Biopolymer particle preparation

Abstract

The present disclosure provides a process for preparing biopolymer particles, the process comprising emulsifying a dispersed phase film into a continuous phase, wherein the dispersed phase comprises a biopolymer in a solvent, and wherein the dispersed phase forms an emulsion of the biopolymer in the continuous phase through the film; and phase inversion with an antisolvent to form particles of the biopolymer; wherein prior to (b), the emulsion is cooled to a temperature T1. Also provided are biopolymer particles obtained from the process.

Description

Technical Field

[0001] This invention generally relates to a method for preparing biopolymer particles, and more specifically, to a method leading to an increased yield of said biopolymer particles, wherein yield is defined herein. The invention also provides biopolymer particles obtained by the method of the invention. Background Technology

[0002] Biopolymers represent a significant development in reducing the environmental footprint of consumer products. Materials made from polymers are so widely used due to their adaptability, durability, and affordability that it's difficult to identify consumer products that don't contain any polymer materials. However, many developed synthetic polymers are primarily derived from petroleum and coal as raw materials, meaning they are environmentally incompatible and reliant on unsustainable resources. Polymer particles, in particular, cause serious ecological problems because they often remain in ecosystems after consumers dispose of the products. Therefore, biopolymers and biopolymer particles have come a long way in addressing these issues, as they are generally biodegradable and derived from renewable and sustainable raw materials. However, the production of biopolymer particles can be challenging.

[0003] One method used to prepare biopolymer particles is membrane emulsification followed by phase inversion. In membrane emulsification, the dispersed phase of the biopolymer is forced directly into the continuous phase through the pores of a microporous membrane to form an emulsion from which particles can be extracted. However, this process encounters various problems, including agglomeration or aggregation of particles in the continuous phase. Phase inversion involves exposing the emulsion to an antisolvent, for example by immersing the emulsion in an antisolvent, and deformation and further aggregation and agglomeration can occur during exposure / immersion.

[0004] In general, there remains a need in the art for a method for preparing biopolymer particles that does not suffer from the aforementioned problems. In particular, a method to prevent the aggregation, agglomeration, and / or deformation of biopolymer particles, thereby improving yield. Summary of the Invention

[0005] One object of the present invention is to provide a method for preparing biopolymer particles, the method comprising (a) emulsifying a dispersed phase membrane into a continuous phase, wherein the dispersed phase comprises a biopolymer in a solvent, and wherein the dispersed phase is passed through a membrane to form an emulsion of the biopolymer in the continuous phase, and (b) performing a phase inversion with an antisolvent to form biopolymer particles. The method includes cooling the emulsion to a temperature T1 prior to (b), wherein T1 is greater than the pour point of the continuous phase (T0). cont However, it is equal to or less than the transformation temperature (T) of the dispersed phase. disp The phase transition temperature is selected from the freezing point, glass transition temperature, and pour point.

[0006] T1 is defined as: T cont < T1≤T disp ; where T disp >T cont .

[0007] In various embodiments of the invention, the antisolvent is aqueous, i.e., it contains water. In various embodiments of the invention, the antisolvent contains an organic solvent, such as an alcohol, acetone, etc. In various embodiments, the antisolvent contains both an organic solvent and water. In various embodiments of the invention, the antisolvent is cooled. The antisolvent may, for example, be cooled to a temperature T2, where, for phase inversion (b), T2 is less than T. disp Preferably, T2 is substantially equal to T1, and more preferably, T2 is equal to T1.

[0008] In various embodiments of the present invention, membrane emulsification is selected from cross-flow membrane emulsification, rotating membrane emulsification, vibrating membrane emulsification, and combinations thereof. Preferably, membrane emulsification includes cross-flow membrane emulsification.

[0009] In various embodiments of the invention, cooling of the emulsion occurs at the membrane outlet, for example, when forming an emulsion in which the dispersed phase is in the continuous phase. In various embodiments of the invention, the continuous phase comprises a nonpolar solvent. In various embodiments of the invention, the dispersed phase comprises a polar solvent.

[0010] In various embodiments of the invention, the phase transformation occurs under shear. In various embodiments, the phase transformation includes a filtration process. In various embodiments, the phase transformation occurs under shear and includes a filtration process.

[0011] In various embodiments of the present invention, the method is continuous.

[0012] In various embodiments of the invention, after phase inversion (b), the antisolvent / continuous phase mixture is removed from the particles.

[0013] In various embodiments of the present invention, the biopolymer is a polysaccharide. Preferably, the biopolymer is cellulose.

