KR20070015928A - Process for the formation of particulate material - Google Patents

Abstract

In the present invention,

(i) filling a supercritical fluid into a particle-forming vessel in which temperature and pressure are controlled; (ii) stirring the contents of the particle-forming vessel with a rotary stirrer comprising an impeller surface and an impeller having an impeller diameter, such that a relatively high stirring zone is located within one impeller diameter distance from the impeller surface of the rotary stirrer; and Creating a bulk mixing zone located at a distance greater than one impeller diameter from the impeller surface; (iii) in the stirred particle forming vessel, at least through the first feedstock stream port, the candle via a first feedstock stream and a second feedstock stream port comprising at least a solvent and the desired material dissolved therein; Introducing a second feedstock stream comprising a critical fluid, the material of interest being relatively insoluble in the supercritical fluid relative to solubility in the solvent, the solvent being soluble in the supercritical fluid, The first and second feedstock stream ports are located within one impeller diameter distance from the impeller surface of the rotary stirrer such that the first and second feedstock streams are introduced into the highly stirred zone of the particle forming vessel, and the first 1 a feedstock stream is dispersed in the supercritical fluid by the action of the rotary stirrer so that the solvent Extraction into a base supercritical fluid; And (iv) precipitating the particles of the desired material in the particle forming vessel to a volume-weighted average diameter of less than 100 nm.

Description

PROCESS FOR THE FORMATION OF PARTICULATE MATERIAL}

The present invention relates to a controlled method of forming nanometer-sized particles and / or molecular clusters of a material of interest by a supercritical anti-solvent (SAS) type process.

Supercritical fluids exhibit unique properties that combine gas-like transport properties with liquid-like solvent power. Supercritical fluids are more compressible compared to ideal gases. Thus, even a slight change in temperature or pressure near the threshold value causes a significant change in the density of the fluid and thus the solvent power. These properties can be used to provide easily controllable solvent properties. Carbon dioxide is the most widely used supercritical fluid due to advantageous critical parameters (Tc = 31.1 ° C., Pc = 73.8 bar), cost and non-toxicity.

Two basic principles for precipitation of particles by supercritical fluids: Rapid Expansion of Supercritical Solution (RESS) and Supercritical Antisolvent (SAS) or Gas Anti-Solvent; GAS) precipitation methods have been developed. In a RESS type process, the sensitivity of the supercritical fluid solvent force to small changes in pressure is used to cause the mechanical precipitation of solute particles from the supercritical fluid. However, RESS is not suitable for use with many materials due to the requirement for solubility in supercritical fluids. SAS or GAS processes, on the other hand, can be used to precipitate particles of a substance that does not dissolve in the supercritical fluid, where the supercritical fluid is miscible with the liquid in which the substance is dissolved. RESS type processes are known to produce very small (eg less than 100 nm) molecular clusters, ion pairs, or dispersed individual molecules under certain conditions, while this SAS process is known to produce such molecular clusters to date. none.

The most commonly performed SAS type process employs a suitable carrier fluid, typically a solution or suspension in an organic solvent, which is contacted with a supercritical fluid, generally carbon dioxide, under controlled conditions of pressure, temperature, and rate of addition through a capillary nozzle. . The use of this method has been described in a number of documents: for example, "Strategies for Particle Design using Supercritical Fluid Technologies", Pharmaceutical Science & Technology Today , 2 (11), 430-440 (1999); "Supercritical Antisolvent Precipitation of Micro- and Nano-Particles", J. of Supercritical Fluids , 15, 1-21 (1999); And "Particle Design Using Supercritical Fluids: Literature and Patent Survey", J. of Supercritical Fluids , 20, 179-219 (2001).

WO 95/01221 discloses an apparatus for use in forming particulate products in a controlled manner using a SAS type particle forming system. The apparatus includes a particle forming vessel, which contains a supercritical fluid and a vehicle containing one or more substances of solution or suspension in a vessel such that dispersion and extraction of the vehicle occur substantially simultaneously by the action of the supercritical fluid. Means for controlling the temperature in the vessel, together with means for simultaneous addition. The term "dispersion" means that a droplet of the vehicle is formed. The means for the simultaneous addition of the supercritical fluid and the vehicle to the particle forming vessel preferably comprises a two-pass nozzle whose outlet end communicates with the interior of the vessel, wherein the nozzle comprises coaxial passages which end adjacent to each other at the outlet, At least one of the passages serves to carry the flow of the supercritical fluid, while at least one of the passages serves to carry the flow of the vehicle in which the substance is dissolved or suspended. Such nozzles pulverize the solution by shear forces at the jet boundary of the co-added fluid stream. Thus, jet dispersion and vehicle extraction efficiency are limited by the magnitude of the shear force, where insufficient shear force results in a larger particle size than desired and a wider particle size and morphological distribution. In the disclosed examples, the particle size produced is typically greater than 1 μm. In addition, this process is likely to cause operation problems in terms of the clogging tendency of the nozzles.

