solid porogen covers the use of any solvent or component b) as defined herein.

[0158] As used herein, the term "about”, "around” "substantially” or "approximately” in relation to a number or a range of numbers will generally indicate that the number or range specified is preferred but that such a number may be varied to a certain extend without materially affecting the properties of the relevant material, composition, method or product. The skilled worker will typically be able to readily establish the extent by which such numbers may be varied without prejudicing the key advantages of the present invention. As a general guide, such numbers or the ends of such ranges referred to with such terms may be varied by ± 20% or ± 10%, preferably ± 5% and more preferably ±1%. A corresponding meaning may be attributed to compositions "consisting essentially of” certain components, which may include up to 20% or up to 10%, preferably up to 5% and most preferably up to 1% of other components in addition to those specified. Compositions described as comprising or consisting essentially of certain components include the compositions consisting solely of those components. All percentages herein are given by weight unless otherwise specified or unless context requires another meaning. The abbreviation “PC” as used herein refers to Propylene Carbonate, unless otherwise stated. Key Embodiments

[0159] The present invention may be illustrated by the following non-exhaustive list of embodiments, any of which may be used in any technically feasible combination:

[0160] 1) A method of producing a porous material comprising:

[0161] (i) Forming a homogenous solution of a) at least one polyester polymer and b) at least one solvent, by heating to a temperature above the melting point of component a); and

[0162] (ii) Cooling said homogenous solution of step (i) to a temperature at which the polymer solidifies, forming the porous material; wherein component b) has a melting point less than 60 °C and a boiling point higher than 80 °C.

[0163] 2) The method of embodiment 1 wherein step (ii) comprises:

[0164] (ii-a) Cooling said homogenous solution of step (i) to form micro-scale phase separation between polymer component a) and solvent component b); and

[0165] (ii-b) Cooling further to a temperature at which the polymer component a) solidifies, forming the porous material.

[0166] 3) The method of embodiment 2 wherein step (ii-a) comprises cooling to a temperature of 80 to 40 C, and step (ii-b) comprises cooling to a temperature between 0 to 40 C.

[0167] 4) The method of any of embodiments 1 to 3 wherein the content of component b) is more than 30 wt% of the homogenous solution, such as between 35 to 75 wt%.

[0168] 5) The method of any of embodiments 1 to 4 wherein the content of component b) is less than 50 wt%, such as 10 to 40 wt%.

[0169] 6) The method of any of embodiments 1 to 5 wherein step (ii) comprises cooling to a temperature of 0 to 40 C.

[0170] 7) The method of any of embodiments 1 to 6 wherein step (i) additionally comprises moulding the homogenous solution to a desired shape e.g. by transferring the homogenous solution to a mould.

[0171] 8) The method of any of embodiments 1 to 7 further comprising:

[0172] (iii) Closing the pores at the surface of the porous material.

[0173] 9) The method of embodiment 8wherein the pores can be closed through contact with a mould surface, through mechanical force (e.g. cutting), and / or through flash heating of the surface of the solid material and / or of the mould containing said porous material.

[0174] 10) The method of any of embodiments 1 to 9 wherein component a) comprises or consists of a biodegradable and / or compostable polymer.

[0175] 11) The method of any of embodiments 1 to 10 wherein component a) comprises at least one polycaprolactone homopolymer or copolymer in an amountof 50 wt% to 100 wt%, preferably wherein component a) consists of polycaprolactone homopolymer or copolymer, such as a polycaprolactone homopolymer..

[0176] 12) The method of any of embodiments 1 to 11 wherein component a) has a melting at least 35 C, preferably atleast 50 C, such as 50 to 100 C. 13) The method of any of embodiments 1 to 12 wherein component b) comprises or consists of a carbonate solvent, preferably at least one of propylene carbonate, dimethyl carbonate or ethylene carbonate, especially propylene carbonate.

[0177] 14) The method of any of embodiments 1 to 13 wherein component b) has a boiling point of 81 to 270 C, such as 150 to 250 C.

[0178] 15) The method of any of embodiments 1 to 14 wherein component b) has a melting point less than 40 C, such as -100 to 39 C or -80 to 10 C, preferably -50 to 0 C.

[0179] 16) The method of any of embodiments 1 to 15 wherein in step (i) the homogenous solution is formed by heatingto a temperature above 50 C, such as 55 to 250 C, preferably 80 to 180 C.