[0014] Another object of the present invention is to provide biopolymer particles obtained by the methods described herein. Therefore, the features described herein in the context of this method also apply to the biopolymer particles obtained by this method. The biopolymer particles obtained by the methods described herein are distinguishable from those of the prior art because they increase yield and exhibit regularity in size and shape. This regularity can be seen, for example, in Figure 5(b).

[0015] These objectives and embodiments are set forth in the appended independent and dependent claims. It should be understood that the features of the dependent claims may be combined with each other and with the features of the independent claims, not just those expressly set forth in the claims. Furthermore, the methods described herein are not limited to specific embodiments, such as those set forth below, but include and are contemplated any combination of the features presented herein.

[0016] The foregoing and other objects, features, and advantages of the present invention will be more fully appreciated hereinafter by taking into consideration the following detailed description and the accompanying drawings. However, it should be clearly understood that the drawings are for illustrative purposes and should not be construed as limiting the scope of the invention. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of membrane emulsification.

[0018] Figure 2 Contains 4 particle images showing the desired particle size (< 50 µm) and shape (spherical). Figure 2 (a) and the deformation and aggregation problems that occur in the prior art ( Figure 2 Examples from (b) to 2(d)).

[0019] Figure 3 A schematic diagram containing existing technical methods ( Figure 3 (a) and a schematic diagram of an embodiment of the emulsion cooling of the present invention ( Figure 3 (b)).

[0020] Figure 4 This is a graphical representation of an embodiment of the method of the present invention.

[0021] Figure 5 includes two photographs; Figure 5(a) is a photograph of cellulose particles obtained from the comparative embodiment according to the present invention without emulsion cooling, and Figure 5(b) is a photograph of cellulose particles obtained according to the present invention by the following embodiment. Detailed Implementation

[0022] While various exemplary embodiments are described or suggested herein, other exemplary embodiments utilizing methods and materials similar to or equivalent to those described or suggested herein are included within the overall inventive concept. For the sake of brevity, aspects and features of conventionally implemented embodiments may not be discussed or described in detail. Therefore, it should be appreciated that aspects and features of the apparatuses and methods not described in detail herein can be implemented according to any conventional techniques used to implement these aspects and features.

[0023] The overall inventive concept focuses on increasing the yield of biopolymer particles from membrane emulsification and phase inversion processes, where the term "yield" refers to the mass of spherical particles or beads within a defined size distribution. Membrane emulsification is known in the art; it is a technique in which a dispersed phase is forced directly into a continuous phase through the pores of a microporous membrane, wherein emulsion droplets form and separate at the pore ends via a droplet-by-drop mechanism. A schematic diagram of the membrane emulsification process is shown below. Figure 1 As shown, the arrows indicate the flow direction.

[0024] The dispersed phase typically comprises a first liquid containing a biopolymer dissolved in a solvent, while the continuous phase comprises a second liquid immiscible with the first liquid. The interaction between the two liquids as the dispersed phase is propelled or otherwise transported through a membrane is called a dispersion process, and the resulting heterogeneous mixture is called an emulsion, where droplets of the dispersed phase are surrounded by the continuous phase.

[0025] The advantages of membrane emulsification over conventional emulsification are widely recognized in the art; these include the ability to obtain extremely fine emulsions with controllable droplet size and narrow droplet size distribution. Furthermore, successful emulsification can be achieved with significantly less emulsifier and energy consumption, and membrane emulsification allows the use of shear-sensitive components, such as starch and protein, due to the reduced shear stress effect. However, to expand the industrial applications of membrane emulsification, it has been recognized that the production capacity of this method must be increased.

[0026] In the context of biopolymer production, dispersed phase droplets in a continuous phase have been successfully separated via phase inversion. In the context of cellulose, this... ACS Sustainable Chem. Eng. Described in 2017, 5, 7, 5931-5939, which is incorporated herein by reference. Phase inversion is a chemical phenomenon utilized in the manufacture of artificial membranes and is carried out by removing the solvent from a liquid polymer solution. Various phase inversion methods exist, including immersing the polymer solution in a third liquid called an antisolvent. Antisolvent-based phase inversion has been shown to be particularly effective in precipitating biopolymer droplets from dispersed / continuous emulsions into particles.

[0027] Unfortunately, the dispersed phase droplets in the emulsion are at risk of participating in undesirable processes that reduce yield (where yield, as referred to herein, means the mass of spherical particles or beads within a defined size distribution). Droplets may interact irreversibly with each other (also referred to herein as coalescence or aggregation), and / or deform irreversibly, for example, during phase inversion.