International Publication No. WO 96/00610 discloses a three-pass coaxial nozzle for a SAS particle formation process, which simultaneously combines two vehicles that are substantially miscible with one another but only one of which is substantially dissolved in the supercritical fluid. -Can be added. The advantage of this process is that the SAS technology allows the production of particles of a material which is very low in solubility in the required solvent or incompatible with the solvent and otherwise could not be used. However, this process does not improve the size, morphology, and operational limitations disclosed in WO 95/01221. In the disclosed embodiments, the nozzles can produce particles of size typically greater than 1 μm.

Unlike the prior art, which teaches co-flow of a fluid stream through coaxial passages, US Pat. No. 6,440,337 uses an impingement jet arrangement to disperse a solution or suspension of two fluid streams and provide fluid to the particle formation chamber. Disclosed is a SAS process for forming particles, which extracts the vehicle upon addition of. The collision results in a higher loss of kinetic energy, facilitating improved dispersion, which in turn improves contact between the solution and the supercritical fluid. A further advantage is that particles formed from solution quickly deviate from the point of formation, which can reduce nozzle clogging. However, kinetic energy loss is still limited by nozzle geometry and flow rate, and the contact time between impingement streams may be insufficient for complete mixing. The partially mixed stream can only be sufficiently mixed in the downstream region, where the kinetic energy for mass transfer can be much lower. In this case, the size distribution becomes wider and the average particle size becomes large. The average size of typical particles was 0.5 μm.

International Publication No. WO 97/31691 teaches an improvement on the two-pass SAS nozzles of the prior art. The first nozzle passage provides a second convergence / diffusion for the energizing gas so as to slowly generate high energy sound downstream of the nozzle outlet, affecting dispersion and extraction, as well as being substantially independent of the forces typical of prior art nozzles. Surrounded by passage. Although this process improves the kinetic energy loss rate in the particle formation region, it is inherently less controlled because the frequency of sound waves is not constant and deductive specification is difficult. In the disclosed examples, typical particle sizes exceeded 0.5 μm.

US application 2002/0000681 teaches a further SAS type technique in which the jet is bent to be dispersed by an oscillating surface that atomizes the jet into finer droplets. According to this, no special nozzle is required for this process. In addition, the frequency of vibration can be precisely controlled. In addition, the oscillating surface creates a flow field that oscillates inside the supercritical phase, which increases mixing to improve mass transfer. However, the application states that the increase in ultrasonic power does not significantly reduce the particle size beyond the limit. In the disclosed examples, the particle size typically exceeded 0.1 μm. This process also appears to result in a relatively wide distribution of particle size and morphology.

WO 02/058674 discloses a uniform size (greater than 0.1 μm) due to the presence of the regulator when the first liquid (consisting of water, the subject material and the regulator) is in contact with the second liquid (consisting of supercritical antisolvent and organic solvent). A SAS process is disclosed in which ultrafine particles of) are provided.

WJ Schmitt et al., " Finely-divided powders by carrier solution injection into a near or supercritical fluid ", AIChEJ, 41 (11), 2476-2485 (1995). The introduction discloses another SAS type of process where the introduction does not require a special nozzle. Figure 1 of the document shows the apparatus including a conventional stirrer located far from the introduction area as the main mixing apparatus. The specification indicates that the stirrer diameter is 5.08 cm, located 9 cm below the top of the chamber, and the fluid introduction point is 6 mm into the chamber. Thus, the stirrer is located further than one impeller diameter from the fluid introduction point. As a result of this spacing position, the disclosed apparatus does not provide a high kinetic energy dissipation zone in the fluid stream introduction region. The size of the resulting particles is reported to be as large as 1 to 10 μm and some to 20 to 30 μm. Similarly, US Pat. No. 5,707,634 of Schmidt similarly describes a schematic scheme including a mixing chamber autoclave 1 and a stirring element 2, but does not provide any details thereof.

Despite the prospects in these documents, the SAS type of technique is used on an industrial scale only in limited cases. In addition, in general, so far, the documents have found that known SAS type processes cannot produce particles smaller than 0.1 μm (100 nm) (average size). This is believed to be due to improper understanding of the control factors (see, eg, "Current issues relating to anti-solvent micronisation techniques and their extension to industrial scales", J. of Supercritical Fluids , 21, 159-177 (2001)). See). While the prior art teaches that mixing is a factor, the problem with "fast kinetics" processes such as particle formation is only partially addressed.