[0180] 17) The method of any of embodiments 1 to 16 wherein the ratio of component a) and component b) in step (i) is between 9:1 to 1:9, preferably 5:1 to 1:1 (w / w).

[0181] 18) The method of any of embodiments 1 to 17 wherein the micro-scale phase separation comprises a dispersion of droplets of component b) throughout the solution of component a).

[0182] 19) The method of any of embodiments 1 to 18 wherein the cooling of step (ii) comprises cooling the homogenous solution of (i) to room temperature.

[0183] 20) The method of any of embodiments 1 to 19 wherein a solid porogen is not used.

[0184] 21) The method of any of embodiments 1 to 20 wherein component a) is hydrophobic.

[0185] 22) The method of any of embodiments 1 to 21 wherein the porous material of step (ii) is dried through evaporation of the solvent, optionally at reduced pressure.

[0186] 23) The method of any of embodiments 1 to 22 wherein component a) comprises a polymer with a number average molecular weight of 5,000 to 500,000 g mol1.

[0187] 24) The method of any of embodiments 1 to 23 wherein component b) comprises at least one additional component, such as an active agent (e.g. API).

[0188] 25) A method of any of embodiments 1 to 24 additionally comprising:

[0189] (iv) Contacting the porous material with an aqueous solvent; and optionally

[0190] (v) Isolating and drying the porous material of step (iv).

[0191] 26) The method of embodiment 25 wherein the drying of step (v) is at room temperature and ambient pressure.

[0192] 27) The method of embodiment 25 or embodiment 26 wherein the aqueous solvent consists of water.

[0193] 28) The method of any of embodiments 25 to 1 wherein step (v) is included and is carried out at room temperature and ambient pressure.

[0194] 29) A porous material which is formed or formable by the method of any preceding embodiment.

[0195] 30) A porous material comprising or consisting of a polyester, further comprising pores filled with air, wherein the material has a largest dimension of at least 100pm. 31) A porous material comprising or consisting of a polyester, further comprising pores filled with a solvent, wherein the solvent comprises or consists of water and / or at least one carbonate solvent.

[0196] 32) The porous material of embodiment 31 wherein the solvent consists of water, wherein the water is deionised water and is free of any mineral or salt or wherein the solvent consists of propylene carbonate

[0197] 33) The porous material of any of embodiments 30 to 32 wherein the polyester consists essentially of or consists of at least one polycaprolactone homopolymer and / or polycaprolactone copolymer.

[0198] 34) The porous material of any of embodiments 30 to 33 wherein the average pore size is 10 nm to 5 pm, such as 100 nm to 1 pm.

[0199] 35) The porous material of any of embodiments 30 to 33 wherein the density of the porous material is less than 1.5 g cm3, such as 0.2 to 1.0 g cm3

[0200] 36) The porous material of any of embodiments 30 to 35 wherein the porous material has been surface treated so the pores at the surface are closed.

[0201] 37) The porous material of any of embodiments 30 to 36 wherein the porous material comprises less than 10 wt% of solid porogen, especially less than 5 wt%, such as less than 1 wt%, or between 0 and 0.5 wt%.

[0202] 38) The porous material of any of embodiments 30 to 37 which is biodegradable and / or compostable.

[0203] 39) The porous material of any of embodiments 30 to 38 which is biocompatible.

[0204] 40) The porous material of any of embodiments 30 to 39 which can fully decompose in acidic and / or basic and / or neutral aqueous solutions.

[0205] 41) The porous material of any of embodiments 30 to 40 which can fully decompose in basic solutions comprising at least one of sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, ammonia, or sodium carbonate within 1000 hours, preferably 200 hours.

[0206] 42) The porous material of any of embodiments 30 to 41 which can fully decompose in acidic solutions comprising at least one of hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid or formic acid within 2000, preferably 1000 hours.

[0207] 43) The porous material of any of embodiments 30 to 42 which is hydrophobic.

[0208] 44) The porous material of any of embodiments 30 to 43 which comprises a colourant

[0209] 45) The porous material of any of embodiments 30 to 44 which has a porosity value within the range of 5 % to 90 %.

[0210] 46) The porous material of any of embodiments 30 or to 45 which contains at least one drug or medicine, preferably wherein the drug(s) and / or medicine(s) are water-soluble.