[0028] Four types of biopolymer particles have the following shapes: Figure 2 As shown in (a) to 2(d). Figure 2 (a) Exemplary particle shapes and sizes that may be desirable in certain applications: single spherical beads with a diameter < 50 µm; Figure 2(b) Displaying undesirable shape deformation: single teardrop-shaped particles; Figure 2 (c) Showing undesirable aggregation of multiple spherical particles with a diameter >200 µm; and Figure 2 (d) shows undesirable asymmetric aggregation of multiple beads. Deformation and aggregation affect both the size and shape distribution of biopolymer particles, which negatively impacts the yield of biopolymer particles.

[0029] In-situ examination of particles during formation is challenging, and therefore can only be speculated about where and how any deformed shapes, coalesced structures, aggregated structures, etc., form. Not wishing to be bound by any single theory, the inventors believe that dispersed phase droplets may undesirably interact with each other as they flow in apparatuses generally used for membrane emulsification or in subsequent process piping, fittings, and equipment. For example, these droplets may coalesce when the fluid transport flow regime changes (e.g., laminar to turbulent transition point, recirculation zone, change in flow direction, etc.). Another theory is that dispersed phase droplets may deform due to shear forces, for example, during phase inversion processes (e.g., when the emulsion flows through an antisolvent), and these deformed shapes (e.g., teardrops) may be retained by the antisolvent. Dispersed phase droplets may also interact during phase inversion processes before or during contact with the antisolvent and may coalesce to form larger droplets or aggregate to form larger structures, which are then retained by the antisolvent. Other mechanisms may also exist, including larger droplets consuming smaller phase inversion particles during the phase inversion process and subsequently retaining these structures by the antisolvent.

[0030] This invention unexpectedly avoids these deformation and aggregation problems, thereby improving overall yield. The increased yield is achieved by cooling the emulsion formed via membrane emulsification to a temperature T1 prior to phase inversion. Specifically, T1 is greater than (i.e., above) the pour point of the continuous phase and equal to or less than (i.e., below) the phase transition temperature of the dispersed phase as defined herein, provided that the phase transition temperature of the dispersed phase is greater than / greater than the pour point of the continuous phase. Since deformation and aggregation are considered to occur when the dispersed phase droplets are in a liquid state, cooling the emulsion to or below the pour point of the dispersed phase is considered to temporarily (at least partially) alter the "colloidal class" of the emulsion (from an emulsion (i.e., liquid within liquid) to a sol (liquid within solid)), thus making the dispersed phase more maneuverable in downstream processes.

[0031] In addition, a dispersed phase having a transition temperature higher than the pour point of the continuous phase (the transition temperature is selected from the freezing point, glass transition temperature, and pour point) means that the continuous phase surrounding the solidified dispersed phase can still serve as a transport medium. Figure 3 (b) A graphical representation showing the emulsion undergoing cooling and temporary transformation into a sol in a cooling coil heat exchanger.

[0032] Figure 3(a) represents the prior art; the continuous phase and the dispersed phase droplets (microdroplets in this example; see definition below) together form an emulsion, and stagnation and turbulence in the flow can lead to undesirable coalescence and reduced yield. Figure 3 (b) is an example in which the emulsion is cooled in a coil heat exchanger to a temperature below the dispersed phase transition temperature but above the continuous phase pour point, so that the continuous phase remains fluid and can transport the transitioned droplets. Figure 3 (b) The exemplary implementation avoids [the following] Figure 3 (a) The prior art process encounters particle aggregation, deformation, agglomeration and the resulting reduction in yield.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0034] The term "biopolymer" refers to a polymer produced by a living organism. In other words, a polymerized biomolecule. Based on the monomer units used and the resulting biopolymer structure, there are three main classes of biopolymers: polynucleotides (RNA and DNA), which are polymers composed of 13 or more nucleotide monomers; polypeptides, which are polymers of amino acids; and polysaccharides, which are generally polymerized carbohydrate structures. Other examples of biopolymers include rubber, suberin, melanin, chitin, and lignin, preferably chitin and lignin.

[0035] In various embodiments of the invention, the biopolymer is selected from polynucleotides, polypeptides, and polysaccharides. Preferably, the biopolymer is selected from polypeptides and polysaccharides. More preferably, the biopolymer is a polysaccharide, such as starch, cellulose, chitin, chitosan, or glycogen. Most preferably, the biopolymer is starch or cellulose.

[0036] The term "particle" is used interchangeably with "bead" herein and refers to a solid formed after the phase transformation of a dispersed phase droplet. In various embodiments of the invention, the particle or bead is a microparticle or microsphere. As will be understood by those skilled in the art, a microparticle or microsphere is a particle / bead with a diameter between 1 and 1000 micrometers (μm). Such particles are readily identifiable by those skilled in the art, for example, using optical microscopy images and image analysis software with suitable detection algorithms (e.g., ImageJ using edge detection algorithms), laser diffraction with commercially available equipment such as the Mastersizer (e.g., Mastersizer 3000) from Malvern Panalytical, or with a sieve of appropriate size.