Mixing can occur on different lengths and time scales. Mixing on the length scale of the jet diameter is called mesomixing, mixing on the length scale of the minimum turbulent vortex in the effective flow field is called micromixing, and mixing on the length scale of the particle forming vessel diameter. Is referred to as macromixing (see, eg, "Turbulent Mixing and Chemical Reactions", J. Baldyga and JR Bourne, ISBN 0-471-98171-0 John Wiley & Sons, (1999)). Literature of conventional SAS type processes include meso- and micro-mixing (see eg WO-95 / 01221, WO-96 / 00610, US 6,440,337, WO-97 / 31691, US 2002/0000681) or macromixing (eg , US 5,707,634, but none of them together. The usefulness of meso- and micro-mixing is generally limited to systems that are small in size. They do not perform efficiently when the system is scaled up. This is because they have a limited dynamic range with respect to micro- and meso-mixing efficiencies as a function of the volumetric flow rate of the jet solution, and also because macro-mixing defects lead to increasingly high heterogeneous concentrations in the particle formation vessel. This nonuniformity on the one hand contributes to a wide range of size and shape distributions, and on the other hand, to larger particle sizes. The usefulness of macro-mixing is very limited because the resulting particle size is much larger than that produced from other processes, and the defects of efficient micro- and meso-mixing make the original less controlled process. The present invention addresses process engineering issues for processes of the "quick kinetics" mediated SAS type process for industrial scale, in particular particle size below 100 nm.

Summary of the Invention

According to one embodiment of the present invention, a method of forming particulate material of a desired material is disclosed, the method comprising the steps of (i) to (iv):

(i) filling a supercritical fluid into a particle-forming vessel in which temperature and pressure are controlled;

(ii) stirring the contents of the particle-forming vessel with a rotary stirrer comprising an impeller surface and an impeller having an impeller diameter, such that a relatively high stirring zone is located within one impeller diameter distance from the impeller surface of the rotary stirrer; and Creating a bulk mixing zone located at a distance greater than one impeller diameter from the impeller surface;

(iii) in the stirred particle forming vessel, at least through the first feedstock stream port, the candle via a first feedstock stream and a second feedstock stream port comprising at least a solvent and the desired material dissolved therein; Introducing a second feedstock stream comprising a critical fluid, the material of interest being relatively insoluble in the supercritical fluid relative to solubility in the solvent, the solvent being soluble in the supercritical fluid, The first and second feedstock stream ports are located within one impeller diameter distance from the impeller surface of the rotary stirrer such that the first and second feedstock streams are introduced into the highly stirred zone of the particle forming vessel, and the first 1 a feedstock stream is dispersed in the supercritical fluid by the action of the rotary stirrer so that the solvent Extraction into a base supercritical fluid; And

(iv) precipitating particles of the desired material in the particle forming vessel to a volume-weighted average diameter of less than 100 nm.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following detailed description of the preferred embodiments of the present invention described below refers to the drawings.

1 is an optical microscope image of the particles obtained in Example 1. FIG.

2 is an optical microscope image of the particles obtained in Example 2. FIG.

3 is an optical microscope image of the particles obtained in Example 3. FIG.

4 is a particle size distribution graph of the particles obtained in Example 4.

5 is a transmission electron microscope graph of the particles obtained in Example 5. FIG.

6 is a transmission electron microscope graph of the particles obtained in Example 6. FIG.

7A is a transmission electron microscope graph of the particles obtained in Example 7. FIG.

7B is a graph of particle size frequency of the particles obtained in Example 7.

8 is a transmission electron microscope graph of the particles obtained in Example 8. FIG.

In accordance with the present invention, it has been found that particles of the desired material in nanometer (nm) size can be prepared by precipitation of the desired material from solution upon contact with a supercritical fluid antisolvent under the conditions disclosed herein. In the practice of the present invention, the feed material (ie supercritical fluid antisolvent and solvent / solute solution) is mixed directly in the particle formation vessel in the zone of highly stirred turbulence to precipitate particles of the solute. The particles are then discharged from the highly stirred zone by the action of bulk mixing in the particle forming vessel. In the practice of the present invention, it is generally preferred to introduce the feedstock stream in a highly stirred mixing zone in the opposite direction (although it may be introduced in the same direction as needed). An important feature of the present invention is that precipitated particles of size less than 100 nm can be produced without having a high level of non-uniform large particles.

The method of the present invention is useful in pharmaceutical, agricultural, food, chemical, image (including photographs and prints, and in particular inkjet prints), cosmetics, electronics (electronic display device products, and especially) that benefit from the use of small particle materials. Precipitated particles of various materials for use in color filter arrays and organic light emitting diode display devices), data recording, catalysts, polymers (including polymeric filler products), pesticides, explosives, and microstructure / nanostructure constructions Applicable to the preparation of. The material of the precipitated material of interest according to the invention is, for example, organic, inorganic, metallo-organic, polymerizable, oligomeric, metallic, alloy, ceramic, synthetic and / or natural polymers, and composite materials thereof as described above. Can be. Precipitated materials include, for example, colorants (including dyes and pigments), agricultural chemicals, pharmaceutically useful compounds, commercial chemicals, fine chemicals, food items, nutrients, pesticides, photographic chemicals, explosives, cosmetics , Protective agents, metal coated precursors, or other industrial materials in the form of deposited films, fine particle dispersions or powders of desired form. Dyes and pigments are particularly preferred functional materials for use in printing applications.