[0211] 47) The porous material of any of embodiments 30 or 46 which further comprises a coating, such as a polysaccharide coating, wherein the coating is not porous.

[0212] 48) The porous material of embodiment 47 wherein the coating has a thickness between 50 nm and 1 mm. 49) The use of a porous material as disclosed in any of embodiments 30 to 48 in biotechnology and / or pharmaceutical fields.

[0213] 50) The use as disclosed in embodiment 49 for delivery of at least one API.

[0214] 51) The use as disclosed in embodiment 50 for sustained delivery of atleastone API.

[0215] 50) The use of a solvent, preferably a carbonate solvent, to produce a porous material in the absence of a solid porogen, wherein the porous material comprises atleastone polyester polymer.

[0216] Examples

[0217] Materials:

[0218] Polycaprolactone (PCL) used herein refers to CAPA6500 from Ingevity, UK.

[0219] Propylene carbonate (PC) used herein refers to Propylenecarbonate S (>99.7%) from BASF.

[0220] Example 1: Solvent Concentration

[0221] PCL-polymer was melted by heating (up to ca. 60 °C), and various amounts PC was mixed with the melted polymer to obtain homogeneous liquid mixtures. Up to a certain PC-content, a solid polymer blend was obtained upon cooling to room temperature and the solid material was seemingly homogeneous. At PC additions exceeding some 40 wt%, cooling of the homogeneous mixture to room temperature induced expulsion of excess liquid. The separated liquid became visible by pressing / squeezing / bending the cooled material. The separating liquid is believed to be virtually pure PC and the solid phase in equilibrium is believed to be a PCL-PC mixture hosting the remaining PC. The liquid inhomogeneities weakens the material and at very high PC-content (above ca. 55 wt%) the material appears 'wet' and is 'brittle'.

[0222] This example shows that the porous material can host large amounts of solvent and still be characterised by a liquid to solid transition when lowering the temperature to below the melting temperature of the mixture. At higher a solvent content, a separation of PC is induced by lowering the temperature. The separation may occur just at, or above, or below the liquid to solid transition temperature of the blend.

[0223] Example 2: Melting Temperature

[0224] The melting temperature of PCL / PC-blends of various compositions can be investigated with differential scanning calorimetry (DSC) and the enthalpy associated with the melting can be recorded. Here DSC measurements were performed using a DSC 1 (Mettler Toledo, Switzerland) equipped with STARe Software following the ISO standard (ISO 11357-2:1999). Temperature calibration and heat flow calibration was done using indium and an empty aluminum crucible was used as a reference. Depending on the investigated sample a DSC-scan can be composed of one single peak or be more complex. 'Onset' and 'endset' temperatures were estimated by straight line extrapolations, Figure 1. Up to a certain concentration of PC the melting temperature (i.e. 'onset' temperature) of the PCL / PC-blend decreases, and above that PC-concentration the melting temperature attains a more constant value, Figure 2.

[0225] This example shows that the PCL / PC solid phases seem to be characterised by a molecular mixture up to a certain PC-content, also in the solid phase, while at higher PC contents a phase separation is induced when the temperature is decreased. The separation into one phase virtually without PCL and one phase with PCL and the remaining PC, may be located above, at, or below the liquid to solid transition temperature of the blend. This observation seems to be in line with a phase separation upon cooling at higher PC-content in the mixtures (see Example 1).

[0226] Example 3: Weight vs. Time

[0227] Solid PCL / PC rods, 3 mm in diameter and ca. 10 mm long, were prepared with the aid of a 2 mL sized syringe. Molten PCL / PC-blends were injected into silicone tubing with an inner diameter of 3 mm and cooled to room temperature to form a solid PCL / PC rod, Figure 3.

[0228] The solid PCL / PC-rods (ca. 80 mg each) with various PCL / PC compositions were contacted with excess water and weight was followed over time, Figure. 4a to Figure 4d. All PCL / PC-blends show related weight vs. time patterns. PC is soluble in water to some 240 g / L at 20 °C (ref 1), and loss of weight of the rods upon contact with water is believed to be a result from loss of PC.

[0229] Starting at 0 minutes when the rods were immersed for the first time in excess water (40 mL) the weight decreased. This first weight decrease of the blend is always much less than expected from complete loss of PC. At 9810 minutes when the rods were removed from the aqueous environment and exposed to ambient atmosphere, there was a further decrease in weight where the rods dry in air.