[0037] The membrane emulsification step of the method of the present invention includes passing a dispersed phase through a membrane into a continuous phase to form an emulsion. The membrane is not limited; it can be any porous structure suitable for the membrane emulsification process. For example, the membrane can be a plate with pores (e.g., micrometer-sized pores) acting as pores, a perforated metal tube, or a sintered porous glass.

[0038] The term "emulsion" refers to a two-phase system in which both phases are liquid. Emulsions are a type of colloid and typically consist of two immiscible liquids. In various embodiments of the invention, the emulsion may be a coarse emulsion; this is an emulsion in which the dispersed phase particles have a diameter of about 1-1000 micrometers. The term "sol" refers to a general category of two-phase systems in which the continuous phase is a liquid and the dispersed phase is a solid.

[0039] The term "aggregate" refers to a structure composed of primary particles that are generally redispersible. The term "aggregate" refers to a structure composed of primary particles that are not redispersible.

[0040] The term "pour point" refers to the temperature at which a substance (e.g., a liquid) loses its flow properties. It is generally defined as the lowest temperature at which a liquid (e.g., oil) can be poured from a beaker. Pour point can be measured using standard methods known in the art. For example, ASTM D7346, the standard test method for pour point and no-pour-point tests for petroleum products and liquid fuels, can be used. For commercially available materials, the pour point is typically provided by the supplier or manufacturer.

[0041] The term "freezing point" refers to the temperature at which a substance changes from a liquid to a solid state under standard atmospheric pressure (1 atmosphere). Freezing point can be measured using standard methods known in the art. For example, ASTM E794, a standard test method for melting and crystallization temperatures through thermal analysis, can be used. For commercially available materials, the freezing point can be provided by the supplier or manufacturer.

[0042] The term "glass transition point" or "glass transition temperature" refers to the temperature at which a polymer structure transitions from a rigid or glassy material to a soft, rubbery material. This temperature can be measured using differential scanning calorimetry (DSC) according to a standard test method: ASTM E1356, the standard test method for glass transition temperature by differential scanning calorimetry. For commercially available materials, the glass transition temperature can be provided by the supplier or manufacturer.

[0043] For ease of reference, these and further features of the invention are now discussed under the appropriate section headings. However, the teachings under each section are not limited to the section in which they are located.

[0044] membrane emulsification

[0045] As described above, membrane emulsification is not limited and can be any membrane emulsification method known in the art. For example, membrane emulsification methods can be cross-flow membrane emulsification, rotating membrane emulsification, vibrating membrane emulsification, or combinations thereof. As understood in the art, the terms "cross-flow," "rotating," and "vibrating" refer to methods used to generate shear at the membrane surface. For example, the continuous phase can be moved relative to a stationary membrane to generate shear, or the membrane can be moved relative to a stationary phase. Alternatively, a dispersed phase can be injected into a stationary continuous phase. Known method parameters such as membrane type, average pore size and porosity, cross-flow velocity, transmembrane pressure, and emulsifier can also be used. In various embodiments of the invention, membrane emulsification can involve cross-flow systems, stirred tank tubular membranes, stirred tank flat membranes, rotating flat membranes, vibrating / rotating tubular membranes, and / or premixed membrane emulsification.

[0046] International Patent Application No. WO 01 / 45830 describes an example of rotating membrane emulsification. International Patent Application No. WO 2012 / 094595 describes an example of cross-flow membrane emulsification. Pedro S. Silva et al., “ Azimuthally Oscillating Membrane Emulsification for Controlled Droplet Production AIChE Journal 2015 Vol. 00, No. 00 describes vibrating film emulsification: specifically, the film emulsification system comprises a tubular metal film that periodically oscillates at an azimuth angle within a gently cross-flowing continuous phase. WO 2019 / 092461 describes cross-flowing film emulsification. Each of these method descriptions is incorporated herein by reference.

[0047] In various embodiments of the invention, membrane emulsification is cross-flow membrane emulsification. Preferably, it is an emulsification process in which the continuous phase moves relative to a stationary membrane.

[0048] As those skilled in the art will understand, the dispersed phase and the continuous phase will depend on the resulting biopolymer. The dispersed phase will contain a solvent that disperses or dissolves the biopolymer, while the continuous phase will contain a solvent that is immiscible with the dispersed phase, such that an emulsion is formed when the dispersed phase is forced through a porous membrane.