The desired material to be precipitated is first dissolved in a suitable liquid carrier solvent. As is known in SAS type processes, solvents for use in the present invention may be selected based on their ability to dissolve the desired material, miscibility with supercritical fluid antisolvents, toxicity, cost, and other factors. Can be. The solvent / solute solution is then contacted with a supercritical fluid antisolvent in a particle forming vessel in which temperature and pressure are controlled, wherein the supercritical fluid initiates precipitation of the solute from the solvent upon rapid extraction of the solvent into the supercritical fluid. It is selected based on the solubility of the solvent and the relative insolubility (relative to solubility in the solvent) of the preferred particulate material. Any supercritical fluid known in the SAS type process can be used and generally supercritical CO ₂ is preferred.

In accordance with the present invention, the solvent / solute solution and supercritical fluid antisolvent provide a feedstock stream of these components so that the first solvent / solute feedstock stream is dispersed in the compacted fluid by operation of a rotary stirrer. This introduction into the stir zone causes contact in the particle forming vessel. Effective micro and meso mixing, and intimate contact of the resulting feedstock stream components are made possible by introduction of the feedstock stream into the vessel within an impeller diameter distance from the surface of the impeller of the rotary stirrer, and preferably less than 100 nm, preferably 50 Enables precipitation of particles of the desired material in a particle weighted vessel of a volume weighted average diameter of less than nm, most preferably less than 10 nm. In addition, narrow size-frequency dispersions for the particles can be obtained. Measurement of volume weighted size-frequency variance, or coefficient of variation (average diameter of variance divided by standard deviation of variance) is typically, for example, 50% or less, with a coefficient of variation of less than 20% possible. Thus, the size-frequency dispersion can be monodisperse. Process conditions may be controlled in the particle forming vessel and may be varied to the desired particle size if desired.

Preferred mixing apparatus that can be used in the process of the present invention is described above for use in the field of photographic silver halide emulsions for precipitation of silver halide particles by reaction of a simultaneously introduced silver and halide salt solution feedstock stream. Rotary stirrer of the type. Such rotary stirrers may include, for example, turbines, marine propellers, discs, and other mixing impellers known in the art (eg, US Pat. Nos. 3,415,650; 6,513,965; 6,422,736; 5,690,428 5,334,359, 4,289,733; 5,096,690; 4,666,669, EP 1156875, WO-0160511).

The specific configuration of a rotary stirrer that can be used in the present invention can vary significantly, but it will preferably use one or more impellers having a surface and diameter, where the impeller is effective to create a high stir zone near the stirrer. The term “high stirring zone” is described as the tightly close zone of the rotary stirrer within a substantial amount of power provided since the mixing is dissipated by the material flow. Typically contained within the impeller diameter distance from the rotating impeller surface. The introduction of the supercritical fluid antisolvent feedstock stream and the solvent / solute feedstock stream into the particle forming vessel in close proximity to the rotary mixer such that the feedstock stream is introduced into the relatively high stirring zone by operation of a rotary stirrer is substantially To the extent useful to achieve meso-, micro-, and macro-mixing of the feedstock stream components. Depending on the processing fluid characteristics and the dynamic time scale of the transfer or conversion process associated with the particular supercritical fluid, the solvent and solute material used, the specific rotary stirrer used is selected to optimize meso-, micro-, and macro-mixing. Will actually change the degree of usefulness.

Mixing apparatus that can be used in one particular aspect of the invention is described in Research Disclosure, Vol. 382, February 1996, Item 38213. In such an apparatus, means are provided for introducing the feedstock stream from the distant source by a conduit terminated close to the adjacent inlet zone (impeller diameter less than 1 from the surface of the mixing impeller) of the mixing device. To facilitate mixing of the feedstock streams, they are introduced in opposite directions near the inlet zone of the mixing device. The mixing device is located perpendicular to the reaction vessel and is attached to the end of the shaft driven at high speed by suitable means, such as a motor. The low end of the rotary mixing device is spaced from the bottom of the reaction vessel but below the surface of the fluid contained within the vessel. Sufficient baffles may be located around the mixing device to inhibit horizontal rotation of the contents of the container. Such mixing devices are also shown schematically in US Pat. Nos. 5,549,879 and 6,048,683.

Mixing apparatus that can be used in another aspect of the present invention is a separate control of the feedstock stream dispersion (micro-mixing and meso-mixing) and bulk circulation in the precipitation reactor, for example as disclosed in US Pat. No. 6,422,736. Mixers that promote (macro-mixing). Such a device includes a vertically oriented draft tube, a bottom impeller located in the draft tube, and an upper impeller positioned on the draft tube over a first impeller and spaced therefrom a sufficient distance for independent operation. The bottom impeller is preferably a planar blade turbine (FBT) and is used to effectively disperse the feedstock stream and add it to the bottom of the draft tube. The upper impeller is preferably a pitched blade turbine (PBT) and is used to circulate the bulk fluid in the ascending direction through a draft tube which provides narrow circulation time dispersion through the reaction zone. Suitable baffles can be used. Two impellers are located at a distance at which independent operation is obtained. This independent operation and the simplicity of its structure is a feature that makes this mixer suitable for scale-up of the precipitation process. Such a device provides vigorous micro-mixing, ie it provides very high power dissipation in the introduction band of the feedstock stream.