[0230] At 20145 minutes the rods were again immersed in excess water (40 mL), there was virtually no changes to the weight. At 21330 minutes, the rods were removed from the aqueous environment and exposed to ambient atmosphere, there was virtually no changes to the weight. These results reflect the hydrophobic nature of the PCL with a high contact angle (i.e. greater than 110 degrees) which results in virtually no water entering the pores on reimmersion in water, and thus virtually no water being lost when dried for the second time in air.

[0231] At 21690 minutes, the rods were immersed in more PCL-compatible liquid (PC) where a sharp increase in weight was observed which plateaued close to the initial weight of the rods. At 40050 minutes, the PC soaked rods were removed from the liquid and dried in air, wherein a reduction of weight was observed due to evaporation of PC. The weight was almost identical to that before soaking the dry rods in PC at 21690 minutes.

[0232] This example shows that filling pores with water must be facilitated by first filling the pores with propylene carbonate, since water cannot directly enter air-filled pores due to the hydrophobicity of the PCL porous material.

[0233] Example 4: High Concentration of PC

[0234] PCL and PC was melted and mixed at ca. 80 °C to a homogeneous liquid mixture at a weight ratio of 33 wt% PCL and 67 wt% PC, which is a very high PC-content. A 'cube' was shaped ca. 0.9 g and ca. 11.5mm x 11mm x 7mm, and the temperature decreased to room temperature were the PCL / PC- matrix solidified. Because of the (very) high PC-content there was clear sweating of liquid when the temperature decreased, and the PCL porous material solidified, in line with Example 1.

[0235] Similar investigations to Example 3, relating to the effect of contacting the porous material with water were carried out for this sample, see Figure 5. A similar pattern was observed.

[0236] At 0 minutes, the cube was contacted with excess water (ca. 1000 times excess) and the weight decreased from the exchange of PC with water. At 8280 minutes the cube was lifted into air and dried in ambient conditions resulting in further weight loss. At 18360 minutes, the cube was contacted once more with water and virtually no change in weight is observed. A 19710 minutes, the cube was removed from the water and dried in air. Virtually no change in weight was observed.

[0237] At 21195 minutes the cube was immersed in PC which entered the pores and resulted in a sharp increase of weight. However, unlike Example 3, the weight plateaued at ca. 0.64 g and did not return to the weight value in line with the initial material. At 28590 the cube was contacted once more with water wherein the weight decreased in line with the PC being replaced by water. Finally, at 41430 minutes the cube was lifted from the water and dried in air to obtain the almost identical weight as in the previous drying cycle.

[0238] This example again demonstrates the hydrophobicity of the water as illustrated in Example 3. Furthermore, upon immersion of the porous material in PC, the weight does not fully recover and levels off ca. 0.64 g. This corresponds to a PCL / PC composition of 50 wt% PC within the porous material. At (very) high PC concentrations, the general behavior prevails, but a certain amount of the PC is lost by macroscopic separation when forming the solidified porous material in line with Example 1.

[0239] Example 5: Melting Temperature for Porous Material with Water

[0240] In line with Example 2, DSC was also used to measure melting enthalpy from water incorporated in the porous material. For the rods used in Example 3, when they were withdrawn from the water at 9810 minutes, excess water was removed by blotting the surface of the rods, and ca. 6 to 9 mg of the material was analysed using DSC.

[0241] A peak with an onset temperature of 0 °C was evident which shows that water is present inside the porous material, Figure 6. This peak was absent prior to contact with water, Figure 1. Moreover, as the peak was at 0 °C the water appears to be pure water virtually without PC-content, and thus all the PC has been exchanged with water. PC itself has a melting temperature of -48.8 °C, and if it was present the onset temperature for the solvent would be expected to be lower than 0 °C if PC was present.

[0242] From the DSC analysis, the 'experimental' mass of water can be determined (e.g. from the tabulated heat of fusion of water - 333.55 J / g). Figure 7 shows the experimental mass of water from the DSC trace compared to the possible (i.e. theoretical) amount of water assuming all PC is replaced with water when contacted with water. The difference between the experimental and theoretical values may be expected for many reasons. For example, solvent exchange may have not been fully completed; or the onset peak of 0 °C does not correspond to all the water residing in the PCL porous material. From Figure 6, the onset temperature associated with the PCL porous material is 50 °C, which when compared to Figure 2 suggests that 5 wt% of PC is retained.