[0049] The term "solvent" refers to any substance (e.g., a liquid) that disperses or dissolves biopolymers. The term "solvent" also includes solvent mixtures.

[0050] The identification of suitable solvents for the dispersed and continuous phases is, specifically, within the general knowledge of those skilled in the art. As mentioned above, all that is required is that the two phases (i.e., the dispersed and continuous phases) are immiscible with each other. Therefore, the solvents for each phase must be immiscible with each other. For example, solvents can be aqueous solvents, ionic liquids [salts that are liquid at temperatures between ambient and 100°C, such as imidazolium ionic liquids, such as 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride, etc.], organic solvents, or inorganic non-aqueous solvents.

[0051] In various embodiments of the invention, the solvent for the dispersed phase comprises an ionic liquid, an inorganic non-aqueous solvent, an aqueous solvent, or a combination thereof. In various embodiments of the invention, the solvent for the dispersed phase comprises an ionic liquid, an inorganic non-aqueous solvent, or a combination thereof. In various embodiments of the invention, the solvent for the dispersed phase comprises one or more ionic liquids. In other embodiments, the solvent for the dispersed phase comprises an organic solvent.

[0052] Non-limiting examples of solvents include water, methanol, ethanol, ammonia, acetone, acetic acid, n-propanol, n-butanol, isopropanol, ethyl acetate, dimethyl sulfoxide, sulfonyl chloride, phosphoryl chloride, carbon disulfide, morpholine, N-methylmorpholine, NaOH not bound to urea and thiourea and NaOH bound to urea and thiourea, bromine pentafluoride, hydrogen fluoride, chlorofluorosulfonyl, acetonitrile, dimethylformamide, hydrocarbon oils and their blends, toluene, chloroform, carbon tetrachloride, benzene, hexane, pentane, cyclopentane, cyclohexane, 1,4-dioxane, dichloromethane, nitromethane, and carbonates. Propyl acetate, formic acid, tetrahydrofuran, diethyl ether, phosphoric acid, 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride, 1-methoxymethyl-3-methylimidazolium bromide, N-ethylpyridine chloride, N-methylmorpholine-N-oxide, 1-methylimidazolium, N,N-dimethylformamide, N,N'-dimethylimidazolidine-2-one, N,N-dimethylacetamide, sulfolane, γ-valerolactone, γ-butyrolactone, N,N,N',N'-tetramethylurea, N-methylpyrrolidone, and dichloromethane. Those skilled in the art should readily recognize which of the exemplary solvents are ionic liquids, organic solvents, and / or inorganic non-aqueous solvents.

[0053] Preferably, the solvent used for at least one of the dispersed phase and the continuous phase is environmentally friendly. More preferably, the solvents used for both the dispersed phase and the continuous phase are environmentally friendly. The term "environmentally friendly" means harmless to the environment, allowing the solvent to be disposed of without the need for specialized equipment or processes, i.e., non-toxic.

[0054] It is known in the art that polysaccharides have limited solubility in most commonly used solvents. It is also known in the art that those solvents used to dissolve polysaccharides are often toxic and / or highly selective. When the biopolymer is a polysaccharide such as cellulose, starch, chitin, glycogen, and / or chitosan, the solvent used for the dispersed phase may therefore contain ionic liquids. Cellulose has been dissolved using the ionic liquid 1-butyl-3-methylimidazolium chloride, as discussed, for example, in Richard et al., J. Am. Chem. Soc. 2002, 124, 4974-4975. Verma et al., Sustainable Chemistry and Pharmacy 13 (2019), 100162 similarly discusses the solubility of cellulose in ionic liquids and ionic liquids with co-solvents. Each of these disclosures is incorporated herein by reference.

[0055] The concentration of biopolymer in the dispersed phase is unrestricted and can be any concentration suitable for membrane emulsification.

[0056] The dispersed phase and / or continuous phase may further include optional components. These optional components include, but are not limited to, cosolvents, surfactants, pore-forming agents, active ingredients, cavitation, dual emulsions, pigments, and dyes. The level of any optional component is not important in this invention. In various embodiments, the dispersed phase includes a cosolvent.

[0057] The co-solvent is not limited and may be any solvent known in the art, including those described above for the continuous phase and / or dispersed phase. The co-solvent may further be a mixture of co-solvents. Examples of possible co-solvents include water, 1-methylimidazolium (1-MI), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N'-dimethylimidazolium-2-one (DMI), N,N-dimethylacetamide (DMAc), sulfolane, γ-val, γ-butyrolactone (γ-but), propylene carbonate (PC), N,N,N',N'-tetramethylurea (TMU), or N-methylpyrrolidone (NMP). Examples include 1-methylimidazolium (1-MI), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N,N'-dimethylimidazolidine-2-one (DMI), N,N-dimethylacetamide (DMAc), sulfolane, γ-valactone (γ-val), γ-butonolactone (γ-but), propylene carbonate (PC), N,N,N',N'-tetramethylurea (TMU), or N-methylpyrrolidone (NMP).