Rapid dispersion of the feedstock stream is important in the present invention to control several factors such as supersaturation caused by mixing of the supercritical fluid antisolvent and solvent / solute. More intense turbulent mixing will occur in the feedstock zone and the feedstock will dissipate more quickly and mix with the bulk. This is preferably achieved by using a planar blazed impeller and introducing the feedstock stream directly into the high energy dissipation zone of the impeller. Planar blazed impellers have high shear and dissipation characteristics using the simplest design possible. The device disclosed in US Pat. No. 6,422,736 also provides good bulk circulation, or macro-mixing. Fast homogenization rates and limited circulation time dispersion are required to achieve process uniformity. This is achieved by using an axially directed flow field, where the flow field is further reinforced by the use of draft tubes. This type of flow provides a single continuous circular loop without dead bands. In addition to directing fluid movement in the axial direction, the draft tube provides a means for operating the impeller at much higher rpms and limits the precipitation zone to the vigorously mixed interior of the tube. To further stabilize the flow field, a grinder device can be attached to the discharge of the draft tube to reduce the rotational component of the flow.

The use of a mixed device of the type disclosed in US Pat. No. 6,422,736 also provides a means for easily changing power dissipation independent of bulk circulation. This provides flexibility in selecting the mixing conditions that are optimal for the particular material used. This separation of the bulk and hot zone mixing can be achieved by the location of the pitch bladed impeller near the outlet of the draft tube. Pitch-bladed impellers provide a high flow-to-power ratio that is easily converted and are simple in design. It controls the circulation speed through the draft tube, which is a function of pitch angle of the blades, number and size of blades, and the like. Because the pitch-bladed impeller dissipates much less power than the flat-bladed impeller and is located far enough from the feedstock point, the pitch-bladed impeller does not interfere with the intense hot zones that are mixed in the draft tube, but only This interferes with the speed of circulation. By placing the impeller a certain distance away, the effect of this independent mixing is maximized. The distance between the impellers also has a strong influence on the degree of reverse mixing in the hot zone, thus providing another mixing parameter that can be varied. To further enable independent control of the mixing parameters, the upper and lower impellers can have different diameters or be operated at different speeds than the same speed. In addition, the feedstock stream may be introduced by multiple tubes in various orifice designs at various locations within the draft tube.

In a SAS type process, the present invention firstly suitably represents an associated mixing method that can produce surprisingly dramatically smaller particle sizes. In fact, it would be more appropriate to refer to these particle molecular clusters which consist of only a small number of molecules. Rapid expansion of supercritical solvent (RESS) methods are known for producing very small molecular clusters, ion pairs, or dispersed individual molecules under certain conditions, but SAS processes are not known to produce such molecular clusters. . Thus, the present invention provides for the first time the ability to match the properties of a SAS type process to a RESS process in terms of particle size, shape and generated features. Thus, while the RESS process is generally limited to materials that are soluble in supercritical fluids, the present invention is open to a much broader class of materials for processing through the use of conventional organic solvents. Because of the superior treatment of mixed interactions, the present invention also draws additional advantages in terms of more limited particle size and morphological dispersion. In addition, the same control of the mixing method makes the method of the present invention more powerful and measurable.

Advancement to the fully continuous particle formation method is well recognized that in the SAS type technology, the powder of the desired material is typically collected in the particle formation vessel under pressure, and in the RESS type technology it is limited by the depletion of the expanding stock solvent. In a preferred embodiment of the present invention, the process comprises a supercritical fluid, solvent from the particle forming vessel, while maintaining the temperature and pressure in the vessel at the required level so that formation of the particulate material occurs under essentially steady state continuous conditions. , And the desired material may be carried out in an essentially continuous manner by discharging the supercritical fluid, solvent and the desired material from the particle forming vessel at a rate substantially equivalent to the rate of addition of these components to the vessel during the step. This continuous operation is believed to be facilitated by the ultrafine characteristics of the precipitated particles, which causes the supercritical fluid, solvent and the desired material to be discharged from the particle forming vessel to the expansion chamber by passages. In such an embodiment, the passage to the expansion chamber may, for example, pass through a backpressure regulator, capillary, or flow disperser. Once passed through the expansion chamber, particles of the desired material can be collected in the stirred particle formation vessel without interruption of precipitation. If desired, the supercritical fluid, solvent and the desired material can be withdrawn directly from the particle forming vessel into the solution to form a dispersion of formed particles of the desired material.