[0243] Example 6: SEM Images

[0244] Scanning electron microscopy (SEM) can be used to visualize the structure of the solid PCL porous material. Three preparations varying by the initial PCL / PC ratio were investigated; 100 / 0; 67 / 33; and 50 / 50. PC was (deliberately) removed / replaced by washing with excess water (see Example 3). The water was then evaporated in ambient air at room temperature leaving the pores in the PCL porous material filled with air. Samples were cut with a scalpel to a convenient size (ca. 6 mg) and glued to SEM aluminum sample stubs using Leit-C conducting carbon cement (Agar Scientific) and sputtered with gold using an automatic sputter coater (Agar Scientific). SEM micrographs were obtained using a scanning electron microscope (Zeiss EVO LS10) equipped with a LaB6 filament. Imaging was done in high vacuum mode, Figure 8. Independently of the magnification (lOOx, 500x, and 25000x), the PCL / PC 100 / 0 (pure PCL) is virtually without interesting structure (Figure 8; a-c). Traces from the scalpel cutting can be seen, and the knife seems to have influenced the outermost macroscopic structure.

[0245] The PCL / PC 67 / 33 preparation has like the pure PCL a rather smooth surface after the cutting, but some larger voids at the lowest magnification (lOOx) (Figure 8; d). The mechanical cutting with the scalpel seems to have had an effect on the outermost surface, such that the inner structure is 'hidden' and the surface (partly) closed. This may be a method to delay / tune access to the inner regions of the porous material. At larger magnification (Figure 8; e) it is possible to look into the inside of the holes, via the larger void structures. At the highest magnification (Figure 8; f)) looking at the surfaces located inside the larger voids, a structure with pores becomes visible. Both the larger voids and the smaller pores are believed to have formed as a result from cooling / freezing the PCL / PC solution and from PC leaving the PCL porous material in the preparation step.

[0246] As compared to the other preparations the PCL / PC 50 / 50 has a clearly different structure at the lowest magnification (Figure 8; g). The larger voids are more common than in the 67 / 33 sample. The larger voids are believed to form in conjunction with a more pronounced macroscopic separation of PC. With higher magnification the surfaces of these droplets have the porous appearance as was seen also in the 67 / 33 sample (Figure 8; h-i).

[0247] This example illustrates that porous structures form from the PCL / PC mixtures upon lowering the temperature, which have both larger voids and smaller pores.

[0248] Example 7: Degradation

[0249] The degradation of the porous material was analysed by exposing rods (ca. 3 mm diameter, ca. 10 mm length, and a weight of ca. 80 mg) in various aqueous solution (10 mL).

[0250] The relative weight of the porous material was calculated by determining the value of X / Y. Herein, X refers to the value of the relative weight of the porous material (PCL / PC 50 / 50) exposed to the 'degrading' aqueous solution divided by the relative weight of the porous material exposed to pure deionized water. Herein, Y refers to the relative weight of a non-porous sample (i.e. PCL / PC 100 / 0) exposed to the 'degrading' aqueous solution divided by the relative weight of the non-porous material exposed to pure deionized water. All samples were prepared in duplicates and presented as their mean value.

[0251] Figure 9a shows the response of the porous material (X / Y) over time upon exposure in H2O2(5wt%), HCI (5 wt%) and NaOH (5 wt%). Only NaOH (5 wt%) has a clear degrading effect during the first 36000 minutes. This is visually notable wherein the rods being 'fluffy' and 'soft' on the surface.

[0252] Before the rods fully degrade, there is a temporary increase in weight which is believed to reflect the swelling of the porous material when the inner surface of the porous material has started to degrade.

[0253] Figure 9b shows the response of the porous material (X / Y) over time upon exposure in H2O2(20 wt%), HCI (20 wt%) and NaOH (20 wt%). The degradation process with NaOH (20 wt%) is further speeded up compared to the 5 wt%. With HCI (20 wt%) almost complete degradation is observed after 36000 minutes.