[0058] Surfactants can be any suitable surfactant known in the art, such as any ionic or nonionic surfactant. Ionic surfactants can include sulfates, sulfonates, phosphates, and carboxylates, such as alkyl sulfates, ammonium lauryl sulfate, sodium lauryl sulfate, alkyl ether sulfates, sodium laureth sulfate and sodium myristyl ether sulfate, sodium dioctyl sulfosuccinate, perfluorooctyl sulfonate, perfluorobutyrate sulfonate, alkylbenzene sulfonate, alkyl aryl ether phosphates, alkyl ether phosphates, and alkyl carboxylates. Nonionic surfactants can include polyethers, polyoxyethylene derivatives of hexyl alcohol, some long-chain fatty acid esters such as sorbitan oleate, ethylene oxide derivatives of long-chain alcohols, ethoxylated vegetable oils, polydimethylsiloxanes, and ethylene oxide / propylene oxide copolymers.

[0059] Cooling of emulsion

[0060] The main advantage of this invention stems from cooling the emulsion formed by membrane emulsification prior to phase inversion. The emulsion is cooled to a temperature T1, which is greater than the pour point of the continuous phase (T0). cont And equal to or less than the freezing point, glass transition temperature, and pour point (T) selected from the dispersed phase. disp The transition temperature of ), where T disp >T cont However, the absolute value of T1 is not critical to this invention; rather, what is important is the relationship between T1 and the respective temperatures of the dispersed and continuous phases.

[0061] The cooling method is also unrestricted. The emulsion can be cooled by any means known in the art for removing heat (energy) from the system. The emulsion can be further cooled at any point prior to phase inversion. In various embodiments, this means that the emulsion is cooled simultaneously with or separately from the membrane emulsification process. The emulsion can be cooled, for example, during its formation (e.g., by a cooling device located at the membrane outlet). Alternatively, the emulsion can be cooled in a post-membrane emulsification step, for example, in a cooling device separate from the membrane emulsification apparatus. Advantageously, cooling should be performed as soon as possible after emulsification to reduce the possibility of coalescence and / or aggregation of liquid dispersed phase droplets.

[0062] In various embodiments, the emulsion can be cooled by a cooling medium (e.g., water, ice, etc.) at least partially surrounding the container in which the emulsion is formed. In a preferred embodiment, the container (e.g., a pipe) in which the emulsion is formed may have a cooling jacket containing a cooling medium. The cooling medium is not limited and includes any medium with a temperature lower than that of the emulsion.

[0063] In various embodiments, the emulsion can be cooled by a cooling device connected to the membrane emulsification unit. The cooling device can be a heat exchanger, such as an immersion heat exchanger. In the exemplary embodiments described below, the coil heat exchanger is immersed in a cooling medium (e.g., a cold water bath), but the invention is not limited in this respect. For example, any type of heat exchanger can be used, such as a shell-and-tube heat exchanger, a plate-and-frame heat exchanger, or a jacketed tube. Additionally, the immersion heat exchanger can be used in conjunction with another cooling medium, such as antifreeze, dry ice, etc., to cool the emulsion to T1.

[0064] Phase transformation

[0065] Phase inversion is not subject to similar limitations and can be any phase inversion method known in the art involving the use of an antisolvent. As described above, phase inversion is carried out by removing the solvent from a liquid-polymer solution, in this invention, where the liquid-polymer solution is a continuous phase containing a frozen dispersed phase.

[0066] The antisolvent can be any suitable solvent or solvent mixture known in the art. In various embodiments of the invention, the antisolvent is aqueous. In various embodiments, the antisolvent is non-aqueous. The antisolvent may, for example, comprise an organic solvent (such as an alcohol or acetone) or any other organic solvent known in the art. Suitable alcohols include ethanol and / or methanol. In various embodiments, the antisolvent comprises an organic solvent, water, or a mixture thereof, such as an alcohol, acetone, water, or a mixture thereof.