Ultrafine particles obtained according to the present invention may be further printed on a substrate upon expansion of the supercritical fluid mixture in a process similar to that disclosed in co-pending, co-pending, commonly assigned USSN 10 / 815,026 and 10 / 185,010 May be coated, or otherwise deposited. Since the process of the present invention produces fine powders that are comparable to those produced by RESS technology, RESS-based thin film deposition techniques (methods and apparatus with small variations due to low levels of organic solvents present in supercritical mixtures) May also be used for the particles produced by the present invention. For example, after forming particles in a particle forming vessel by a SAS type process according to the present invention, the resulting mixture of ultra fine precipitated particles and the compressed supercritical fluid are described in US Pat. Nos. 4,582,731, 4,734,227, 4,734,451, 4,970,093, 4,737,384, 5,106,650, and Fulton et al., Polymer, Vol. Similar to the RESS (and other similar) type coating methods disclosed in 44, 3627-3632 (2003), can be expanded under controlled conditions and a thin film of particles can be coated onto a substrate. Condensation of solvents from supercritical fluids, solvents, and precipitated solute mixtures upon expansion of the mixture is avoided, or minimized, if necessary, by selection of the solvent with a sufficiently high vapor pressure, and / or control of the temperature and pressure of the expansion chamber. Can be.

In addition, the ultrafine particles obtained according to the present invention are similar to those disclosed in the deposition or printing methods of WO 02/45868 A2, US 6471327, US 6692906, US 20020118246 A1, US20020118245 A1, and US20030107614. It can be printed, coated or otherwise deposited. The ultrafine particles obtained in accordance with the present invention are co-flowing and commonly assigned USSN 10 / 313,549, 10 / 460,814 and US Pat. No. 6,790,483 (systems for producing patterned deposition from compressed fluids); US Patent 6,843,556 (system for producing patterned deposition from compressed fluid in a dual controlled deposition chamber); US Patent 6,780,249 (system for producing patterned deposition from compressed fluid in a partially opened deposition chamber); USSN 10 / 313,591 (supercritical CO ₂ based marking system to make organic small molecule and polymeric light emitting diode devices); USSN 10 / 224,783 and 10 / 300,099 (solid-state lighting using dense gas coatings); USSN 10 / 602,429 and 10 / 602,134 (method of color tuning light emitting displays); USSN 10 / 602,430 (color gamut improvement by process variations in supercritical fluid printing); USSN 10 / 602,840 (method and apparatus for altering printed colors with process changes); And further printed, coated, or otherwise upon expansion of the supercritical fluid mixture in the process, similar to that disclosed in USSN 10 / 625,426 (security method using supercritical fluid printing), which is incorporated herein by reference in its entirety. Can be deposited.

Example 1 (control)

A nominal 1800 ml stainless steel particle forming vessel was matched with a 4 cm diameter stirrer of the type disclosed in US Pat. No. 6,422,736, including a draft tube and a bottom and top impeller. The feedstock port for the solution (of die 1 in acetone) is outside the relatively high stir zone created such that the feedstock port is at least 5 cm away from the end of the bottom impeller (ie, within a distance of the impeller diameter from the impeller surface). , Out of the draft tube above the plane of the bottom impeller. It is also expressed in tangent to the draft tube diameter. The feedstock port for CO ₂ was placed very close to the mixing impeller, as disclosed for the inlet tube for the mixer in US Pat. No. 6,422,736. The outlet port of the particle forming vessel has a protective stainless steel pre-filter with a nominal filtration efficiency of 90% for 0.5 μm particles. In addition, a stainless steel sampling cell having a high surface gloss was mounted in the particle formation container to capture the particles formed by the above method. The outlet port of the particle forming vessel was connected to an expansion chamber in which ambient temperature and pressure prevailed through a 25.4 cm long stainless steel capillary with a diameter of 0.0254 cm. CO ₂ was added to the particle formation vessel while the temperature was adjusted to 90 ° C., the pressure was adjusted to 300 bar and stirred at 2775 rpm. Subsequently, the addition of CO ₂ at 60 g / min through a feedstock port with a 200 μm orifice at its end, and the addition of a 0.1 wt% solution of Dye-1 in acetone at 2 g / min through a 100 μm end Started. The molecular structure of Di-1 is as follows:

The pressure in the particle formation chamber began to rise and reached 315 bar in 29 minutes. At this point, the filter was considered clogged and feedstock addition was stopped. The vessel was then carefully reduced to atmospheric pressure for 20 minutes and opened for irradiation. After removing the sampling cell, the particles deposited on the sampling cell were irradiated with an optical microscope as shown in FIG. The preponderance of particles (single or aggregate) of more than 1 μm is evident.

Example 2 (Invention)

As described for the inlet tube for the mixer in US Pat. No. 6,422,736 to introduce the solution and CO ₂ feedstock stream into the highly stirred zone within one impeller diameter of the bottom impeller (CO ₂ feedstock port and Similarly, the procedure of Example 1 was repeated except that the solution feedstock port was located close to the bottom impeller. The pressure in the particle formation chamber was increased for 54 minutes from 280 bar at the start of solution addition to 315 bar at the end of solution addition. After depressurizing, the particles deposited on the sampling cell surface were irradiated with an optical microscope as shown in FIG. 2. Despite nearly twice as long operation time as in Example 1, the sampling cell surface showed significantly fewer single or aggregated particles greater than 1 μm, with finer particles predominating.