[0254] From Figure 10, the effect of the exposure to NaOH (20 wt%) is evident. For the porous material (PCL / PC 50 / 50) the sample has degraded into dispersed fragments, but for the non-porous material (PCL / PC 100 / 0) the rod remains intact. The graph further illustrates that the degradation of the non- porous rod is much slower than for the porous rod in NaOH (20 wt%). This example illustrates that the porous structure clearly enhances the rate of degradation when exposed to an aqueous degradation media. The contact area is thus one parameter which may influence rate of degradation, which is naturally higher for the porous material compared to the non-porous material.

Claims

Claims1) A method of producing a porous material comprising:(i) Forming a homogenous solution of a) at least one polyester polymer and b) at least one solvent, by heating to a temperature above the melting point of component a); and(ii) Cooling said homogenous solution of step (i) to a temperature at which the polymer solidifies, forming the porous material; wherein component b) has a melting point less than 60 °C and a boiling point higher than 80 °C.2) The method of claim 1 wherein step [ii] comprises:(ii-a) Cooling said homogenous solution of step (i) to form micro-scale phase separation between polymer component a] and solvent component b); and(ii-b) Cooling further to a temperature at which the polymer component a] solidifies, forming the porous material.3) The method of claim 2 wherein step [ii-a] comprises cooling to a temperature of 80 to 40 C, and step (ii-b) comprises cooling to a temperature between 0 to 40 C.4) The method of any of claims 1 to 3 wherein the content of component b) is more than 30 wt% of the homogenous solution, such as between 35 to 75 wt%.5) The method of any of claims 1 to 4 wherein the content of component b) is less than 50 wt%, such as 10 to 40 wt%.6) The method of any of claims 1 to 5 wherein step (ii) comprises cooling to a temperature of 0 to 40 C.7) The method of any of claims 1 to 6 wherein step (i) additionally comprises moulding the homogenous solution to a desired shape e.g. by transferring the homogenous solution to a mould.8) The method of any of claims 1 to 7 further comprising:(iii) Closing the pores at the surface of the porous material.9) The method of claim 8wherein the pores are closed through contact with a mould surface, through mechanical force (e.g. cutting), and / or through flash heating of the surface of the solid material and / or of the mould containing said porous material.10) The method of any of claims 1 to 9 wherein component a) comprises or consists of a biodegradable and / or compostable polymer.11) The method of any of claims 1 to 10 wherein component a) comprises at least one polycaprolactone homopolymer or copolymer in an amount of 50 wt% to 100 wt%, preferably wherein component a) consists of polycaprolactone homopolymer or copolymer, such as a polycaprolactone homopolymer..12) The method of any of claims 1 to 11 wherein component b) comprises or consists of a carbonate solvent, preferably at least one of propylene carbonate, dimethyl carbonate or ethylene carbonate, especially propylene carbonate.13) The method of any of claims 1 to 12 wherein in step (i) the homogenous solution is formed by heatingto a temperature above 50 C, such as 55 to 250 C, preferably 80 to 180 C.14) The method of any of claims 1 to 13 wherein the ratio of component a) and component b) in step (i) is between 9:1 to 1:9, preferably 5:1 to 1:1 (w / w).15) The method of any of claims 1 to 14 wherein a solid porogen is not used.16) The method of any of claims 1 to 15 wherein the porous material of step (ii) is dried through evaporation of the solvent, optionally at reduced pressure.17) The method of any of claims 1 to 16 wherein component b) comprises at least one additional component, such as an active agent (e.g. API).18) A method of any of claims 1 to 17 additionally comprising:(iv) Contacting the porous material with an aqueous solvent; and optionally(v) Isolating and drying the porous material of step (iv).19) The method of claim 18 wherein the drying of step (v) is at room temperature and ambient pressure.20) A porous material which is formed or formable by the method of any preceding claim.21) A porous material comprising or consisting of a polyester, further comprising pores filled with air, wherein the material has a largest dimension of at least 100pm.22) A porous material comprising or consisting of a polyester, further comprising pores filled with a solvent, wherein the solvent comprises or consists of water and / or at least one carbonate solvent.23) The porous material of any of claims 20 to 22 wherein the polyester consists essentially of or consists of at least one polycaprolactone homopolymer and / or polycaprolactone copolymer.24) The porous material of any of claims 20 to 23 wherein the average pore size is 10 nm to 5 pm , such as 100 nm to 1 pm.25) The porous material of any of claims 20 to 24 wherein the porous material has been surface treated so the pores at the surface are closed.

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