[0067] In various embodiments of the invention, the phase transformation occurs at ambient temperature, i.e., between about 20-25°C. In this embodiment, the antisolvent has a temperature between about 20-25°C. Alternatively and preferably, the antisolvent is cooled to a temperature below ambient temperature, i.e., below about 20°C. In various embodiments of the invention, the antisolvent has a temperature T2 below the freezing point of the dispersed phase. Controlling the antisolvent temperature (T2) has the advantage of preventing premature thawing of the frozen droplets. In various embodiments of the invention, T2 is equal to T1, where T1 is as defined above.

[0068] Unwilling to be bound by any particular theory, the inventors believe that by cooling the antisolvent to T2, the droplets remain in a frozen state (and are therefore spherical and non-aggregated), while simultaneously stripping away the surrounding continuous phase through phase inversion. The antisolvent is able to contact the droplet surface, leading to biopolymer precipitation and hardening of the precipitation surface. Furthermore, when the frozen dispersed phase droplets thaw, the antisolvent causes the dissolved biopolymer droplets to transform into their beads / particles, while simultaneously impregnating the solvent system into the antisolvent.

[0069] In various embodiments of the invention, the phase transformation occurs under shear; those skilled in the art will understand suitable shear conditions for the phase transformation. Shear can be achieved, for example, by using a stirred vessel (e.g., a mechanically stirred vessel) or a settling vessel (e.g., a gravity settling vessel). The term “shear force” is used herein to refer to an external force acting on an object or surface parallel to the inclined plane or plane on which the object or surface lies, and this stress tends to produce strain.

[0070] Shearing is advantageous because it increases the rate of removal of the continuous phase from the dispersed phase droplets, and thus increases the overall rate of phase transition. Phase transition processes are diffusion-rate limited (Fickian diffusion), and shearing reduces the thickness of the continuous phase layer around the dispersed phase droplets, decreasing the travel distance of antisolvent molecules to the surface of the dispersed phase droplets, thereby accelerating the phase transition process. However, its use is generally not applied to current phase transition processes due to the negative impact of shearing on particle shape and size. Currently, mild phase transition steps are used, where the emulsion is allowed to settle through a stagnant antisolvent (at room temperature). Surprisingly, frozen dispersed phase droplets are more tolerant to other methods of separating from the continuous phase, and this improved tolerance enhances the efficiency of such separation.

[0071] In various embodiments of the invention, the phase inversion includes a filtration process. The filtration process is not limited and may involve mechanical or any other type of filtration (e.g., using devices known in the art, such as hydrocyclones). The filtration process may also include a phase inversion under shear as described above. In various embodiments, a filter medium (e.g., a filter) may be used to filter the emulsion through an antisolvent, thereby collecting the biopolymer particles. In this embodiment, the emulsion may be gravity-sedimented (sheared) through the antisolvent and into the filter, while the continuous phase passes through the filter (filtrate). The frozen droplets may then be collected in the filter as a filter cake.

[0072] If not collected as part of a phase inversion (e.g., by filtration or otherwise), the biopolymer particles can be separated from the antisolvent / continuous phase mixture, or the antisolvent / continuous phase mixture can be removed from the particles. The removal method is not limited. However, in various embodiments, the removal method depends on whether the method is operated in batch or continuous mode.

[0073] When the method of the present invention is operated in batch mode, the phase inversion step can be carried out first in a closed container, and then the resulting mixture can be transferred to a decanter container to allow for settling. Once settling has occurred, the layers can be removed sequentially from the bottom of the container. The typical sequence of the layers is (1) the continuous phase, (2) the interfacial layer containing the wetted biopolymer particles, and (3) the remaining antisolvent. However, the invention is not limited to this and those skilled in the art should recognize that the sequence of the layers will depend on their respective densities.

[0074] In various embodiments of the invention, the method is continuous and operates in a continuous mode, with the phase inversion step performed with the continuous input of the emulsion and antisolvent and the continuous output of the multiphase mixture to the decanter. Within the decanter, a steady-state distribution of the mixture can occur, and it can be removed continuously and preferably simultaneously from each phase. For example, it can be removed continuously and preferably simultaneously from: (1) the continuous phase, (2) the antisolvent, and (3) the wetted biopolymer particles. The order of these layers will, of course, vary, and the invention is not limited to any particular order.

[0075] Alternatively, multiphase (e.g., three-phase) mixtures can be separated using techniques known in the art, such as disk stack separators (e.g., centrifugal separators, such as those manufactured by Andritz).

[0076] To provide continuous cooling and continuous phase inversion, the cooling medium (e.g., the medium surrounding a container containing an emulsion or used with a heat exchanger connected to a membrane emulsification unit) may need to be recirculated or recirculated using suitable devices. For example, devices such as recirculating coolers (ThermoFlex, available from ThermoFisher Scientific) can be used to maintain the cooling medium at the desired temperature.