Example 3 (Invention)

The procedure of Example 2 was repeated except that the stirring speed was maintained at 2078 rpm. The pressure in the particle formation chamber was increased for 60 minutes from 280 bar at the start of solution addition to 320 bar at the end of solution addition. After depressurizing, the particles deposited on the sampling cell surface were irradiated with an optical microscope as shown in FIG. 3. Compared to Example 1, the sampling cell surface shows significantly less deposition of particles larger than 1 μm and finer particles dominate, despite nearly a 2x increase in operating time and a 25% decrease in the stirring speed. gave.

Example 4 (Invention)

Using the particle forming vessel and feedstock pot arrangement used in Example 2, CO ₂ was added while adjusting the temperature to 90 ° C. at 300 bar. Stirring speed was maintained at 2775 rpm. Subsequently, the addition of CO ₂ at 60 g / min through a feedstock pot with a 200 μm orifice at its end, and the di-1 in acetone at 2 g / min through a 100 μm end (same as the dyes of Examples 1-3) However, addition of 0.5 wt% solution of 5 times concentrated) was started. The bottom of the particle forming vessel was connected to an expansion chamber in which the temperature and pressure of the ambient conditions prevailed through an automatic back pressure regulator. The temperature and pressure of the particle formation chamber were controlled at constant levels of 90 ° C. and 300 bar, respectively. After 1 hour of continuous operation, the discharge flow from the particle forming vessel was re-delivered away from the expansion chamber. The particles deposited on the walls of the expansion chamber were stripped off and dispersed in water. The particle size distribution was then measured using a Melbourne high performance particle size meter (Malvern Instruments Ltd., UK). As shown in Figure 4, the volume weighted average particle size is 1.37 nm, and the standard deviation of the size distribution was 0.237 (17% coefficient of deviation).

Example 5 (Invention)

Using the particle forming vessel and feedstock pot arrangement used in Example 2, CO ₂ was added while adjusting the temperature to 63 ° C. to 180 bar. Stirring speed was maintained at 2775 rpm. Subsequently, the addition of CO ₂ at 40 g / min via a feedstock port having a 200 μm orifice at its end, and the di-1 in acetone at 1 g / min through the 100 μm end (same as the dyes of Examples 1-3) However, the addition of a 0.75% by weight solution of 7.5 times concentrated) was started. The bottom of the particle forming vessel was connected to an expansion chamber with an ambient pressure and a temperature of 55 ° C. via an automatic back pressure regulator. The temperature and pressure of the particle formation chamber were controlled at constant levels of 63 ° C. and 180 bar, respectively. After 25 minutes of continuous operation, the acetone solution addition was stopped. After an additional 15 minutes, the CO ₂ addition was stopped. The particles deposited on the walls of the expansion chamber were stripped off and dispersed in water. The particle size distribution was then measured using a transmission electron microscope. As shown in FIG. 5, the average particle size was less than 5 nm.

Example 6 (Invention)

1147 g of CO ₂ was added to a nominal 1800 ml stainless steel particle forming vessel matched with a 4 cm diameter stirrer of the type disclosed in RD 38213, adjusting the temperature to 45 ° C., the pressure to 150 bar and stirring at 2775 rpm. Then a solution of di-2 [dispers red-60 (C ₂₀ H ₁₃ NO ₄ )] in acetone having a concentration of CO _{2 at} 80 g / min and (2 g dye) / (100 g acetone) at 1 g / min. The addition of was started.

As disclosed in RD 38213, CO ₂ and solution feedstock streams were introduced through feedstock ports terminating near the inlet zone of the mixing device (within the impeller diameter from the surface of the mixer impeller). The bottom of the particle forming vessel was connected to an expansion chamber in which the temperature and pressure of the ambient conditions prevailed through an automatic back pressure regulator. The temperature and pressure of the particle formation chamber were controlled at constant levels of 45 ° C. and 150 bar, respectively. After 30 minutes of continuous operation, the dye solution addition was stopped and the CO ₂ flow was adjusted to 60 g / min. After 25 minutes, the CO ₂ flow was stopped and the particle forming chamber was gradually depressurized to ambient pressure for 21 minutes. The particles deposited on the walls of the expansion chamber were stripped off and dispersed in water and observed by transmission electron microscopy. As shown in FIG. 6, the average particle size was found to be less than 20 nm.

Example 7 (Invention)

1096 g of CO in a nominal 1800 ml stainless steel particle forming vessel with a feedstock port, matched with a 4 cm diameter stirrer of the type disclosed in U.S. Pat. ₂ was added. Then CO ₂ is added at 30 g / min through a feedstock port with a 200 μm orifice at its end, and a solution of salicylic acid in acetone having a concentration of (2 g salicylic acid) / (100 g acetone) at 5 g / min is added. Started to. The bottom of the particle forming vessel was connected to an expansion chamber in which the temperature and pressure of the ambient conditions prevailed through an automatic back pressure regulator. The temperature and pressure of the particle formation chamber were controlled at constant levels of 70 ° C. and 300 bar, respectively. After 1 hour of continuous operation, the discharge flow from the particle forming vessel was re-delivered away from the expansion chamber. The particles deposited on the walls of the expansion chamber were stripped off and dispersed in heptane and turned on. Sizes were analyzed by transmission electron microscopy (FIG. 7A) and image analyzer (FIG. 7B). The average particle size was less than 5 nm.