[0077] Another advantage of the method of the present invention is the flexibility in the sequence of events. This flexibility arises because the droplets of the dispersed phase can be frozen in the emulsion. Therefore, in various embodiments of the invention, the removal of biopolymer particles as described above following a phase inversion involves the removal of biopolymer particles as described above. Decantation may be performed after the phase inversion, and then the biopolymer particles may be removed from the mixture, and / or the phase inversion may involve mechanically filtering wetted particles from the antisolvent / continuous phase / particle mixture.

[0078] Alternatively, the biopolymer particles can be removed from the continuous phase prior to the phase inversion. In this embodiment, the wetted cryogenic droplets can be removed from the sol (e.g., using filtration), and then a phase inversion can be performed to precipitate the biopolymer and form its beads / particles.

[0079] The invention has been generally described, and further understanding can be obtained by referring to certain specific embodiments described below. These embodiments are for illustrative purposes only and are not intended to be all-encompassing or limiting unless otherwise stated. Example

[0080] A dispersed phase comprising 8 wt% cellulose in 70 wt% 1-ethyl-3-methylimidazolium acetate and 30 wt% dimethyl sulfoxide was prepared according to conventional methods known in the art. The transformation temperature (e.g., freezing point) of this dispersed phase was about 11 °C. An aqueous continuous phase was also prepared according to conventional methods known in the art. The pour point of the continuous phase was -15 °C.

[0081] The dispersed phase and continuous phase are fed into, for example... Figure 4 The emulsion is then formed in the membrane emulsification unit shown. The emulsion is then cooled to a temperature between 0 and 11°C and then transferred to a phase inversion unit with an ethanol antisolvent to form cellulose particles.

[0082] The emulsion is cooled using an immersion coil heat exchanger, such as... Figure 4 As shown in the illustration. An immersion coil heat exchanger was selected to maintain laminar flow and minimize fluid disturbance during emulsion cooling. The coil heat exchanger, containing coils of diameter D and pitch P of length (L) in a 0°C cold water bath, was sufficient to cool the emulsion from 0.5 L / min to below 11°C. The temperature of the emulsion was monitored at the outlet of the coil heat exchanger using a thermometer.

[0083] Comparative examples were also provided, in which cellulose particles were prepared without a cooling step. Figure 5 includes two photographs (5x magnification) of the comparative example (a) and the example of the present invention (b). These photographs demonstrate how using a cooling step prior to phase inversion significantly reduces the aggregation and agglomeration of cellulose particles. This translates into an increased yield.

Claims

1. A method for preparing biopolymer particles, the method comprising: a. Emulsifying a dispersed phase membrane into a continuous phase, wherein the dispersed phase comprises the biopolymer in a solvent, and wherein the dispersed phase is passed through the membrane to form an emulsion of the biopolymer in the continuous phase; and b. A phase inversion is performed using an antisolvent to form particles of the biopolymer; Before step b, the emulsion is cooled to temperature T1. T1 is greater than the pour point T of the continuous phase. cont And equal to or less than the transformation temperature T of the dispersed phase. disp :T cont <T1≤T disp The transition temperature is selected from the freezing point, glass transition temperature, and pour point; and Where T disp >T cont .

2. The method of claim 1, wherein the transformation temperature of the dispersed phase is the freezing point.

3. The method of claim 1, wherein the transition temperature of the dispersed phase is the pour point.

4. The method of claim 1, wherein the transition temperature of the dispersed phase is the glass transition temperature.

5. The method of any one of claims 1-4, wherein the antisolvent is cooled to a temperature T2, where for the phase inversion b, T2 is less than T. disp .

6. The method of any one of claims 1-4, wherein the cooling of the emulsion is at the outlet of the membrane.

7. The method of any one of claims 1-4, wherein the phase transformation is carried out under shear.

8. The method of any one of claims 1-4, wherein the phase transformation includes a filtration process.

9. The method of any one of claims 1-4, wherein the membrane emulsification is selected from cross-flow membrane emulsification, rotating membrane emulsification, vibrating membrane emulsification, and combinations thereof.

10. The method of any one of claims 1-4, wherein the antisolvent is aqueous or contains an organic solvent.

11. The method of any one of claims 1-4, wherein the method is continuous.

12. The method of any one of claims 1-4, wherein after phase inversion b, the antisolvent / continuous phase mixture is removed from the particles.

13. The method of any one of claims 1-4, wherein the biopolymer is a polysaccharide.

14. The method of claim 5, wherein T2 is equal to T1.

15. The method of any one of claims 1-4, wherein the biopolymer is cellulose.

16. Biopolymer particles prepared by any one of claims 1-15.

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