Example 8 (Invention)

Using the particle formation vessel and feedstock pot arrangement used in Example 2, CO ₂ was added while adjusting the temperature to 45 ° C. and the pressure to 180 bar. Stirring speed was maintained at 2775 rpm. Subsequently, the addition of CO ₂ at 80 g / min through a feedstock port having a 200 μm orifice at its end, and the organic light emitting diode dopant compound in acetone at 1 g / min through a 100 μm end (C545-T, the compound above) The structure of (shown below) began the addition of a 0.5% by weight solution.

The bottom of the particle forming vessel was connected to an expansion chamber with an ambient pressure and a temperature of 55 ° C. via an automatic back pressure regulator. The temperature and pressure of the particle formation chamber were controlled at constant levels of 45 ° C. and 180 bar, respectively. After 25 minutes of continuous operation, the acetone solution addition was stopped and the CO ₂ flow rate was reduced to 60 g / min. Particles deposited on the walls of the expansion chamber were stripped and dispersed in heptane. The particle size distribution was then examined by transmission transmission electron microscopy. As shown in FIG. 8, the average particle size was less than 10 nm.

Claims (18)

(i) filling a supercritical fluid into a particle-forming vessel in which temperature and pressure are controlled; (ii) stirring the contents of the particle-forming vessel with a rotary stirrer comprising an impeller surface and an impeller having an impeller diameter, such that a relatively high stirring zone is located within one impeller diameter distance from the impeller surface of the rotary stirrer; and Creating a bulk mixing zone located at a distance greater than one impeller diameter from the impeller surface; (iii) in the stirred particle forming vessel, at least through the first feedstock stream port, the candle via a first feedstock stream and a second feedstock stream port comprising at least a solvent and the desired material dissolved therein; Introducing a second feedstock stream comprising a critical fluid, the material of interest being relatively insoluble in the supercritical fluid relative to solubility in the solvent, the solvent being soluble in the supercritical fluid, The first and second feedstock stream ports are located within one impeller diameter distance from the impeller surface of the rotary stirrer such that the first and second feedstock streams are introduced into the highly stirred zone of the particle forming vessel, and the first 1 a feedstock stream is dispersed in the supercritical fluid by the action of the rotary stirrer so that the solvent Extraction into a base supercritical fluid; And (iv) precipitating particles of the desired material in the particle forming vessel to a volume-weighted average diameter of less than 100 nm. The method of claim 1, (v) addition of a supercritical fluid, solvent, and desired material from the particle forming vessel to the container in step (iii) while maintaining the temperature and pressure in the particle forming vessel at the required constant levels. Evacuating at a rate substantially equal to the rate such that the formation of particulate material occurs under essentially steady state continuous conditions. The method of claim 2, Wherein said supercritical fluid, solvent and desired material are discharged from said particle formation vessel by passage to an expansion chamber. The method of claim 3, wherein Wherein said supercritical fluid, solvent, and desired material are discharged from said particle forming vessel by a passage through a backpressure regulator. The method of claim 3, wherein Wherein the supercritical fluid, solvent and desired material are discharged from the particle forming vessel by a passage through capillary. The method of claim 3, wherein Said supercritical fluid, solvent and desired material are discharged from said particle forming vessel by passages through a flow distributor. The method of claim 3, wherein Collecting the particles of desired material in the expansion chamber. The method of claim 1, Wherein said supercritical fluid, solvent and desired substance are discharged directly from said particle forming vessel into solution to form a dispersion of formed particles of the desired substance. The method of claim 1, And particles of the desired material are precipitated in the particle forming vessel with a volume-weighted average diameter of less than 50 nm. The method of claim 1, And particles of the desired material are precipitated in the particle forming vessel to a volume-weighted average diameter of less than 10 nm. The method of claim 10, And wherein the coefficient of variation of the particle size distribution of the particles of the desired substance precipitated in the particle forming vessel is less than 50%. The method of claim 11, And wherein the coefficient of variation of the particle size distribution of the particles of the desired substance precipitated in the particle forming vessel is less than 20%. The method of claim 1, And wherein the coefficient of variation of the particle size distribution of the particles of the desired substance precipitated in the particle forming vessel is less than 50%. The method of claim 13, And wherein the coefficient of variation of the particle size distribution of the particles of the desired substance precipitated in the particle forming vessel is less than 20%. The method of claim 1, Wherein said desired material comprises a colorant. The method of claim 15, Wherein said desired material comprises a dye. The method of claim 1, Wherein said substance of interest comprises a pharmaceutically useful compound. The method of claim 1, Wherein said material of interest comprises a compound used to make an organic electroluminescent device.

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